Paul D. Carey

Gender differences in the prevalence of childhood sexual abuse and in the development of pediatric PTSD.

SummaryDespite an extensive literature on the links between childhood sexual abuse (CSA) and posttraumatic stress disorder (PTSD), our knowledge on the effects of gender in relation to the risks for sexual victimization and subsequent PTSD is limited. We review current knowledge of gender differences in prevalence of CSA and the role of gender in subsequent development of child and adolescent PTSD with specific attention to rates, phenomenology, biological correlates, and risk factors. Despite the heavy bias toward female representation in studies, the literature supports increased rates of CSA and heightened vulnerability to PTSD in girls, as well as possible gender differences in the biological correlates and psychiatric sequelae of CSA. Further work is needed to explore the mechanisms that underlie these differences.

Quetiapine augmentation of SRIs in treatment refractory obsessive-compulsive disorder: a double-blind, randomised, placebo-controlled study [ISRCTN83050762]

BackgroundAlthough serotonin reuptake inhibitors are effective in the treatment of OCD, many patients fail to respond to these agents. Growing evidence from open-label and placebo-controlled trials suggests a role for augmentation of SRIs with atypical antipsychotics in OCD. Quetiapine is generally well tolerated and previous open-label data has produced mixed results in OCD and additional controlled data is needed.MethodsWe undertook a double-blind, randomised, parallel-group, flexible-dose, placebo-controlled study of quetiapine augmentation in subjects who had responded inadequately to open-label treatment with an SRI for 12 weeks. Following informed consent and screening, forty-two subjects were randomised to either placebo or quetiapine for six weeks.ResultsThere was significant improvement from baseline to endpoint on the Yale-Brown Obsessive-Compulsive Scale in both the quetiapine and placebo groups (quetiapine, n = 20, p < 0.0001; placebo, n = 21, p = 0.001) with 40% (n = 8) of quetiapine and 47.6% (n = 10) of placebo treated subjects being classified as responders. Quetiapine did not demonstrate a significant benefit over placebo at the end of the six-week treatment period (p = .636). Similarly quetiapine failed to separate from placebo in the subgroup of subjects (n = 10) with co-morbid tics. Quetiapine was generally well tolerated.ConclusionsIn this study, quetiapine augmentation was no more effective than placebo augmentation of SRIs. A number of limitations in study design make comparisons with previous studies in this area difficult and probably contributed to our negative findings. Future work in this important clinical area should address these limitations.

Post-traumatic stress disorder in women: epidemiological and treatment issues.

Although women are exposed to proportionately fewer traumatic events in their lifetime than men, they have a higher lifetime risk of post-traumatic stress disorder (PTSD). In addition to gender-differential rates of rape and sexual assault, including greater exposure to intimate partner violence, the preponderance of PTSD in women may be attributable to factors other than trauma type, such as sensitisation of stress hormone systems in response to early adverse experiences, inherent neuroendocrine factors, subjective interpretation of the event, and peritraumatic dissociation. Women with PTSD arguably experience a greater symptom burden, longer course of illness and have worse quality-of-life outcomes than men. An expanding knowledge base of the psychobiological alterations in PTSD is providing stimulus for the development of improved pharmacological and psychosocial treatment options. Recent randomised controlled studies conducted in large samples of women with chronic PTSD indicate that: (i) SSRIs have efficacy on all three symptom clusters of PTSD and should be used as first-line pharmacotherapy; and (ii) cognitive behavioural strategies (e.g. prolonged exposure treatment and cognitive processing) are effective in sexually and non-sexually assaulted women. Studies also suggest that female gender may be associated with better response rates to pharmacotherapy. Emerging empirical data on the potential usefulness of antiadrenergic agents and preventive cognitive behavioural treatments in managing acute trauma reactions and stemming the emergence of PTSD are paving the way for further work in this area. However, additional innovative treatments are needed for traumatised women and for female children/adolescents presenting with acute stress reactions and PTSD.

Trauma and posttraumatic stress disorder in an urban Xhosa primary care population: prevalence, comorbidity, and service use patterns.

Despite increased awareness of the prevalence and morbidity of psychiatric illnesses, relatively few studies have been undertaken in primary care settings in the African context. The authors determined the prevalence of trauma exposure and posttraumatic stress disorder (PTSD) in a South African township primary health care clinic and assessed associated demographic factors, comorbidity, service use, service satisfaction, and quality of life. Subjects were directly interviewed using translated, standardized instruments to assess variables described. Retrospective chart analysis assessed clinician case identification and psychotropic drug-prescribing habits. Of the 201 participants, 94% reported exposure to traumatic events (mean, 3.8). Trauma was associated with single status (p = .01), and PTSD was associated with poverty and single status (p = .04). Both sexes were equally likely to develop PTSD. PTSD (current; 19.9%), depression (37%), and somatization disorder (18.4%) were the most common diagnoses. Comorbidity with PTSD was high and included depression (75%, p < .01), somatization (35%, p < .01), and panic disorder (25%, p < .01). Levels of functional impairment were higher for subjects with PTSD, depression, and somatization than for those without (p < .05). PTSD comorbid with depression compounded impairment (p = .04). Levels of trauma, PTSD, and depression did not increase service use or dissatisfaction with services. Clinicians did not identify trauma (0%) or psychopathology (0%), and psychotropic medication was prescribed for only 1% of participants. In this population, trauma and PTSD were highly prevalent and associated with significant unidentified morbidity and comorbidity. Patients remain untreated for years in the current system of primary care consultations.

Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram.

BackgroundSeveral studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment.MethodsSingle photon emission computed tomography (SPECT) using Tc-99 m HMPAO to assess brain perfusion was performed on subjects with OCD, PTSD, and SAD before and after 8 weeks (SAD) and 12 weeks (OCD and PTSD) treatment with the SSRI citalopram. Statistical parametric mapping (SPM) was used to compare scans (pre- vs post-medication, and responders vs non-responders) in the combined group of subjects.ResultsCitalopram treatment resulted in significant deactivation (p = 0.001) for the entire group in the superior (t = 4.78) and anterior (t = 4.04) cingulate, right thalamus (t = 4.66) and left hippocampus (t = 3.96). Deactivation (p = 0.001) within the left precentral (t = 4.26), right mid-frontal (t = 4.03), right inferior frontal (t = 3.99), left prefrontal (3.81) and right precuneus (t= 3.85) was more marked in treatment responders. No pattern of baseline activation distinguished responders from non-responders to subsequent pharmacotherapy.ConclusionsAlthough each of the anxiety disorders may be mediated by different neurocircuits, there is some overlap in the functional neuro-anatomy of their response to SSRI treatment. The current data are consistent with previous work demonstrating the importance of limbic circuits in this spectrum of disorders. These play a crucial role in cognitive-affective processing, are innervated by serotonergic neurons, and changes in their activity during serotonergic pharmacotherapy seem crucial.

The effects of eicosapentaenoic acid in tardive dyskinesia: A randomized, placebo-controlled trial

OBJECTIVE Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Escitalopram in obsessive-compulsive disorder: response of symptom dimensions to pharmacotherapy.

INTRODUCTION There is a substantial body of evidence that obsessive-compulsive disorder (OCD) symptoms can be grouped into a series of discrete dimensions, and some evidence that not all OCD symptom dimensions respond equally well to pharmacologic or psychotherapeutic intervention. The response of OCD symptom dimensions to 12 weeks of treatment with escitalopram or placebo was investigated. METHODS Data from a randomized, double-blind, placebo-controlled study of escitalopram in 466 adults with OCD were analyzed. Exploratory factor analysis of individual items of the Yale-Brown Obsessive-Compulsive Scale checklist was performed and subscale scores based on the extracted factors were determined. Analyses of covariance were undertaken to determine whether inclusion of each subscale score in these models impacted on the efficacy of escitalopram versus placebo. RESULTS Exploratory factor analysis of individual Yale-Brown Obsessive-Compulsive Scale items yielded 5 factors (contamination/cleaning, harm/checking, hoarding/symmetry, religious/sexual, and somatic/hypochondriacal). Analyses of covariance including all the subscales demonstrated that escitalopram was more effective than placebo. There was a significant interaction for the hoarding/symmetry factor, which was associated with a poor treatment response. CONCLUSION Escitalopram shows good efficacy across the range of OCD symptom dimensions. Nevertheless, hoarding/symmetry was associated with a poorer treatment response. Hoarding/symmetry may be particularly characteristic of an early-onset group of OCD patients, with the involvement of neurotransmitters other than serotonin. Further work is needed to delineate fully the subtypes of OCD, and their correlates with underlying psychobiology and treatment responsivity.

Grey matter abnormalities in social anxiety disorder: a pilot study

While a number of studies have explored the functional neuroanatomy of social anxiety disorder (SAD), data on grey matter integrity are lacking. We conducted structural MRI scans to examine the cortical thickness of grey matter in individuals with SAD. 13 unmedicated adult patients with a primary diagnosis of generalized social anxiety disorder and 13 demographically (age, gender and education) matched healthy controls underwent 3T structural magnetic resonance imaging. Cortical thickness and subcortical volumes were estimated using an automated algorithm (Freesurfer Version 4.5). Compared to controls, social anxiety disorder patients showed significant bilateral cortical thinning in the fusiform and post central regions. Additionally, right hemisphere specific thinning was found in the frontal, temporal, parietal and insular cortices of individuals with social anxiety disorder. Although uncorrected cortical grey matter volumes were significantly lower in individuals with SAD, we did not detect volumetric differences in corrected amygdala, hippocampal or cortical grey matter volumes across study groups. Structural differences in grey matter thickness between SAD patients and controls highlight the diffuse neuroanatomical networks involved in both social anxiety and social behavior. Additional work is needed to investigate the causal mechanisms involved in such structural abnormalities in SAD.

The role of the brain-derived neurotrophic factor (BDNF) val66met variant in the phenotypic expression of obsessive-compulsive disorder (OCD)

Evidence suggests that the Val66Met variant of the brain‐derived neurotrophic factor (BDNF) gene may play a role in the etiology of Obsessive‐Compulsive Disorder (OCD). In this study, the role of the BDNF Val66Met variant in the etiology and the phenotypic expression of OCD is investigated. Associations between the BDNF Val66Met variant and OCD, obsessive‐compulsive symptom dimensions, Yale‐Brown Obsessive Compulsive Scale (YBOCS) severity scores, age of onset and family history of obsessive‐compulsive symptoms were assessed. The BDNF Val66Met variant was genotyped in 419 patients with sub‐/clinical OCD and 650 controls. No differences in allele or genotype frequency were observed between cases and controls. In females with OCD, the Met66Met genotype was associated with later age of onset and a trend for a negative family history, whereas the Val66Val genotype was associated with a trend for lower YBOCS severity scores. Item‐level factor analysis revealed six factors: 1) Contamination/cleaning; 2) Aggressive obsessions/checking; 3) Symmetry obsessions, counting, ordering and repeating; 4) Sexual/religious obsessions; 5) Hoarding and 6) Somatic obsessions/checking. A trend was found for a positive association between Factor 4 (Sexual/religious obsessions) and the BDNF Val66Val genotype. The results suggest that BDNF function may be implicated in the mediation of OCD. We found that for the BDNF Met66Met genotype may be associated with a milder phenotype in females and a possible role for the BDNF Val66Val genotype and the BDNF Val66 allele in the sexual/religious obsessions.

Olanzapine monotherapy in posttraumatic stress disorder: efficacy in a randomized, double-blind, placebo-controlled study.

Although there have been important advances in the treatment of posttraumatic stress disorder (PTSD), many patients fail to respond to first‐line pharmacotherapy. Limited evidence suggests that second generation antipsychotics may have a role to play as monotherapy in PTSD.