In order to determine the extent to which depression complicates Huntington's disease (HD), we have analyzed the existing literature on depression in HD in order to report the prevalence, clinical manifestations, and treatment of HD depression. By means of MEDLINE literature searches and reviews of HD articles' bibliographies, we identified for our analysis 16 HD depression studies. Our results indicate that the prevalence of depression is 30% for all HD patients. Clinical manifestations of HD depression include a marked increased risk for suicide. The etiology of HD depression is unclear, but may be due to a number of factors, such as dysfunction in the caudate nucleus, dysfunction in the ventral striatum, and various genetic factors that are discussed in this review. Case reports and case series support the efficacy of standard antidepressant interventions in resolving symptoms of depression. Efficacious treatments reported in the literature include tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, and electro-convulsive therapy. In this study, the successful anecdotal treatment of seven consecutive HD depressed patients with sertraline suggests that sertraline may be a safe and efficacious treatment of HD depression.

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.

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.

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.

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.

Development of extrapyramidal symptoms (EPS), particularly tardive dyskinesia (TD), has long been a troubling side effect for patients taking antipsychotics. Atypical antipsychotics have been hailed as an improvement over conventional antipsychotics, offering similar efficacy with more favorable EPS profiles. In the recent Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study, which compared the conventional antipsychotic perphenazine with atypical antipsychotics olanzapine, quetiapine, risperidone, and ziprasidone in patients with schizophrenia, no significant differences in time to treatment discontinuation due to intolerability were observed between treatment groups. However, perphenazine was associated with a higher rate of patients experiencing EPS as well as a significantly higher rate of discontinuation due to EPS, despite the fact that patients with TD at baseline were excluded from the perphenazine group. Unfortunately, due to short treatment duration, the CATIE study did not have the assay sensitivity to detect differences in TD risk among any of the drugs. Thus, the atypical antipsychotics remain the first line of treatment for most patients, with specific drug selection based on benefit-risk profiles that best fit the individual patient's needs. Frequent monitoring, while noting a patient's subjective experience, remains the best strategy for choosing therapy to maximize symptom relief and minimize the impact of EPS and other side effects over the long-term. This article explores the reported results of the CATIE trial regarding EPS and emphasizes the differentiation of the atypicals from perphenazine on EPS and how these results should be incorporated into daily practice for the clinician.

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.

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.

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.

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.

Introduction: Aripiprazole is a novel second-generation antipsychotic approved for the treatment of bipolar disorder in adults but there is no systematic data available in pediatric bipolar disorder.

Methods: This was an 8-week, open-label, prospective study of aripiprazole 9.4±4.2 mg/day monotherapy to assess the efficacy and tolerability of this compound in treating pediatric bipolar disorder. Assessments included the Young Mania Rating Scale, Clinical Global Impressions-Improvement scale, and Brief Psychiatric Rating Scale. Adverse events were assessed through spontaneous self-reports, vital signs weight monitoring, and laboratory analysis.

Results: Fifteen of the 19 bipolar youth (79%) completed the study. Aripiprazole treatment was associated with clinically and statistically significant improvement in mean Young Mania Rating Scale scores (−18.0±6.9, P<.0001). With the important exception of two cases of extrapyramidal symptoms that precipitated dropout, aripiprazole was well tolerated with no statistically significant increase in body weight (1.8±1.7 kg, P=.2).

Conclusion: Open-label aripiprazole treatment was beneficial in the treatment of mania in youth with bipolar disorder. Future placebo-controlled, double blind studies are warranted.

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.

The presence of obsessive-compulsive symptoms (OCS) and obsessive-compulsive disorders (OCD) in schizophrenia is frequent, and a new clinical entity has been proposed for those who show the dual diagnosis: the schizo-obsessive disorder. This review scrutinizes the literature across the main academic databases, and provides an update on different aspects of schizo-obsessive spectrum disorders, which include schizophrenia, schizotypal personality disorder (SPD) with OCD, OCD with poor insight, schizophrenia with OCS, and schizophrenia with OCD (schizo-obsessive disorder). An epidemiological discussion on the discrepancies observed in the prevalence of OCS and OCD in schizophrenia across time is provided, followed by an overview of the main clinical and phenomenological features of the disorder in comparison to the primary conditions under a spectral perspective. An updated and comparative analysis of the main genetic, neurobiological, neurocognitive, and pharmacological treatment aspects for the schizo-obsessive spectrum is provided, and a discussion on endophenotypic markers is introduced in order to better understand its substrate. There is sufficient evidence in the literature to demonstrate the clinical relevance of the schizo-obsessive spectrum, although little is known about the neurobiology, genetics, and neurocognitive aspects of these groups. The pharmacological treatment of these patients is still challenging, and efforts to search for possible specific endophenotypic markers would open new avenues in the knowledge of schizo-obsessive spectrum.

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.