DRD2 haplotype associated with negative symptoms and sustained attention deficits in Han Chinese with schizophrenia in Taiwan.

Previous studies have reported significant associations between schizophrenia and the dopamine receptor D2 gene (DRD2) variants. The relationships between DRD2 and clinical phenotypes are of particular interest because DRD2 has been shown to associate with treatment response and prefrontal dopamine transmission. Glatt et al.

Early traumatic experiences in those at clinical high risk for psychosis.

Aim: Several lines of evidence suggest a possible association between a history of trauma in childhood and later psychosis or psychotic-like experiences. The purpose of this study was to determine the extent of childhood trauma and bullying in young people at clinical high risk (CHR) of developing psychosis.

Methods: The sample consisted of 360 individuals who were at CHR of developing psychosis and 180 age- and gender-matched healthy controls.

Sexual dimorphisms and prediction of conversion in the NAPLS psychosis prodrome.

Sex differences in age at onset, symptomatology, clinical course (see Walker et al., 2002) and functional impairment (Thorup et al., 2007) are well documented in psychosis.

Performance on the Wisconsin Card Sorting Test in families of schizophrenia patients with different familial loadings.

Despite the consistent presence of performance deficits on the Wisconsin Card Sorting Test (WCST) in schizophrenia patients, whether poorer performance is also present in their nonpsychotic relatives is not certain. This study aimed to estimate both the recurrence risk ratio (λs) and the heritability of WCST scores in simplex and multiplex families, respectively, and to examine the influence of familial loading on these estimates. Participants were patients with schizophrenia and their nonpsychotic first-degree relatives from 168 simplex families and 653 multiplex families as well as 440 normal comparisons.

Transcriptomic analysis of postmortem brain identifies dysregulated splicing events in novel candidate genes for schizophrenia.

The diverse spatial and temporal expression of alternatively spliced transcript isoforms shapes neurodevelopment and plays a major role in neuronal adaptability. Although alternative splicing is extremely common in the brain, its role in mental illnesses such as schizophrenia has received little attention. To examine this relationship, postmortem brain tissue was obtained from 20 individuals with schizophrenia (SZ) and 20 neuropsychiatrically normal comparison subjects.

North American Prodrome Longitudinal Study (NAPLS 2): overview and recruitment.

The North American Prodrome Longitudinal Study (NAPLS) is a consortium of eight programs focusing on the psychosis prodrome. Funded by the National Institute of Mental Health (NIMH), the sites are located at Emory University, Harvard University, University of Calgary, UCLA, UCSD, University of North Carolina Chapel Hill, Yale University, and Zucker Hillside Hospital. Although the programs initially developed independently, they previously collaborated to combine their historical datasets and to produce a series of analyses on predictors of psychosis in one of the largest samples of longitudinally followed prodromal subjects worldwide.

A combined analysis of microarray gene expression studies of the human prefrontal cortex identifies genes implicated in schizophrenia.

Small cohort sizes and modest levels of gene expression changes in brain tissue have plagued the statistical approaches employed in microarray studies investigating the mechanism of schizophrenia. To combat these problems a combined analysis of six prior microarray studies was performed to facilitate the robust statistical analysis of gene expression data from the dorsolateral prefrontal cortex of 107 patients with schizophrenia and 118 healthy subjects. Multivariate permutation tests identified 144 genes that were differentially expressed between schizophrenia and control groups.

Blood-based gene expression signatures of infants and toddlers with autism.

Objective: Autism spectrum disorders (ASDs) are highly heritable neurodevelopmental disorders that onset clinically during the first years of life. ASD risk biomarkers expressed early in life could significantly impact diagnosis and treatment, but no transcriptome-wide biomarker classifiers derived from fresh blood samples from children with autism have yet emerged.

Method: Using a community-based, prospective, longitudinal method, we identified 60 infants and toddlers at risk for ASDs (autistic disorder and pervasive developmental disorder), 34 at-risk for language delay, 17 at-risk for global developmental delay, and 68 typically developing comparison children.

A comparison of heritability maps of cortical surface area and thickness and the influence of adjustment for whole brain measures: a magnetic resonance imaging twin study.

Understanding the genetic and environmental contributions to measures of brain structure such as surface area and cortical thickness is important for a better understanding of the nature of brain-behavior relationships and changes due to development or disease. Continuous spatial maps of genetic influences on these structural features can contribute to our understanding of regional patterns of heritability, since it remains to be seen whether genetic contributions to brain structure respect the boundaries of any traditional parcellation approaches. Using data from magnetic resonance imaging scans collected on a large sample of monozygotic and dizygotic twins in the Vietnam Era Twin Study of Aging, we created maps of the heritability of areal expansion (a vertex-based area measure) and cortical thickness and examined the degree to which these maps were affected by adjustment for total surface area and mean cortical thickness.

A pilot study exploring the effects of a 12-week t'ai chi intervention on somatic symptoms of depression in patients with heart failure.

Background: Patients with chronic heart failure (HF) and with elevated depression symptoms are at greater risk of morbidity and mortality. Somatic symptoms of depression are particularly prevalent in HF and are related to worse disease prognosis. T'ai chi practice is related to increased emotional well-being in various clinical populations; however, relatively little is known about t'ai chi's effects on somatic versus cognitive symptom dimensions of depression in HF.

Neurocognitive and clinical dysfunction in adult Chinese, nonpsychotic relatives of patients with schizophrenia: Findings from the Changsha study and evidence for schizotaxia.

Many first-degree relatives of patients with schizophrenia demonstrate deficits in neurocognitive, social, clinical and other dimensions, in the absence of psychosis. Based on a reformulation of Meehl's concept of "schizotaxia" as a clinically meaningful syndrome reflecting liability to schizophrenia, we proposed research criteria in relatives focused on negative symptoms and neurocognitive deficits. Here we assess validity of the syndrome in a sample of Chinese adult relatives by assessing measures of concurrent validity, and by using cluster analysis to test the hypothesis that relatives could be grouped into distinct schizotaxic and non-schizotaxic subgroups based on our diagnostic criteria.

Convergent functional genomics of schizophrenia: from comprehensive understanding to genetic risk prediction.

We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability.

Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies.

Background: Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning.

Auditory working memory impairments in individuals at familial high risk for schizophrenia.

Objectives: The search for predictors of schizophrenia has accelerated with a growing focus on early intervention and prevention of psychotic illness. Studying nonpsychotic relatives of individuals with schizophrenia enables identification of markers of vulnerability for the illness independent of confounds associated with psychosis. The goal of these studies was to develop new auditory continuous performance tests (ACPTs) and evaluate their effects in individuals with schizophrenia and their relatives.

Genetics of smoking and depression.

Smoking and depression are significant public health problems with multiple etiological dimensions and outcomes. Although each condition is important by itself, they are important because they often potentiate each other. Consequently, it is also essential to understand the nature their relationship.

Genetic and environmental influences of white and gray matter signal contrast: a new phenotype for imaging genetics?

The estimation of cortical thickness is in part dependent on the degree of contrast in T1 signal intensity between white matter and gray matter along the cortical mantle. The ratio of white matter to gray matter signal (WM/GM contrast) has been found to vary as a function of age and Alzheimer's disease status, suggesting a biological component to what might otherwise be labeled as a nuisance variable. The aim of the present study was to determine if measures of WM/GM contrast are genetically influenced, as well as the degree to which this phenotype may be related to the genetic and environment determinants of cortical thickness.

Are neurocognitive, clinical and social dysfunctions in schizotaxia reversible pharmacologically?: Results from the Changsha study.

The Changsha study identifies adult, non-psychotic relatives of patients with schizophrenia who show deficits in neurocognitive, social, clinical and other dimensions, and who meet provisional criteria for a liability syndrome for schizophrenia ('schizotaxia'). In this study, we investigated whether negative symptoms, neurocognitive deficits, or other measures of clinical and social function in subjects who met our research criteria for schizotaxia were amenable to pharmacological remediation with a low dose (2.0 mg) of risperidone, a second generation antipsychotic medication.

Genetic and environmental multidimensionality of well- and ill-being in middle aged twin men.

The goals of the study were to determine the extent to which the underlying structure of different types of well-being was multidimensional and whether well- and ill-being were influenced by similar or different genetic and environmental factors. Participants were 1226 male twins ages 51-60, from the Vietnam Era Twin Study of Aging. Measures included: psychological well-being, Multidimensional Personality Questionnaire Well-Being scale (MPQWB), life satisfaction, self-esteem, and depressive symptoms.

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men.

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.

Hierarchical genetic organization of human cortical surface area.

Surface area of the cerebral cortex is a highly heritable trait, yet little is known about genetic influences on regional cortical differentiation in humans. Using a data-driven, fuzzy clustering technique with magnetic resonance imaging data from 406 twins, we parceled cortical surface area into genetic subdivisions, creating a human brain atlas based solely on genetically informative data. Boundaries of the genetic divisions corresponded largely to meaningful structural and functional regions; however, the divisions represented previously undescribed phenotypes different from conventional (non-genetically based) parcellation systems.

Negative symptoms in individuals at clinical high risk of psychosis.

Negative symptoms are present in the psychosis prodrome. However, the extent to which these symptoms are present prior to the onset of the first episode of psychosis remains under-researched. The goal of this study is to examine negative symptoms in a sample of individuals at clinical high risk (CHR) for psychosis and to determine if they are predictive of conversion to psychosis.

Predictive value of thought disorder in new-onset psychosis.

Objective: This research addresses the relationship of formal thought disorder in the early stages of psychotic illness to the long-term outcome of mental health many years later. The specific topic of concern was to evaluate the prognostic significance of thought disorder on the severity of psychosis over time.

Methods: Subjects with new-onset psychosis were evaluated on a variety of measures including education, physical health, Brief Psychiatric Rating Scale scores.

Genetic influences on cortical regionalization in the human brain.

Animal data demonstrate that the development of distinct cortical areas is influenced by genes that exhibit highly regionalized expression patterns. In this paper, we show genetic patterning of cortical surface area derived from MRI data from 406 adult human twins. We mapped genetic correlations of areal expansion between selected seed regions and all other cortical locations, with the selection of seed points based on results from animal studies.