Psychiatry - Research Publications
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ItemNo Preview AvailableNeurological Soft Signs Are Not "Soft" in Brain Structure and Functional Networks: Evidence From ALE Meta-Analysis(OXFORD UNIV PRESS, 2014-05-01)BACKGROUND: Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. METHOD: We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. RESULTS: The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. CONCLUSIONS: Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.
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ItemNovel implications of Lingo-1 and its signaling partners in schizophrenia(NATURE PUBLISHING GROUP, 2014-01-01)Myelination and neurite outgrowth both occur during brain development, and their disturbance has been previously been implicated in the pathophysiology of schizophrenia. Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) is a potent negative regulator of axonal myelination and neurite extension. As co-factors of Lingo-1 signaling (Nogo receptor (NgR), With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1)) have been implicated in the genetics of schizophrenia, we explored for the first time the role of Lingo-1 signaling pathways in this disorder. Lingo-1 protein, together with its co-receptor and co-factor proteins NgR, tumor necrosis factor (TNF) receptor orphan Y (TROY), p75, WNK1 and Myt1, have never been explored in the pathogenesis of schizophrenia. We examined protein levels of Lingo-1, NgR, TROY, p75, WNK1, Myt1 and myelin basic protein (MBP) (as a marker of myelination) within the post-mortem dorsolateral prefrontal cortex (DLPFC) (37 schizophrenia patients versus 37 matched controls) and hippocampus (Cornu Ammonis, CA1 and CA3) (20 schizophrenia patients versus 20 matched controls from the same cohort). Both of these brain regions are highly disrupted in the schizophrenia pathophysiology. There were significant increases in Lingo-1 (P<0.001) and Myt1 (P=0.023) and a reduction in NgR (P<0.001) in the DLPFC in schizophrenia subjects compared with controls. There were also increases in both TROY (P=0.001) and WNK1 (P=0.011) in the CA1 of schizophrenia subjects and, in contrast to the DLPFC, there was an increase in NgR (P=0.006) in the CA3 of schizophrenia subjects compared with controls. No significant difference was reported for MBP levels (P>0.05) between the schizophrenia and control groups in the three tested regions. This is the first time that a study has shown altered Lingo-1 signaling in the schizophrenia brain. Our novel findings may present a direct application for the use of a Lingo-1 antagonist to complement current and future schizophrenia therapies.
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ItemCognitive Behavioural Therapy for Auditory Hallucinations: Effectiveness and Predictors of Outcome in a Specialist Clinic(CAMBRIDGE UNIV PRESS, 2011-03-01)BACKGROUND: Cognitive behavioural therapy has been established as an effective treatment for residual psychotic symptoms but a substantial proportion of people do not benefit from this treatment. There has been little direct study of predictors of outcome, particularly in treatment targeting auditory hallucinations. METHOD: The Psychotic Symptom Rating Scales (PSYRATS) and Positive and Negative Syndrome Scale (PANSS) were administered pre- and post-therapy to 33 people with schizophrenia-related disorders receiving CBT for auditory hallucinations in a specialist clinic. Outcome was compared with pre-therapy measures of insight, beliefs about the origin of hallucinations, negative symptoms and cognitive disorganization. RESULTS: There were significant improvements post-treatment on the PSYRATS and PANSS Positive and General Scales. Improvement on the PSYRATS was associated with lower levels of negative symptoms, but was unrelated to overall insight, delusional conviction regarding the origins of hallucinations, or levels of cognitive disorganization. CONCLUSIONS: Lack of insight and presence of formal thought disorder do not preclude effective cognitive-behavioural treatment of auditory hallucinations. There is a need to further understand why negative symptoms may present a barrier to therapy.
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ItemUnderstanding the role of inflammatory-related pathways in the pathophysiology and treatment of psychiatric disorders: evidence from human peripheral studies and CNS studies(OXFORD UNIV PRESS, 2011-08-01)Many lines of evidence now support the hypothesis that inflammation-related pathways are involved in the pathophysiology of psychiatric disorders. Much of the data underpinning this hypothesis has come from the study of inflammation-related proteins in blood of individuals with mood disorders and schizophrenia. Significantly, recent data have emerged to suggest that changes in inflammation-related pathways are present in the CNS of subjects with psychiatric disorders. It is therefore timely to overview how such data, plus data on the role of inflammation-related proteins in CNS function, is contributing to understanding the pathophysiology of mood disorders and schizophrenia. In addition, it has been suggested that antidepressants, mood stabilizers and antipsychotic drugs act on inflammation-related pathways and therefore measuring levels of inflammation-related proteins in blood may be useful in monitoring treatment responsiveness. Despite these important neuropsychopharmacological discoveries, there is no clear understanding as to how inflammatory-related pathways can precipitate the onset of psychiatric symptoms. This review will focus on data suggesting that acute-reactive proteins and cytokines are affected by the pathophysiology of mood disorders and schizophrenia, that levels of blood inflammation-related proteins before and after treatment might be useful in the diagnosis of psychiatric disorders or measuring responsiveness to drug treatment. Finally, it will be postulated how changes in these proteins affect CNS function to cause psychiatric disorders.