Schizophrenia bulletin
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Schizophrenia bulletin · Nov 2014
Partial genetic deletion of neuregulin 1 modulates the effects of stress on sensorimotor gating, dendritic morphology, and HPA axis activity in adolescent mice.
Stress has been linked to the pathogenesis of schizophrenia. Genetic variation in neuregulin 1 (NRG1) increases the risk of developing schizophrenia and may help predict which high-risk individuals will transition to psychosis. NRG1 also modulates sensorimotor gating, a schizophrenia endophenotype. ⋯ Further, repeated stress increased dendritic spine density in pyramidal neurons of the medial prefrontal cortex (mPFC) selectively in Nrg1 HET mice. Partial genetic deletion of Nrg1 also modulated the adaptive response of the hypothalamic-pituitary-adrenal axis to repeated stress, with Nrg1 HET displaying a reduced repeated stress-induced level of plasma corticosterone than WT mice. Our results demonstrate that Nrg1 confers vulnerability to repeated stress-induced sensorimotor gating deficits, dendritic spine growth in the mPFC, and an abberant endocrine response in adolescence.
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Schizophrenia bulletin · Sep 2014
Aberrant coupling within and across the default mode, task-positive, and salience network in subjects at risk for psychosis.
The task-positive network (TPN) is anticorrelated with activity in the default mode network (DMN), and possibly reflects competition between the processing of external and internal information, while the salience network (SN) is pivotal in regulating TPN and DMN activity. Because abnormal functional connectivity in these networks has been related to schizophrenia, we tested whether alterations are also evident in subjects at risk for psychosis. Resting-state functional magnetic resonance imaging was tested in 28 subjects with basic symptoms reporting subjective cognitive-perceptive symptoms; 19 with attenuated or brief, limited psychotic symptoms; and 29 matched healthy controls. ⋯ In particular, the typically observed antagonistic relationship in MPFC-rDLPFC, rAI-PCC, and internetwork connectivity of DMN-TPN was absent in both at-risk groups. Notably, those connectivity patterns were associated with symptoms related to reality distortions, whereas enhanced connectivity strengths of MPFC-rDLPFC and TPN-DMN were related to poor performance in cognitive functions. We propose that the loss of a TPN-DMN anticorrelation, accompanied by an aberrant spatial extent in the DMN, TPN, and SN in the psychosis risk state, reflects the confusion of internally and externally focused states and disturbance of cognition, as seen in psychotic disorders.
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Schizophrenia bulletin · Sep 2014
Reduced frontal glutamate + glutamine and N-acetylaspartate levels in patients with chronic schizophrenia but not in those at clinical high risk for psychosis or with first-episode schizophrenia.
Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). ⋯ The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.
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Schizophrenia bulletin · Jul 2014
Performance-based empathy mediates the influence of working memory on social competence in schizophrenia.
Empathic deficits have been linked to poor functioning in schizophrenia, but this work is mostly limited to self-report data. This study examined whether performance-based empathy measures account for incremental variance in social competence and social attainment above and beyond self-reported empathy, neurocognition, and clinical symptoms. Given the importance of working memory in theoretical models of empathy and in the prediction of functioning in schizophrenia, we also examined whether empathy mediates the relationship between working memory and functioning. ⋯ Performance-based measures of empathy were sensitive to functionally relevant disturbances in schizophrenia. Working memory deficits appear to have an important effect on these disruptions in empathy. Empathy is emerging as a promising new area for social cognitive research and for novel recovery-oriented treatment development.
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Schizophrenia bulletin · Jul 2014
ReviewPsychological therapies for auditory hallucinations (voices): current status and key directions for future research.
This report from the International Consortium on Hallucinations Research considers the current status and future directions in research on psychological therapies targeting auditory hallucinations (hearing voices). Therapy approaches have evolved from behavioral and coping-focused interventions, through formulation-driven interventions using methods from cognitive therapy, to a number of contemporary developments. ⋯ This review shows that psychological therapies are broadly effective for people with positive symptoms, but that more research is required to understand the specific application of therapies to voices. Six key research directions are identified: (1) moving beyond the focus on overall efficacy to understand specific therapeutic processes targeting voices, (2) better targeting psychological processes associated with voices such as trauma, cognitive mechanisms, and personal recovery, (3) more focused measurement of the intended outcomes of therapy, (4) understanding individual differences among voice hearers, (5) extending beyond a focus on voices and schizophrenia into other populations and sensory modalities, and (6) shaping interventions for service implementation.