The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) categorization of mental disorders places “separation anxiety disorder” within the broad group of anxiety disorders, and its diagnosis no longer rests on establishing an onset during childhood or adolescence. In previous editions of DSM, it was included within the disorders usually first diagnosed in infancy, childhood, or adolescence, with the requirement for an onset of symptoms before the age of 18 years: symptomatic adults could only receive a retrospective diagnosis, based on establishing this early onset. The new position of separation anxiety disorder is based upon the findings of epidemiological studies that revealed the unexpectedly high prevalence of the condition in adults, often in individuals with an onset of symptoms after the teenage years; its prominent place within the DSM-5 group of anxiety disorders should encourage further research into its epidemiology, etiology, and treatment. This review examines the clinical features and boundaries of the condition, and offers guidance on how it can be distinguished from other anxiety disorders and other mental disorders in which “separation anxiety” may be apparent.

Beyond its formal indications (epilepsy, bipolar disorder, and migraine), valproate sodium (VPA) is widely used in a number of other clinical conditions. Recently, however, the U.S. Food and Drug Administration (FDA) issued a warning regarding a decrease in IQ scores in children prenatally exposed to the drug. For patients with migraine, the pregnancy labeling of VPA will be changed from Category “D” to “X.” VPA products will remain in pregnancy category “D” for treating epilepsy and manic episodes associated with bipolar disorder. Thus, this article aims to assess (through a computerized Medline/PubMed search) the neurobehavioral teratogenicity of valproate monotherapy, in order to evaluate alternative regulatory decisions. Reviewed information suggests a detrimental impact of antenatal valproate exposure on the global child neurodevelopment. Affected areas include not just reduced IQ scores, but also behavioral problems and a potential increase in the risk for a future diagnosis of attention-deficit/hyperactivity disorder. An increased risk of developing autism-spectrum disorders has also been reported. Thus, in my opinion, VPA should be assigned definitively to the Category “X,” independent of any considerations about its clinical indications, and should be strictly avoided during pregnancy, due to the demonstrated risk of both neurobehavioral and neurocognitive teratogenicity.

Previous work from this laboratory hypothesized that the multimodal antidepressant vortioxetine enhances cognitive function through a complex mechanism, using serotonergic (5-hydroxytryptamine, 5-HT) receptor actions to modulate gamma-butyric acid (GABA) and glutamate neurotransmission in key brain regions like the prefrontal cortex (PFC) and hippocampus. However, serotonergic receptors have circumscribed expression patterns, and therefore vortioxetine’s effects on GABA and glutamate neurotransmission will probably be regionally selective. In this article, we attempt to develop a conceptual framework in which the effects of 5-HT, selective serotonin reuptake inhibitors (SSRIs), and vortioxetine on GABA and glutamate neurotransmission can be understood in the PFC and striatum—2 regions with roles in cognition and substantially different 5-HT receptor expression patterns. Thus, we review the anatomy of the neuronal microcircuitry in the PFC and striatum, anatomical data on 5-HT receptor expression within these microcircuits, and electrophysiological evidence on the effects of 5-HT on the behavior of each cell type. This analysis suggests that 5-HT and SSRIs will have markedly different effects within the PFC, where they will induce mixed effects on GABA and glutamate neurotransmission, compared to the striatum, where they will enhance GABAergic interneuron activity and drive down the activity of medium spiny neurons. Vortioxetine is expected to reduce GABAergic interneuron activity in the PFC and concomitantly increase cortical pyramidal neuron firing. However in the striatum, vortioxetine is expected to increase activity at GABAergic interneurons and have mixed excitatory and inhibitory effects in medium spiny neurons. Thus the conceptual framework developed here suggests that vortioxetine will have regionally selective effects on GABA and glutamate neurotransmission.

Binge eating disorder (BED) is the most common type of eating disorder. According to the most recent data available, the estimated lifetime prevalence of BED among US adults in the general population is 0.85% (men 0.42% and women 1.25%). Among psychiatric treatment populations, prevalence is several-fold higher. Although many people with BED are obese (BMI ≥ 30 kg/m2), roughly half are not. In the DSM-5, BED is defined by recurrent episodes of binge eating (eating in a discrete period of time, an amount of food larger than most people would eat in a similar amount of time under similar circumstances and a sense of lack of control over eating during the episode), occurring on average at least once a week for 3 months, and associated with marked distress. BED often goes unrecognized and thus untreated; in one study, 344 of 22,387 (1.5%) survey respondents met DSM-5 criteria for BED, but only 11 out of the 344 had ever been diagnosed with BED by a health-care provider. Psychiatric comorbidities are very common, with most adults with BED also experiencing anxiety disorders, mood disorders, impulse control disorders, or substance use disorders, suggesting that clinicians have patients in their practice with unrecognized BED. Multiple neurobiological explanations have been suggested for BED, including dysregulation in reward center and impulse control circuitry. Additionally, there is interplay between genetic influences and environmental stressors. Psychological treatments such as cognitive behavioral interventions have been recommended as first line and are supported by meta-analytic reviews; however, access to such treatments may be limited because of local availability and/or cost, and these treatments generally lead to little to no weight loss, although successfully eliminating binge eating can protect against future weight gain. Routine medication treatments for anxiety and depression do not necessarily ameliorate the symptoms of BED, but there are approved and emerging medication options, lisdexamfetamine and dasotraline, respectively, that specifically address the core drivers behind binge eating, namely obsessive thoughts and compulsive behaviors regarding food, resulting in marked decreases in binge eating behaviors as well as weight loss.

Anticipation refers to the increase in disease severity or decrease in age of onset in successive generations. The concept evolved from the theories and dogma of degeneration that were pervasive in psychiatry and medicine in the late 19th century and into the early 20th century. The term was set aside with the criticism of geneticist Lionel Penrose, who argued that anticipation was the result of ascertainment biases. The renewed interest in anticipation followed the identification of its molecular genetic basis in the form of unstable trinucleotide repeats. Subsequently, several diseases have been studied clinically for the presence of anticipation. Although anticipation has been identified in many diseases, including bipolar disorder, only diseases showing a pattern of progressive neurodegeneration have been associated with unstable trinucleotide repeats. This review summarizes the research on anticipation in bipolar disorder and other secular trends in the patterns of the illness such as the cohort effect. The changing nature of bipolar disorder is likely to be a result of combined influences from several genes, some of which are likely to be in a state of flux, as well as environmental or cultural forces that converge to give the clinical picture of anticipation.

Side effects from antipsychotic medications can have a profound effect on patients' lives and may adversely affect their willingness to comply with treatment. Identification of side effects through improved communication between psychiatrists, other members of the healthcare team, and their patients might increase treatment compliance. The Approaches to Schizophrenia Communication (ASC) Steering Group developed two simple, practical checklists for use in the busy clinical setting. The ASC–Self-Report (ASC-SR) checklist is completed by the patient and comprises a list of the more common or clinically important side effects of antipsychotic treatment. The ASC-Clinic (ASC-C) checklist is completed by both clinician and patient together, being used as the basis for a semi-structured interview. In a multicenter pilot study set up to evaluate the utility of checklists, 86% of patients responding considered the ASC-SR to be useful in communicating their problems to psychiatrists and other members of the healthcare team. All healthcare team respondents found both checklists to be helpful when discussing side effect problems with their patients. Moreover, 41% and 47% of healthcare team respondents reported that the ASC-SR and ASC-C, respectively, had assisted them in identifying side-effect problems not previously acknowledged. Preliminary evaluation of the ASC-SR and ASC-C in this multicenter pilot study suggests that both tools were user-friendly, encouraged communication between patients and healthcare professionals about antipsychotic drug side effects, and could readily integrated into everyday clinical practice.

Fibromyalgia syndrome (FMS) presents with widespread soft tissue pain. Common comorbidities include severe insomnia, body stiffness, affective symptoms, irritable bowels, and urethral syndrome. A 1990 research classification depends on a history of widespread pain and prominent tenderness to palpation at 11 or more of 18 specific tender points. It is a criteria-based diagnosis rather than one by exclusion and can accompany other medical conditions. FMS occurs worldwide, and can present any age, but is most common in adult females. Although numerous studies and reviews contend that FMS may be caused by psychological stress such as sexual abuse, a critical epidemiological review fails to support that concept. Existing data suggest that some individuals with FMS may have a dysregulated physiological stress response system that predates the onset of symptoms.

Posttraumatic stress disorder (PTSD) symptoms may develop as a result of an acute, life-threatening traumatic event. Such acute events are quite common in patients with cardiovascular illnesses (ie, a myocardial infarction, acute exacerbations of heart failure or edema). Indeed, PTSD symptoms have been described in a substantial minority of patients who had such events (10% to 25%), and have been shown to be associated with medical morbidity and with non-adherence to medications. This review summarizes available information about these symptoms in patients with cardiovascular illnesses. It also describes the importance of recognizing PTSD as a distinct psychiatric disorder (that can be addressed by specific treatments) and as an important compounding factor in studies of psychopathology in cardiovascular patients. In particular, an argument is made that the understanding of depressive disorders in patients with cardiovascular illnesses should incorporate conceptual and treatment information from the emotional trauma literature if indeed depressive and anxiety disorders are to be successfully treated in these patients. The authors conclude with a description of the challenges and promise of an effort to implement a clinical program to screen for PTSD symptoms in patients with cardiovascular illnesses, and with recommendations for future efforts.

Sexual desire, arousal, and orgasm are mediated by complex—and as yet not fully understood—interactions of the somatic and autonomic nervous systems, operating at cerebral, spinal, and peripheral levels. Furthermore, neural activity within these systems is modulated by the presence of steroid and peptide hormones, which affect male and female response differentially. At the central level, dopaminergic and serotonergic systems appear to play a significant role in various components of sexual response, although adrenergic, cholinergic, nitergic, γ-aminobutyric acidergic, and other neuropeptide transmitter systems may contribute as well. At the peripheral level, adrenergic, cholinergic, and nitergic activation mechanisms control vascular changes that underlie vaginal lubrication and penile erection. In addition, these systems respond to descending brain and spinal influences that generate orgasmic response. Disruption of endocrine, neural, or vascular response—caused by aging, disease, surgery, or medication—has the potential to lead to sexual inadequacy. At the same time, psychological and relationship factors play an important role in healthy sexual response and may enhance or impair sexual functioning.

This article traces the history of the way in which mental disorders were viewed and treated, from before the birth of Christ to the present day. Special attention is paid to the process of deinstitutionalization in the United States and the failure to create an adequately robust community mental health system to care for the people who, in a previous era, might have experienced lifelong hospitalization. As a result, far too many people with serious mental illnesses are living in jails and prisons that are ill-suited and unprepared to meet their needs.

We report two cases of serotonin syndrome in elderly patients during treatment of psychotic depression with atypical antipsychotics and antidepressants. The first case is a 69-year-old man who was admitted for depression with psychosis and treated with trazodone, risperidone, and sertraline. Subsequently, he developed myoclonus, tremor, cogwheel rigidity, and diaphoresis. The second case is a 72-year-old female initially admitted to a medical inpatient unit for a change in mental status that presented as increased confusion, lethargy, slurred speech, and a fever of 101.5°. She had been on phenelzine and quetiapine. In both cases, all symptoms resolved within 24 hours of the psychotropics being stopped. In both cases, we believe that serotonin syndrome was produced by a combination of an antidepressant and an atypical antipsychotic. There have been several case reports of serotonin syndrome from similar combinations of antidepressant and atypical antipsychotic treatment. Clinicians treating elderly patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome.

The aim of this review was to summarize evidence from research on psychopharmacological options for adult patients with anorexia nervosa (AN). Database searches of MEDLINE and PsycINFO (from January 1966 to January 2014) were performed, and original articles published as full papers, brief reports, case reports, or case series were included. Forty-one papers were screened in detail, and salient characteristics of pharmacological options for AN were summarized for drug classes. The body of evidence for the efficacy of pharmacotherapy in AN was unsatisfactory, the quality of observations was questionable (eg, the majority were not blinded), and sample size was often small. More trials are needed, while considering that nonresponse and nonremission are typical of patients with AN.

Neuropsychological (NP) testing is now recognized as an important method for evaluating treatment effects. However, there are limitations to how these tests are currently used in most drug treatment protocols. Changes in cognition are typically defined in statistical terms, with little knowledge as to whether the observed differences are meaningful in any other sense. Methods for assessing changes in test scores need to account for test-retest reliability, practice effects, regression to the mean, and the impact of initial performance. All of these factors may vary according to the individual characteristics of the subject. This article reviews two methods from the NP literature that have attempted to account for these sources of test-retest bias. The reliable change index provides a confidence interval for predicted change by taking into account the test-retest reliability of the measure. Standardized regression-based measures use a more sophisticated statistical approach that enables them to better account for other potential sources of confound. Use of this methodology has been limited to studies of epilepsy surgery and sports-related concussion. These methods have the potential for enhancing the interpretation of NP test data in drug treatment protocols by providing an empirically based definition of clinically meaningful change.

Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.