Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals.

Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66).

The prediction of discharge from in-patient psychiatric rehabilitation: a case-control study.

Background: At any time, about 1% of people with severe and enduring mental illness such as schizophrenia require in-patient psychiatric rehabilitation. In-patient rehabilitation enables individuals with the most challenging difficulties to be discharged to successful and stable community living. However, the length of rehabilitation admission that is required is highly variable and the reasons for this are poorly understood.

Impact of cannabis use on thalamic volume in people at familial high risk of schizophrenia.

Background: No longitudinal study has yet examined the association between substance use and brain volume changes in a population at high risk of schizophrenia.

Aims: To examine the effects of cannabis on longitudinal thalamus and amygdala-hippocampal complex volumes within a population at high risk of schizophrenia.

Method: Magnetic resonance imaging scans were obtained from individuals at high genetic risk of schizophrenia at the point of entry to the Edinburgh High-Risk Study (EHRS) and approximately 2 years later.

Similarity-based extraction of individual networks from gray matter MRI scans.

The characterization of gray matter morphology of individual brains is an important issue in neuroscience. Graph theory has been used to describe cortical morphology, with networks based on covariation of gray matter volume or thickness between cortical areas across people. Here, we extend this research by proposing a new method that describes the gray matter morphology of an individual cortex as a network.

Common and distinct neural correlates of emotional processing in Bipolar Disorder and Major Depressive Disorder: a voxel-based meta-analysis of functional magnetic resonance imaging studies.

Neuroimaging studies have consistently shown functional brain abnormalities in patients with Bipolar Disorder (BD) and Major Depressive Disorder (MDD). However, the extent to which these two disorders are associated with similar or distinct neural changes remains unclear. We conducted a systematic review of functional magnetic resonance imaging studies comparing BD and MDD patients to healthy participants using facial affect processing paradigms.

The neural basis of familial risk and temperamental variation in individuals at high risk of bipolar disorder.

Background: Bipolar disorder is a highly heritable psychiatric disorder characterized by episodic elevation or depression of mood. Bipolar disorder is associated with structural and functional brain abnormalities but it is unclear whether these are present in relatives of affected individuals and if they are associated with subclinical symptoms or traits associated with the disorder.

Methods: Functional magnetic resonance imaging scans were conducted on 93 unrelated relatives of bipolar disorder patients and 70 healthy comparison subjects performing the Hayling sentence completion paradigm.

Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies.

Background: It is well established that schizophrenia is associated with structural brain abnormalities, but whether these are static or progress over time remains controversial.

Methods: A systematic review of longitudinal volumetric studies using region-of-interest structural magnetic resonance imaging in patients with schizophrenia and healthy control subjects. The percentage change in volume between scans for each brain region of interest was obtained, and data were combined using random effects meta-analysis.

White matter integrity in individuals at high genetic risk of bipolar disorder.

Background: Bipolar disorder is a familial psychiatric disorder associated with reduced white matter integrity, but it is not clear whether such abnormalities are present in young unaffected relatives and, if so, whether they have behavioral correlates. We investigated with whole brain diffusion tensor imaging whether increased genetic risk for bipolar disorder is associated with reductions in white matter integrity and whether these reductions are associated with cyclothymic temperament.

Methods: Diffusion tensor imaging data of 117 healthy unaffected relatives of patients with bipolar disorder and 79 control subjects were acquired.

The Neuro/PsyGRID calibration experiment: identifying sources of variance and bias in multicenter MRI studies.

Calibration experiments precede multicenter trials to identify potential sources of variance and bias. In support of future imaging studies of mental health disorders and their treatment, the Neuro/PsyGRID consortium commissioned a calibration experiment to acquire functional and structural MRI from twelve healthy volunteers attending five centers on two occasions. Measures were derived of task activation from a working memory paradigm, fractal scaling (Hurst exponent) from resting fMRI, and grey matter distributions from T(1) -weighted sequences.

Do we have any solid evidence of clinical utility about the pathophysiology of schizophrenia?

A diagnosis of schizophrenia, as in most of psychiatric practice, is made largely by eliciting symptoms with reference to subjective, albeit operationalized, criteria. This diagnosis then provides some rationale for management. Objective diagnostic and therapeutic tests are much more desirable, provided they are reliably measured and interpreted.

The effects of DISC1 risk variants on brain activation in controls, patients with bipolar disorder and patients with schizophrenia.

Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n=33), patients with schizophrenia (n=20) and patients with bipolar disorder (n=36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus.

Prefrontal cortex gyrification index in twins: an MRI study.

Cortical development and folding seems to be under environmental as well as genetic control. The aim of our study was to estimate the genetic influence on gyrification and cortical volumes, comparing prefrontal gyrification index (GI) in monozygotic (MZ) and dizygotic (DZ) twin pairs, and unrelated pairs. Twenty-four subjects (6 pairs of MZ and 6 pairs of DZ twins) were included in this study.

Effects of the BDNF Val66Met polymorphism on neural responses to facial emotion.

The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with affective disorders, but its role in emotion processing has not been fully established. Due to the clinically heterogeneous nature of these disorders, studying the effect of genetic variation in the BDNF gene on a common attribute such as fear processing may elucidate how the BDNF Val66Met polymorphism impacts brain function. Here we use functional magnetic resonance imaging examine the effect of the BDNF Val66Met genotype on neural activity for fear processing.

Genetic variants in the ErbB4 gene are associated with white matter integrity.

Variations in the signalling NRG1-ErbB4 pathway have been associated with genetic susceptibility for both bipolar disorder and schizophrenia, although the underlying neural mechanisms are still uncertain. Reduced integrity of the anterior limb of the internal capsule (ALIC) has been found in association with risk-associated genetic variation in the 5' region of the NRG1 gene. We hypothesised that variation in the gene encoding the NRG1 receptor, ErbB4, would also be associated with reduced ALIC integrity and with cognitive impairments characteristic of individuals with bipolar disorder and schizophrenia.

Longitudinal volume reductions in people at high genetic risk of schizophrenia as they develop psychosis.

Background: Structural differences between the brains of people with schizophrenia and control subjects are highly replicated but the timing and clinical correlates are unclear. In the Edinburgh High Risk Study, we have followed up 162 individuals at high genetic risk of schizophrenia and 36 healthy control subjects over 10 years.

Methods: Participants received detailed clinical and up to five structural magnetic resonance imaging (MRI) assessments at 2-year intervals.

DISC1 in schizophrenia: genetic mouse models and human genomic imaging.

Schizophrenia and related disorders have a major genetic component. Several large-scale studies have uncovered a number of possible candidate genes, but these have yet to be consistently replicated and their underlying biological function remains elusive. One exception is 'Disrupted in schizophrenia 1' (DISC1), a gene locus originally identified in a large Scottish family, showing a heavy burden of major mental illnesses associated with a balanced t(1;11)(q42.

Midbrain activation during Pavlovian conditioning and delusional symptoms in schizophrenia.

Context: Recent theories have suggested that the inappropriate activation of limbic motivational systems in response to neutral stimuli may underlie the development of delusions in schizophrenia.

Objective: To investigate the activation of the amygdala, midbrain, and ventral striatum during an aversive pavlovian conditioning task in patients with schizophrenia and healthy control participants using functional magnetic resonance imaging.

Design: Cross-sectional case-control functional neuroimaging study.

The 'continuum of psychosis': scientifically unproven and clinically impractical.

The limitations of current diagnostic categories are well recognised but their rationale, advantages and utility are often ignored. The scientific support for a 'continuum of psychosis' is limited, and the examination of whether categories, a continuum or more than one continua, and alternatives such as subtypes or hybrid models, best account for the distributions of symptoms in populations has simply not been done. There is a lack of discussion, let alone consensus, about the critical aspects of psychosis to measure, the best ways to quantify those and how these would be applied in clinical practice.

Schizophrenia risk genes: Implications for future drug development and discovery.

Present-day development of improved treatments for schizophrenia is hindered by uncertain models of disease, inter-individual response variability in clinical trials and a paucity of sensitive measures of treatment effects. Findings from genetic research emphasize the potential for schizophrenia risk genes to help develop focused treatments, discover new drug targets and provide markers of clinical subtypes. Advances in genetic technologies also provide novel modes of drug discovery in schizophrenia such as transcriptomics, epigenetics and transgenic animal models.

Effects of the BDNF val66met polymorphism on prefrontal brain function in a population at high genetic risk of schizophrenia.

A single nucleotide polymorphism (val66met) in the brain derived neurotrophic factor (BDNF) gene has been shown to be a risk factor for a number of psychiatric disorders, including schizophrenia. This polymorphism has also been shown to have effects on prefrontal brain morphology and function. This study aims to clarify the effects of the val66met polymorphism on prefrontal brain function in a population at high genetic risk for schizophrenia.

Between- and within-scanner variability in the CaliBrain study n-back cognitive task.

Psychiatric neuroimaging techniques are likely to improve understanding of the brain in health and disease, but studies tend to be small, based in one imaging centre and of unclear generalisability. Multicentre studies have great appeal but face problems if functional magnetic resonance imaging (fMRI) data from different centres are to be combined. Fourteen healthy volunteers had two brain scans on different days at three scanners.

Functional magnetic resonance imaging of BDNF val66met polymorphism in unmedicated subjects at high genetic risk of schizophrenia performing a verbal memory task.

Multiple strands of evidence suggest a role for Brain Derived Neurotrophic Factor (BDNF) in the pathophysiology of schizophrenia. It is not yet clear, however, how BDNF may contribute to altered brain function seen in the disorder, or in those at high genetic risk. The current study examines functional imaging correlates of the BDNF val66met polymorphism in a population at high genetic risk of schizophrenia.