Introduction: The objective of the study was to examine gender differences in the relationship between weight group (under-weight to severely obese), and Axis I and Axis II psychopathology.

Methods: Data from the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC) were analyzed. Logistic regression models examined the past-year likelihood for meeting diagnostic criteria for psychiatric disorders. Interactions between weight group and gender were utilized to determine whether associations were significantly different in men and women after adjusting for demographic characteristics.

Results: First, consistent with previous NESARC analyses, the prevalence estimates of psychiatric disorders were higher among people of higher body mass index groups, regardless of gender. However, these patterns differed across genders. Both severely obese women and men, in comparison to normal weight respondents, were much more likely to meet criteria for affective and anxiety disorders, but these associations were significantly (1.5–2 times) stronger among women. For Axis II disorders, while there were very few associations between personality disorders and weight in men, among women increases in weight group were associated with increases in the likelihood of meeting criteria for a personality disorder.

Conclusion: Weight and psychopathology appear more strongly associated in women than in men. While these data do not allow for identification of underlying mechanisms, they highlight the importance of assessing for psychopathology in overweight and obese patients, and suggest that weight management may be an important consideration in the treatment of psychiatric disorders.

Women with epilepsy are at risk for reproductive health dysfunction. Sex-steroid hormone abnormalities have been reported in women with epilepsy, but it has been difficult to determine whether these abnormalities are due to epilepsy-related hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84 reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20 nonepileptic controls. Estrone, free testosterone, and androstenedione were significantly lower in subjects receiving enzyme-inducing AEDs than in nonepileptic controls. Free testosterone was significantly elevated in subjects receiving valproate compared to nonepileptic controls. Subjects with epilepsy receiving gabapentin or lamotrigine were no different from the nonepileptic controls in any of the endocrine variables. Subjects with epilepsy who are receiving AEDs that alter cytochrome P450 enzymes are at risk for significant abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones compared with nonepileptic controls. With new AEDs available that do not alter cytochrome P450 enzymes, physician selection of therapy should consider not only seizure control, but also potential effects on reproductive physiology.

Quality of life (QoL) is increasingly recognized as a pivotal outcome parameter in research on obsessive-compulsive disorder (OCD). While the concept remains somewhat ill-defined, there is now little dispute that the patients’ personal goals deserve foremost consideration during the course of treatment as the primary aim of treatment should be relief from individual despair, which is related but by no means synonymous to symptom reduction. Studies using generic (ie, illness-unspecific) instruments have confirmed poor QoL in OCD patients across a wide range of domains, especially with respect to social, work role functioning, and mental health aspects. Scores are sometimes as low as those obtained by patients with schizophrenia. Depression and obsessions are the symptom clusters that most strongly contribute to low QoL. Findings from a novel survey of 105 OCD participants point to multiple daily life problems, poor work status, and tense social networks in these patients. In order to achieve therapeutic success and improve QoL, functional problems at work and comorbid disorders such as secondary depression and physical impairments should be targeted. While successful treatment sometimes positively impacts well-being, in some studies symptom decline did not translate into improved QoL.

Flibanserin is a novel multifunctional serotonin agonist and antagonist (MSAA) that improves sexual functioning in premenopausal women who suffer from reduced sexual interest and desire.

The clinical presentation of obsessive-compulsive disorder (OCD) varies not only across patients but over the course of the disorder. This diversity indicates that OCD is a heterogeneous disorder, which may have an important impact on psychopathological, longitudinal, genetic, and treatment research. To better understand OCD heterogeneity, more homogeneous phenotypic descriptions are necessary to delimiting clinically meaningful subgroups of patients. Besides phenotypic descriptions, another method of delimiting OCD patient subgroups includes the search for endophenotypes (extended phenotypes) based on neurophysiological, immunological, genetic, neuropsychological, or neuroanatomic (neuroimaging) paradigms. This article will describe some strategies that deal with OCD heterogeneity, including the identification of more homogeneous phenotypical categories, an improved understanding of obsessive-compulsive symptom dimensions and how to use them as quantitative traits, and broadening the diagnostic boundaries of OCD to include other related conditions. The relevance and limitations of each approach are also discussed. Since the etiological mechanisms associated with the expressions of OCD are unknown, there is probably not one but several heuristic strategies to search for more homogeneous OCD subgroup, that combined may provide the most fruitful results.

This monograph summarizes the proceedings of a roundtable meeting convened to discuss pseudobulbar affect (PBA). Two didactic lectures were presented, followed by a moderated discussion among 11 participants. Post-meeting manuscript development synthesized didactic- and discussion-based content and incorporated additional material from the neuroscience literature. A conceptual framework with which to distinguish between disorders of mood and affect is presented first, and disorders of affect regulation are then reviewed briefly. A detailed description of the most common of these disorders, PBA, is the focus of the remainder of the monograph. The prevalence, putative neuranatomic and neurochemical bases of PBA are reviewed, and current and emerging methods of evaluation and treatment of persons with PBA are discussed. The material presented in this monograph will help clinicians better recognize, diagnose, and treat PBA, and will form a foundation for understanding and interpreting future studies of this condition.

Neuropathic pain is defined as a chronic pain condition that occurs or persists after a primary lesion or dysfunction of the peripheral or central nervous system. Traumatic injury of peripheral nerves also increases the excitability of nociceptors in and around nerve trunks and involves components released from nerve terminals (neurogenic inflammation) and immunological and vascular components from cells resident within or recruited into the affected area. Action potentials generated in nociceptors and injured nerve fibers release excitatory neurotransmitters at their synaptic terminals such as L-glutamate and substance P and trigger cellular events in the central nervous system that extend over different time frames. Short-term alterations of neuronal excitability, reflected for example in rapid changes of neuronal discharge activity, are sensitive to conventional analgesics, and do not commonly involve alterations in activity-dependent gene expression. Novel compounds and new regimens for drug treatment to influence activity-dependent long-term changes in pain transducing and suppressive systems (pain matrix) are emerging.

Background: Studies on the effects of antipsychotics on cognitive deficits in schizophrenia mostly suggest a superior effect of atypical over typical compounds, although findings are inconsistent and effect sizes small. Several methodological issues, such as heterogenous patient samples, incomparable drug doses, effects of prior medication, construct validity, and retest effects on neuropsychological tasks, confound most results and the comparability between studies. Consequently, the conclusion concerning effects of antipsychotics on cognition is still equivocal.

Objective: The present randomized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic (zuclopenthixol) and an atypical antipsychotic (risperidone) in a homogenous group of drug-naïve first-episode schizophrenic patients in a longitudinal setting.

Methods: First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment (N-25) were randomly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design. Cognitive functions were examined both when patients were drug-naïve, and after 13 weeks of treatment. A comprehensive neuropsychological battery was used in order to optimize construct validity, and principal components of cognitive functions were extrapolated in order to reduce type I errors. A healthy control group was tested at baseline and after 13 weeks, in order to examine retest effects. The cognitive domains studied were executive functions, selective attention, and reaction time.

Results: The patients showed considerable cognitive deficits when drug-naïve. There were few differential effects of risperidone and zuclopenthixol on cognitive deficits, except for a differential significance, respectively, tendency towards improved reaction and movement times in the risperidone group, and a lack of such in the zuclopenthixol group. These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls.

Conclusion: The study underscores the importance of examining impact of factors, such as clinical improvement, extrapyramidal side effects, anticholinergic medication and retest effects in longitudinal efficacy studies. This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naïve schizophrenia patients after 3 months of medication, because neither could be distinguished from retest effects of the healthy control group.

Introduction: Research suggests that obsessive-compulsive disorder (OCD) is not a unitary entity, but rather a highly heterogeneous condition, with complex and variable clinical manifestations.

Objective: The aims of this study were to compare clinical and demographic characteristics of OCD patients with early and late age of onset of obsessive-compulsive symptoms (OCS); and to compare the same features in early onset OCD with and without tics. The independent impact of age at onset and presence of tics on comorbidity patterns was investigated.

Methods: Three hundred and thirty consecutive outpatients meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for OCD were evaluated: 160 patients belonged to the “early onset” group (EOG): before 11 years of age, 75 patients had

Results: The EOG had a predominance of males, higher frequency of family history of OCS, higher mean scores on the “aggression/violence” and “miscellaneous” dimensions, and higher mean global DY-BOCS scores. Patients with EOG without tic disorders presented higher mean global DY-BOCS scores and higher mean scores in the “contamination/cleaning” dimension.

Conclusion: The current results disentangle some of the clinical overlap between early onset OCD with and without tics.

A lack of motivation and anhedonia represent frequent and pervasive symptoms in depression, although with poor specificity. Historically described as a response bias, reward-related impairments in depression may account for the important aspects of the cognitive impairments associated with diagnosis of major depressive disorder. Reward processing is a broad psychological construct that can be parsed into 3 distinct components known as “reinforcement learning” (learning), “reward responsiveness” (liking), and “motivation to obtain a reward” (wanting). Depressed patients respond hyposensitively to reward and maladaptively to punishment: this pattern is related to a dysfunction in the frontostriatal systems modulated by the monoamine systems; seems to be observed in medicated and unmedicated patients with depression and in healthy individuals with high levels of anhedonia; and could be observed in patients with a history of depression, even when in full remission. Considered to be cognitive impairments, reward-related-impairments may also constitute part of an underlying neurobiological vulnerability to major depressive disorder (MDD). For example, the reward-related impairment is state dependent and, more or less, correlated with symptom severity in some studies but has also been proposed as being trait like, with endophenotype characteristics, possibly contributing to the persistence of the disease or treatment resistance. The 3 core aspects of reward processing have specific neurobiological correlates that involve the ventral and dorsal striatum, lateral habenula, ventral tegmental area, orbitofrontal cortex, anterior cingulate cortex, and ventromedial and dorsolateral prefrontal cortex. These structures underline the important role of the dopaminergic mesolimbic pathway, but glutamate and serotonin could also have an important role, at least in some aspects of reward-related impairments.

Despite the fact that monoamine oxidase inhibitors (MAOIs) can be highly effective therapeutic agents for depression and some anxiety disorders, they tend to be underutilized in clinical practice. This is due at least in part to the fact that there is a great deal of misinformation and mythology about their dietary and drug interactions. This article is intended to serve as a guide for clinicians who are not particularly familiar with MAO inhibitors; its aim is to help these clinicians competently integrate these agents into clinical practice when appropriate.

The present paper aims at reviewing and commenting on the relationships between sleep and circadian phasing alterations and neurodegenerative/neuroprogressive processes in mood disorder. We carried out a systematic review, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, in PubMed, PsycINFO, and Embase electronic databases for literature related to mood disorders, sleep disturbances, and neurodegenerative/neuroprogressive processes in relation to (1) neuroinflammation, (2) activation of the stress system, (3) oxidative stress, (4) accumulation of neurotoxic proteins, and (5) neuroprotection deficit. Seventy articles were collectively selected and analyzed. Experimental and clinical studies revealed that insomnia, conditions of sleep loss, and altered circadian sleep may favor neurodegeneration and neuroprogression in mood disorders. These sleep disturbances may induce a state of chronic inflammation by enhancing neuroinflammation, both directly and indirectly, via microglia and astrocytes activation. They may act as neurobiological stressors that by over-activating the stress system may negatively influence neural plasticity causing neuronal damage. In addition, sleep disturbances may favor the accumulation of neurotoxic proteins, favor oxidative stress, and a deficit in neuroprotection hence contributing to neurodegeneration and neuroprogression. Targeting sleep disturbances in the clinical practice may hold a neuroprotective value for mood disorders.

Research on pathological gambling has begun to demonstrate the significant pathophysiologic role of several neurotransmitter systems in this disorder. Challenge studies with various pharmacologic agents have suggested the importance of potential dysregulation of the serotonergic system in pathological gambling, as this system is linked to dysfunction in behavioral initiation and inhibition. In addition, the noradrenergic system has been associated with mediation of arousal, increases of which are manifested by pathological gamblers. The interactions between these and other neurotransmitter systems, as well as the similarities between pathological gambling and other behavioral disorders, may provide important clues for pharmacologic intervention.

There is increasing recognition that coronory artery bypass grafting (CABG) may be a risk factor for subtle cognitive decline although the presence and pattern of such decline has varied across studies. Cognitive deficits may present as short-term memory loss, executive dysfunction and psychomotor slowing. Although they are usually are not severe enough to meet criteria for mild cognitive impairment or vascular dementia, they lower quality of life and add to hospitalization and out-of-hospital costs. Proposed mechanisms include surgical-related trauma, genetic susceptibility (eg, apolipoprotein E4 allele), microembolization, other vascular or ischemic changes, and temperature during surgery. Depression and anxiety levels predict subjective perception of these deficits more than objective cognitive performance. Both nonpharmacologic (eg, emboli reduction, temperature, or glucose management) and pharmacologic (eg, dexanabinol, glypromate, nootropics) strategies to prevent post-CABG cognitive deficits are under investigation. Given the large numbers of subjects who may already have CABG associated cognitive deficits, clinical trials of agents being tested for Alzheimer's disease (eg, donepezil, rivastigmine, memantine, neramexane, ginkgo) may also be informative. The results of multicenter long-term outcome studies (with matched control groups) as well as ongoing treatment trials will more conclusively address some of these issues. These data emphasize the need for clinicians to monitor cognitive function before and after coronary bypass surgery, and to educate patients.

The concatenation of convergent lines of evidence from basic to clinical research continues to reveal that norepinephrine (NE) is a crucial regulator of a myriad of behaviors ranging from stress response to memory formation. Furthermore, many neuropsychiatric disorders involve neurocircuitry that is directly modulated by NE. This report summarizes the physiological roles of NE, as well as the main findings implicating a role for NE system dysfunction in mood and anxiety disorders, posttraumatic stress disorder, attention-deficit/hyperactivity disorder, and Alzheimer's disease. In each of these disorders, there appears to be a complex dysregulation of NE function, with changes in locus ceruleus firing, NE availability, and both pre- and postsynaptic receptor regulation. Many symptoms of these disorders are attributable to abnormalities within distributed neural circuits regulated by NE. Appreciation of NE's role in modulating the neural circuitry mediating cognition and affect should help elucidate the pathophysiology of a variety of neuropsychiatric disorders and the development of novel treatments.