Schizophrenia bulletin
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Schizophrenia bulletin · Nov 2012
Meta AnalysisWhite matter development in adolescence: diffusion tensor imaging and meta-analytic results.
In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence. ⋯ These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.
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Schizophrenia bulletin · Sep 2012
ReviewHas an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia.
Over the last 20 years, glutamatergic models of schizophrenia have become increasingly accepted as etiopathological models of schizophrenia, based on the observation that phencyclidine (PCP) induces a schizophrenia-like psychosis by blocking neurotransmission at N-methyl-D-aspartate (NMDA)-type glutamate receptors. This article reviews developments in two key predictions of the model: first, that neurocognitive deficits in schizophrenia should follow the pattern of deficit predicted based on underlying NMDAR dysfunction and, second, that agents that stimulate NMDAR function should be therapeutically beneficial. As opposed to dopamine receptors, NMDAR are widely distributed throughout the brain, including subcortical as well as cortical brain regions, and sensory as well as association cortex. ⋯ Treatment studies have been performed with compounds acting directly at the NMDAR glycine site, such as glycine, D-serine, or D-cycloserine, and, more recently, with high-affinity glycine transport inhibitors such as RG1678 (Roche). More limited studies have been performed with compounds targeting the redox site. Overall, these compounds have been found to induce significant beneficial effects on persistent symptoms, suggesting novel approaches for treatment and prevention of schizophrenia.
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Schizophrenia bulletin · Jun 2012
Meta AnalysisQuantitative meta-analysis on state and trait aspects of auditory verbal hallucinations in schizophrenia.
Auditory verbal hallucinations (AVHs) have a high prevalence in schizophrenic patients. An array of studies have explored the neural correlates of AVHs by means of functional neuroimaging and have associated AVHs with diverse brain regions, some of which have been shown to be involved in speech generation, speech perception, and auditory stimulus processing. We divided these studies into "state" studies comparing periods of presence and absence of AVHs within-subject and "trait" studies comparing patients experiencing AVHs with patients without AVHs or healthy controls during tasks with verbal material. ⋯ State studies were associated with activation in bilateral inferior frontal gyrus, bilateral postcentral gyrus, and left parietal operculum. Trait studies on the other hand showed convergence of decreases in hallucinating subjects in left superior temporal gyrus, left middle temporal gyrus, anterior cingulate cortex, and left premotor cortex activity. Based on the clear dissociation of brain regions that show convergence across state in comparison to trait studies, we conclude that the state of experiencing AVHs is primarily related brain regions that have been implicated in speech production ie, Broca's area, whereas the general trait that makes humans prone to AVHs seems to be related to brain areas involved in auditory stimuli processing and speech perception, ie, auditory cortex.
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Schizophrenia bulletin · Mar 2012
At issue: Cochrane, early intervention, and mental health reform: analysis, paralysis, or evidence-informed progress?
Among the noncommunicable diseases, mental ill-health represents the major threat to social and economic progress because it impacts so powerfully on the most critical decades of life. Consequently, mental health reform is increasingly recognized as an urgent priority worldwide. This brings into sharp focus the role of evidence, and more specifically the Cochrane paradigm, in influencing decisions about health system reform. ⋯ So on the one hand, the evidence-based paradigm must not be misused to stifle or paralyze urgent reform. Alternatively, there is a real risk that, if we do not improve the sophistication of EBHC, the whole paradigm will be sidelined and reform will remain reactive, impulsive, and desultory. The recent Cochrane review on early intervention in psychosis provides an opportunity to consider these issues and their wider significance.