A guide on gene prioritization in studies of psychiatric disorders.

There has been an increasing interest in the identification of genetic variants causing individual differences in human behavior. Psychiatrists have contributed to the genetics field by defining the most important behavioral characteristics and by studying the association between genetic variants and behavioral differences within phenotypically well-characterized samples in which detailed assessments have been collected (e.g.

Heritability of cortical thickness changes over time in twin pairs discordant for schizophrenia.

Background: Cortical thickness and surface area changes have repeatedly been found in schizophrenia. Whether progressive loss in cortical thickness and surface area are mediated by genetic or disease related factors is unknown. Here we investigate to what extent genetic and/or environmental factors contribute to the association between change in cortical thickness and surface area and liability to develop schizophrenia.

Changes in brain regions associated with food-intake regulation, body mass and metabolic profiles during acute antipsychotic treatment in first-episode schizophrenia.

We investigated whether morphological brain changes occurred in brain regions associated with body-weight homeostasis during acute antipsychotic treatment, and if so, whether they were related to changes in body mass and metabolic profile. Twenty-two antipsychotic-naive patients with first-episode schizophrenia received either risperidone long acting injection or flupenthixol decanoate over 13 weeks and were compared by structural MRI with 23 matched healthy volunteers at weeks 0, 4 and 13. Images were reconstructed using freesurfer fully-automated whole brain segmentation.

Failure to use corollary discharge to remap visual target locations is associated with psychotic symptom severity in schizophrenia.

Corollary discharge (CD) refers to "copies" of motor signals sent to sensory areas, allowing prediction of future sensory states. They enable the putative mechanisms supporting the distinction between self-generated and externally generated sensations. Accordingly, many authors have suggested that disturbed CD engenders psychotic symptoms of schizophrenia, which are characterized by agency distortions.

Association of IQ Changes and Progressive Brain Changes in Patients With Schizophrenia.

Importance: Although schizophrenia is characterized by impairments in intelligence and the loss of brain volume, the relationship between changes in IQ and brain measures is not clear.

Objective: To investigate the association between IQ and brain measures in patients with schizophrenia across time.

Design, Setting, And Participants: Case-control longitudinal study at the Department of Psychiatry at the University Medical Center Utrecht, Utrecht, the Netherlands, comparing patients with schizophrenia and healthy control participants between September 22, 2004, and April 17, 2008.

Linkage analysis in a Dutch population isolate shows no major gene for left-handedness or atypical language lateralization.

Cerebral dominance of language function and hand preference are suggested to be heritable traits with possible shared genetic background. However, joined genetic studies of these traits have never been conducted. We performed a genetic linkage study in 37 multigenerational human pedigrees of both sexes (consisting of 355 subjects) enriched with left-handedness in which we also measured language lateralization.

Treatment adherence in schizophrenia: a patient-level meta-analysis of combined CATIE and EUFEST studies.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) obtained a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) studied a sample of 498 patients. We have combined these two samples to study the predictors and correlates of adherence to treatment.

Cognitive enhancing agents in schizophrenia and bipolar disorder.

Cognitive dysfunction is a core feature of schizophrenia and is also present in bipolar disorder (BD). Whereas decreased intelligence precedes the onset of psychosis in schizophrenia and remains relatively stable thereafter; high intelligence is a risk factor for bipolar illness but cognitive function decreases after onset of symptoms. While in schizophrenia, many studies have been conducted on the development of cognitive enhancing agents; in BD such studies are almost non-existent.

On the relationship between degree of hand-preference and degree of language lateralization.

Language lateralization and hand-preference show inter-individual variation in the degree of lateralization to the left- or right, but their relation is not fully understood. Disentangling this relation could aid elucidating the mechanisms underlying these traits. The relation between degree of language lateralization and degree of hand-preference was investigated in extended pedigrees with multi-generational left-handedness (n=310).

Effects of a culturally sensitive assessment on symptom profiles in native Dutch and Moroccan patients with a first psychosis referral.

Previous studies have reported a higher incidence of psychosis in Moroccan immigrants in the Netherlands than among native-born residents. However, this disparity was substantially attenuated when cultural differences in symptom presentation were taken into account. To better understand the impact of different diagnostic procedures on incidence rates, we examined the effects of the use of a culturally sensitive diagnostic interview, compared to a standard semi-structured diagnostic interview, on symptom profiles among Moroccan immigrant and native Dutch patients in the Netherlands.

Abnormalities in the experience of self-agency in schizophrenia: A replication study.

People usually experience agency over their actions and subsequent outcomes. These agency inferences over action-outcomes are essential to social interaction, and occur when an actual outcome corresponds with either a specific goal (goal-based), and matches with action-outcome information that is subtly pre-activated in the situation at hand (prime-based). Recent research showed that schizophrenia patients exhibit goal-based inferences, but not prime-based inferences.

Treatment Outcome-Related White Matter Differences in Veterans with Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a debilitating disorder that has been associated with brain abnormalities, including white matter alterations. However, little is known about the effect of treatment on these brain alterations. To investigate the course of white matter alterations in PTSD, we used a longitudinal design investigating treatment effects on white matter integrity using diffusion tensor imaging (DTI).

Physical Exercise Keeps the Brain Connected: Biking Increases White Matter Integrity in Patients With Schizophrenia and Healthy Controls.

It has been shown that learning a new skill leads to structural changes in the brain. However, it is unclear whether it is the acquisition or continuous practicing of the skill that causes this effect and whether brain connectivity of patients with schizophrenia can benefit from such practice. We examined the effect of 6 months exercise on a stationary bicycle on the brain in patients with schizophrenia and healthy controls.

Genetic Mapping in Mice Reveals the Involvement of Pcdh9 in Long-Term Social and Object Recognition and Sensorimotor Development.

Background: Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development.

Methods: Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits.

Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

Rationale: Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results.

The optimization of treatment and management of schizophrenia in Europe (OPTiMiSE) trial: rationale for its methodology and a review of the effectiveness of switching antipsychotics.

Background: Most of the 13 542 trials contained in the Cochrane Schizophrenia Group's register just tested the general efficacy of pharmacological or psychosocial interventions. Studies on the subsequent treatment steps, which are essential to guide clinicians, are largely missing. This knowledge gap leaves important questions unanswered.

The promise of biological markers for treatment response in first-episode psychosis: a systematic review.

Successful treatment of first-episode psychosis is one of the major factors that impacts long-term prognosis. Currently, there are no satisfactory biological markers (biomarkers) to predict which patients with a first-episode psychosis will respond to which treatment. In addition, a non-negligible rate of patients does not respond to any treatment or may develop side effects that affect adherence to the treatments as well as negatively impact physical health.

Modeling determinants of medication attitudes and poor adherence in early nonaffective psychosis: implications for intervention.

We aimed to design a multimodal intervention to improve adherence following first episode psychosis, consistent with current evidence. Existing literature identified medication attitudes, insight, and characteristics of support as important determinants of adherence to medication: we examined medication attitudes, self-esteem, and insight in an early psychosis cohort better to understand their relationships. Existing longitudinal data from 309 patients with early Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, nonaffective psychosis (83% first episode) were analyzed to test the hypothesis that medication attitudes, while meaningfully different from "insight," correlated with insight and self-esteem, and change in each influenced the others.

Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.

Importance: Patients with 22q11.2 deletion syndrome (22q11DS) have an elevated (25%) risk of developing schizophrenia. Recent reports have suggested that a subgroup of children with 22q11DS display a substantial decline in cognitive abilities starting at a young age.

Impact of aging on frontostriatal reward processing.

Healthy aging is associated with a progressive decline across a range of cognitive functions. An important factor underlying this decline may be the age-related impairment in stimulus-reward processing. Several studies have investigated age-related effects, but compared young versus old subjects.

Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment.

The MR is an important regulator of the hypothalamic-pituitary-adrenal (HPA) axis and a prime target for corticosteroids. There is increasing evidence from both clinical and preclinical studies that the MR has different effects on behavior and mood in males and females. To investigate the hypothesis that the MR sex-dependently influences the relation between childhood maltreatment and depression, we investigated three common and functional MR haplotypes (GA, CA, and CG haplotype, based on rs5522 and rs2070951) in a population-based cohort (N = 665) and an independent clinical cohort from the Netherlands Study of Depression and Anxiety (NESDA) (N = 1639).

Relevance of Five-Factor Model personality traits for obsessive-compulsive symptoms in patients with psychotic disorders and their un-affected siblings.

High rates of obsessive-compulsive symptoms (OCS) in schizophrenia require pathogenic explanations. Personality traits may represent risk and resiliency factors for the development of mental disorders and their comorbidities. The aim of the present study was to explore the associations between Five-Factor Model (FFM) personality traits and the liability for OCS in patients with psychotic disorders and in their un-affected siblings.