5-HT(1A) [corrected] receptors in mood and anxiety: recent insights into autoreceptor versus heteroreceptor function.

Rationale: Serotonin (5-HT) neurotransmission is intimately linked to anxiety and depression and a diverse body of evidence supports the involvement of the main inhibitory serotonergic receptor, the serotonin-1A (5-HT(1A)) subtype, in both disorders.

Objectives: In this review, we examine the function of 5-HT(1A) receptor subpopulations and re-interpret our understanding of their role in mental illness in light of new data, separating both spatial (autoreceptor versus heteroreceptor) and the temporal (developmental versus adult) roles of the endogenous 5-HT(1A) receptors, emphasizing their distinct actions in mediating anxiety and depression-like behaviors.

Results: It is difficult to unambiguously distinguish the effects of different populations of the 5-HT(1A) receptors with traditional genetic animal models and pharmacological approaches.

A hypothesis-driven association study of 28 nuclear-encoded mitochondrial genes with antipsychotic-induced weight gain in schizophrenia.

Mitochondria are the main source of energy for neurons and have a role in many vital neuronal functions. Mitochondrial dysfunction has been described in schizophrenia, and antipsychotics such as clozapine and olanzapine have been associated with differences in gene expression in mitochondria. We investigated the hypothesis that nuclear-encoded mitochondrial genes, particularly those involved in oxidative phosphorylation or involved in oxidative stress, mitochondrial biogenesis, inflammation, and apoptosis, would be associated with antipsychotic-induced weight gain (AIWG).

Neural correlates of reward-based spatial learning in persons with cocaine dependence.

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory.

Global epigenomic reconfiguration during mammalian brain development.

DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis.

Naltrexone treatment for opioid dependence: does its effectiveness depend on testing the blockade?

Background: FDA approval of long-acting injectable naltrexone (Vivitrol) for opioid dependence highlights the relevance of understanding mechanisms of antagonist treatment. Principles of learning suggest an antagonist works through extinguishing drug-seeking behavior, as episodes of drug use ("testing the blockade") fail to produce reinforcement. We hypothesized that opiate use would moderate the effect of naltrexone, specifically, that opiate-positive urines precede dropout in the placebo group, but not in the active-medication groups.

Developing mental health-care quality indicators: toward a common framework.

Objective: Inconsistent performance measurement schemes hinder attempts to make international comparisons about mental health-care quality. This report describes a project undertaken by an international collaborative group that aims to develop a common framework of measures that will allow for international comparisons of mental health system performance.

Design: Representatives from each country submitted reports of quality measurement initiatives in mental health.

MethylomeDB: a database of DNA methylation profiles of the brain.

MethylomeDB (http://epigenomics.columbia.edu/methylomedb/index.

Role of CpG context and content in evolutionary signatures of brain DNA methylation.

DNA methylation is essential in brain function and behavior; therefore, understanding the role of DNA methylation in brain-based disorders begins with the study of DNA methylation profiles in normal brain. Determining the patterns and scale of methylation conservation and alteration in an evolutionary context enables the design of focused but effective methylation studies of disease states. We applied an enzymatic-based approach, Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS), which utilizes second-generation sequencing technology to provide an unbiased representation of genome-wide DNA methylation profiles of human and mouse brains.

Is there a role for young hippocampal neurons in adaptation to stress?

The hippocampus has been implicated in many cognitive and emotional behaviors and in the physiology of the stress response. Within the hippocampus, the dentate gyrus has been implicated in the detection of novelty. The dentate is also a major target for stress hormones and modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress.

Parental familism and antisocial behaviors: development, gender, and potential mechanisms.

Objective: To examine the relation between parental familism (strong values of attachment to nuclear and extended family members) and youth antisocial behaviors over time.

Method: Puerto Rican children 5 to 13 years of age at baseline residing in the South Bronx in New York (n = 1,138) and in the Standard Metropolitan Area in San Juan and Caguas, Puerto Rico (n = 1,353) were followed over two waves 1 year apart from 2000 to 2004. Parental familism was assessed using an adaptation of the Sabogal Familism Scale.

Eating behavior in anorexia nervosa: before and after treatment.

Objective: The purpose of this study was to assess eating behavior in patients with anorexia nervosa before and after weight normalization and healthy controls using a standardized, multiple-item lunch meal paradigm.

Method: Eighteen patients were studied shortly after inpatient admission and again after gaining to a BMI ≥ 19.5 kg m(-2) .

Specificity of verbal learning impairment and recovery in a marijuana-dependent male: the effects of sustained marijuana abstinence.

Introduction: We present the case of a young adult in treatment for marijuana dependence, with recurrent depression and a history of possible traumatic brain injury, complaining of concentration, memory, and initiation problems.

Methods: The patient was assessed longitudinally during treatment with a brief neuropsychological battery, as well as measures of marijuana use and mood.

Results: Testing at treatment baseline revealed performance that was generally in the high average range or higher on measures of reaction time and attention, with a selective impairment in verbal learning (borderline to extremely low range).

Patterns and correlates of tic disorder diagnoses in privately and publicly insured youth.

Objective: This study examined the prevalence and demographic and clinical correlates of children diagnosed with Tourette disorder, chronic motor or vocal tic disorder, and other tic disorders in public and private insurance plans over the course of a 1-year period.

Method: Claims were reviewed of Medicaid (n = 10,247,827) and privately (n = 16,128,828) insured youth (4-18 years old) focusing on tic disorder diagnoses during a 1-year period. Rates are presented for children with each tic disorder diagnosis overall and stratified by demographic characteristics and co-identified mental disorders.

Serotonin receptor imaging: clinically useful?

Serotonin is a modulatory neurotransmitter in the human brain that regulates mood, anger, reward, aggression, and appetite and plays a central role in brain development. These effects are mediated through the interaction of serotonin with at least 15 different receptor molecules. Through the development and careful characterization of novel radiotracers, we have been able to visualize and quantify in vivo many of the key molecular sites-including serotonin receptors, reuptake transporters, and enzymes-responsible for serotonin metabolism.

Genome-wide divergence of DNA methylation marks in cerebral and cerebellar cortices.

Background: Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function.

Methodology/significant Findings: Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum.

Diagnosing consciousness: neuroimaging, law, and the vegetative state.

In this paper, we review recent neuroimaging investigations of disorders of consciousness and different disciplines' understanding of consciousness itself. We consider potential tests of consciousness, their legal significance, and how they map onto broader themes in U.S.

Trends in antipsychotic drug use by very young, privately insured children.

Objective: This study describes recent trends and patterns in antipsychotic treatment of privately insured children aged 2 through 5 years.

Method: A trend analysis is presented of antipsychotic medication use (1999-2001 versus 2007) stratified by patient characteristics. Data are analyzed from a large administrative database of privately insured individuals.

Abuse liability of oxycodone as a function of pain and drug use history.

The relationship between pain and prescription opioid abuse is poorly understood. Determining whether a patient is seeking additional opioid medications in order to alleviate pain or to abuse the drugs can be difficult. The present study was designed to evaluate two variables that may influence the abuse liability of opioids: drug use history and the presence or absence of experimentally induced pain.

Normal development of brain circuits.

Spanning functions from the simplest reflex arc to complex cognitive processes, neural circuits have diverse functional roles. In the cerebral cortex, functional domains such as visual processing, attention, memory, and cognitive control rely on the development of distinct yet interconnected sets of anatomically distributed cortical and subcortical regions. The developmental organization of these circuits is a remarkably complex process that is influenced by genetic predispositions, environmental events, and neuroplastic responses to experiential demand that modulates connectivity and communication among neurons, within individual brain regions and circuits, and across neural pathways.

Minor depression during adolescence and mental health outcomes during adulthood.

Data from a community-based prospective longitudinal study were used to investigate the association of minor depressive disorder during adolescence with adverse mental health outcomes during adulthood. Structured diagnostic interviews were administered to a community-based sample of 755 individuals during adolescence and adulthood. Results indicated that minor depressive disorder during adolescence was associated with elevated risk for subsequent psychiatric disorders during adulthood, including major depressive disorder, >or= 1 disruptive disorders and clinically relevant impairment after corresponding and co-occurring disorders were controlled statistically.

Stigmatization and receptivity to mental health services among recently bereaved adults.

Severe grief symptoms, treatment receptivity, attitudes about grief, and stigmatization concerns were assessed in a community-based sample of 135 widowed participants in the Yale Bereavement Study. There was a statistically significant association between the severity of grief symptoms and reported negative reactions from friends and family members. However, more than 90% of the respondents with complicated grief, a severe grief disorder, reported that they would be relieved to know that having such a diagnosis was indicative of a recognizable psychiatric condition, and 100% reported that they would be interested in receiving treatment for their severe grief symptoms.

Does study design influence outcome?. The effects of placebo control and treatment duration in antidepressant trials.

Background: Clinicians and researchers synthesize data from randomized controlled trials (RCTs) of antidepressants to make conclusions about the efficacy of medications for depression. All treatments include nonspecific factors in addition to the specific effects of drugs, and study design may influence patient outcomes via nonspecific factors. This study investigated whether placebo control and treatment duration affect the outcome in antidepressant RCTs.