Depression is among the most prevalent mental disorders worldwide, and a substantial proportion of patients do not respond adequately to standard antidepressants. Our understanding of the pathophysiology of depression is no longer limited to the chemical imbalance of neurotransmitters, but also involves the interplay of proinflammatory modulators in the central nervous system, as well as folate metabolism. Additional factors such as stress and metabolic disorders also may contribute. Multiple inflammatory, metabolic, and genetic markers have been identified and may provide critical information to help clinicians individualize treatments for patients to achieve optimal outcomes. Recent advancements in research have clarified underlying causes of depression and have led to possible new avenues for adjunctive treatment. Among these is L-methylfolate, a medical food that is thought to enhance synthesis of monoamines (serotonin, norepinephrine, and dopamine), suppress inflammation, and promote neural health. Clinical studies that assessed supplemental use of L-methylfolate in patients with usual care-resistant depression found that it resulted in improved outcomes. Patients with selective serotonin reuptake inhibitor-resistant depression, and particularly subgroups with biomarkers of inflammation or metabolic disorders or folate metabolism-related genetic polymorphisms (or ≥2 of these factors), had the best responses. Considering this, the goals of this review are to 1) highlight recent advances in the pathophysiology of major depressive disorder as it pertains to folate and associated biomarkers and 2) establish the profiles of patients with depression who could benefit most from supplemental use of L-methylfolate.

Forensic psychiatry is an established medical specialty in England and Wales. Although its origins lie in the 19th century, the development of secure hospitals accelerated in the late 20th century. Services for mentally disordered offenders in the community have developed most recently and it is these services, which are the focus of this article. We have looked broadly at community services and have included criminal justice liaison and diversion services in our remit. We have also considered partnerships between health and justice agencies as well as mental health and criminal legislation. We consider the limited research evidence in relation to community forensic services and the discussion this has provoked.

Major depression is the most common serious brain disorder with a lifetime prevalence of up to 17%. Despite numerous options currently available for the treatment of depression, ~2 million people in the United States may experience an inadequate response to treatment (treatment-resistant depression [TRD]) at some point in their lives. The definition of TRD is variable, ranging from a failure to respond to two or more trials of antidepressant monotherapy to a failure to respond to four or more trials of different antidepressant therapies, including augmentation, combination therapy, and electroconvulsive therapy. It has been reported that as many as one-third of patients experience only a partial response to initial therapy, while nearly one-fifth are considered nonresponders. In addition to the obvious quality of life issues for the patient with TRD, the economic cost of TRD is significant. Annual healthcare costs increase significantly for patients with TRD with each successive change in antidepressant medication. Early in treatment (two medication changes), the annual costs are <$7,000/Year. By the eighth medication change, annual costs double to nearly $14,000/year.

There is a well-documented need for better long-term treatments for TRD, as witnessed by multiple efforts to establish treatment algorithms and best treatment steps when first and subsequent treatment measures prove inadequate. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, which analyzed outcome following several standardized antidepressive treatment steps, reported that 33% of patients did not respond even after four evidence-based treatment steps. A substantial proportion of patients are inadequately treated and some of these will go on to suffer from chronic, debilitating, and life-threatening symptoms.

The classical point of view—that major depressive episodes (MDEs), no matter what additional symptoms are present, should be treated first line with antidepressants—is now giving way to new a notion. The idea is that MDEs mixed with a few symptoms of mania/hypomania should be viewed very differently in terms of their natural history, clinical outcome, and treatment, and perhaps certain antipsychotics should be given as first-line treatment rather than antidepressant monotherapy.

ISSUE:Reports of rapid-onset but short-duration antidepressant effects in patients with treatment-resistant mood disorders after intravenous administration of ketamine have prompted efforts to find an agent with ketamine's properties that can be administered orally in repeated doses in order to sustain that action. One candidate for this is dextromethorphan, and here the pharmacologic mechanism of action is compared and contrasted with that of ketamine.

Despite increased attention to obsessive-compulsive disorder (OCD) in recent years, relatively little work has focused on cross-cultural issues. This paper reports on current thinking in this area, and considers ways of advancing the field.

An important theoretical distinction in medical anthropology is that between “disease” and “illness.” This distinction was employed to help review past cross-cultural studies of OCD and to consider further questions for empirical research. Several studies indicate that the medical disease of OCD is found in a range of cultures, with no apparent need for modification of diagnostic criteria. However, there is almost no work on how OCD as an illness—its subjective perception and experience—varies across cultures. Given the possibility that such variations may influence course and outcome, it is important to attend to them in future work. Further research on OCD needs to address unanswered questions about the epidemiology of the disease and to focus on neglected questions about variations in the subjective illness experience. Cross-cultural variations in illness experience are likely to lead to differences in the path of presentation, and may even result in variations in course and outcome.

Psilocybin is a tryptamine alkaloid found in some mushrooms, especially those of the genus Psilocybe. Psilocybin has four metabolites including the pharmacologically active primary metabolite psilocin, which readily enters the systemic circulation. The psychoactive effects of psilocin are believed to arise due to the partial agonist effects at the 5HT2A receptor. Psilocin also binds to various other receptor subtypes although the actions of psilocin at other receptors are not fully explored. Psilocybin administered at doses sufficient to cause hallucinogenic experiences has been trialed for addictive disorders, anxiety and depression. This review investigates studies of psilocybin and psilocin and assesses the potential for use of psilocybin and a treatment agent in neuropsychiatry. The potential for harm is also assessed, which may limit the use of psilocybin as a pharmacotherapy. Careful evaluation of the number needed to harm vs the number needed to treat will ultimately justify the potential clinical use of psilocybin. This field needs a responsible pathway forward.

More than 1.7 million American women are expected to reach menopause each year. Recent Canadian statistics show that a 50-year-old woman can now expect to live until her mid-80s, which implies living at least one-third of her life after menopause. The menopausal transition is typically marked by intense hormonal fluctuations, accompanied by vasomotor symptoms (eg, hot flashes, night sweats), sleeps disturbance, and changes in sexual function, as well as increased risk for osteoporosis, cardiovascular disease, and cognitive decline. More importantly, recent studies have demonstrated a significant association between menopausal transition and a higher risk for developing depression. In the post-Women's Health Initiative Study era, physicians and patients are questioning the safety and efficacy of long-term hormone therapy use. This article reviews the current literature on the benefits and risks of using hormone therapy for the treatment of menopause-related mood disturbances and alternate strategies currently available for the management of menopause-related problems, including antidepressants, complementary and alternative medicine, and selective estrogen receptor modulators.

Bipolar disorder in women presents special diagnostic and treatment challenges to the clinician. The presentation of female bipolar may resemble depressive disorders, comorbid Axis I disorders, Axis II personality disorders, behavioral dysregulation, or general medical disorders; thus, it is critically important for clinicians to assess for a history of hypomania or mania when determining diagnosis in any woman presenting with psychological symptoms. Several gender differences may exist in the epidemiology and symptomatology of bipolar disorder, and each must be kept in mind during assessment. Rapid cycling and mixed states have been associated with female gender and may present diagnostic challenges as each often presents as major depression. Symptoms of postpartum psychosis tend to differ from the symptoms typically seen in bipolar mania; therefore, if postpartum psychosis is actually a manifestation of bipolar disorder, accurate diagnosis depends upon a knowledge of these differences. Special treatment considerations for bipolar disorder in women involve interactions between the illness and the female reproductive cycle. A risk of fetal malformation exists when some mood-stabilizing agents are used during conception and/or during the first trimester of pregnancy. Neurobehavioral teratogenicity and neonatal toxicity is also possible. Careful treatment management is necessary to reduce the risks to the fetus/infant and to effectively manage bipolar disorder in the mother. In treating women with bipolar disorder, clinicians should discuss the issue of pregnancy and associated risks of treatment versus no treatment with every patient of reproductive age. Further studies are needed on gestational timing and exposure to mood-stabilizing agents, especially newer agents recently approved or currently being considered for the treatment of bipolar disorder.

While second-generation antipsychotics treat negative as well as positive symptoms, recovery for persons with schizophrenia remains elusive, in part because there are no FDA-approved medications that treat the cognitive deficits of schizophrenia (CDS). Recent work has identified agents that, when added to antipsychotics, improve cognition in schizophrenia. This work and hypothesized mechanisms of action will be reviewed.

Long-term memory is believed to depend on long-lasting changes in the strength of synaptic transmission known as synaptic plasticity. Understanding the molecular mechanisms of long-term synaptic plasticity is one of the principle goals of neuroscience. Among the most powerful tools being brought to bear on this question are genetically modified mice with changes in the expression or biological activity of genes thought to contribute to these processes. This article reviews how strains of mice with alterations in the cyclic adenosine monophosphate/protein kinase A/cyclic adenosine monophosphate-response element-binding protein signaling pathway have advanced our understanding of the biological basis of learning and memory.

Introduction: The aim of this study was to compare the level of insight in patients with body dysmorphic disorder (BDD) with and without comorbid obsessive-compulsive disorder (OCD), and to measure its possible relationships with clinical features.

Methods: Thirty outpatients affected by BDD, according to Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria, of whom 18 were also suffering from OCD, were included in the study. Clinical assessment was carried out by means of the Yale-Brown Obsessive-Compulsive Scale modified for BDD and a specially designed OCD Questionnaire. The level of insight was measured by means of the score at item 11 of the Yale-Brown Obsessive-Compulsive Scale modified for BDD.

Results: The insight resulted to be excellent in four cases, good in four, fair in five, poor in 15 and absent in two. Significant and positive correlations were observed between the level of insight and the following items: resistance to thoughts and to activities as well as to time spent on activities and control on activities related to the defect. The insight was significantly lower in patients affected by both BDD and OCD.

Conclusion: The findings indicate that the majority of BDD patients in this study, and especially those with comorbid OCD, have a low degree of insight that is significantly correlated to symptoms specific of the disorder.

Use of augmenting agents in schizophrenia is a common practice in response to resistant symptoms or comorbid illness. Increasingly, clinicians are combining more than one antipsychotic agent, despite a lack of evidence from controlled studies to support this approach. A rationale can be made for adding higher-potency agents to clozapine in an attempt to optimize D2 dopamine receptor blockade, but this strategy requires further study before it should be adopted in clinical practice. Older reports have explored the use of antidepressants, mood stabilizers, and anxiolytics as augmenting agents. These agents appear to improve comorbid affective or anxiety symptoms, but earlier evidence of improvement in psychotic or negative symptoms has not been replicated consistently. Glutamatergic agents acting at the glycine coagonist site of the N-methyl-D-aspartate receptor, including glycine, D-cycloserine, and D-serine, have demonstrated impressive therapeutic effects for negative symptoms when added to conventional neuroleptic agents, but do not appear to enhance clozapine efficacy. Given the high rates of symptom persistence and disability associated with schizophrenia, the need for augmentation strategies is great, but no approach has clearly emerged as effective for a substantial portion of patients. Although certain approaches may prove helpful for individual patients, augmentation should not be used unless monotherapy has been optimized, and should not be continued long-term unless benefits are clear.

Tics and Tourette syndrome are common comorbidities of patients diagnosed with attention-deficit/hyperactivity disorder (ADHD). One of the mainstay pharmacologic therapies for ADHD has been stimulants. However, this class of drugs has been associated with tic exacerbations, thus limiting their utility in this patients subgroup. Atomoxetine has been explored as an alternative treatment as one of the few non-stimulants available to treat ADHD. Early data identifies atomoxetine's influence on Tourette symptomatology to be not merely equivocal but potentially suppressive in the manifestation of tics. There are, however, case studies describing patients experiencing recurrences of tics following treatment with atomoxetine. We present a unique case of a patient, without any prior history of a movement disorder, who developed tics following a single dose of atomoxetine that did not improve until interventional therapy was initiated.

Objective: Understanding variations in disease presentation in men and women is clinically important as differences may reflect biological and sociocultural factors and have implications for prevention and treatment strategies. Few empirical investigations have been performed in kleptomania, particularly with respect to gender-related influences.

Methods: From 2001–2007, 95 adult subjects (n = 27 [28.4%] males) with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined kleptomania were assessed on sociodemographics and clinical characteristics, including symptom severity, comorbidity, and functional impairment, to identify gender-related differences.

Results: Men and women showed substantial symptom severity and functional impairment. Compared with affected men, women with kleptomania were more likely to be married (47.1% vs 25.9%; P = .039), have a later age at shoplifting onset (20.9 vs 14 years of age; P = .001), steal household items (P <.001), hoard stolen items (P =.020), and have an eating disorder (P = .017) and less likely to steal electronic goods (P < .001) and have another impulse-control disorder (P = .018).

Conclusion: Kleptomania is similarly associated with significant impairment in women and men. Gender-related differences in clinical features and co-occurring disorders suggest that prevention and treatment strategies incorporate gender considerations.