We performed a qualitative review of treatment studies of binge eating disorder (BED), focusing on randomized clinical trials (RCTs). Limited effectiveness has been demonstrated for self-help strategies, and substantial effectiveness has been shown for cognitive behavioral therapy (CBT) and interpersonal therapy (IPT). CBT and IPT may each be more effective than behavior weight loss therapy (BWLT) for reducing binge eating over the long term. The stimulant pro-drug lisdexamfetamine dimesylate (LDX) is the only drug approved by the FDA for the treatment of BED in adults based on 2 pivotal RCTs. Topiramate also decreases binge eating behavior, but its use is limited by its adverse event profile. Antidepressants may be modestly effective over the short term for reducing binge eating behavior and comorbid depressive symptoms, but are not associated with clinically significant weight loss. A RCT presented in abstract form suggests that intranasal naloxone may decrease time spent binge eating. There is no RCT of obesity surgery in BED, but many patients with BED seek and receive such surgery. While some studies suggest patients with BED and obesity do just as well as patients with obesity alone, other studies suggest that patients with BED have more post-operative complications, less weight loss, and more weight regain. This evidence suggests that patients with BED would benefit from receiving highly individualized treatment.

Background: Continuous performance tasks (CPTs) embedded in a virtual reality (VR) classroom environment have been shown to be a sensitive and user-friendly assessment tool to detect cognitive deficits related to attention-deficit/hyperactivity disorder (ADHD). The aim of the current study was to compare the performance of children with ADHD on a VR-CPT while on and off treatment with methylphenidate (MPH) and to compare the VR-CPT to a cgrrently used CPT, Test of Variables of Attention (TOVA).

Methods:Twenty-seven children with ADHD underwent the VR-CPT, the same CPT without VR (no VR-CPT), and theTOVA, 1 hour after the. ingestion of either placebo or 0.3 mg/kg MPH, in a double-blind, placebo-controlled, crossover design. Immediately following CPT, subjects described their subjective experiences on the Short Feedback Questionnaire.

Results: MPH reduced omission errors to a greater extent on the VR-CPT compared to the no VR-CPT and the TOVA, and decreased other CPT measures on all types of CPT to a similar degree. Children rated the VR-CPT as more enjoyable compared to the other types of CPT.

Conclusions: It is concluded that the VR-CPT is a sensitive and user-friendly assessment tool in measuring the response to MPH in children with ADHD.

How should sleep-related rhythmic movements in children be assessed and treated? Rhythmic movement disorder (RMD) represents an unusual variety of childhood parasomnia characterized by repetitive motion of the head, trunk, or extremities, which usually occurs during the transition from wakefulness to sleep or arises during sustained sleep. Although the condition most often affects infants and toddlers in a transient and self-limited fashion, the condition occasionally persists in a problematic fashion, which may nevertheless be amenable to treatment. Since RMD may occasionally cause injury or resemble nocturnal seizure, prompt recognition, and appropriate management on the part of the clinician is essential. This article will examine the spectrum of RMD in children, including their common clinical manifestations; data regarding their epidemiology and natural history; the role of polysomnography, electroencephalography; and other diagnostic testing. Potential causes of the condition and available methods of treatment are also examined.

Clinical and epidemiological data suggest that generalized anxiety disorder (GAD) is a chronic illness causing patients to suffer for many years leading to significant distress in daily life functioning. The literature suggests the several conclusions. GAD is a disorder in need of appropriate treatment and often has a chronic course with comorbid conditions, such as major depression and other anxiety disorders. Benzodiazepines, while effective anxiolytic agents acutely, when prescribed for >4 weeks cause rebound anxiety and following prolonged therapy may lead to withdrawal symptoms. Antidepressants cause significant anxiety relief compared with placebo and for psychosocial treatment cognitive-behavioral therapy is an efficacious psychosocial treatment. Many GAD patients are in need of long-term medication management. Furthermore, there is limited data for patients diagnosed with GAD the treatment outcome with the combination of medication and psychotherapy both acutely and long-term; how to best sequence these treatments; for those patients who do not meet remission criteria what is the ideal approach for augmentation; and for patients with treatment-refractory GAD the empirical evidence is lacking on medication switching and augmentation strategies. Research is needed in the area of developing treatment strategies for patients suffering from treatment-refractory GAD. There is still an urgent need to explore treatment combinations and duration strategies in the management of patients suffering with GAD.

Background: Ischemic stroke during infancy and childhood has the potential to result in neurological impairments and affect a child's ability to function at home, school, and play. There are limited data on the effect of ischemic stroke on quality of life (QOL) of child survivors of ischemic stroke.

Objective: To examine parent and child perspectives on QOL and examine factors that correlate with reduced QOL for child survivors of stroke.

Methods: A prospective single-center cohort design was used. Participants included children 2–18 years of age surviving ischemic stroke. The Pediatric Quality of Life 4.0 Generic Inventory Scale (PedsQL) parent proxy -report (2–18 years of age) and child self-report (5–18 years of age) were completed by participants. Scores were compared with standardized normative data of healthy children and those with chronic medical conditions. Neurological deficits were measured with the Pediatric Stroke Outcome Measure, a standardized evaluation for children. The relationships between stroke type, neurological deficit, and health-related quality of life (HRQOL) were examined.

Results: We assessed the QOL in 84 children with arterial ischemic stroke and 16 with cerebral sinovenous thrombosis at a mean age of 8.4 (4.12) years; 4.4 (2.93) years after their stroke. Results showed that both the parent-proxy and child self-report HRQOL scores were significantly reduced (P<.01) compared with normative data of healthy children. Of greatest concern for both parents and children was the effect of stroke on school, followed by its impact on emotional and social functions. In contrast to other studies, scores in physical domain were better than those in the psychosocial domain. Multivariate analysis showed that of neurological deficits after stroke was a significant predictor of poor HRQOL (P<. 05). The children with poor neurological recovery had the lowest mean PedsQL scores and their QOL was significantly poorer compared with normative data of children with chronic health, conditions (ie, diabetes, cancer).

Conclusion: The PedsQL appears to be a promising assessment tool of HRQOL for children following stroke. Both parent and child perspectives should be included because of the potential for there to be significant differences in perspectives. Although severity of neurological outcome is a significant predictor of reduced HRQOL, it accounted for a small proportion of variance in QOL scores. Further research is required to delineate other factors that are significant predictors of outcome.

The central nervous system is one of the main target tissues for sex steroid hormones, which act on both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through non-genomic mechanisms, influencing electrical excitability, synaptic function, morphological features, and neuron-glia interactions. During the climacteric period, sex steroid deficiency causes many neuroendocrine changes. At the hypothalamic level, estrogen withdrawal gives rise to vasomotor symptoms, to eating behavior disorders, and altered blood pressure control. On the other hand, at the limbic level, the changes in serotoninergic, noradrenergic, and opioidergic tones contribute to the modifications in mood, behavior, and nociception. Hormone replacement therapy (HRT) positively affects climateric depression throughout a direct effect on neural activity and on the modulation of adrenergic and serotoninergic tones and may modulate the decrease in cognitive efficiency observed in climaterium. The identification of the brain as a de novo source of neurosteroids, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women may also be related to a change in the levels of neurosteroids. These findings open new perspectives in the study of the effects of sex steroids on the central nervous system and on the possible use of alternative and/or auxiliary HRT.

This review addresses the methodologic issues relevant to the study of comorbidity and provides a broad overview of the medical and psychiatric conditions associated with migraine. Since the body of literature examining the comorbidity of migraine is enormous, the scope of this review will largely focus on community and case-control studies. Among the selected comorbid medical conditions, including disorders of the cardiovascular, respiratory, neurologic, gastrointestinal and immunologic systems, stroke, asthma, and allergies appear to be most strongly associated with migraine. Among the psychiatric illnesses, mood and anxiety disorders have been shown to be most strongly associated with migraine in the general population. Further research is indicated and necessary to elucidate the precise mechanism of migraine comorbidity.

This narrative review provides an overview of the epidemiology of binge eating disorder (BED), highlighting the medical history of this disorder and its entry as an independent condition in the Feeding and Eating Disorders section of the recently published Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Estimates of prevalence are provided, as well as recognition that the female to male ratio is lower in BED than in other eating disorders. Evidence is also provided of the most common comorbidities of BED, including mood and anxiety disorders and a range of addiction disorders. In addition, discussion of the viewpoint that BED itself may be an addiction — at least in severe cases — is presented. Although the genetic study of BED is still in its infancy, current research is reviewed with a focus on certain neurotransmitter genes that regulate brain reward mechanisms. To date, a focal point of this research has been on the dopamine and the μ-opioid receptor genes. Preliminary evidence suggests that a predisposing risk factor for BED may be a heightened sensitivity to reward, which could manifest as a strong dopamine signal in the brain’s striatal region. Caution is encouraged, however, in the interpretation of current findings, since samples are relatively small in much of the research. To date, no genome-wide association studies have focused exclusively on BED.

Background: Inadequate response to antidepressant monotherapy in women with major depressive disorder is common. Testosterone administration has been shown to be an effective augmentation therapy in depressed hypogonadal men with selective serotonin reuptake inhibitor-resistant depression. However, the effects of low-dose testosterone as augmentation therapy in women with treatment-resistant depression have not been studied.

Methods: Low-dose transdermal testosterone (300 mcg/day, Intrinsa, Procter and Gamble Pharmaceuticals) was administered to nine women with treatment-resistant depression in an 8 week open-label pilot protocol.

Results: There was a statistically significant improvement in mean Montgomery-Asberg Depression Rating Scale (MADRS) scores at 2 weeks, sustained through the 8 week period. Two-thirds of subjects achieved a response to the treatment (decrease in MADRS score of ≥50%) and 33% achieved remission (final MADRS score <10) after 8 weeks of therapy. Mean levels of fatigue, as measured by the MADRS lassitude item, significantly decreased at all time points with a mean 38% decrease from baseline to 8 weeks.

Conclusion: These preliminary pilot data suggest that low-dose transdermal testosterone may be an effective augmentation therapy in women with treatment-resistant depression. Further studies are warranted.

Akathisia is one of the most vexing problems in neuropsychiatry. Although it is one of the most common side effects of antipsychotic medications, it is often difficult to describe by patients, and is difficult to diagnose and treat by practitioners. Akathisia is usually grouped with extrapyramidal movement disorders (ie, movement disorders that originate outside the pyramidal or corticospinal tracts and generally involve the basal ganglia). Yet, it can present as a purely subjective clinical complaint, without overt movement abnormalities. It has been subtyped into acute, subacute, chronic, tardive, withdrawal-related, and “pseudo” forms, although the distinction between many of these is unclear. It is therefore not surprising that akathisia is generally either underdiagnosed or misdiagnosed, which is a serious problem because it can lead to such adverse outcomes as poor adherence to medications, exacerbation of psychiatric symptoms, and, in some cases, aggression, violence, and suicide. In this article, we will attempt to address some of the confusion surrounding the condition, its relationship to other disorders, and differential diagnosis, as well as treatment alternatives.

A review of the literature demonstrates that the incidence of new mental disorders and their prevalence during pregnancy is similar to the 12-month incidence of mental disorders in women during other periods of their lives. The prevalence of severe mood, behavior, and cognitive symptoms during pregnancy is rather high. Severe mental symptoms during pregnancy have been reported to be associated with an increased rate of complications during pregnancy and delivery, preterm deliveries, low birth weight, a higher rate of postpartum depression, and a longer-term impact on the offspring's development. Several pre-pregnancy risk factors to develop dysphoric symptoms have been reported, but their utility for primiparous women with no previous history of mental disorders is unclear. The association of mental symptoms with general symptoms and biological changes during pregnancy is also unclear. Given the short- and long-term impact of dysphoric symptoms and stress during pregnancy on mother and child, efficacious, efficient, and safe prevention and treatment modalities are essential and achievable. Clarification of the nature and phenotyping of mental and general symptoms during pregnancy is an important step for the development of effective interventions.

Mild cognitive impairment (MCI) is a clinical diagnosis in which deficits in cognitive function are evident but not of sufficient severity to warrant a diagnosis of dementia. For the majority of patients, MCI represents a transitional state between normal aging and mild dementia, usually Alzheimer's disease. Multiple subtypes of MCI are now recognized. In addition to presentations featuring memory impairment, symptoms in other cognitive domains (eg, executive function, language, visuospatial) have been identified. Neuropsychological testing can be extremely useful in making the MCI diagnosis and tracking the evolution of cognitive symptoms over time. A comprehensive test battery includes measures of baseline intellectual ability, attention, executive function, memory, language, visuospatial skills, and mood. Informant-bassed measures of neuropsychiatric symptoms, behaviors, and competency in instrumental activity are also included. Careful assessment can identify subtle deficits that may otherwise elude detection, particularly in individuals of superior baseline intellectual ability. As we move closer to disease-modifying therapy for Alzheimer's disease, early identification becomes critical for identifying patients who have an opportunity to benefit from treatment.

There is controversy about whether mindfulness-based approaches to psychotherapy represent a new wave of cognitive-behavioral therapy or a core process in all psychotherapies. One way of conceptualizing mindfulness is in terms of emotion regulation; mindfulness is a strategy aimed at opposing suppression and avoidance. Dispositional mindfulness has been associated with greater activation in prefrontal cortex and greater deactivation of amygdala during affect labeling. A number of rigorous studies of mindfulness-based cognitive therapy for depression have been positive. However, much remains to be discovered about the underlying mechanisms of and clinical indications for mindfulness-based approaches.

Parkinson's disease is a neurodegenerative disorder characterized by bradykinesia, rigidity, postural instability, and resting tremor. Increasingly, Parkinson's disease has been associated with a broad spectrum of non-motor symptoms, such as olfactory loss, sleep disorders, autonomic dysfunction, cognitive impairment, psychosis, depression, anxiety, and apathy. In addition, a minority of Parkinson's disease patients develop compulsive behaviors while receiving dopamine-replacement therapy, including medication hoarding, pathological gambling, binge eating, hyperlibidinous behavior, compulsive shopping, and punding. These behaviors may result in psychosocial impairment for patients and therapeutic challenges for clinicians. This article reviews the anatomic substrates, behavioral spectrum, associated factors, and potential treatments for dopamine-replacement therapy-related compulsions in Parkinson's disease.

Obesity has reached epidemic prevalence, and much research has focused on homeostatic and nonhomeostatic mechanisms underlying overconsumption of food. Mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), is a key substrate for nonhomeostatic feeding. The goal of the present review is to compare changes in mesolimbic dopamine function in human obesity with diet-induced obesity in rodents. Additionally, we will review the literature to determine if dopamine signaling is altered with binge eating disorder in humans or binge eating modeled in rodents. Finally, we assess modulation of dopamine neurons by neuropeptides and peripheral peptidergic signals that occur with obesity or binge eating. We find that while decreased dopamine concentration is observed with obesity, there is inconsistency outside the human literature on the relationship between striatal D2 receptor expression and obesity. Finally, few studies have explored how orexigenic or anorexigenic peptides modulate dopamine neuronal activity or striatal dopamine in obese models. However, ghrelin modulation of dopamine neurons may be an important factor for driving binge feeding in rodents.

Folate deficiency may increase the risk of depression and reduce the action of antidepressants. Individuals with an inherited polymorphism that reduces the efficiency of folate formation may be at high risk for folate deficiency and for major depression. Antidepressant effects have been reported when antidepressants are augmented with folic acid, folinic acid, or the centrally active L-methylfolate (known formally as (6(S)-5-methyltetrahydrofolate [MTHF]), particularly in depressed patients with folate deficiency whose major depressive episodes have failed to respond to antidepressants. The putative mechanism of action of MTHF as an augmenting agent to antidepressants is that it acts as a trimonoamine modulator (TMM), enhancing the synthesis of the three monoamines: dopamine (DA), norepinephrine (NE), and serotonin (5-HT), resulting in a boost to the efficacy of antidepressants.