Biological Psychiatry

Article in Press, Corrected Proof

Long-term treatment with paroxetine increases verbal declarative memory and hippocampal volume in posttraumatic stress disorder

Eric Vermetten, Meena Vythilingam, Steven M. Southwick, Dennis S. Charney and J. Douglas Bremner

            Animal studies have shown that stress is associated with damage to the hippocampus, inhibition of neurogenesis, and deficits in hippocampal-based memory dysfunction. Studies in patients with posttraumatic stress disorder (PTSD) found deficits in hippocampal-based declarative verbal memory and smaller hippocampal volume, as measured with magnetic resonance imaging (MRI). Recent preclinical evidence has shown that selective serotonin reuptake inhibitors promote neurogenesis and reverse the effects of stress on hippocampal atrophy. This study assessed the effects of long-term treatment with paroxetine on hippocampal volume and declarative memory performance in PTSD. Methods Declarative memory was assessed with the Wechsler Memory Scale–Revised and Selective Reminding Test before and after 9–12 months of treatment with paroxetine in PTSD. Hippocampal volume was measured with MRI. Of the 28 patients who started the protocol, 23 completed the full course of treatment and neuropsychological testing. Twenty patients were able to complete MRI imaging. Results Patients with PTSD showed a significant improvement in PTSD symptoms with treatment. Treatment resulted in significant improvements in verbal declarative memory and a 4.6% increase in mean hippocampal volume. Conclusions These findings suggest that long-term treatment with paroxetine is associated with improvement of verbal declarative memory deficits and an increase in hippocampal volume in PTSD.



Single photon emission computed tomography in posttraumatic stress disorder before and after treatment with a selective serotonin reuptake inhibitor, J Affective Disorders, In Press, Soraya Seedat, James Warwick, Barend van Heerden, Charmaine Hugo, Nompumelelo Zungu-Dirwayi, Jeanine Van Kradenburg, and Dan J. Stein

            Background: Posttraumatic stress disorder (PTSD) is recognized as a disorder mediated by specific neurobiological circuits. Functional imaging studies using script-driven trauma imagery and pharmacological challenges have documented altered cerebral function (activation and deactivation) in several brain regions, including the amygdala, hippocampus, prefrontal cortex and anterior cingulate. However, the neural substrates of PTSD remain poorly understood and the effect of selective serotonin reuptake inhibition on regional cerebral activity is deserving of further investigation. Methods: Eleven adult patients (seven men, four women) (mean age+S.D.=33.6±9.2 years) with a DSM-IV diagnosis of PTSD, as determined by the Structured Clinical Interview for DSM-IV (SCID-I) and the Clinician-Administered PTSD Scale (CAPS), underwent single photon emission computed tomography (SPECT) with Tc-99m HMPAO pre- and post-8 weeks of treatment with the selective serotonin reuptake inhibitor, citalopram. Symptoms were assessed at baseline and at 2-week intervals with the Clinician-Administered PTSD Scale (CAPS), Montgomery–Asberg Depression Rating Scale (MADRS), and the Clinical Global Impression Scale (CGI). Image analysis of baseline and post-treatment scans was performed using Statistical Parametric Mapping (SPM). Results: Treatment with citalopram resulted in significant deactivation in the left medial temporal cortex irrespective of clinical response. On covariate analysis, a significant correlation between CAPS score reduction and activation in the left paracingulate region (medial prefrontal cortex) was observed post-treatment. No significant pre-treatment differences were observed between responders and non-responders in anterior cingulate perfusion. Conclusions: These preliminary findings are consistent with clinical data indicating temporal and prefrontal cortical dysfunction in PTSD and preclinical data demonstrating serotonergic innervation of these regions. However, further studies, in particular in vivo receptor imaging studies, are needed to confirm whether these regional abnormalities correlate with clinical features and treatment response.




Journal of Rehabilitation Research and Development Vol. 40, No. 5, Sept/Oct 2003 Pages 397–

An examination of the relationship between chronic pain and post-traumatic stress disorder

John D. Otis, PhD; Terence M. Keane, PhD; Robert D. Kerns, PhD

            This review summarizes the current literature pertaining to the prevalence and development of chronic pain and PTSD. Research describing the comorbidity of both conditions is reviewed, and several theoretical models are presented to explain the mechanisms by which these two disorders may be maintained. Future directions for research and clinical implications are discussed.




J Neuropsychiatry Clin Neurosci 15:367-370, August 2003

In Vivo Proton Magnetic Resonance Spectroscopy of the Medial Temporal Lobes of Former Prisoners of War With and Without Posttraumatic Stress Disorder

Shelley Brown, M.D., Thomas Freeman, M.D., Tim Kimbrell, M.D., David Cardwell, B.S. and Richard Komoroski, Ph.D.; Thomas.Freeman@med.va.gov

            Proton magnetic resonance spectroscopy was used to compare medial temporal lobe (MTL) concentrations of N-acetylaspartate and choline between former prisoners of war (POWs) with and without posttraumatic stress disorder (PTSD). MTL N-acetylaspartate and reexperiencing symptoms correlated strongly in the POW subjects with PTSD, suggesting a relationship between reexperiencing symptoms and the integrity of MTL structures.



Neuropsychopharmacology (2003) 28, 1656-1665

Higher Cortisol Levels Following Exposure to Traumatic Reminders in Abuse-Related PTSD

Bernet M Elzinga1, Christian G Schmahl2, Eric Vermetten3, Richard van Dyck4 and J Douglas Bremner5,6,7

E-mail: elzinga@fsw.leidenuniv.nl

            Animal studies have found that prior stressful events can result in increased reactivity in the HPA-axis. However, baseline function of the HPA-axis has typically been normal or decreased in post-traumatic stress disorder (PTSD). The first purpose of this study was to assess cortisol responsivity to traumatic reminders in women with PTSD related to childhood abuse. The second aim was to assess the relationship between stress-induced cortisol levels and neutral and emotional memory. Salivary cortisol levels were measured before, during and after exposure to personalized trauma scripts in abused women with (N=12) and without current PTSD (N=12). Memory for neutral and emotional material was assessed immediately after trauma scripts exposure and 3 days later. PTSD patients had 122% higher cortisol levels during script exposure, 69% higher cortisol levels during recovery, and 60% higher levels in the period leading up to the script exposure compared to controls. PTSD symptoms were highly predictive of cortisol levels during trauma script exposure (r=0.70), but not during periods of rest. Both in PTSD patients and controls, memory consolidation after the trauma scripts was impaired relative to baseline (P<0.001), with no differences between the two groups on memory performance. There was no association between memory performance and cortisol levels. These results are consistent with higher cortisol levels following exposure to traumatic stressors in PTSD.





Volume 28, Issue 6 , August 2003, Pages 733-750

Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse

J. D. Bremnerb, c, , , a, M. Vythilingamd, E. Vermettenb, c, a, J. Adilb, c, a, S. Khanb, c, a, A. Nazeerb, c, a, N. Afzalb, c, a, T. McGlashane, B. Elzingab, c, a, G. M. Andersonf, G. Heningere, S. M. Southwicke and D. S. Charneyd

            Preclinical studies show that animals with a history of chronic stress exposure have increased hypothalamic-pituitary-adrenal (HPA) axis reactivity following reexposure to stress. Patients with posttraumatic stress disorder (PTSD) have been found to have normal or decreased function of the HPA axis, however no studies have looked at the HPA response to stress in PTSD. The purpose of this study was to assess cortisol responsivity to a stressful cognitive challenge in patients with PTSD related to childhood abuse. Salivary cortisol levels, as well as heart rate and blood pressure, were measured before and after a stressful cognitive challenge in patients with abuse-related PTSD (N=23) and healthy comparison subjects (N=18). PTSD patients had 61% higher group mean cortisol levels in the time period leading up to the cognitive challenge, and 46% higher cortisol levels during the time period of the cognitive challenge, compared to controls. Both PTSD patients and controls had a similar 66–68% increase in cortisol levels from their own baseline with the cognitive challenge. Following the cognitive challenge, cortisol levels fell in both groups and were similar in PTSD and control groups. PTSD patients appeared to have an increased cortisol response in anticipation of a cognitive challenge relative to controls. Although cortisol has been found to be low at baseline, there does not appear to be an impairment in cortisol response to stressors in PTSD.




Neuropsychopharmacology advance online publication, 11 June 2003;

Delta Sleep Response to Metyrapone in Post-Traumatic Stress Disorder

Thomas C Neylan, Maryanne Lenoci, Melissa L Maglione, Nicholas Z Rosenlicht, Thomas J Metzler, Christian Otte, Frank B Schoenfeld, Rachel Yehuda and Charles R Marmar; E-mail: neylan@itsa.ucsf.edu

Metyrapone blocks cortisol synthesis, which results in the stimulation of hypothalamic cortiocotropin-releasing factor (CRF) and a reduction in delta sleep. We examined the effect of metyrapone administration on endocrine and sleep measures in male subjects with and without chronic PTSD. We hypothesized that metyrapone would result in a decrease in delta sleep and that the magnitude of this decrease would be correlated with the endocrine response. Finally, we utilized the delta sleep response to metyrapone as an indirect measure of hypothalamic CRF activity and hypothesized that PTSD subjects would have decreased delta sleep at baseline and a greater decrease in delta sleep induced by metyrapone. Three nights of polysomnography were obtained in 24 male subjects with combat-related PTSD and 18 male combat-exposed normal controls. On day 3, metyrapone was administered during normal waking hours until habitual sleep onset preceding night 3. Endocrine responses to metyrapone were measured in plasma obtained the morning following sleep recordings, the day before and after administration. Repeated measures ANOVAs were conducted to compare the endocrine and sleep response to metyrapone in PTSD and controls. PTSD subjects had significantly less delta sleep as indexed by stages 3 and 4, and total delta integrated amplitude prior to metyrapone administration. There were no differences in premetyrapone cortisol or ACTH levels in PTSD vs controls. PTSD subjects had a significantly decreased ACTH response to metyrapone compared to controls. Metyrapone caused an increase in awakenings and a marked decrease in quantitative measures of delta sleep that was significantly greater in controls compared to PTSD. The decline in delta sleep was significantly associated with the magnitude of increase in both 11-deoxycortisol and ACTH. The results suggest that the delta sleep response to metyrapone is a measure of the brain response to increases in hypothalamic CRF. These data also suggest that the ACTH and sleep EEG response to hypothalamic CRF is decreased in PTSD.




Psychiatry Research: Neuroimaging, Volume 123, Issue 2, 30 June 2003

Single-voxel proton MR spectroscopy of right versus left hippocampi in PTSD, Pages 101-108

P. Mohanakrishnan Menon, Henry A. Nasrallah, Judith A. Lyons, Mertis F. Scott and Vincent Liberto

            Previous magnetic resonance (MR) volume imaging and proton MR spectroscopy studies have suggested a reduction in the hippocampal size and/or neuronal/axonal density in posttraumatic stress disorder (PTSD). The lack of agreement on the laterality of the hippocampal dysfunction prompted this study. A total of 20 veterans (18 men and two women) and one female non-veteran participated in this study conducted in accordance with approved human study protocols. Six of the male veterans and the female non-veteran were without PTSD. Vietnam veterans formed a large subset of the study subjects. Single-voxel proton MR spectra were obtained from the hippocampal region bilaterally on a clinical MR scanner operating at 1.5 T. Analysis of the proton MR spectra showed a decrease in hippocampal NAA/creatine ratio in PTSD subjects significantly higher on the left than the right for the entire study group, as well as for the Vietnam subset. It was concluded that the hippocampal dysfunction in PTSD is lateralized with the left side being more impaired than the right.



Psychiatry Research

Volume 119, Issues 1-2 , 15 July 2003, Pages 171-175

Prospective evaluation of plasma cortisol in recent trauma survivors with posttraumatic stress disorder

Omer Bonne, , a, Dalia Brandesa, Ronen Segmana, Roger K. Pitmanb, Rachel Yehudac, d and Arieh Y. Shaleva

            Hypothalamic pituitary adrenal axis abnormalities have been described in posttraumatic stress disorder (PTSD), and among the recently traumatized. Plasma cortisol and continuous measures of PTSD symptoms were obtained from 21 survivors, at 1 week and 6 months after traumatic events. Eight survivors met Clinician Administered PTSD Scale criteria for PTSD at 6 months. Cortisol levels at 1 week did not predict subsequent PTSD. Survivors with and without PTSD had similar mean levels of cortisol at both time points. Cortisol levels at 6 months negatively correlated with self-reported PTSD symptoms within PTSD subjects.






Volume 19, Issue 3 , July 2003, Pages 587-600

Sensing the invisible: differential sensitivity of visual cortex and amygdala to traumatic context

Talma Hendler, , a, Pia Rotshteina, Yaara Yeshuruna, Tal Weizmannb, c, Itamar Kahna, Dafna Ben-Bashata, Rafael Malachd and Avi Bleichb, c

            To what extent does emotional traumatic context affect sensory processing in the brain? A striking example of emotional impact on sensation is manifested in posttraumatic stress disorder (PTSD), in which a severe emotional trauma produces recurrent and vivid unpleasant sensory recollections. Here we report on an fMRI study exploring the sensory processing of trauma-related pictures in the visual cortex and amygdala in respect to PTSD. The impact of traumatic experience on brain responses was tested in relation to stimuli content and its level of recognition in a parametric factorial design. Twenty combat veterans, 10 with and 10 without PTSD, viewed backward-masked images of combat and noncombat content, presented at below, near, and above recognition thresholds. The response to combat content evoked more activation in the visual cortex in PTSD subjects than in non-PTSD subjects, only when images were presented at below recognition threshold. By contrast, the amygdala demonstrated increased activation in PTSD subjects irrespective of content and recognition threshold of the images. These intriguing findings are compatible with the notion that in PTSD, emotional traumatic experience could modify visual processing already at the preattentive level. On the other hand, lack of content specificity in the amygdala point to a possible predisposed mechanism for pathological processing of traumatic experience. The differential sensitivity of the amygdala and visual cortex to traumatic context implies distinct roles of limbic and sensory regions in the registration and recollection of emotional experience in the brain.




Article in Press, Corrected Proof - Note to users

Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder

Rachel Yehuda, , Sarah L. Halligan, Julia A. Golier, Robert Grossman and Linda M. Bierer

            Objective: To evaluate cortisol suppression following 0.5 mg of dexamethasone (DEX) in trauma survivors (N=52) with posttraumatic stress disorder (PTSD), major depressive disorder (MDD), both, or neither disorder, and in subjects never exposed to trauma (N=10), in order to examine interactions between diagnosis and trauma history on cortisol negative feedback inhibition. Method: Lifetime trauma exposure and psychiatric diagnoses were assessed and blood samples were obtained at 8:00 a.m. for the determination of baseline cortisol. Participants ingested 0.5 mg of DEX at 11:00 p.m. and blood samples for determination of cortisol and DEX were obtained at 8:00 a.m. the following day.Results: PTSD was associated with enhanced cortisol suppression in response to DEX. Among trauma survivors, the presence of a traumatic event prior to the "focal" trauma had a substantial impact on cortisol suppression in subjects with MDD. Such subjects were more likely to show cortisol alterations similar to those associated with PTSD, whereas subjects with MDD with no prior trauma were more likely to show alterations in the opposite direction, i.e. relative non-suppression. Conclusions: Cortisol hypersuppression in PTSD appears not to be dependent on the presence of traumatic events prior to the focal trauma. However, prior trauma exposure may affect cortisol suppression in MDD. This finding may have implications for understanding why only some depressed patients show non-suppression on the DST





Article in Press, Corrected Proof - Note to users

Blunted growth hormone response to clonidine in post-traumatic stress disorder

Philip Morris, , a, Malcolm Hopwoodb, Kay Maguirec, Trevor Normanb and Isaac Schweitzerc

            Hyperactivity of the sympathetic and noradrenergic systems is thought to be a feature of post-traumatic stress disorder (PTSD). Assessment of noradrenergic receptor function can be undertaken by measuring the growth hormone (GH) response to the 2-agonist clonidine. The aim of this study was to examine whether subjects with combat-related PTSD (with or without co-morbid depression) have a blunted growth hormone response to clonidine, compared to a combat-exposed control group. Twenty-three Vietnam veterans suffering from PTSD alone, 27 suffering from PTSD and co-morbid depression, and 32 veteran controls with no psychiatric illness were administered 1.5 g/kg clonidine i.v. Plasma growth hormone was measured every 20 min for 120 min. The growth hormone response to clonidine was significantly blunted in the non-depressed PTSD group compared to both the depressed PTSD group and the control group as measured by peak growth hormone, delta growth hormone and AUC growth hormone. Subjects with PTSD and no co-morbid depressive illness show a blunted growth hormone response to clonidine. This suggests that post-synaptic 2-receptors are subsensitive. This finding is consistent with other studies showing increased noradrenergic activity in PTSD.



Clinical Psychology Review

Volume 23, Issue 4 , July 2003, Pages 587-603

Posttraumatic disorders following injury: an empirical and methodological review

Meaghan L. O'Donnella, b, , , Mark Creamerb, c, Richard A. Bryantd, Ulrich Schnydere and Arik Shalevf

            Although there has been a marked increase in research on psychological disorders following physical injury in recent years, there are many discrepancies between the reported findings. This paper reviews the prevalence outcomes of recent studies of the mental health sequelae of physical injury with a focus on posttraumatic stress disorder (PTSD), acute stress disorder (ASD), and depression. The review critically outlines some of the methodological factors that may have contributed to these discrepancies. The phenomenological overlap between organic and psychogenic symptoms, the use of narcotic analgesia, the role of brain injury, the timing and content of assessments, and litigation are discussed in terms of their potential to confound findings with this population. Recommendations are proposed to clarify methodological approaches in this area. It is suggested that a clearer understanding of the psychological effects of physical injury will require the widespread adoption of more rigorous, standardized and transparent methodological procedures.




Journal of Anxiety Disorders

Volume 17, Issue 5 , 2003, Pages 479-499

Prolonged exposure counterconditioning as a treatment for chronic posttraumatic stress disorder

Nenad Paunovi, 

Department of Psychology, Stockholm University, Stockholm, Sweden

            A counterconditioning model is presented from which the behavioral treatment prolonged exposure counterconditioning (PEC) was developed. The first part of a PEC session is intended to increase trauma exposure tolerance and counter numbing symptoms, the second to elicit trauma responses fully, and the third to weaken trauma responses. The first client with chronic posttraumatic stress disorder (PTSD) who was treated with PEC is presented. A statistical technique for analyzing single-case subject designs was used to evaluate the treatment. PEC effectively decreased the client's PTSD and associated psychopathology. Crucial differences between PEC and other behavioral treatments are discussed. An associative functional model is presented as a potentially useful conceptualization of PTSD, depression, and other anxiety disorders.



Behaviour Research and Therapy

Volume 41, Issue 9 , September 2003, Pages 1105-1112

Posttraumatic stress disorder and psychosocial functioning within two samples of MVA survivors

Eric Kuhn, , a, Edward B. Blancharda and Edward J. Hicklingb, a

            To examine criterion F variables of PTSD, the psychosocial functioning of two samples of motor vehicle accident (MVA) survivors was investigated. Within each sample, comparisons between MVA survivors with and without PTSD were conducted on four psychosocial functioning indices at three time points. In addition, the relationships between specific PTSD symptom clusters and psychosocial functioning indices were examined. The study revealed that, in general, MVA survivors with PTSD evidenced poorer psychosocial functioning than did survivors without PTSD. The emotional numbing symptoms of PTSD emerged as the most consistent predictors of the psychosocial functioning indices. The implications of these findings to the comprehensive treatment of PTSD are discussed.




Clin Psychol Rev. 2003 May;23(3):339-376

Psychological theories of posttraumatic stress disorder,

Chris R. Brewin and Emily A. Holmes

            We summarize recent research on the psychological processes implicated in posttraumatic stress disorder (PTSD) as an aid to evaluating theoretical models of the disorder. After describing a number of early approaches, including social-cognitive, conditioning, information-processing, and anxious apprehension models of PTSD, the article provides a comparative analysis and evaluation of three recent theories: Foa and Rothbaum's [Foa, E. B. & Rothbaum, B. O. (1998). Treating the trauma of rape: cognitive behavioral therapy for PTSD. New York: Guilford Press] emotional processing theory; Brewin, Dalgleish, and Joseph's [Psychological Review 103 (1996) 670] dual representation theory; Ehlers and Clark's [Behaviour Research and Therapy 38 (2000) 319] cognitive theory. We review empirical evidence relevant to each model and identify promising areas for further research.



Clin Psychol Rev. 2003 May;23(3):377-407.

Sleep and posttraumatic stress disorder: a review, Pages 377-407

Allison G. Harvey, Charlie Jones and D. Anne Schmidt

            Research seeking to establish the relationship between sleep and posttraumatic stress disorder (PTSD) is in its infancy. An empirically supported theory of the relationship is yet to emerge. The aims of the present paper are threefold: to summarise the literature on the prevalence and treatment of sleep disturbance characteristic of acute stress disorder (ASD) and PTSD, to critically review this literature, and to draw together the disparate theoretical perspectives that have been proposed to account for the empirical findings. After a brief overview of normal human sleep, the literature specifying the relation between sleep disturbance and PTSD is summarized. This includes studies of the prevalence of sleep disturbance and nightmares, content of nightmares, abnormalities in rapid eye movement (REM) sleep, arousal threshold during sleep, body movement during sleep, and breathing-related sleep disorders. In addition, studies of the treatment of sleep disturbance in individuals with PTSD are reviewed. We conclude that the role of sleep in PTSD is complex, but that it is an important area for further elucidating the nature and treatment of PTSD. Areas for future research are specified. In particular, a priority is to improve the methodology of the research conducted.



Clin Psychol Rev. 2003 May;23(3):409-448

Posttraumatic stress disorder following medical illness and treatment,

Josephine E. Tedstone and Nicholas Tarrier

            Studies describing posttraumatic stress disorder (PTSD) as a result of physical illness and its treatment were reviewed. PTSD was described in studies investigating myocardial infarction (MI), cardiac surgery, haemorrhage and stroke, childbirth, miscarriage, abortion and gynaecological procedures, intensive care treatment, human immunodeficiency virus (HIV) infection, awareness under anaesthesia, and in a group of miscellaneous conditions. Cancer medicine was not included as it had been the subject of a recent review in this journal. Studies were reviewed in terms of the prevalence rates for PTSD, intrusive and avoidance symptoms, predictive and associated factors and the consequences of PTSD on healthcare utilization and outcome. There was considerable variability both in the study methodology and design and in the results. The highest prevalence rates were identified in patients treated in intensive care units (ICUs) and those with HIV infection. Irrespective of the physical illness, posttraumatic symptomatology is more common than PTSD caseness. Existing characteristics of the patient may well predispose individuals to the development of PTSD as do other factors such as poor social support and negative interactions with healthcare staff. Generally, the severity of the illness itself is not predictive of PTSD. Issues relating to sampling, attrition, diagnosis, the course of symptoms, aetiological pathways, and the consequences of the disorder are discussed. The presence of PTSD most probably influences the patient's use of healthcare resources and may affect their clinical outcome.



Clin Psychol Rev. 2003 May;23(3): 449-480

Vicarious traumatization: implications for the mental health of health workers?, 449-480

Rachel Sabin-Farrell and Graham Turpin

            It has been suggested that a unique feature of some mental heath practitioners' work is exposure through their role as therapists to clients' descriptions of and reactions to trauma, and that these experiences may actually indirectly cause distress and traumatization to the therapist. This proposed phenomenon has been termed "vicarious traumatization" (VT) and is the focus of the current review. The concept of VT, together with other related concepts such as "burnout," "compassion fatigue," "secondary traumatic stress" (STS), and "work stress" are appraised. Psychological mechanisms that might be theoretically involved in VT are considered. The measurement of VT is reviewed alongside the limited research evidence supporting its existence. Factors such as direct trauma exposure and the personal attributes of mental health workers, which have been suggested to be associated with VT, are also assessed. It is concluded that the evidence to support the existence of VT is meager and inconsistent. Future research needs to be directed at distinguishing VT from other sources of distress arising within the workplace. Finally, the organizational relevance of VT and its possible implications for the management of mental health workers are critically appraised.



Clin Psychol Rev. 2003 May;23(3): 481-499

Single-session early psychological interventions following traumatic events 481-499

Jonathan I. Bisson

            Single-session early psychological interventions became widely advocated during the 1980s and 1990s as a way to prevent the development of psychological sequalae following traumatic events. There have now been 13 randomised controlled trials of single-session interventions within 1 month of a traumatic event. Notwithstanding their methodological shortcomings and clinical heterogeneity, the results are neutral overall in terms of clinical effectiveness. Possible explanations include a failure to encourage individuals' personal coping mechanisms and defence mechanisms and that insufficient time was allowed for habituation to intense exposure to occur. With the present evidence, the routine use of single-session interventions following traumatic events cannot be justified. This does not mean that there should be nothing offered, as many individuals involved in traumatic events clearly have emotional needs. Hopefully, future research will identify alternative forms of early intervention that prove useful to those individuals who would otherwise develop more significant psychological difficulties.




Clin Psychol Rev. 2003 May;23(3): 501-522

Cognitive behaviour therapy for posttraumatic stress disorder

Allison G. Harvey, Richard A. Bryant and Nicholas Tarrier

            Following considerable empirical scrutiny, cognitive behaviour therapy (CBT) has proven to be a safe and effective treatment for posttraumatic stress disorder (PTSD). This article overviews the general principles of treatment and describes the components that comprise CBT for PTSD. We then move on to review the efficacy of CBT for the treatment of PTSD caused by various traumas, including assault, road traffic accident (RTA), combat, and terrorism. Recent advances in early intervention and in the treatment of disorders that are comorbid with PTSD are reviewed. Finally, future directions are discussed. In particular, it is proposed that randomised controlled trials (RCT) of CBT for PTSD must be conducted with enhanced methodological rigour and public health relevance.



Prospective evaluation of plasma cortisol in recent trauma survivors with posttraumatic stress disorder, Psychiatry Research, Volume 119, Issues 1-2, 15 July 2003, Pages 171-175

Omer Bonne, Dalia Brandes, Ronen Segman, Roger K. Pitman, Rachel Yehuda and Arieh Y. Shalev

            Hypothalamic pituitary adrenal axis abnormalities have been described in posttraumatic stress disorder (PTSD), and among the recently traumatized. Plasma cortisol and continuous measures of PTSD symptoms were obtained from 21 survivors, at 1 week and 6 months after traumatic events. Eight survivors met Clinician Administered PTSD Scale criteria for PTSD at 6 months. Cortisol levels at 1 week did not predict subsequent PTSD. Survivors with and without PTSD had similar mean levels of cortisol at both time points. Cortisol levels at 6 months negatively correlated with self-reported PTSD symptoms within PTSD subjects.




Performance on visuospatial copying tasks in individuals with chronic posttraumatic stress disorder, Psychiatry Research, Volume 112, Issue 3, 15 November 2002, Pages 263-268

Tamara V. Gurvits, Natasha B. Lasko, Ann L. Repak, Linda J. Metzger, Scott P. Orr and Roger K. Pitman

            The ability to copy figures was evaluated in 41 subjects with chronic posttraumatic stress disorder (PTSD) and 27 trauma-exposed, non-PTSD comparison subjects. Individuals with PTSD demonstrated significantly impaired performance. However, after adjusting for pre-trauma variables, there was only a marginally significant association between figure-copying performance and PTSD. These findings are consistent with pre-trauma visual-spatial impairment as being among the risk factors for chronic PTSD.




A pilot study of noradrenergic and HPA axis functioning in PTSD vs. panic disorder, Psychiatry Research, Volume 110, Issue 3, 31 July 2002, Pages 219-230

Randall D. Marshall, Carlos Blanco, David Printz, Michael R. Liebowitz, Donald F. Klein and Jeremy Coplan

            The biological literature in the anxiety disorders has focused on comparisons between patient groups and normal volunteers, with relatively little comparative study of the anxiety disorders. We therefore conducted this pilot study to compare a group of patients with post-traumatic stress disorder (PTSD) (n=7) to a contiguously studied panic disorder group (n=17) and healthy control subjects (n=16) on baseline levels of cortisol and 3-methoxy-4-hydroxyphenylglycol (MHPG), and response to clonidine challenge. Despite the small sample size, highly significant differences were found on the following measures: PTSD patients had lower cortisol, lower MHPG, reduced MHPG volatility to clonidine challenge, and marginally reduced cortisol volatility compared to patients with panic disorder. These biological findings support existing clinical, epidemiologic, family study, and clinical trial findings that distinguish these two disorders as distinct syndromes.




PTSD symptoms and cognitive performance in recent trauma survivors, Psychiatry Research, Volume 110, Issue 3, 31 July 2002, Pages 231-238

Dalia Brandes, Gershon Ben-Schachar, Assaf Gilboa, Omer Bonne, Sara Freedman and Arieh Y. Shalev

            Chronic post-traumatic stress disorder (PTSD) has been associated with cognitive impairments involving memory and attention. The association between cognitive impairment and early PTSD symptoms is unknown, yet such association may lead to poorer processing of traumatic memories and thereby contribute to subsequent PTSD. This study evaluated the relationship between PTSD symptoms and cognitive functioning within 10 days of traumatic events. Forty-eight survivors were assessed for symptoms of PTSD, anxiety, depression and dissociation and for immediate and delayed verbal and figural memory, attention, learning and IQ. Survivors with high levels of PTSD symptoms showed impaired attention and immediate recall for figural information and lower IQ. They did not show, however, an impairment of verbal recall and learning. The observed difference was not explained by anxiety or dissociation. It disappeared, however, when the effect of depressive symptoms was controlled for. Lower IQ and impaired attention are associated with early PTSD and depressive symptoms. Poorer attention may have a role in shaping traumatic memories.





Journal of Traumatic Stress

16 (4): 319-323, August 2003

Hypothalamic–Pituitary–Adrenal Activity Among Armenian Adolescents with PTSD Symptoms

Armen K. Goenjian: agoenjia@aol.com

Robert S. Pynoos, Alan M. Steinberg, David Endres , Khachik Abraham , Mitchell E. Geffner, Lynn A. Fairbanks

            This study evaluated basal levels and responsiveness to exercise of plasma adrenocorticotropic hormone (ACTH), and serum thyroid stimulating hormone (TSH), growth hormone (GH) and cortisol among adolescents from two differentially exposed groups 6[half] years after the 1988 earthquake in Armenia. Severity of total PTSD and Category C and D symptoms were negatively correlated with baseline cortisol. Preexercise ACTH was significantly lower, and preexercise TSH higher, among adolescents with more exposure. Depressive symptoms were negatively correlated with baseline cortisol and positively with TSH. Mean GH, TSH, and cortisol levels in both groups fell within normal limits. The pre- to postexercise increase in GH, TSH, and cortisol suggests that exercise challenge may be useful in the field investigation of neurohormonal activity among traumatized individuals



Curr Psychiatry Rep. 2003 Oct;5(5):369-83.

Neuroimaging and Neurocircuitry in Post-traumatic Stress Disorder: What Is Currently Known?

Tanev K.

Department of Psychiatry, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA. tanev@psychiatry.uchc.edu

            Neurobiologic, psychologic, and social factors interact jointly to create and perpetuate the symptoms of post-traumatic stress disorder (PTSD). The fear conditioning paradigm in animal research helped researchers gather preclinical evidence for the possible contribution of several brain areas to PTSD symptoms. In the past 10 years, highly sophisticated neuroimaging techniques made it possible for researchers to look at the brain of patients with PTSD and draw conclusions about the neurocircuitry underlying PTSD symptoms. In this article, the author will review the evidence from neuroimaging studies for the involvement of the following brain areas in PTSD neurocircuitry: the amygdala, the anterior cingulate cortex and subcallosal gyrus, the inferior frontal gyrus, the posterior cingulate cortex, and the hippocampus. Neuroimaging studies have shown these areas as altered in structure or function in patients with PTSD. The author also presents the normal functions that these areas subserve and, whenever possible based on the evidence, infer how their dysfunction may contribute importantly to the symptomatology of PTSD.




Hypoactivation of the prefrontal cortex during verbal fluency test in PTSD: a near-infrared spectroscopy study.

Matsuo K, Taneichi K, Matsumoto A, Ohtani T, Yamasue H, Sakano Y, Sasaki T, Sadamatsu M, Kasai K, Iwanami A, Asukai N, Kato N, Kato T.

Several studies have suggested that there is frontal dysfunction in subjects with posttraumatic stress disorder (PTSD). We investigated the relationship between alterations of the hemodynamic response of the prefrontal cortex during a cognitive task (verbal fluency task; VFT) and memory function measured using the Wechsler Memory Scale-Revised (WMS-R). The subjects were victims of the Tokyo Subway Sarin attack with (n=8) or without (n=26) PTSD. Hemodynamic response in the prefrontal cortex was measured using a 24-channel near-infrared spectroscopy (NIRS) system. Subjects with PTSD had a significantly smaller response of oxygenated hemoglobin and total hemoglobin during the VFT compared with those without PTSD, although there was no significant difference in performance on the VFT. Subjects with PTSD had significantly lower scores on attention and concentration in the WMS-R, which was positively correlated with the increase of total hemoglobin during the VFT. The 'frontal dysfunction' observed in subjects with PTSD may be a secondary phenomenon to reduced attentional capacity.





Event-related potential dysfunction in posttraumatic stress disorder: the role of numbing, Psychiatry Research, Volume 109, Issue 2, 15 March 2002, Pages 171-179

Kim L. Felmingham, Richard A. Bryant, Carmen Kendall and Evian Gordon

            The purpose of this study was to examine the relationship between disturbance in event-related potentials (ERPs) and symptom clusters in posttraumatic stress disorder (PTSD). ERPs were recorded in 17 unmedicated civilian PTSD patients and 17 age- and sex-matched controls during a conventional auditory oddball task. PTSD symptom clusters (re-experiencing, active avoidance, numbing, hyperarousal) were correlated with ERP measures. The PTSD group showed ERP disturbances to target stimuli (reduced P200 and P300 and increased N200 amplitude, increased N200 and P300 latency) and reduced P200 amplitude to common stimuli compared to the control group. A significant negative correlation was found between the intensity of numbing symptoms and parietal P300 amplitude. This study replicates findings of disturbed N200 and P300 components in PTSD, reflecting impairments in stimulus discrimination and attention. The finding that numbing was associated with reduced attention processing (P300) is consistent with models positing a relationship between disordered arousal and attention in PTSD.



European Psychiatry

Volume 18, Issue 4 , June 2003, Pages 172-176

Prediction of the occurrence and intensity of post-traumatic stress disorder in victims 32 months after bomb attack

Louis Jehel, , a, Sabrina Paternitib, Alain Brunetc, Clara Ducheta and Julien Daniel Guelfid

            Introduction. – Our objective was to identify factors that predict occurrence and severity of post-traumatic stress disorder (PTSD) after a terrorism attack. Population. – We evaluated 32 victims of a bomb attack in a Paris subway in December 1996 at 6 and 32 months. Method.Sociodemographic characteristics, clinical data and physical injuries were used to predict PTSD occurrence and severity in 32 victims. The Watson's PTSD Inventory (PTSD-I) and the Impact of Event Scale (IES) by Horowitz were used to evaluate occurrence and severity of PTSD, respectively. Results. – Thirty-nine percent of participants met PTSD criteria at 6 months, 25% still had PTSD at 32 months. Women had PTSD 32 months after the bomb attack more frequently than men. Employment predicted PTSD severity at 32 months. PTSD scores assessed by PTSD-I at 6 months were significantly and positively associated with IES scores at 32-month follow-up (r = 0.55, P = 0.004). Psychotropic drug use before the bomb attack significantly predicted PTSD occurrence and severity at 6 and 32 months. In a linear regression model, physical injuries, employment status and psychotropic drug use before the bomb attack were independent predictors of severity of PTSD at 32 months. Conclusions. – Bomb attack exposure resulted in persisting PTSD in a significant proportion of victims; the severity was predicted at 32 months by physical injuries and psychotropic drug use before the terrorism attack and by the PTSD score few months after the bomb attack.



Annals of General Hospital Psychiatry

Risk and resiliency factors in posttraumatic stress disorder

Marcia A Voges1 and David M Romney

Email: Marcia A Voges - mavoges@ucalgary.ca; David M Romney* - romney@ucalgary.ca

            Background: Not everyone who experiences a trauma develops posttraumatic stress disorder (PTSD). The aim of this study was to determine the risk and resiliency factors for this disorder in a sample of people exposed to trauma. Method: Twenty-five people who had developed PTSD following a trauma and 27 people who had not were asked to complete the Posttraumatic Stress Diagnostic Scale, the Coping Inventory for Stressful Situations, and the State-Trait Anxiety Inventory. In addition, they completed a questionnaire to provide information autobiographic and other information. Analysis: Five variables that discriminated significantly between the two groups using chi-square analysis or t-tests were entered into a logistic regression equation as predictors, namely, being female, perceiving a threat to one's life, having a history of sexual abuse, talking to someone about the event, and the "intentionality" of the trauma.

Results: Only being female and perceiving a threat to one's life were significant predictors of PTSD. Taking base rates into account, 96.0% of participants with PTSD were correctly classified as having the disorder and 37.0% of participants without PTSD were correctly classified as not having the disorder, for an overall success rate of 65.4% Conclusions: Because women are more likely than men to develop PTSD, more preventive measures should be directed towards them. The same is true for trauma victims (of both sexes) who feel that their life was in danger



Comorbidity of PTSD and depression: associations with trauma exposure, symptom severity and functional impairment in Bosnian refugees resettled in Australia, J Affective Disorders, In Press, Corrected Proof, Available online 28 June 2003

Shakeh Momartin, Derrick Silove, Vijaya Manicavasagar and Zachary Steel

            Background: Posttraumatic stress disorder (PTSD) is common in refugees but its association with longer-term psychosocial dysfunction remains unclear. We examined whether a subgroup of refugees with comorbid PTSD and depression were at particularly high risk of disability. We also investigated whether specific trauma experiences were linked to this comorbid pattern. Methods: Consecutive Bosnians (and one or two compatriots nominated by them) were recruited from a community centre, yielding a total sample of 126 participants (response rate 86%). Measures included a trauma inventory, the Clinician Administered PTSD Scale (CAPS) ([Blake et al]) and the depression module of the Structured Clinical Interview (SCID) ( [First et al]). Results: Three diagnostic groupings emerged: normals (n=39), pure PTSD (n=29), and comorbid PTSD and depression (n=58). Of four trauma dimensions derived from principle components analysis (human rights violations, dispossession and eviction, life threat and traumatic loss), life threat alone was associated with pure PTSD, with life threat and traumatic loss both being associated with comorbidity. Compared to normals and those with pure PTSD, the comorbid group manifested more severe PTSD symptoms as well as higher levels of disability on all indices (global dysfunction: odds RATIO=5.0, P<0.001, distress: odds RATIO=6.0, P<0.001, social impairment: odds ratio 5.9, P<0.001, and occupational disability: odds ratio 5.0, P<0.001). Limitations: Recruitment was not random, the sample size was modest, and trauma event endorsement was based on retrospective accounts. Conclusions: The combination of life threat and traumatic loss may be particularly undermining to the psychological well-being of refugees and consequent comorbidity of PTSD and depression may be associated with longer-term psychosocial dysfunction. The findings raise the question whether the comorbid pattern identified should be given more recognition as a core posttraumatic affective disorder.




Partial posttraumatic stress disorder revisited, J Affective Disorders, In Press, Corrected Proof, Available online 11 September 2002

Jacques Mylle and Michael Maes

            Background: It is thought that the decision rule for a positive diagnosis of Posttraumatic Stress Disorder (PTSD) may be too restrictive, leaving too many victims of a trauma out in the cold for care, compensation, etc. Several authors have proposed the concept of Subthreshold or Partial PTSD (PPTSD). This concept considers that a subject may present a number of symptoms below threshold for criteria C or D (subthreshold syndromes) and may even present without any symptom for one or more of the criteria B, C and D (partial syndromes). Method: Data have been collected by means of the Composite International Diagnostic Interview (CIDI) PTSD-module, in a group exposed to two different traumatic events (130 fire victims and 55 car accident victims). The syndrome patterns has been assessed by means of hierarchical class analyses. Each of the criteria B, C and D has been analyzed separately, showing the symptom patterns as hierarchically order clusters. Results: Depending on the threshold used for criterion C (i.e. 3 or 2 symptoms), 18.4 and 22.7% of the subjects respectively satisfy the criteria for PTSD. 8.7% of the subjects show subthreshold syndromes. 60.7% of the subjects show partial syndromes and 16.7% of the subjects have partial syndromes while fulfilling criterion F, i.e. a clinically significant impairment in functioning. Conclusions: The results show a considerable number of partial and subthreshold syndromes. It is argued that subthreshold syndromes and partial syndromes, which fulfill criterion F, should be regarded as specific nosological categories or as specified PTSD subcategories, i.e. subsyndromal or partial PTSD.



The mediating effects of sleep in the relationship between traumatic stress and health symptom in urban police officers.

Psychosom Med 2003;65:485–489.

            2. Objectives To explore the degree to which sleep disturbance mediate the relationship between post-traumatic stress disorder (PTSD) symptoms and health in a sample of police officers. 3. Study design A cross-sectional convenience sampling from three urban police departments, with greater recruitment of minority and female officers. 4. Study population A total of 1200 officers were mailed questionnaires, 790 (66%) returned materials, 741 (62%) packages were usable, and 713 (59%) contained complete data sets. 5. Methods Two sets of independent variables (PTSD and sleep quality) were used in a series of stepped logistic regression analyses to examine the strength of their relative effects on self-reported health status. PTSD was assessed using the Mississippi Scale–Civilian Version (MS-CV), sleep- and health-related items were excluded. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), excluding items assessing absolute sleep latency and duration of sleep. Two dependent measures of health status were physical functioning, assessed using the Physical Composite Score (PCS) of the SF-12, and somatic symptoms, assessed using the Somatization subscale of the Symptom Checklist-90-R (SCL-90). Three sets of potential confounding variables (demographics ––specifically age and Hispanic ethnicity; alcohol abuse, and duty-related trauma history) were entered in the first step of each hierarchical logistic regression analysis. The relative changes in the proportion of variance explained by PTSD or sleep quality were explored. 6. Results Controlling for potential confounders, 18% of the variance in somatic symptoms was predicted by PTSD symptoms directly, this was significantly reduced to 8% when the sleep quality was entered as a primary factor. Conversely, the association between sleep quality and somatization was considerably strengthened from 15 to 25% when sleep quality was entered before the PTSD. Although the strengths of the observed relationships are relatively weak, this finding suggests that sleep disturbance may mediate somatic symptoms in this population. In a second set of analyses predicting residual physical health status, 2% of the variance was (very weakly) predicted by PTSD symptoms, dropping essentially to zero (0.3%) when the sleep quality was entered in the prior step. 7. Conclusions The authors argue that, in general, the results support the hypothesis that relationship between PTSD and health is mediated by sleep quality; more specifically, that sleep quality acts as a partial mediator of the effects of PTSD on somatic symptoms and a full mediator of health function.





The Forensic Examiner, Sept-Oct 2003 v12 i9-10 p27(7)

Childhood trauma: its relationship to behavioral and psychiatric disorders.

Kathryn Seifert.

            It is important to understand the relation ships among family violence, child maltreatment, and psychiatric and behavioral disorders in order to prevent, assess, and treat these very serious social problems. This study demonstrates a strong level of comorbidity among these problems. All subgroups (Psychiatric, Violent, Sexual Offending, Delinquent, Attachment Disordered, and Substance Abusers) had a high percentage of childhood trauma, family violence, and psychiatric problems. The psychiatric population had substantial aggression, but were less aggressive (57%) than other groups. Seventy-three to 92% of all groups had psychiatric disorders. Over 75% of all groups had histories of childhood trauma with the Attachment Disordered group having the highest percentage (98%). The study points to the need for professionals to assess a broad range of individual and family problems when persons are referred for services, regardless of the presenting problem. However, more study is needed.



J Trauma Stress. 2003 Oct;16(5):451-7.

A preliminary examination of treatment for posttraumatic stress disorder in chronic pain patients: a case study.

Shipherd JC, Beck JG, Hamblen JL, Lackner JM, Freeman JB.

            Manualized treatments have become popular, despite concern about their use when comorbid diagnoses are present. In this report, the efficacy of manualized posttraumatic stress disorder (PTSD) treatment was examined in the presence of chronic pain. Additionally, the effect of PTSD treatment on chronic pain and additional psychiatric diagnoses was explored. Six female patients with both PTSD and chronic pain following motor vehicle accidents were treated for PTSD using a multiple baseline design. The results indicate that manualized treatment for PTSD was effective in reducing PTSD symptoms in these patients. Although there were no changes in subjective pain, there were pain-related functional improvements and reductions in other psychiatric diagnoses for the majority of patients.



Scandinavian Journal of Psychology

Volume 44 Issue 5 Page 415  - December 2003

Social network as a moderator in the relation between trauma exposure and trauma reaction: A survey among UN soldiers and relief workers

Marianne Kaspersen1, Stig Berge Matthiesen2 and K. Gunnar Götestam1

            Social network as a moderator between trauma exposure and post-trauma symptomatology was studied. Two samples - relief workers and UN soldiers - were assessed on trauma exposure, social network and three dependent measures related to post-trauma reactions. Regression analysis and interaction plots were used to determine the presence of interaction effects between trauma exposure and social network. All four network variables moderated the relationship between trauma exposure and post-trauma reactions among relief workers, while among UN soldiers only two such buffer effects were found. Furthermore, among UN soldiers one of these interaction effects was reversed, indicating social support to be important for those low on trauma exposure, while among relief workers support was important in the high-exposure condition. The results indicate a difference with respect to the importance of social network as a moderator between groups exposed to different kinds of war trauma. Differences in motivational systems may also exist. However, further research will have to establish this.



Journal of Traumatic Stress

16 (6): 555-562, December 2003

Do Patients Drop Out Prematurely from Exposure Therapy for PTSD?

Elizabeth A. Hembree; Edna B. Foa; Nicole M. Dorfan; Gordon P. Street; Jeanne Kowalski; Xin Tu:  Email:  hembree@mail.med.upenn.edu


Many studies have demonstrated the efficacy of exposure therapy in the treatment of chronic posttraumatic stress disorder (PTSD). Despite the convincing outcome literature, a concern that this treatment may exacerbate symptoms and lead to premature dropout has been voiced on the basis of a few reports. In this paper, we examined the hypothesis that treatments that include exposure will be associated with a higher dropout rate than treatments that do not include exposure. A literature search identified 25 controlled studies of cognitive–behavioral treatment for PTSD that included data on dropout. The results indicated no difference in dropout rates among exposure therapy, cognitive therapy, stress inoculation training, and EMDR. These findings are consistent with previous research about the tolerability of exposure therapy.


Bisson, J.I., Shepherd, J.P., Joy, D., Probert, R., Newcombe, R.G. (2004).

Early cognitive­behavioural therapy for post-traumatic stress symptoms after physical injury: Randomised controlled trial.

The British Journal of Psychiatry (2004) 184: 63-69:BissonJI@Cardiff.ac.uk
Background Early single-session psychological interventions, including psychological debriefing following trauma, have not been shown to reduce psychological distress. Longer early psychological interventions have shown some promise.  Aims To examine the efficacy of a four-session cognitive­behavioural intervention following physical injury. Method A total of 152 patients attending an accident and emergency department displaying psychological distress following physical injury were randomised 1­3 weeks post-injury to a four-session cognitive­behavioural intervention that started 5­10 weeks after the injury or to no intervention and then followed up for 13 months. Results At 13 months, the total Impact of Event Scale score was significantly more reduced in the intervention group (adjusted mean difference=8.4,95% CI 2.4­14.36). Other differences were not statistically significant.  Conclusions A brief cognitive­behavioural intervention reduces symptoms of post-traumatic stress disorder in individuals with physical injury who display initial distress.



The British Journal of Psychiatry (2004) 184: 63-69

Early cognitive–behavioural therapy for post-traumatic stress symptoms after physical injury: a randomised controlled trial


Background Early single-session psychological interventions, including psychological debriefing following trauma, have not been shown to reduce psychological distress. Longer early psychological interventions have shown some promise.  Aims To examine the efficacy of a four-session cognitive–behavioural intervention following physical injury.  Method A total of 152 patients attending an accident and emergency department displaying psychological distress following physical injury were randomised 1–3 weeks post-injury to a four-session cognitive–behavioural intervention that started 5–10 weeks after the injury or to no intervention and then followed up for 13 months.  Results At 13 months, the total Impact of Event Scale score was significantly more reduced in the intervention group (adjusted mean difference=8.4,95% CI 2.4–14.36). Other differences were not statistically significant.  Conclusions A brief cognitive–behavioural intervention reduces symptoms of post-traumatic stress disorder in individuals with physical injury who display initial distress.



J Neuropsychiatry Clin Neurosci 16:102-108, February 2004

A CNV-Distraction Paradigm in Combat Veterans With Posttraumatic Stress Disorder

Matthew Kimble, Ph.D., Kathryn Ruddy, B.A., Patricia Deldin, Ph.D. and Milissa Kaufman, B.A.; M.Kimble@bangor.ac.uk (E-mail).

            Fourteen veterans with posttraumatic stress disorder (PTSD) and 14 without PTSD participated in a contingent negative variation (CNV)-distraction paradigm. Subjects were instructed to press a button after hearing a high-pitched tone (S2) preceded by a low-pitched tone (S1). One-half of the trials included a white-noise distracter placed in the S1–S2 interval. Posttraumatic stress disorder subjects had larger frontal, but smaller central and parietal CNVs, regardless of condition (distracter, no distracter) or epoch (early CNV, late CNV). In PTSD subjects, the N1/P2 complex was smaller to warning (S1) and distracter stimuli and did not show the extent of facilitation present in non-PTSD subjects. Findings highlight PTSD-related differences in phasic cortical excitability and attention.






Neuroscience & Biobehavioral Reviews

Article in Press, Corrected Proof

Adaptations or pathologies? Long-term changes in brain and behavior after a single exposure to severe threat

Christoph P. Wiedenmayer, , a, b

a Department of Psychiatry, Columbia University College of Physicians and Surgeons, 1051 Riverside Drive, Unit 40, New York, NY 10032, USA

b Division of Developmental Psychobiology, NY State Psychiatric Institute, New York, NY 10032, USA

            The experience of a single threatening situation may alter the behavior of an animal in a long-lasting way. Long-lasting changes in behavior have been induced in laboratory animals to model and investigate the development and neural substrate of human psychopathologies. Under natural conditions, however, changes in behavior after an aversive experience may be adaptive because behavioral modifications allow animals to adjust to a threat for extended periods of time. In the laboratory setting, properties of the aversive situation and the potential of the animal to respond to the threat may be altered and lead to extensive, prolonged changes, indicating a failure in behavioral regulation. Such long-term changes seem to be mediated by neuronal alterations in components of the fear pathway. To understand psychopathologies, determinants of exaggerated responsivity and the underlying molecular and neural processes have to be analyzed in a comparative way under conditions that produce normal and abnormal fear and anxiety.





Clinical Neuroscience Research

Volume 3, Issues 4-5 , December 2003, Pages 245-251

Stress models of depression

Barbara Vollmayr,  and Fritz A. Henn

            In order to understand the molecular changes underlying major depression animal models are needed. The best animal model of depression simulates the etiology and replicates symptoms, course and treatment of human depression. This article reviews the two most valid and best established animal models of depression, learned helplessness and chronic mild stress. Both models use uncontrollable stress to induce depressive like behavior, both have excellent face validity and replicate anhedonia and anergia in analogy to loss of interest and pleasure, one of two essential features of depression. In addition, both models demonstrate a variety of less specific symptoms like changes in locomotion, impaired learning ability, sleep alterations, loss of weight and decrease of sexual behavior. Endocrine disturbances of major depression as hypercortisolemia and dexamethasone non-suppression are also simulated in the two animal models. Neurobiological changes accompanying the depressive like behavior include dynamic changes of the monoamine systems and several peptide systems including the opioid system. Behavioral and neurobiological changes can be renormalized in both models by antidepressant treatment, which adds predictive validity to these models.



Am J Psychiatry 161:36-44, January 2004

The Nature of Traumatic Memories: A 4-T fMRI Functional Connectivity Analysis

Ruth A. Lanius, M.D., Ph.D., Peter C. Williamson, M.D., Maria Densmore, B.Sc., Kristine Boksman, M.A., R. W. Neufeld, Ph.D., Joseph S. Gati, M.Sc., and Ravi S. Menon, Ph.D.

            OBJECTIVE: This study used functional connectivity analyses to assess interregional brain activity correlations during the recall of traumatic memories in traumatized subjects with and without posttraumatic stress disorder (PTSD). METHOD: Both 4-T functional magnetic resonance imaging (fMRI) and functional connectivity analyses were used to assess interregional brain activity correlations during script-driven symptom provocation in traumatized subjects with (N=11) and without (N=13) PTSD. Functional connectivity analyses were carried out by using data for brain regions activated in both the PTSD group and the comparison group. The use of functional connectivity analyses in addition to subtraction analyses allowed assessment of specific brain regions involved in the recall of traumatic events and of the neuronal networks underlying the recall of such events. RESULTS: Significant between-group differences in functional connectivity were found. Comparison of connectivity maps at coordinates x=2, y=20, z=36 (right anterior cingulate gyrus) for the two groups showed that the subjects without PTSD had greater correlation than the PTSD subjects in the left superior frontal gyrus (Brodmann’s area 9), left anterior cingulate gyrus (Brodmann’s area 32), left striatum (caudate), left parietal lobe (Brodmann’s areas 40 and 43), and left insula (Brodmann’s area 13). In contrast, the PTSD subjects showed greater correlation than the subjects without PTSD in the right posterior cingulate gyrus (Brodmann’s area 29), right caudate, right parietal lobe (Brodmann’s areas 7 and 40), and right occipital lobe (Brodmann’s area 19). CONCLUSIONS: The differences in brain connectivity between PTSD and comparison subjects may account for the nonverbal nature of traumatic memory recall in PTSD subjects, compared to a more verbal pattern of traumatic memory recall in comparison subjects.



Am J Psychiatry 161:45-52, January 2004

Posttraumatic Stress Disorder and Health-Related Quality of Life in Long-Term Survivors of Acute Respiratory Distress Syndrome

Hans P. Kapfhammer, M.D., Ph.D., Hans B. Rothenhäusler, M.D., Till Krauseneck, M.D., Christian Stoll, M.D., and Gustav Schelling, M.D.

           OBJECTIVE: Intensive care often means exposure to physical and psychological stress, with long-lasting emotional sequelae for most patients. Psychiatric morbidity and negative effects on health-related quality of life were assessed in long-term survivors of acute respiratory distress syndrome. METHOD: Forty-six long-term survivors were enrolled in a psychiatric follow-up study. All patients had received standard, protocol-driven treatment during intensive care. The median follow-up time was 8 years after treatment. DSM-IV was used for psychiatric diagnosis. Psychological tests were performed to measure posttraumatic stress symptoms; depression; state anxiety; somatization; symptoms regarding concentration, attention, and short-term memory; social support; and health-related quality of life. RESULTS: At time of discharge, 20 of the patients suffered from posttraumaatic stress disorder (PTSD) and four from sub-PTSD. At follow-up, 11 patients continued to suffer from PTSD and eight from sub-PTSD. The patients with PTSD demonstrated a pronounced tendency for somatization and state anxiety. Among the groups with PTSD, sub-PTSD, and no PTSD, there were no statistically significant differences regarding social support and symptoms of cognitive dysfunction. Those with PTSD showed major impairments in some dimensions of health-related quality of life, whereas those without PTSD had scores that were in the range of the general population. Except for duration of stay on the intensive care unit, neither age, gender, sociodemographic variables, premorbid psychopathology, nor initial severity of illness discriminated between the groups. CONCLUSIONS: Long-term survivors of acute respiratory distress syndrome seem to face a major risk of PTSD and major impairments in health-related quality of life in the long term.






Psychiatry Research

Volume 119, Issues 1-2 , 15 July 2003, Pages 133-143

Abnormal P600 in obsessive–compulsive disorder. A comparison with healthy controls

Charalabos C. Papageorgiou, , a and Andreas D. Rabavilasa, b

Recently, the P600 component of the event-related potential (ERP), a waveform that is thought to be generated and/or modulated by the anterior cingulate gyrus and basal ganglia has been considered as an index of second pass-parsing processes of information processing, having much in common with working memory (WM) operation. Moreover, dysfunction of these brain structures as well as WM deficits have been implicated in the pathophysiology of obsessive–compulsive disorder (OCD). The present study is focused on P600 elicited during a WM test in OCD patients compared with healthy controls. Twenty drug-free OCD patients and an equal number of normal subjects matched for age, sex and educational level were studied via a computerized version of the Wechsler digit span test. Auditory P600 was measured during the anticipatory period of this test. The patient group, as compared with healthy controls, showed significantly enhanced amplitudes of P600 at the right temporoparietal area and prolonged latencies at the right parietal region. Moreover, the memory performance of patients was significantly impaired. These findings may indicate that OCD patients manifest abnormal aspects of second pass-parsing processes of information processing as they are reflected by P600 amplitudes and latencies.




Psychological Medicine (2003), 33:917-925

Neuropsychological performance of OCD patients before and after treatment with fluoxetine: evidence for persistent cognitive deficits

M. M. A. NIELEN a1c1 and J. A. DEN BOER a1

            Background. There is an ongoing debate about the nature of executive dysfunction that accompanies obsessive–compulsive disorder (OCD). One reason for this may be that state-related factors, such as use of medication or co-morbid symptoms, confound with task performance. This study tried to isolate trait- from state-dependent cognitive impairments by examining variability of cognition following treatment.

Method. Nineteen OCD patients were tested on the Cambridge Neuropsychological Test Automated Battery (CANTAB) before and after treatment with fluoxetine. Their pattern of performance was compared to the one observed in healthy volunteers (N=24).

Results. OCD patients displayed impairments in planning ability, spatial memory and motor speed that persisted after clinical improvement. With treatment, OCD performance diverged from that of controls on measures of focused attention and strategic ability. However, these effects were rather mild as they did not entail a significant deterioration of performance within the OCD sample. Conclusions. Our data suggest that cognitive impairments in OCD are not secondary to symptoms and therefore form a trait feature of the disorder. The nature of the deficits refers to a chronic dysfunction of the dorsolateralstriatal circuit. The minor effects of treatment on task performance is in line with recent evidence that serotonin mediates cognitive functions of orbitofrontal cortex to a greater extent than those associated with dorsolateral prefrontal regions.





Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 27, Issue 4 , June 2003, Pages 601-606

Event-related potentials and neuropsychological tests in obsessive–compulsive disorder

Berna Binnur Kvrcka, , , Görsev G. Yenerb, Köksal Alptekina and Huriye Aydnb

            Objective: Previous studies have provided evidence from event-related potentials (ERPs) and neuropsychological testing of abnormal cognitive processing in obsessive–compulsive disorder (OCD). The aim of this study was to further characterize the cognitive functions of the patients with OCD by utilizing ERPs and neuropsychological tests. Methods: ERPs were recorded in a group of 31 drug-free OCD patients without depression and 30 normal controls following verbal auditory stimuli using an oddball paradigm. The specific neuropsychological tests administered to assess cognitive functions in all participants were the Stroop Test, Trail Making Test, Design Fluency Test, Controlled Word Association Test (Verbal Fluency test). Results: The patient group showed shorter P300 duration compared to normal controls. In neuropsychological tests, no significant differences were found between the two groups. Negative correlations between Stroop duration and P300 amplitudes in occipital, parietal, and temporal anterior regions were observed. Conclusion: Shorter P300 duration may indicate an acceleration in the P300 process, and speeding of cognitive processing, dysfunction of cortico-subcortical circuits, or some combination of all of the above.



Psychiatry Res. 2003 Jun 30;123(2):109-23

Neuropsychological correlates of P300 abnormalities in patients with schizophrenia and obsessive–compulsive disorder

Myung-Sun Kim, Seung-Suk Kang, Tak Youn, Do-Hyung Kang, Jae-Jin Kim and Jun Soo Kwon

            The cognitive significance of P300 abnormalities in schizophrenia and obsessive–compulsive disorder (OCD) was investigated. P300 was measured by an auditory oddball paradigm, in which a series of standard tones (1000 Hz) and target tones (1500 Hz) were presented. The subject's task was to count the number of the presented target tones. Cognitive unctions were evaluated by neuropsychological tests, which were chosen to be sensitive to frontal and temporal dysfunction. Twenty-two schizophrenic patients, 19 OCD patients and 21 healthy controls participated. Event-related potentials measured at 15 electrode sites, which consisted of five levels on the left–right dimension and three levels on the anterior–posterior dimension, were included in the statistical analysis. P300 amplitudes on all 15 electrode sites were significantly smaller in schizophrenic and OCD patients than in the controls. Schizophrenic patients performed poorly on almost all neuropsychological tests, while OCD patients showed impaired performance on the ReyOsterrieth Complex Figure Test and on a controlled oral word association test. In schizophrenic patients, P300 amplitude was associated with performance on verbal memory and learning by the Luria–Nebraska Neuropsychological Battery, while for OCD patients, P300 amplitude was related to the Trail Making Test, Part B response time. These results indicate that schizophrenic patients have generalized cognitive impairments, which are substrated by a wide range of cortical dysfunctions. The major cognitive deficits observed in OCD patients were impairments of controlled attention and self-guided, flexible behavior, which are mediated by the fronto-striatal system. The neurophysiological mechanisms underlying P300 abnormalities observed in schizophrenic and OCD patients are discussed.




Progress in Neuro-Psychopharmacology and Biological Psychiatry

Volume 27, Issue 4 , June 2003, Pages 657-665

Neuropsychological performance and regional cerebral blood flow in obsessive–compulsive disorder

Acioly L. T. Lacerdaa, b, , , Paulo Dalgalarrondob, Dorgival Caetanob, Gretchen L. Haasa, c, Edwaldo E. Camargod and Matcheri S. Keshavana

a Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Room 984, 3811 O'Hara Street, Pittsburgh, PA 15213, USA

            Convergent findings from neuropsychological and neuroimaging studies have suggested that neural dysfunction in frontal–subcortical circuits may play a central role in the pathophysiology of obsessive–compulsive disorder (OCD). To further examine the relationship between these two sets of findings we investigated both neuropsychological functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls matched for age, gender, handedness, and education were assessed on neuropsychological tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with 99 mTc-hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearman's correlations indicated that severity of OCD correlated inversely with performance on the RCF (copy and recall scores) and positively with rCBF in the right thalamus. Positive correlations were observed between nonperseverative errors (WCST) and rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated negatively with rCBF in the right thalamus. These findings are consistent with most previously published studies and suggest neural dysfunctions in the frontal–subcortical circuits probably more pronounced in the right hemisphere. They also extend the existing research, showing associations between deficits in cortical–subcortical circuitry and performance on neuropsychological tests of controlled attention and visuospatial functions.




Psychiatry Res. 2003 Jun 30;123(2):125-134

Elevated thalamic and prefrontal regional cerebral blood flow in obsessive–compulsive disorder: a SPECT study,

Acioly L. T. Lacerda, Paulo Dalgalarrondo, Dorgival Caetano, Edwaldo E. Camargo, Elba C. S. C. Etchebehere and Jair C. Soares

            Functional neuroimaging studies have pointed to a possible role of cerebral circuits involving the prefrontal and anterior cingulate cortices, the striatum, and thalamus in the pathophysiology of obsessive–compulsive disorder (OCD). Regional cerebral blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects matched for age, gender, handedness and level of education was measured with [99m-Tc] HMPAO single photon emission computed tomography. Analysis of covariance identified four regions of interest with significantly higher rCBF: the right superior and inferior frontal cortex and the right and left thalamus. Positive correlations between symptom severity measured by Clinical Global Impression scores and rCBF were found in the right and left inferior frontal lobes and in the right basal ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus, and duration of illness correlated positively with rCBF in the right and left superior frontal lobes and with the right thalamus. The findings of this SPECT study conducted in Brazil are in agreement with prior studies and provide additional support for the involvement of prefrontal–subcortical circuits in the pathophysiology of OCD. Furthermore, the study suggests that similar brain mechanisms appear to be involved cross-culturally.




Clinical Psychology Review

Volume 23, Issue 1 , February 2003, Pages 95-117

Neuropsychology of obsessive-compulsive disorder: a review and treatment implications

Scott Greisberg and Dean McKay, 

Department of Psychology, Fordham University, 441 East Fordham Road, Bronx, NY 10458-5198, USA

            The existing literature examining neuropsychological features of obsessive-compulsive disorder (OCD) is reviewed. The accumulated research points to a deficit in organizational strategies in general, suggesting problems in executive functioning. The available research is inconsistent in identifying memory deficits in OCD. However, memory problems are most evident when tests are used that require an implicit organizational strategy. While the majority of the research reviewed involves adult samples, there is emerging evidence that these deficits are present in children as well. It is suggested here that the interaction between organizational strategy deficits and the effort to recall unstructured information contributes to doubting, an important feature of OCD. Implications of this body of research for behavior therapy are considered.



Psychiatry Res. 2003 Jun 30;123(2):135-143

Evaluation of regional cerebral blood flow changes in panic disorder with Tc99m-HMPAO SPECT, Pages 135-143

brahim Eren, Rait Tükel, Aslhan Polat, Remzi Karaman and Seher Ünal

            The objective of this study is to investigate differences in regional cerebral blood flow (rCBF) and rCBF asymmetry index values between panic disorder patients (n=22) and normal comparison subjects (n=19) using Tc99m-hexamethylpropyleneamine oxime single photon emission tomography imaging. A decrease in perfusion in the bilateral frontal regions and a relative increase in perfusion in the right medial and superior frontal regions were found. There were significant positive correlations between scores on the Panic and Agoraphobia Scale and rCBF asymmetry index values of the parietal, superior temporal and lateral temporal regions in the panic disorder patients. These correlations point to a relationship between the severity of panic disorder and relative right brain activation. Activation of the amygdala, increased CBF in the frontal region, or hyperactivation of the locus ceruleus seen in panic disorder may explain the decrease in the rCBF in the inferior frontal region.



*** a rational study that integrates vs reduces information, and employs a biopsychosocial model...)***

European Psychiatry

Volume 18, Issue 5 , August 2003, Pages 241-248

Neuropsychological function in obsessive-compulsive disorder: effects of comorbid conditions on task performance

Ayse Aycicegia, Wayne M. Dinn, , b, Catherine L. Harrisb and Husnu Erkmenc

            Background. – Neuropsychological testing reveals a pattern of impairment among patients with obsessive-compulsive disorder (OCD) which implicates the orbitofrontal region. Studies of neuropsychological function in OCD differ regarding performance deficits on classical tests of frontal executive function. In some studies, OCD patients did not demonstrate impaired performance on tests of executive function. However, other researchers have documented performance deficits among OCD patients on measures of executive function. Patients with OCD also exhibit performance deficits on tests of visual/spatial memory and verbal memory. Again, in some studies, OCD patients did not demonstrate impaired performance on tests of memory function. How can we account for the conflicting findings? One possibility is that performance deficits on tests of cognitive function are associated with comorbid conditions. In prior work, we observed that OCD patients who did poorly on executive function tasks obtained high scores on a measure of schizotypal personality. A second possibility is that executive function deficits among patients with OCD are associated with comorbid depressive symptoms. Method. – In the present study, a comprehensive neuropsychological test battery was administered to patients with OCD and matched healthy control subjects. We also administered dimensional measures of schizotypal personality and depression to patients with OCD and controls. We conducted analyses of covariance (ANCOVA), with scores on measures of schizotypal personality and depression used as covariates. Results.OCD patients demonstrated performance deficits on measures of delayed memory, response inhibition, alternation learning, and obtained significantly higher scores on measures of disinhibition, impulsivity, and temporolimbic symptoms; however, OCD patients did not exhibit impaired performance on tests of executive function and verbal fluency, and did not report a significantly greater number of dysexecutive symptoms, when coexistent depressive and schizotypal symptoms were taken into account.  Conclusion.Findings are consistent with the contention that dysfunction of an orbitofrontal-limbic network underlies OCD.





Psychiatry Research: Neuroimaging,

Volume 122, Issue 1, Pages 37-47  January 2003 Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive–compulsive disorder

Jun Soo Kwon, Jae-Jin Kim, Dong Woo Lee, Jae Sung Lee, Dong Soo Lee, Myung-Sun Kim, In Kyoon Lyoo, Maeng Je Cho and Myung Chul Lee

            Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive–compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral–metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive–compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive–compulsive symptoms. In particular, the frontal–subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD.




J Neuropsychiatry Clin Neurosci 15:359-362, August 2003

The Frontal Lobe Neuropsychological Tests in Patients With Schizophrenia and/or Obsessive-Compulsive Disorder

Alina Borkowska, Ph.D., Ewa Pilaczyńska, M.D. and Janusz K. Rybakowski, M.D.

Address correspondence to Dr. Alina Borkowska, Clinical Neuropsychology Unit, University School of Medicine, Bydgoszicz, Poland; alab@amb.bydgoszcz.pl (E-mail).

            This study compared the performances of matched schizophrenia patients with or without obsessive-compulsive (OC) symptoms, patients with obsessive-compulsive disorder (OCD), and control subjects on selected frontal lobe tests. Schizophrenic patients without OC were the most impaired; and OCD patients were the least, while schizophrenic patients with OC scored between these two groups.



Clinical EEG

Volume 34, 2003, 70-74

Quantitative Electroencephalography in OCD Patients Treated with Paroxetine

Elsebet S. Hansen, Leslie S. Prichep, Tom G. Bolwig and E. Roy John

            The effectiveness of drugs that have a specific effect on the activity of the serotonergic neurotransmitter system has changed the outlook for patients suffering from obsessive-compulsive disorder (OCD). With a response rate of about 70% to such compounds and the great amount of brain imaging studies conducted over the past decades, an understanding of the biochemical nature and origins of OCD is beginning to unfold. Convergent data including ethological and experimental observations, clinico-pathological findings and different imaging methods have implicated the basal ganglia along with the cortical and related thalamic structures to be involved in the pathophysiology of OCD.

            In a previous study using the quantitative electroencephalographic (QEEG) method known as neurometrics, in which QEEG data from OCD patients were compared statistically with those from an age-appropriate normative population, two subtypes within a clinically homogeneous patient group were classified. Patients with relative excess theta activity, especially in the frontal regions, were nonresponders to treatment with serotonin reuptake inhibitors (SSRI), while those with increased relative power in alpha activity were responders to pharmacological treatment. These findings suggested at least two subgroups in a patient population with similar symptoms but differential responses to treatment.

            In the present study we used neurometric QEEG to subtype a group of 20 non-depressed OCD patients, fulfilling DSM-R-III criteria, treated with paroxetine, of whom 18 were responders to treatment. Of the treatment responders, 94.4% were predicted by subtype membership to be SSRI responsers. In these subjects there was a strong relative alpha baseline activity; after successful treatment through at least 3 months this activity decreased, looking more normal. The group average topographic maps showed none of the characteristics seen in the nonresponder cluster (no excess relative power in theta). As in the previous investigation, baseline QEEG profile membership points to a predictive value with regard to therapeutic response.




Psychiatry Research

Volume 118, Issue 2 , 30 May 2003, Pages 107-116

Neurosteroid secretion in panic disorder

Francesca Brambilla, , a, Giovanni Biggiob, Maria Giuseppina Pisub, Laura Bellodia, Giampaolo Pernaa, Vesna Bogdanovich-Djukica, Robert H. Purdyc and Mariangela Serrab

            Evidence that neurosteroids have anxiolytic effects in animal models of anxiety has suggested that alterations of neurosteroid secretion might be implicated in the pathogenetic mechanisms of anxiety disorders in humans. In 25 female patients with panic disorder (PD) and 11 healthy female controls, we measured plasma concentrations of progesterone (PROG), pregnenolone (PREG), allopregnanolone (3,5-tetrahydroprogesterone=3,5-THPROG), dehydroepiandrosterone (DHEA) and tetrahydrodeoxycorticosterone (3,5-THDOC) during a drug-free month and during the following month of paroxetine therapy. The neurosteroids were measured during the early follicular phase, the mid-luteal phase and the premenstrual phase of both months (days 7, 22 and 27 from the beginning of the cycle). Significantly higher levels in patients than controls were found in PROG during the mid-luteal phase of both months, PREG in the premenstrual phase in the drug-free month, 3,5-THPROG during the follicular phase of the drug-free month and during the premenstrual phase of the therapy month, and 3,5-THDOC during the premenstrual phases of both months. DHEA levels did not differ in patients and controls. These results suggest that neurosteroids in PD are hypersecreted, possibly as an attempt to counteract the anxiogenic underlying hyperactivity of the hypothalamo-pituitary-adrenal axis and to improve a reduced GABAA receptor sensitivity.



Journal of Behavior Therapy and Experimental Psychiatry

Volume 34, Issue 2 , June 2003, Pages 129-140

Copyright © 2003 Elsevier Science Ltd. All rights reserved.

Treatment of panic disorder via the Internet: a randomized trial of CBT vs. applied relaxation

Per Carlbring, Lisa Ekselius and Gerhard Andersson, 

            A randomized trial was conducted of two different self-help programs for panic disorder (PD) on the Internet. After confirming the PD-diagnosis with an in-person structured clinical interview for DSM-IV (SCID) interview 22 participants were randomized to either applied relaxation (AR) or a multimodal treatment package based on cognitive behavioral therapy (CBT). Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail has a significant medium to large effect (Cohen's d=0.71 for AR and d=0.42 for CBT). The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.




Biol Psychiatry. 2003 Oct 1;54(7):751-6.

Brain activation by disgust-inducing pictures in obsessive-compulsive disorder.

Shapira NA, Liu Y, He AG, Bradley MM, Lessig MC, James GA, Stein DJ, Lang PJ, Goodman WK.

Department of Psychiatry, College of Medicine, University of Florida, Gainesville, Florida, USA.

            BACKGROUND: There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive disorder (OCD). METHODS: Eight OCD subjects with contamination preoccupations and eight gender- and age-matched healthy volunteers viewed pictures from the International Affective Picture System during functional magnetic resonance imaging scans. RESULTS: A different distribution of brain activations was found during disgust-inducing visual stimulation in several areas, most notably the insula, compared with neutral stimulation in both OCD subjects and healthy volunteers. Furthermore, whereas activation during the threat-inducing task in OCD subjects showed a pattern similar to that in healthy volunteers, the pattern of activation during the disgust-inducing task was significantly different, including greater increases in the right insula, parahippocampal region, and inferior frontal sites. CONCLUSIONS: This pilot study supports the relevance of disgust in the neurocircuitry of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD individuals with high disgust ratings, non-contamination-preoccupied OCD individuals, and individuals with other anxiety disorders are needed.




Psychiatry Res. 2003 Oct 15;120(3):265-71.

Reduced response-inhibition in obsessive-compulsive disorder measured with topographic evoked potential mapping.

Herrmann MJ, Jacob C, Unterecker S, Fallgatter AJ.

            Recent neuroimaging studies have suggested that a hyperactivity of the frontal-striate neuronal circuits, including the orbitofrontal cortex and the basal ganglia, mediates the symptomatology of obsessive-compulsive disorder (OCD). However, there is also some evidence that the superior frontal cortex is less activated in OCD, and this local hypoactivity has been shown to be negatively associated with the symptomatology. As the superior frontal cortex is believed to be involved in inhibitory control, this study investigated the brain electrical activity during response inhibition in OCD. Twelve patients with OCD and 12 healthy controls performed a cued Go-NoGo task (continuous performance test), while event-related potentials were registered with 21 electrodes. Patients reacted significantly faster than controls, but did not differ from controls regarding the error rate. As a main result, we found a reduced frontal activity during the NoGo condition in OCD, which was condensed in a reduced anteriorisation of the brain electrical field. We suggest that this inhibitory deficit in OCD has a major contribution to the pathophysiology of OCD, which is underscored by the fact that the anteriorisation during the NoGo condition (NGA) was negatively correlated with the symptomatology as measured by the Yale-Brown Obsessive-Compulsive Scale.



Journal of Anxiety Disorders

Article in Press, Corrected Proof - Note to users

Symptom subtypes of obsessive-compulsive disorder and their relation to dissociation

David Watson, , Kevin D. Wu and Cynthia Cutshall

Department of Psychology, University of Iowa, E11 Seashore Hall, Iowa City, IA 52242-1407

            We examined relations between obsessive-compulsive disorder (OCD) symptoms and dissociation in three studies. Studies 1 and 2 established a strong level of convergence between our two OCD symptom measures. Specific types of symptoms showed a clear convergent/discriminant pattern, indicating that they can be meaningfully distinguished from one another. In both studies, dissociation correlated more strongly with checking and obsessive intrusions than with cleaning, ordering, and hoarding. Moreover, these associations remained substantial even after controlling for neuroticism (Study 1) and other types of anxiety (Study 2). In Study 3, we replicated our key findings in a psychiatric outpatient sample, indicating that they are generalizable to clinical participants. Taken together, our results (a) establish a strong link between dissociation and OCD, and (b) illustrate the importance of analyzing different types of OCD symptoms separately.




J Neuropsychiatry Clin Neurosci 15:371-374, August 2003

Obsessive-Compulsive Symptoms, Obsessive-Compulsive Disorder, and Related Disorders in Parkinson's Disease

Alex F. Maia, M.D., Adriana S. Pinto, M.D., Egberto R. Barbosa, M.D., Ph.D., Paulo R. Menezes, M.D., Ph.D. and Euripedes C. Miguel, M.D., Ph.D.


            This study evaluated the frequency of obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms (OCS), and related disorders (e.g., tic disorders, trichotillomania, and body dysmorphic disorder) in 100 patients with Parkinson's disease (PD) and 100 individually matched controls. When compared with controls, OCD, OCS, and related disorders were not higher in PD. Findings revealed an association of some OCS with left side motor symptom predominance in PD patients, particularly for symmetry and ordering/arranging. These findings suggest that the right hemisphere likely functions in the expression of OCS.




In Press, Corrected Proof , Available online 27 October 2003

Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex

Nic J. A. van der Weea, 1, Nick F. Ramsey, , a, Johan M. Jansmaa, Damiaan A. Denysa, Harold J. G. M. van Megena, Herman M. G. Westenberga and René S. Kahna

            Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD.






Journal of Anxiety Disorders

Volume 17, Issue 6 , 2003, Pages 627-646

Structural differentiation of self-reported depression and anxiety in late life

Suzanne Meeks, , Janet Woodruff-Borden and Colin A. Depp

            Research has shown impressive support for tripartite models of anxiety and depression that include a common factor of negative affect, and the unique factors positive affect and arousal. It is not clear whether this structure extends into later life. The current study used confirmatory factor analysis to model the structural relationship of anxiety and depression in two samples of older adults: a large probability sample (N=1429) and a smaller convenience sample (N=210). Across all analyses, a correlated, two-factor, psychometric model was most parsimonious. The tripartite model could be fit to the data, but added no explanatory power; in some cases a one-factor model also fit. The results suggest that there is a unitary factor of "distress" that incorporates anxiety and depression, but that the structure is not consistent with factor structures found in younger samples. Instead, the broad constructs may be represented in a more complex manner among older adults, and are less easily differentiated.




Am J Psychiatry 161:72-78, January 2004

Left Hemisphere Dysfunction During Verbal Dichotic Listening Tests in Patients Who Have Social Phobia With or Without Comorbid Depressive Disorder

Gerard E. Bruder, Ph.D., Franklin R. Schneier, M.D., Jonathan W. Stewart, M.D., Patrick J. McGrath, M.D., and Frederic Quitkin, M.D.

            OBJECTIVE: Behavioral, electrophysiological, and imaging studies have found evidence that anxiety disorders are associated with left hemisphere dysfunction or higher than normal activation of right hemisphere regions. Few studies, however, have examined hemispheric asymmetries of function in social phobia, and the influence of comorbidity with depressive disorders is unknown. The present study used dichotic listening tests to assess lateralized cognitive processing in patients with social phobia, depression, or comorbid social phobia and depression. METHOD: The study used a two-by-two factorial design in which one factor was social phobia (present versus absent) and the second factor was depressive disorder (present versus absent). A total of 125 unmedicated patients with social phobia, depressive disorder, or comorbid social phobia and depressive disorder and 44 healthy comparison subjects were tested on dichotic fused-words, consonant-vowel syllable, and complex tone tests. RESULTS: Patients with social phobia with or without a comorbid depressive disorder had a smaller left hemisphere advantage for processing words and syllables, compared with subjects without social phobia, whereas no difference between groups was found in the right hemisphere advantage for processing complex tones. Depressed women had a larger left hemisphere advantage for processing words, compared with nondepressed women, but this difference was not seen among men. CONCLUSIONS: The results support the hypothesis that social phobia is associated with dysfunction of left hemisphere regions mediating verbal processing. Given the importance of verbal processes in social interactions, this dysfunction may contribute to the stress and difficulty experienced by patients with social phobia in social situations.



Scandinavian Journal of Psychology

Volume 45 Issue 2 Page 123  - April 2004

Effects of age and anxiety on episodic memory: Selectivity and variability

Juan Li1,2, Lars-Göran Nilsson2 and Zhenyun Wu3

Li, J., Nilsson, L.-G. & Wu, Z. (2004). Effects of age and anxiety on episodic memory: Selectivity and variability.    Scandinavian Journal of Psychology, 45, 123-129.

            Selective age-related differences in source memory relative to item memory, and individual differences in memory performance in relation to anxiety were explored with high- and low-anxious subjects screened from normal young and elderly adults. They were read false facts about the locations of well-known and unknown sights in a male or female voice. Intentional and incidental learning instructions were administered for source memory. Selective age-related deficits in source memory were observed under both encoding conditions. Higher level of anxiety was related to lower memory performance only in the old group; this relation was stronger in source recall. The findings suggest that the presence of such selectivity is unrelated to the tradeoff between item encoding and source encoding. Anxiety affects the variability, and mediates the selectivity of age effects on episodic memory.





Clinical Applications of Breathing Regulation: Beyond Anxiety Management   

Christopher Gilbert    

Behavior Modification      Volume: 27 Number: 5 Page: 692 -- 709

            Abstract: Breathing training is widely used as an aid in reducing anxiety states, but several other applications also show promise. This article reviews evidence that normalizing breathing patterns may offer help in some cases of essential hypertension, angina, functional chest disorder, chronic obstructive pulmonary disease (COPD), and cardiac rehabilitation. Hyperventilation and hypo-ventilation, inhibited breathing, and breath suspension are all deviations from an optimal breathing pattern in which breathing volume is closely matched to metabolic needs. Such disordered breathing has varying effects on acid/base balance, arterial diameter, and sodium retention by the kidneys. Therefore, a chronic breathing imbalance can contribute to pathophysiology, which may be remediable to an extent by altering habitual breathing pattern






Journal of Anxiety Disorders

Volume 15, Issues 1-2 , January-April 2001, Pages 1-7

Special issue on the interface of balance disorders and anxiety: an introduction and overview

Daniel A. Sklare, Horst R. Konrad, Jack D. Maser and Rolf G. Jacob

            Clinical accounts suggesting a potential link between dizziness/vertigo, imbalance, and anxiety have been in the medical literature from antiquity to more recent times, yet the causal linkage for this correlative observation has not been investigated experimentally until recently. The presence of these and related somatic symptoms, as well as abnormal findings on tests of vestibular function in patients with panic disorder (PD), particularly in association with agoraphobia, has been underscored by several recent reports, (Hoffman; Jacob; Sklare and Yardley). Neuroanatomic studies showing direct connections between the vestibular nuclei, the locus coeruleus, and brainstem pathways that process visceral sensory information provide a potential neural substrate for the autonomic and affective signs and symptoms often associated with both vestibular dysfunction and anxiety disorders (see Balaban; Gorman; Gorman and Maser). There is also a potential neurochemical/neuropharmacological linkage between vestibular dysfunction and anxiety disorders/PD/psychiatric illness in the domain of monoaminergic neurotransmission (Balaban & Thayer, this issue). The co-occurrence of spatial disorientation, impaired balance, and anxiety can result in a distressing and disabling syndrome in the affected individual.


At the present time the Diagnostic and Statistical Manual, 4th Revision (American Psychiatric Association, 1994) recognizes this combination by including "feeling dizzy, unsteady, lightheaded, or faint" as one among 13 diagnostic criteria for PD. Dimensional systems of classification, for example, Cassano's panic spectrum diagnostic system, also recognize the clinical overlap of balance symptoms and anxiety (Cassano, Michelini, et al., 1997). In Cassano's panic spectrum diagnostic instrument there are questions related to balance and panic that tap into this somatic/phenomenological symptom. The standardized clinical interview for panic agoraphobia asks: "Does it sometimes feel as if your legs are made of rubber?," "Does it sometimes feel as if you were walking on velvet?," and "Are you fearful that you will suddenly lose your balance?" (Cassano and Cassano). Not all PD patients answer these questions affirmatively and not all panic patients experience dizziness, spatial disorientation, and/or imbalance. However, a subgroup of PD patients do answer affirmatively and are very likely to have vestibular dysfunction (Yardley and Yardley), particularly if these symptoms occur between, rather than during, panic attacks (Jacob, Furman, Durrant, & Turner, 1996).


What remains to be discovered is whether or not some balance disorders and some anxiety disorders have a common pathophysiology in the central nervous system or is the observed comorbidity merely the chance co-occurence of two quite separate disorders? Approaches to answering this question are varied, but they can certainly begin with epidemiology.


In a large survey of working-age adults in the UK, randomly sampled from the rosters of four general medical practices, over 20% reported experiencing dizziness during the previous month and approximately 11% reported that this condition imposed some degree of handicap (Yardley, Owen, Nazareth, & Luxon, 1998). Almost half of the individuals with dizziness also reported anxiety and/or avoidance behavior. While the actual coprevalence of balance disorders and anxiety disorders is unknown, it appears to be higher than previously thought. Furthermore, the co-occurrence of these disorders is rarely recognized by clinicians examining and treating patients presenting with either balance disorders or anxiety disorders. In order to better assess the magnitude of the problem and the significance of these disorders clinically, it is important to better understand the epidemiology of the convergence between balance disorders and anxiety. In order to understand the relationship between the mechanisms by which anxiety and balance disorders occur individually and together, we need empirical, laboratory investigations informed by clinical observation.


The experience of space and motion discomfort followed by phobic avoidance has been suggested as the thematic link between these conditions (Jacob; Jacob and Jacob). Patients who become anxious about the possibility of increases in dizziness or attacks of panic will tend to avoid relevant physical activities and situations in which such consequences may be embarrassing or dangerous. In the case of patients with balance disorders, this avoidance response is a protective behavioral strategy that prevents exposure to environmental stimuli (e.g., a flowing river, fog, escalators, or parapets) that present a danger of falling or spatial disorientation. Indeed, such avoidance behaviors were recommended to vertiginous patients by a 16th century practitioner: "suche men havynge this passion let them beware of clymnge or goynge up upon highe hylles or round stayres" (Borde, 1971). However, the avoidance of such movements and environments deprive the balance system of the sensory and motor experiences necessary for recovery following a vestibular disorder. Avoidance also deprives the anxious individual of extinction situations and of the opportunity to desensitize to provocative conditions.


During the last two decades, physical rehabilitation has been shown to be effective in reducing the symptoms and improving the function of patients with balance disorders. Rehabilitation works by utilizing normal behavioral mechanisms such as adaptation, substitution, and relearning. In order to accomplish these goals, exercises are aimed at the specific injuries or deficits. These exercises require movements of the head, body, and the eyes eliciting symptoms similar to those associated with the patient's disorder. These symptoms are unpleasant and may produce anxiety and phobic reactions that are observed in many of these patients. It is not surprising that these patients are reluctant to do their exercises and that the level of anxiety in patients with balance disorders is the highest negatively correlated finding for predicting success from therapy (Yardley, 1994). On the other hand, anxiety symptoms associated with dizziness and vertigo respond to vestibular rehabilitation (Yardley, Beech, Zander, Evans, & Weinman, 1998). Furthermore, some patients with anxiety disorders develop symptoms of imbalance/disequilibrium and disorientation as part of their anxiety reaction. We suspect that neither of these patient groups respond well to treating one component of their disorder complex/syndrome (balance or anxiety) without also treating the other.


This special issue, comprising eight papers, will highlight findings and ideas emerging from the first dedicated forum we are aware of for discussion of the interface of balance disorders and anxiety. The Workshop on the Interface of Balance Disorders and Anxiety: An Integrated View, jointly sponsored by the National Institute on Deafness and Other Communication Disorders, the National Institute of Mental Health, and the Office of Rare Diseases of the National Institutes of Health, was held in the Washington, DC, area on September 15 and 16, 1997. A diverse group of 15 biomedical and behavioral scientists discussed the diagnosis and treatment of patients presenting with a complex of balance and anxiety disorders and explored the central nervous system mechanisms that may account for this clinical syndrome. Each group informed the other of relevant findings and phenomena and much was learned about the perception and control of space and motion and the psychobiological basis of anxiety in normal and dysfunctional humans.


The workshop participants determined that several areas were ripe for further investigation. A discussion of some of these areas follows:


1. It emerged from discussions at the workshop that there are different levels of interaction between balance/vestibular disorders and anxiety disorders across clinical patients An accurate and meaningful classification system for disorders of balance and spatial orientation and their associated psychiatric symptoms is necessary for the timely, accurate diagnosis, and efficacious treatment of patients with dizziness and anxiety.


2. Research is needed to develop and validate treatment plans incorporating the physical positioning maneuvers and sensory retraining components of balance/vestibular rehabilitation with behavioral and behavioral–cognitive therapy approaches employed in the treatment of PD and other anxiety disorders.


3. The pathogenesis and pathophysiology of anxiety/balance disorders may reflect linkages at different levels of the neuraxis. Each of these potential linkages needs to be investigated.


The eight papers in this special issue of the Journal of Anxiety Disorders are organized thematically according to the following plan:


Drs. Furman and Jacob present a clinical taxonomy for the interface of dizziness and anxiety based on a model of the levels of linkage of these domains. To the degree that anxiety disorder patients share symptomatology with balance disorder patients, clinicians treating either set of disorders need to be aware of the taxonomy developed by both disciplines. With this knowledge too, a taxonomy common to and acceptable by both disciplines can emerge, as might be the case with "psychiatric dizziness" that can be observed clinically in abasia during somatoform disorders (in which the vestibular system is not dysfunctional), depression, and panic attacks.


Balaban and Jacob provide a scholarly review of historical background for the interface of balance disorders and anxiety, which, some may be surprised to learn, began in antiquity. In the middle to late 19th century, agoraphobia was seen by some authorities as one aspect of a vertiginous state, while modern views of abnormal behavior see vertigo as one aspect (symptom) of panic agoraphobia. Students of anxiety disorders should find the historical review of balance disorders as an outstanding scholarly contribution to the balance–anxiety disorder linkage. The discussion of the relationship between the vestibular and visual systems and fear brings to mind eye movement desensitization and reprocessing as a controversial, but possible, treatment for posttraumatic stress disorder, another anxiety disorder (Levin, Lazrove, & van der Kolk, 1999).


Balaban and Thayer then review neurological linkage models for (1) fear and anxiety, (2) emotion, (3) autonomic control, and (4) vestibular information processing. These models share common pathways in the brain and could be a reasonable neurological underpinning for those anxiety disorder patients who have balance problems as a prominent symptom. Conversely, the intimate linkage between these pathways may provide a neurological basis for balance disorder patients who report an anxiety disorder as a prominent symptom. Critical areas of overlap include: the parabrachial nucleus, locus coeruleus, and serotonergic pathways. It is proposed that information processing in these structures may mediate the comorbidity of balance disorders and anxiety.


Redfern et al. discuss the visual influences on the balance and orientation in patients with vestibular disorders and in patients with anxiety disorders who also suffer from space and motion discomfort. Both patient groups show increased reliance on vision for balance and increased postural sway when confronted with conflicting perceptions of their visual environments. This visual dependence of balance control is a primary feature of space and motion discomfort (Furman & Jacob, 2001). In fact, the phenomena of visual dependence and visual provocation of space and motion discomfort are a recurrent theme in the history of the balance–anxiety interface (Balaban & Jacob, 2001).


Clark and Swartz's paper provides a taxonomy of these disorders from a phenomenological, clinical perspective. Patients with balance disorders face psychiatric problems similar to individuals with pain and other disabilities (i.e., stress, anxiety depression). Issues that are more prominent with this group are social anxiety and depression related to the loss of life goals.


There are three papers that are focused on treatment. Yardley and Redfern review the psychosomatic factors, including habituation, arousal level, and attention, that might affect recovery from balance disorders. When the vestibular system is damaged, the individual must, consciously or unconsciously, change his or her perceptual–motor strategy and compensate for the dysfunctional organ. How this multifaceted compensation is accomplished is the subject of Yardley and Redfern's paper. The focus is on rehabilitating the balance system, but the processes that are manipulated are clearly psychological. Even standard physical therapy regimens, whose goals are balance retraining, include teaching the patient that s/he can cope behaviorally. Attention, anxiety, motor control, and motor activity are all involved. Beidel and Horak compare behavioral treatment for patients with anxiety disorders and vestibular rehabilitation for balance-disordered patients. They underscore the remarkable similarities between vestibular rehabilitation and behavior therapy for PD. Finally, Jacob et al. report preliminary results on the effects of providing both behavioral therapy and vestibular rehabilitation to vestibular-impaired PD/agoraphobic patients. As the patients switched back and forth from behavior therapy to vestibular rehabilitation, there was progressive improvement. The data are also informative concerning the concepts of agoraphobic etiology, since the results support the notion that vestibular dysfunction can maintain agoraphobic symptoms.


It is the hope of the organizers of the workshop that this special issue, highlighting the areas of overlap of balance disorders and anxiety disorders, will provide the impetus for systematic and collaborative investigations of the relationships between these two clinical domains that translate into improved interventions for affected patients.







Stress and Health

Volume 19, Issue 4 , Pages 195 - 204

Job stress, personality, and psychological distress as determinants of somatization and functional somatic syndromes in a population of nurses

Véronique De Gucht, Benjamin Fischler, Willem Heiser (degucht@fsw.leidenuniv.nl)

            The objective of the present study was to examine the respective contribution of job stress dimensions (work demands, job control, and social support at work), personality traits (neuroticism and alexithymia), and psychological distress (anxiety and depression) to somatization in a population of nurses. Therefore, a number of logistic regression analyses were conducted, with the presence versus absence of three functional somatic syndromes (functional dyspepsia (FD), irritable bowel syndrome (IBS), and idiopathic chronic fatigue (CF) and current somatization, defined as the presence of at least two medically unexplained symptoms (median number of symptoms for the sample) and four medically unexplained symptoms (highest quartile for the sample) during the past month, as the outcome variables. The results pointed out that job stress dimensions significantly and independently contributed to IBS (job control) and CF (work demands). The personality trait neuroticism was a significant predictor of both current somatization and functional somatic syndromes, whereas alexithymia primarily predicted the presence of more severe and/or more enduring forms of somatization. Finally, three out of five outcome variables were predicted by psychological distress. Future studies should examine (a) to what extent distinct patterns of associations can be found between specific job stress dimensions on the one hand, and specific functional somatic syndromes on the other and (b) the potential interaction between job stress and personality dimensions in determining somatization