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.

Sleep dysfunction is common among patients with Parkinson's disease and occurs in approximately two thirds of patients. The problems range from nocturnal issues such as difficulty with sleep initiation, sleep fragmentation, disturbance of circadian rhythm, and rapid eye movement sleep behavior disorder, to daytime problems such as excessive daytime sleepiness. Frequent nighttime awakening and sleep disruption are the most common sleep problems in Parkinson's disease. Dopamine plays an important role in maintaining wakefulness. To improve sleep in Parkinson's disease, it is important to achieve the critical balance of adequate dopaminergic therapy and control of symptoms. Increased dopaminergic agents can cause dyskinesias and painful dystonia, and undertreatment can cause nighttime akinesia, rigidity, and worse quality of sleep. Other nondopaminergic drugs commonly used in Parkinson's disease can also affect sleep. In patients with advanced Parkinson's disease, deep brain stimulation of the subthalamic nucleus has a favorable impact on sleep quality and sleep architecture.

Abnormalities in brain activation using functional magnetic resonance imaging (fMRI) during cognitive and emotional tasks have been identified in bipolar disorder patients, in frontal, subcortical and limbic regions. Several studies also indicate that mood state may be differentiated by lateralization of brain activation in fronto-limbic regions. The interpretation of fMRI studies in bipolar disorder is limited by the choice of regions of interest, medication effects, comorbidity, and task performance. These studies suggest that there is a complex alteration in regions important for neural networks underlying cognition and emotional processing in bipolar disorder. However, measuring changes in specific brain regions does not identify how these neural networks are affected. New analytical techniques of fMRI data are needed in order to resolve some of these issues and identify how changes in neural networks relate to cognitive and emotional processing in bipolar disorder.

In the last decades, increasing attention has been provided to socio-cultural and neurobiological factors involved in the psychopathology of feeding and eating disorders (FED), encouraging a multifactorial approach. In this framework, several authors stressed an association between FED and other kinds of psychiatric disorders from both a psychopathological and a neurobiological point of view. In particular, many promising contributions are focusing on the possible link between FED and autism spectrum disorder (ASD). Growing interest about this association rose from the frequently reported evidence of ASD-like traits amongst FED patients and abnormal eating behaviors amongst patients with ASD. This narrative review overview aims to summarize the most relevant findings about the overlap between different kinds of FED and the autism spectrum, taking into account the most recent hypotheses about the psychopathology of both these conditions. While most of the studies focused on anorexia nervosa, both ASD and autistic traits seem to be detectable also in other kinds of FED. In addition, the recently increased interest toward a dimensional approach to psychopathology led to progressively broadening the concept of ASD, focusing on its subthreshold and gender-specific manifestations and on its link with other psychiatric conditions, including FED. Globally the studies summarized here provide further support to theoretical models featuring a neurodevelopmental approach for mental disorders. In particular, FED have been conceptualized as a possible psychopathological trajectory of a neurodevelopmental alteration, toward which female gender would act as one of many predisposing factors.

Psychotropic drugs are often associated with sexual dysfunction. The frequency of antidepressant-associated sexual dysfunction is greatly underestimated in clinical trials that rely on patient self-report of these adverse events. Direct inquiry reveals that delayed orgasm/ejaculation occurs in ≥50% and anorgasmia in at least one third of patients given selective serotonin reuptake inhibitors. Antidepressant-induced sexual dysfunction can be successfully managed. A different antidepressant without significant sexual effects, such as bupropion or mirtazapine, can often be substituted. Other strategies involve drug holidays or adjunctive therapy with drugs such as sildenafil. Dopamine antagonist antipsychotic drugs are most commonly associated with decreased libido. The newer atypical antipsychotics, with less effect on dopamine, are less commonly associated with sexual dysfunction. Sexual dysfunction is commonly reported with seizure disorders, and many anticonvulsant drugs affect levels of sex hormones. Because sexual dysfunction can be related to many factors, care must be taken to establish the patient's baseline sexual functioning before the initiation of psychotropic drug therapy and to rule out other etiologies before drugs are implicated as causative.

ISSUE:Ketamine induces rapid-onset and short-duration improvement in depressive and suicidal symptoms in both treatment-resistant unipolar depression and bipolar depression, and also reduces chronic pain after short intravenous infusions. In order to develop long-acting oral agents with the same clinical effects, the pharmacologic mechanism of action must be understood, and the leading hypotheses are discussed here.

The safety and efficacy of medications for preventive treatment of migraine is the subject of current concern and investigation in health care. Two single-center, double-blind, placebo-controlled studies were conducted to evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy patients with a diagnosis of migraine were randomly assigned to topiramate-treated and placebo groups. The studies consisted of a 4-week baseline phase, a 6—8 week titration, and 8–12 weeks of maintenance. Topiramate was titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The primary efficacy measure, the mean 28-day migraine frequency, was lower in topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001). Similarly, topiramate treatment resulted in a significantly greater mean reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was the most common side effect reported with topiramate treatment. Other topiramate-associated adverse events included altered taste, memory impairment, diarrhea, and appetite suppression/weight loss. The rates of discontinuation were similar for the topiramate group (n=10) and the placebo group (n=8). These results suggest that topiramate is effective and well tolerated in the preventive treatment of migraine headaches.

Anxiety disorders in the United States are prevalent, widespread, and disabling. These illnesses may account for almost one third of the $148 billion total mental health bill each year. Pharmacologic options include tricyclic antidepressants, monoamine oxidase inhibitors, serotonin norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, and anxiolytics. Psychological treatments include cognitive-behavioral therapy (CBT), cognitive therapy, exposure, and ritual prevention therapies. Despite insufficient evidence, many experts recommend combined treatment, generally medication with CBT. A literature review was conducted to examine studies with random assignment, adequate methods and sample sizes, blind assessments, sufficient dosages and durations of treatment, and satisfactory reporting of data, to determine whether combined treatment was superior to monotherapy. Twenty-six randomized clinical trials were identified; nine met review criteria. A review of relevant studies could not confirm the superiority of combined treatment over monotherapy. In one of four studies of obsessive-compulsive disorder, combined treatment produced better results than monotherapy.  There was no evidence of superiority for combined therapy over monotherapy for the treatment of social phobia or generalized anxiety disorder. There were no studies that met review criteria for either specific phobia or posttraumatic stress disorder (PTSD). With panic disorder, there was evidence that combined treatment might actually lead to worse outcome. Combined treatment is commonly recommended, but empirical support is limited. More research is needed. There are few well-designed studies, and little data regarding PTSD and specific phobias.

New findings regarding the mechanisms of action of electroconvulsive therapy (ECT) have led to novel developments in treatment technique to further improve this highly effective treatment for major depression. These new approaches include novel electrode placements, optimization of electrical stimulus parameters, and new methods for inducing more targeted seizures (eg, magnetic seizure therapy [MST]). MST is the use of transcranial magnetic stimulation to induce a seizure. Magnetic fields pass through tissue unimpeded, providing more control over the site and extent of stimulation than can be achieved with ECT. This enhanced control represents a means of focusing the treatment on target cortical structures thought to be essential to antidepressant response and reducing spread to medial temporal regions implicated in the cognitive side effects of ECT. MST is at an early stage of development. Preliminary results suggest that MST may have some advantages over ECT in terms of subjective side effects and acute cognitive functioning. Studies designed to address the antidepressant efficacy of MST are underway. As with all attempts to improve convulsive therapy technique, the clinical value of MST will need to be established through controlled clinical trials. This article reviews the experience to date with MST, and places this work in the broader context of other means of optimizing convulsive therapy in the treatment of depression.

Repeated episodes of alcohol withdrawal may exacerbate the severity of future withdrawal occurrences. The progressive intensification of withdrawal symptoms may be manifested as a kindling-like mechanism. This sensitization process may reflect persistent perturbation in excitatory and inhibitory influences on brain function. Relapse is also thought to be affected by the kindling mechanism. Successive alcohol withdrawal experiences may also lead to neurologic damage and cognitive impairments. We review the research findings regarding the alcohol withdrawal kindling hypothesis and the implications of the kindling process on mechanisms of dependence, alcohol withdrawal treatment strategies, and the long-term repercussions of alcoholism.

Objective: This study examines the impact of comorbidity of attention-deficit/hyperactivity disorder (ADHD) with disruptive and anxiety disorders in childhood on clinical course and outcome. We consider the relative contribution of each comorbid symptom constellation, and also their interaction, to assess the following questions: (1) Does early comorbidity with conduct disorder (CD) and anxiety disorders define specific developmental trajectories?; (2) Is comorbid anxiety disorders in childhood continuous with anxiety disorders in adolescence?; (3) Does comorbid anxiety disorders mitigate the negative behavioral outcome of youth with ADHD?; and (4) Is there an interaction between comorbid CD and anxiety disorders, when they occur simultaneously, that predicts a different outcome than either comorbid condition alone?

Method: Thirty-two 15- to 18-year-old adolescent males, diagnosed with ADHD between 7 and 11 years of age, were re-evaluated for assessment of adolescent outcome 4.3–9.2 years later. Hierarchical regression analyses were run with each of the eight Child Behavior Checklist and Youth Self-Report problem scales, and the four anxiety symptom subscales of the Multidimensional Anxiety Scale for Children serving as outcome variables.

Results: Findings indicate that comorbid CD at baseline predicteds parent reports of behavior problems in adolescence, while comorbid anxiety disorders in childhood predicted youth reports of anxiety and social problems. Anxiety disorders without CD did not predict poor behavioral outcome. Children with both comorbid CD and anxiety disorder had the highest levels of parent-rated symptoms on follow up. In particular, adolescent social problems were best predicted by the combination of comorbid CD and anxiety disorder in childhood.

Conclusion: These data provide evidence that children with ADHD plus anxiety disorder do in fact have anxiety disorders, and that the combination of anxiety disorder and CD predicts a more rather than less severe course.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that has a strong genetic basis, and is heterogeneous in its etiopathogenesis and clinical presentation. Neuroimaging studies, in concert with neuropathological and clinical research, have been instrumental in delineating trajectories of development in children with ASD. Structural neuroimaging has revealed ASD to be a disorder with general and regional brain enlargement, especially in the frontotemporal cortices, while functional neuroimaging studies have highlighted diminished connectivity, especially between frontal-posterior regions. The diverse and specific neuroimaging findings may represent potential neuroendophenotypes, and may offer opportunities to further understand the etiopathogenesis of ASD, predict treatment response, and lead to the development of new therapies.

Gilles de la Tourette syndrome is a chronic and complex tic disorder accompanied by specific behavioral problems in the majority of patients. With its multifaceted interplay between motion and emotion, this condition is a paradigmatic example of the science and art of clinical neuropsychiatry. This review article encompasses the clinical phenomenology of motor and vocal tics and associated sensory experiences (premonitory urges), as well as the behavioral spectrum of the most common comorbidities, including obsessive-compulsive disorder, attention-deficit and hyperactivity disorder, affective symptoms, and impulsivity. Knowledge of the contributions of both tics and behavioral problems to patients’ health-related quality of life across the lifespan should assist treating clinicians in formulating a targeted management plan. Although the exact pathophysiology of Gilles de la Tourette syndrome remains elusive, research into therapeutic interventions has expanded the range of available interventions across multiple domains. A thorough understanding of the neurology and psychiatry of this condition is of key importance to meet the needs of this patient population, from the formulation of an accurate diagnosis to the implementation of effective treatment strategies.

Diabetes mellitus has long been considered a risk factor for the development of vascular dementia. Epidemiologic evidence has suggested that diabetes mellitus significantly increases risk for the development of Alzheimer's disease, independent of vascular risk factors. As insulin's role as a neuromodulator in the brain has been described, its significance for AD has also emerged. Insulin dysregulation may contribute to AD pathology through several mechanisms including decreased cortical glucose utilization particularly in the hippocampus and entorhinal cortex; increased oxidative stress through the formation of advanced glycation end-products; increased Tau phosphorylation and neurofibrillary tangle formation; increased β-amyloid aggregation through inhibition of insulin-degrading enzyme. Future treatment of AD might involve pharmacologic and dietary manipulations of insulin and glucose regulation.

Many instruments have been published in recent years to improve the ability of mental health clinicians to estimate the likelihood that an individual will behave violently toward others. Increasingly, these instruments are being applied in response to laws that require specialized risk assessments. In this review, we present a framework that goes beyond the “clinical” and “actuarial” dichotomy to describe a continuum of structured approaches to risk assessment. Despite differences among them, there is little evidence that one instrument predicts violence better than another. We believe that these group-based instruments are useful for assessing an individual's risk, and that the instrument should be chosen based on the purpose of the assessment.