Recent evidence suggests that fibromyalgia, a chronic widespread pain condition and related syndromes (chronic fatigue syndrome, irritable bowel syndrome, etc.) may share heritable pathophysiologic features. We review the recent literature on genetic and familial factors found to participate in the pathogenesis of these syndromes, specifically fibromyalgia, including evidence suggesting that serotonin- and dopamine-related genes may play a role in the pathogenesis of these illnesses. The importance of environmental factors triggering these conditions in predisposed individuals is also discussed.

ISSUE:Vilazodone is an antidepressant with a novel mechanism of pharmacologic action: serotonin partial agonist reuptake inhibitor (SPARI).

Depression and apathy are the two most frequent behavioral complications of stroke. This article reviews the prevalence of these conditions in poststroke patients, as well as their clinical correlates, longitudinal course, and possible mediators. A number of controlled clinical trials of the efficacy of various drugs in the treatment of poststroke depression are also reviewed.

This paper discusses the National Bioethics Advisory Commissions (NBAC's) report on research involving persons with mental disorders that may affect decisionmaking capacity. After placing the NBAC recommendations into their historic context, the authors propose a strategy to enroll decisionally incapacitated subjects into neuropsychiatric research. The authors maintained that their proposed consensus model for research authorization, utilizing subject advocates, fosters valuable clinical research while protecting potentially vulnerable subjects.

Valerian is a medicinal agent deriving from the plant Valeriana officinalis L. We reviewed the available literature on the use of valerian preparations in the treatment of neuropsychiatric disorders. Preclinical studies suggest that valerian has sedative and muscle-relaxant effects. Few clinical trials with valerian have been carried out in conditions other than insomnia. The insomnia studies have methodologic shortcomings but suggest that some preparations lead to significant subjective improvement in sleep complaints with remarkably few side effects. Furthermore, some evidence indicates that valerian preparations may have a mechanism of action and clinical characteristics that differ from the benzodiazepine-related sedative/hypnotics, making them more suitable for long-term use. If this safety profile and the plant's sedative/hypnotic efficacy are confirmed in double-blind, placebo-controlled trials with carefully and consistently prepared valerian compounds, then those compounds would fill an important and presently unfilled niche in the treatment of insomnia.

Research has provided considerable evidence for the hypothesis that corticotropin-releasing hormone (CRH), the key central coordinator of stress-hormone homeostasis, also plays a role in the development and course of depression and anxiety disorders. Studies using animal models of anxiety, as well as mouse mutants, in which the gene coding for the CRH type 1 receptor (CRHR1) was genetically deleted supported the notion that enhanced CRH/CRHR1 signaling underlies depression and anxiety disorders. Therefore, a number of small nonpeptide molecules that antagonize CRHR1 have been developed. In animal models, these molecules had anxiolytic and other stress-alleviating effects. An initial clinical study showed that CRHR1 antagonism has beneficial effects on depression and anxiety symptoms at doses unharmful to neuroendocrine stress responsivity.

During the past two decades, it has been amply documented that neuropsychiatric disorders (NPDs) disproportionately account for burden of illness attributable to chronic non-communicable medical disorders globally. It is also likely that human capital costs attributable to NPDs will disproportionately increase as a consequence of population aging and beneficial risk factor modification of other common and chronic medical disorders (e.g., cardiovascular disease). Notwithstanding the availability of multiple modalities of antidepressant treatment, relatively few studies in psychiatry have primarily sought to determine whether improving cognitive function in MDD improves patient reported outcomes (PROs) and/or is cost effective. The mediational relevance of cognition in MDD potentially extrapolates to all NPDs, indicating that screening for, measuring, preventing, and treating cognitive deficits in psychiatry is not only a primary therapeutic target, but also should be conceptualized as a transdiagnostic domain to be considered regardless of patient age and/or differential diagnosis.

Traditional methods for analyzing trends in longitudinal data have typically emphasized average group change over time. In this article, we propose multilevel, regression-based methods for examining inter-individual differences in intra-individual change and apply these methods to research in trauma and posttraumatic stress disorder (PTSD). The outcome or dependent variable of interest is reconceptualized as an index of dynamic change reflecting the trend or trajectory of an individual's PTSD symptom severity scores across time. A basic statistical model is presented, and analyses and findings are demonstrated with an existing database used in previously published studies. The methods offer promise for future study of the natural course of PTSD chronicity or recovery, risk and resilience factors that influence individual growth or decline, and critical timepoints for intervention.

Background: Affective disorders present an important clinical challenge in multiple sclerosis (MS). Due to prohibitive sample size requirements, population-based studies have not yet provided an adequate description of the underlying epidemiology of this association.

Objective: To describe the epidemiology of affective disorders in MS in a general population sample.

Methods: The study presented here accessed administrative data from a universal healthcare insurance plan in the Canadian province of Alberta. Physician billing data recorded in the Alberta Health Care Insurance Plan was used to identify members of the population ≥15 years of age with and without MS. Crude and stratified estimates of the association between affective disorders and MS were made. Logistic regression analysis was used to evaluate statistical interactions and to provide adjusted estimates of the association.

Results: The estimated prevalence of MS in the population within the targeted age range (2.3 million individuals) was 386/100,000 and that of affective disorders was 7.7%. As expected, an association between MS and affective disorders was identified (crude relative prevalence: 2.2). The association varied in strength over age-sex categories. Although the prevalence of affective disorder was higher in women with MS than men with MS, the association of MS with affective disorders was stronger in men. The strength of association declined with age in both men and women. Affective disorder prevalence in people with MS becomes similar to that of the general population in older age groups.

Conclusion: Affective disorders occur with an increased frequency in MS. This is true in men and women and across all relevant age groups, although the association gets weaker with advancing age. Higher frequencies of affective disorder occur in women with MS than in men with MS. The frequency of affective disorder in people with MS is highest in the 25–44 age group, and declines in older age categories.

It is hypothesized that body dysmorphic disorder (BDD) patients are firstly more “aesthetical,” an attribute much like being musical, which varies between different individuals. This results in a greater emotional response to more attractive individuals and placing greater value on the importance of appearance in their identity compared with healthy individuals. Some BDD patients may have greater aesthetic perceptual skills. This is manifested in their education or training in art and design. Secondly, BDD patients may have higher aesthetic standards than the rest of the population. Their failure to achieve an unrealistic aesthetic standard is at the core of BDD, leading to severe distress and handicap.

Unravelling the mystery of dopamine neurotransmission, especially at its 3 most clinically relevant receptors, D3, D2, and D1, helps explain the pathophysiology of numerous psychiatric and neurologic symptoms in various CNS disorders that are theoretically caused by dysregulation of this neurotransmitter.

Individuals with schizophrenia are known to demonstrate cognitive and behavioral difficulties, particularly alterations in executive functions, including working memory. It is unclear whether these deficits reflect trait-related vulnerability to schizophrenia indicators and can be assessed by studying nonpsychotic relatives of patients with schizophrenia. In this study, we used an oculomotor delayed response (ODR) paradigm to examine spatial working memory in 37 “high-risk” child and adolescent offspring and siblings (age range=6–25 years) of patients with schizophrenia or schizoaffective disorder. Compared with 37 age- and sex-matched healthy controls (age range=6–23 years), high-risk subjects showed nonsignificantly greater errors in the ODR task at longer delay intervals. Statistical analyses suggested that performance improved with age in healthy control subjects, whereas it worsened with age in high-risk subjects. In both groups, the ODR errors were generally associated with poorer sustained attention (Continuous Performance Test: visuospatial d prime), some-what poorer executive function (Wisconsin Card Sorting Test), and elevated Heinrichs-Buchanan neurological soft signs scores. These findings indicate the presence of spatial working memory abnormalities in individuals at risk for schizophrenia. Furthermore, these abnormalities may be progressive in nature. The ODR task is a valuable indicator of prefrontal cortical function and spatial working memory and may be a potentially valuable marker for familial risk of schizophrenia.

Prolonged exposure (PE) therapy has been found efficient in reducing posttraumatic stress disorder (PTSD) symptoms mostly among rape victims, but has not been explored in combat-related PTSD. Five patients with severe chronic PTSD, unresponsive to previous treatment (medication and supportive therapy) are described. Patients were evaluated with the PTSD Symptom Scale–Interview, and Beck Depression Inventory, before and after 10–15 sessions of PE therapy. All five patients showed marked improvement with PE, with a mean decrease of 48% in PTSD Symptom Scale–Interview score and 69% in Beck Depression Inventory score. Moreover, four patients maintained treatment gains or kept improving 6–18 months after the treatment. The results suggest that PE was effective in reducing combat-related chronic PTSD symptoms.

Introduction: 99mTc-d,I-hexamethylpropylene amine oxime (99m Tc-HMPAO) retention in brain is proportional to cerebral blood flow and related to both the local hemodynamic state and to the cellular content of reduced glutathione. Alterations of the regional distribution of 99mTc-HMPAO retention, with discrepant results, have been reported at functional brain imaging of unipolar depression. Since mitochondrial involvement has been reported in depressed patients, the aim of the study was to explore whether the 99mTc-HMPAO retention at single-photon emission computed tomography in depressed patients may relate to different levels of mitochondrial function.

Methods: All patients had audiological and muscular symptoms, somatic symptoms that are common in depression. Citrate synthase (CS) activity assessed in muscle mitochondria correlated strongly with the activities of three mitochondrial respiratory chain enzymes and was used as a marker of mitochondrial function. K-means clustering performed on CS grouped eight patients with low and 11 patients with normal CS. Voxel-based analysis was performed on the two groups by statistical parametric mapping.

Results: Voxel-based analysis showed significantly higher 99mTc-HMPAO retention in the patients with low CS compared with the patients with normal CS in the posterior and inferior frontal cortex, the superior and posterior temporal cortex, the somato-sensory cortex, and the associative parietal cortex.

Conclusion: Low muscle CS in depressed patients is related to higher regional 99mTc-HMPAO retention that may reflect cerebrovascular adaptation to impaired intracellular metabolism and/or intracellular enzymatic changes, as previously reported in mitochondrial disorder. Mitochondrial dysfunction in varying proportions of the subjects may explain some of the discrepant results for 99mTc-HMPAO retention in depression.