Variation along P2RX7 interacts with early traumas on severity of anxiety suggesting a role for neuroinflammation.

Emotional stress is a leading risk factor in the development of neuropsychiatric disorders possibly via immune activation. P2X7 receptors promote neuroinflammation, and research suggests a relationship between chromosome region 12q2431, in which the P2X7R gene is located, and development of mood disorders, however, few studies concentrate on its association with anxiety. Our aim was to investigate the effects of P2RX7 variation in interaction with early childhood traumas and recent stressors on anxiety.

Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake.

Past-oriented rumination and future-oriented worry are two aspects of perseverative negative thinking related to the neuroticism endophenotype and associated with depression and anxiety. Our present aim was to investigate the genomic background of these two aspects of perseverative negative thinking within separate groups of individuals with suboptimal versus optimal folate intake. We conducted a genome-wide association study in the UK Biobank database ( = 72,621) on the "rumination" and "worry" items of the Eysenck Personality Inventory Neuroticism scale in these separate groups.

P2RX7 gene variation mediates the effect of childhood adversity and recent stress on the severity of depressive symptoms.

The P2X purinoceptor 7 (P2RX7) mediates inflammatory microglial responses and is implicated in neuroimmune mechanisms of depression and neurodegenerative disorders. A number of studies suggest that psychosocial stress may precipitate depression through immune activation. Genetic association studies of P2RX7 variants with depression have been inconclusive.

Abnormal expression of post-synaptic proteins in prefrontal cortex of patients with schizophrenia.

There is converging evidence of dendritic spine dysfunction in schizophrenia. In the present study we hypothesized that the expression of key proteins involved in dendritic spine development and stability may be affected in schizophrenia. Postmortem frontal cortex (BA6) from patients with schizophrenia, major depressive disorder, bipolar disorder and healthy controls was processed for glutamate post-synaptic fraction extraction and post-synaptic density purification.

Childhood Adversity Moderates the Effects of Epigenetic Regulatory Polymorphisms on Rumination.

The serotonin system has been suggested to moderate the association between childhood maltreatment and rumination, with the latter in its turn reported to be a mediator in the depressogenic effect of childhood maltreatment. Therefore, we investigated whether the associations of two epigenetic regulatory polymorphisms in the serotonin receptor gene with Ruminative Responses Scale rumination and its two subtypes, brooding and reflection, are moderated by childhood adversity (derived from the Childhood Trauma Questionnaire) among 1,501 European white adults. We tested whether the significant associations are due to depression.

Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination.

Ruminative response style is a passive and repetitive way of responding to stress, associated with several disorders. Although twin and candidate gene studies have proven the genetic underpinnings of rumination, no genome-wide association study (GWAS) has been conducted yet. We performed a GWAS on ruminative response style and its two subtypes, brooding and reflection, among 1758 European adults recruited in the general population of Budapest, Hungary, and Manchester, United Kingdom.

Significance of risk polymorphisms for depression depends on stress exposure.

Depression is a polygenic and multifactorial disorder where environmental effects exert a significant impact, yet most genetic studies do not consider the effect of stressors which may be one reason for the lack of replicable results in candidate gene studies, GWAS and between human studies and animal models. Relevance of functional polymorphisms in seven candidate genes previously implicated in animal and human studies on a depression-related phenotype given various recent stress exposure levels was assessed with Bayesian relevance analysis in 1682 subjects. This Bayesian analysis indicated a gene-environment interaction whose significance was also tested with a traditional multivariate analysis using general linear models.

Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans.

C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception.

An investigation into aripiprazole's partial D₂ agonist effects within the dorsolateral prefrontal cortex during working memory in healthy volunteers.

Rationale: Working memory impairments in schizophrenia have been attributed to dysfunction of the dorsolateral prefrontal cortex (DLPFC) which in turn may be due to low DLPFC dopamine innervation. Conventional antipsychotic drugs block DLPFC D2 receptors, and this may lead to further dysfunction and working memory impairments. Aripiprazole is a D2 receptor partial agonist hypothesised to enhance PFC dopamine functioning, possibly improving working memory.

Variability in the effect of 5-HTTLPR on depression in a large European population: the role of age, symptom profile, type and intensity of life stressors.

Background: Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity.

Methods: In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject.

Sample size estimation for comparing parameters using dynamic causal modeling.

Functional magnetic resonance imaging (fMRI) has proved to be useful for analyzing the effects of illness and pharmacological agents on brain activation. Many fMRI studies now incorporate effective connectivity analyses on data to assess the networks recruited during task performance. The assessment of the sample size that is necessary for carrying out such calculations would be useful if these techniques are to be confidently applied.

A validation of cognitive biomarkers for the early identification of cognitive enhancing agents in schizotypy: a three-center double-blind placebo-controlled study.

A number of compounds aimed at improving cognition in schizophrenia have failed to demonstrate efficacy in Phase 2 clinical trials. Translational studies using biomarkers in surrogate populations, such as schizotypy, could be used to assess the efficacy of novel compounds. In this study, we aimed to validate the sensitivity and inter-site reliability of cognitive biomarkers (working memory (N-back), spatial working memory (SWM) and verbal fluency (VF) tasks) to detect the schizotypy phenotype and its reversal by psychotropic drugs.

New visual information processing abnormality biomarker for the diagnosis of Schizophrenia.

INTRODUCTION: Schizophrenia is currently diagnosed on the basis of patient reports and clinical observations. A diagnosis based on aetiology is inherently more reliable due to being closer to the disease process than the overt clinical manifestations. Accordingly, recent research in schizophrenia has focused on the development of biomarkers in a bit to improve the reliability and neurobiological relevance of the diagnosis.

Abnormal neural oscillations in schizotypy during a visual working memory task: support for a deficient top-down network?

Neural oscillatory deficits have been proposed to be a core feature of schizophrenia spectrum disorders. In this study we aimed to confirm this by examining early evoked oscillatory patterns in the EEG theta, beta and gamma bands in individuals with high schizotypal personality trait scores. We carried out an event-related experiment using a computerised delayed matching to sample working memory (WM) task on a sample of volunteers scoring high or low on the Schizotypal Personality Questionnaire (SPQ).

Visual information processing deficits as biomarkers of vulnerability to schizophrenia: an event-related potential study in schizotypy.

We aimed to clarify the importance of early visual processing deficits for the formation of cognitive deficits in the schizophrenia spectrum. We carried out an event-related potential (ERP) study using a computerised delayed matching to sample working memory (WM) task on a sample of volunteers with high and low scores on the Schizotypal Personality Questionnaire (SPQ). The amplitudes of the visual ERPs to the encoding and retrieval stimuli in the task were measured using the BESA software.

A comparison of permutation and parametric testing for between group effective connectivity differences using DCM.

Effective connectivity is becoming an increasingly popular technique for obtaining additional information from functional magnetic resonance imaging (fMRI) cognitive activation studies. It is potentially important for investigating psychiatric illnesses, which are thought to depend on disrupted connections and in observing the action of psychoactive drugs used to treat these disorders. If researchers are to apply these techniques confidently then it is important to establish the level of power that is available in an experiment.

Total agenesis of the corpus callosum in a patient with childhood-onset schizophrenia.

The hypothesis that schizophrenia involves aberrant inter-hemispheric communication has a long pedigree, however its precise role remains unclear. We therefore report the case of a total agenesis of the corpus callosum in a 21-year-old man with childhood-onset schizophrenia. The presence of schizophrenia with very early onset on absence of corpus callosum offers an opportunity to examine neurodevelopmental model and theories regarding to interhemispheric communication in the pathogenesis of psychosis.

Quantitative frontal and temporal structural MRI studies in personality-disordered offenders and control subjects.

High rates of temporal and frontal lobe dysfunction have been reported in neuropsychological and EEG studies of incarcerated personality-disordered (PD) offenders, but there have been few quantitative structural magnetic resonance imaging (MRI) studies. We investigated whether impulsive-aggressive male PD patients showed evidence of reduced brain volumes in frontal and temporal brain regions on MRI compared with healthy control subjects. All subjects were screened for axis I pathology and brain abnormalities.