Association of a risk allele of ANK3 with cognitive performance and cortical thickness in patients with first-episode psychosis.

Background: The gene ANK3 is implicated in bipolar disorder and schizophrenia. The present study investigated the influence of this gene on cognitive performance and brain structure among individuals with first-episode psychosis (FEP). The brief illness duration of an FEP sample makes it well suited for studying the effects of genetic variation.

Childhood trauma and dissociation in first-episode psychosis, chronic schizophrenia and community controls.

Increasing evidence supports the role of childhood trauma in the etiology of psychosis but underlying mechanisms are poorly understood. Early maltreatment has been linked to dissociative symptoms in psychosis patients. We explored associations between childhood trauma (Childhood Trauma Questionnaire) and dissociation (Dissociative Experiences Scale) in first-episode psychotic patients (n=62), chronic psychotic patients (n=43), and non-psychotic community controls (n=66).

Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly.

Background: Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), a disorder characterised by the development of hamartomas or benign tumours in various organs as well as the variable presence of epilepsy, intellectual disability (ID) and autism. TSC1, TSC2 and the recently described protein TBC1D7 form a complex that inhibits mTORC1 signalling and limits cell growth. Although it has been proposed that mutations in TBC1D7 might also cause TSC, loss of its function has not yet been documented in humans.

Sensitivity of scales to evaluate change in symptomatology with psychostimulants in different ADHD subtypes.

Objective: To assess the sensitivity of scales (Conners' Global Index Parent and Teacher form [CGI-P, CGI-T], Clinical Global Impression Scale [CGI], Continuous Performance Test [CPT], and Restricted Academic Situation Scale [RASS]) in evaluating improvement in symptomatology with methylphenidate in different Attention Deficit Hyperactivity Disorder (ADHD) subtypes.

Method: Four hundred and ninety children (309 with ADHD Combined/Hyperactive [ADHD-CH] and 181 with ADHD Inattentive subtype [ADHD-I]) participated in a two week double-blind placebo-controlled crossover methylphenidate trial.

Results: CGI-P showed small effect size for ADHD-I and medium effect size for the ADHD-CH subtype.

Structure of spike count correlations reveals functional interactions between neurons in dorsolateral prefrontal cortex area 8a of behaving primates.

Neurons within the primate dorsolateral prefrontal cortex (dlPFC) are clustered in microcolumns according to their visuospatial tuning. One issue that remains poorly investigated is how this anatomical arrangement influences functional interactions between neurons during behavior. To investigate this question we implanted 4 mm×4 mm multielectrode arrays in two macaques' dlPFC area 8a and measured spike count correlations (rsc ) between responses of simultaneously recorded neurons when animals maintained stationary gaze.

Impairment in verbal memory observed in first episode psychosis patients with persistent negative symptoms.

Negative symptoms are present early on during the first episode of psychosis (FEP). The severity of these symptoms has been linked to cognitive deficits, including memory; however, its relationship with persistent negative symptoms (PNS) remains unclear. Thus, the goals of the current paper were to explore memory profiles in FEP patients identified as having PNS and to delineate this relationship in PNS over a 1-year period.

Association between obesity-related gene FTO and ADHD.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is an etiologically complex heterogeneous behavioral disorder. Several studies have reported that ADHD subjects are more likely to be overweight/obese and that this comorbidity may be due to shared genetic factors. The objective of this study is to explore the association between ADHD and FTO, a gene strongly associated with obesity in genome-wide studies.

Investigation of rare variants in LRP1, KPNA1, ALS2CL and ZNF480 genes in schizophrenia patients reflects genetic heterogeneity of the disease.

Background: Schizophrenia is a severe psychiatric disease characterized by a high heritability and a complex genetic architecture. Recent reports based on exome sequencing analyses have highlighted a significant increase of potentially deleterious de novo mutations in different genes in individuals with schizophrenia.

Findings: This report presents the mutation screening results of four candidate genes for which such de novo mutations were previously reported (LRP1, KPNA1, ALS2CL and ZNF480).

Body weight and ADHD: examining the role of self-regulation.

Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.

Anxiety symptoms severity and short-term clinical outcome in first-episode psychosis.

Aim: In psychotic disorders, a limited number of studies have documented the presence of symptoms of anxiety, especially in first-episode psychosis (FEP). There is a growing interest in better understanding how these symptoms may affect the severity of psychotic symptoms and clinical outcome. This study examined the association between symptoms of anxiety, as measured by the Hamilton Anxiety Rating Scale (HARS) and the Positive and Negative Syndrome Scale (PANSS), and short-term clinical outcome.

The influence of perceived social support on medication adherence in first-episode psychosis.

Objective: Our study examines the unique influence of social and family support on adherence to medication in a sample of patients treated for first-episode psychosis (FEP).

Method: Social and family support using the Multidimensional Scale of Perceived Social Support and medication adherence (consensus of subjective and objective data) were evaluated on a monthly basis during a 6-month period in a sample of 82 FEP patients. The relation between social support and adherence was evaluated using correlational and linear regression analyses, controlling for other relevant variables.

Identifying persistent negative symptoms in first episode psychosis.

Background: Although persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort.

Comprehensive phenotype/genotype analyses of the norepinephrine transporter gene (SLC6A2) in ADHD: relation to maternal smoking during pregnancy.

Objective: Despite strong pharmacological evidence implicating the norepinephrine transporter in ADHD, genetic studies have yielded largely insignificant results. We tested the association between 30 tag SNPs within the SLC6A2 gene and ADHD, with stratification based on maternal smoking during pregnancy, an environmental factor strongly associated with ADHD.

Methods: Children (6-12 years old) diagnosed with ADHD according to DSM-IV criteria were comprehensively evaluated with regard to several behavioral and cognitive dimensions of ADHD as well as response to a fixed dose of methylphenidate (MPH) using a double-blind placebo controlled crossover trial.

Efficacy of Methylphenidate in ADHD Children across the Normal and the Gifted Intellectual Spectrum.

Objective: This study evaluates whether attention-deficit/hyperactivity disorder (ADHD) children with a borderline intelligence quotient (IQ) (70≤FSIQ<80), normal IQ (80≤FSIQ<120) and high IQ (FSIQ≥120) respond differently to psychostimulant treatment.

Method: 502 children, aged 6 to 12 years, with an IQ range from 70 to 150 participated in a two-week, double-blind, placebo-controlled, crossover methylphenidate (MPH) trial.

Results: In addition to differences in socioeconomic background and parental education, higher IQ children were found to present with less severe symptoms.

Family-based association study of ADHD and genes increasing the risk for smoking behaviours.

Objective: To investigate five top single nucleotide polymorphisms (SNPs) located in different genes and loci (CHRNA3, BDNF, DBH and LOC100188947) that were highly associated with different dimensions of smoking behaviour, in relation to attention-deficit hyperactivity disorder (ADHD).

Design: Cohort study consisting of a clinical sample of children with ADHD.

Setting: Douglas Institute ADHD Clinic, Montreal, Canada.

Genetic evidence for the association of the hypothalamic-pituitary-adrenal (HPA) axis with ADHD and methylphenidate treatment response.

Exposure to stressors results in a spectrum of autonomic, endocrine, and behavioral responses. A key pathway in this response to stress is the hypothalamic-pituitary-adrenal (HPA) axis, which results in a transient increase in circulating cortisol, which exerts its effects through the two related ligand-activated transcription factors: the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Genetic polymorphisms in these receptors have been shown to influence HPA axis reactivity, and chronic dysregulation of the HPA axis has been associated with the development of several psychiatric disorders.

Symptom attribution in first episode psychosis: a cortical thickness study.

One dimension of insight in psychosis is the ability to attribute correctly one's symptoms to a mental disorder. Recent work suggests that gray matter volumes of the orbitofrontal cortex (OFC) are correlated with aggregate symptom attribution scores in first-episode schizophrenia. Whether regions beyond the OFC are important for symptom attribution remains to be established.

Medication adherence mediates the impact of sustained cannabis use on symptom levels in first-episode psychosis.

Both medication non-adherence and co-morbid cannabis abuse are associated with poor clinical outcome in first episode psychosis (FEP). The nature of interaction between adherence to medication and continued cannabis use remains unexplored. The objectives of this study were to examine variation in medication adherence associated with cessation or continuation of cannabis use, and to determine the impact of interaction between cannabis use and adherence to medication on symptom outcome at 12 months.

Intranasal oxytocin impedes the ability to ignore task-irrelevant facial expressions of sadness in students with depressive symptoms.

The administration of oxytocin promotes prosocial behavior in humans. The mechanism by which this occurs is unknown, but it likely involves changes in social information processing. In a randomized placebo-controlled study, we examined the influence of intranasal oxytocin and placebo on the interference control component of inhibition (i.

Intranasal oxytocin attenuates the cortisol response to physical stress: a dose-response study.

Introduction: Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose-response relation between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We therefore examined the effects of 24IU and 48IU of intranasal oxytocin on the cortisol response to vigorous exercise.

Blunted cortisol awakening response in men with first episode psychosis: relationship to parental bonding.

Early life adversity has been associated with an increased risk for the development of mental health problems, including psychotic disorders, perhaps mediated by a changed regulation of the Hypothalamic Pituitary Adrenal (HPA) axis. Aim of the present study was to confirm our previous finding of an attenuated cortisol awakening response (CAR) in men with first episode psychosis (FEP) and to explore a possible link between a blunted CAR and early adversity as indicated by perceived parental bonding. Fifty-eight patients (38 men, 20 women; mean age 23.

Dopamine-system genes, childhood abuse, and clinical manifestations in women with Bulimia-Spectrum Disorders.

Objective: We explored interaction effects involving polymorphisms of targeted dopamine system genes and selected forms of childhood abuse (sexual, physical and emotional) acting upon severity of binge-eating and psychopathological symptoms in women with Bulimia-Spectrum Disorders (BSDs).

Methods: Women diagnosed with a BSD (n = 216) were assessed for childhood traumata, eating-disorder (ED) symptoms, and selected psychopathological features (sensation seeking, impulsivity, compulsivity and affective instability), and then provided blood samples for genotyping of main polymorphisms of dopamine-2 receptor (DRD2), dopamine transporter (DAT1) and catechol o-methyltransferase (COMT) genes.

Results: Sensation Seeking was elevated in carriers of the low-function allele of the DRD2 Taq1A polymorphism who also reported childhood sexual abuse, relative to that in individuals showing other combinations of alleles and abuse exposures.