The lack of predictive biomarkers for therapeutic responses to schizophrenia leads clinical procedures to be decided without taking into account the subjects’ neuroanatomical features, a consideration, which could help in identifying specific pharmacological treatments for the remission of symptoms. Magnetic resonance imaging (MRI) is a technique widely used for radiological diagnosis and produces 3-dimensional images in excellent anatomical detail, and with a great capacity to differentiate soft tissue. Various MRI techniques of the human brain have emerged as a result of research, enabling structural tests that may help to in consolidate previous findings and lead to the discovery of new patterns of abnormality in schizophrenia. A literature review was undertaken to assess the superior temporal gyrus (STG) as a possible biomarker in schizophrenia with the use of voxel-based morphometry of the brain using MRI. Many findings in studies of schizophrenia using MRI have been inconclusive and, in some cases, conflicting, although interesting results have been obtained when attempting to correlate neuroimaging changes with aspects of clinical features and prognosis of the disease. The individuals affected by this mental illness appear to have smaller STG volumes when compared to healthy controls and also to subjects with a diagnosis of first-episode affective psychosis or groups of individuals at high risk of psychosis. However, the wide variety of definitions surrounding the STG found in a number of studies is a contributing factor to the lack of correlation between brain abnormalities and clinical symptoms. For instance, disagreements have arisen due to studies using regions of interest to analyze the STG whereas other studies prioritize the analysis of only STG subregions or specific supratemporal plane regions. It is necessary to standardize the nomenclature of the areas to be studied in the future, as this will enable more consistent results, allowing higher clinical and morphological correlations.

Major depression is a multidimensional disorder producing emotional dysregulation, cognitive impairment, and neuro-vegetative symptoms. A pathophysiological model of depression needs to explain how these dimensions interact to produce specific clinical phenotypes and how these interactions may predict remission to specific treatments. It is unlikely that major depression results from discrete brain lesions. Here we propose to define major depression as a disorder of neural networks. We review evidence suggesting that the dynamics of neural networks involved in allocation of attention resources to the internal and external world contribute to cognitive impairment, increased self-focus, and dysfunctional saliency detection in depression. We describe cognitive and emotional tasks that reveal abnormal cooperation between the Central Executive Network and the Default Mode Network. Finally we suggest that depression is associated with increased social rejection sensitivity. Studies on social rejection will shed light on how attachment relates to impairment in allocation of attention resources to produce depressive symptoms such as rumination and cognitive problems.

Although much attention has been paid to patients who lack insight into their obsessional beliefs, less importance has been given to individuals with obsessive-compulsive disorder (OCD) who display perceptual disturbances typically found in psychotic disorders, including schizophrenia, schizoaffective disorders, or mood disorders with psychotic features. We would like to call the attention to a phenomenon that has been neglected in the psychiatric literature: the occurrence of hallucinations and related phenomena in patients with OCD. In this case report, we describe five clinical vignettes of patients with OCD with hallucinations in several different sensory modalities, including the auditory, the visual, the tactile, the olfactory, and the cenesthetic ones. Further psychopathological research should clarify the clinical significance of hallucinations among patients with OCD.

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.

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.

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.

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.

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.

This is a report of a joint World Psychiatric Association/International College of Neuropsychopharmacology (WPA/CINP) workgroup concerning the risk/benefit ratio of antipsychotics in the treatment of schizophrenia. It utilized a selective but, within topic, comprehensive review of the literature, taking into consideration all the recently discussed arguments on the matter and avoiding taking sides when the results in the literature were equivocal. The workgroup’s conclusions suggested that antipsychotics are efficacious both during the acute and the maintenance phase, and that the current data do not support the existence of a supersensitivity rebound psychosis. Long-term treated patients have better overall outcome and lower mortality than those not taking antipsychotics. Longer duration of untreated psychosis and relapses are modestly related to worse outcome. Loss of brain volume is evident already at first episode and concerns loss of neuropil volume rather than cell loss. Progression of volume loss probably happens in a subgroup of patients with worse prognosis. In humans, antipsychotic treatment neither causes nor worsens volume loss, while there are some data in favor for a protective effect. Schizophrenia manifests 2 to 3 times higher mortality vs the general population, and treatment with antipsychotics includes a number of dangers, including tardive dyskinesia and metabolic syndrome; however, antipsychotic treatment is related to lower mortality, including cardiovascular mortality. In conclusion, the literature strongly supports the use of antipsychotics both during the acute and the maintenance phase without suggesting that it is wise to discontinue antipsychotics after a certain period of time. Antipsychotic treatment improves long-term outcomes and lowers overall and specific-cause mortality.

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.

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.

Currently, a major hypothesis for the pathophysiology of schizophrenia proposes that numerous risk factors converge on the N-methyl-D-aspartate (NMDA) receptor for the neurotransmitter glutamate, resulting in neurodevelopmental abnormalities at glutamate synapses and hypofunction of NMDA receptors.This hypothesis was presented in a previous “Trends in Psychopharmacology” column. Novel treatments are now in development that can theoretically boost the function of NMDA receptors by enhancing actions at the glycine co-transmitter site of this receptor complex. Early studies already indicate that this may lead to improvement in negative and cognitive symptoms of schizophrenia, especially when added as augmenting agents to atypical antipsychotics.

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.

Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.