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Mitochondrial function in individuals at clinical high risk for psychosis.

ABSTRACT: Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy controls. We also explored the association between mitochondrial function and brain microglial activation and glutathione levels using a translocator protein 18?kDa [18F]FEPPA PET scan and 1H-MRS scan, respectively. There were no significant differences in mitochondrial complex function and lactate/pyruvate levels between CHR and healthy controls. In the CHR group, mitochondrial complex III function (r?=?-0.51, p?=?0.008) and lactate levels (r?=?0.61, p?=?0.004) were associated with prodromal negative symptoms. As previously reported, there were no significant differences in microglial activation and glutathione levels between groups, however, mitochondrial complex IV function was inversely related to microglial activation in the hippocampus in CHR (r?=?-0.42, p?=?0.04), but not in healthy controls. In conclusion, alterations in mitochondrial function are not yet evident in CHR, but may relate to the severity of prodromal symptoms, particularly negative symptoms.

SUBMITTER: Da Silva T

PROVIDER: S-EPMC5906614 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Mitochondrial function in individuals at clinical high risk for psychosis.

Da Silva Tania T Wu Abbie A Laksono Isabelle I Prce Ivana I Maheandiran Margaret M Kiang Michael M Andreazza Ana C AC Mizrahi Romina R

Scientific reports 20180418 1

Alterations in mitochondrial function have been implicated in the etiology of schizophrenia. Most studies have investigated alterations in mitochondrial function in patients in which the disorder is already established; however, whether mitochondrial dysfunction predates the onset of psychosis remains unknown. We measured peripheral mitochondrial complex (I-V) function and lactate/pyruvate levels in 27 antipsychotic-naïve individuals at clinical high risk for psychosis (CHR) and 16 healthy contr ...[more]

PMID: 29670128

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Project description:A major public health concern associated with schizophrenia and psychotic disorders is the long-term disability that involves impaired cognition, lack of social support, and an inability to function independently in the community. A critical goal of early detection and intervention studies in psychosis is therefore to understand the factors leading to this often profound impairment.To develop a predictive model of functional (social and role) outcome in a clinical high-risk sample for psychosis.Prospective, naturalistic, longitudinal 3- to 5-year follow-up study.The Recognition and Prevention Program in New York, a research clinic located in the Zucker Hillside Hospital in New York.One hundred one treatment-seeking patients at clinical high risk for psychosis. Ninety-two (91%) were followed up prospectively for a mean (SD) of 3 (1.6) years.Neurocognitive and clinical assessment.The primary outcome variables were social and role functioning at the last follow-up visit.Poor social outcome was predicted by reduced processing speed (odds ratio [OR], 1.38; 95% CI, 1.050-1.823; P?=?.02), impaired social functioning at baseline (OR, 1.85; 95% CI, 1.258-2.732; P?=?.002), and total disorganized symptoms (OR, 5.06; 95% CI, 1.548-16.527; P?=?.007). Reduced performance on tests for verbal memory (OR, 1.74; 95% CI, 1.169-2.594; P?=?.006), role functioning at baseline (OR, 1.34; 95% CI, 1.053-1.711; P?=?.02), and motor disturbances (OR, 1.77; 95% CI, 1.060-2.969; P?=?.03) predicted role outcome. The areas under the curve for the social and role prediction models were 0.824 (95% CI, 0.736-0.913; P?<?.001) and 0.77 (95% CI, 0.68-0.87; P?<?.001), respectively, demonstrating a high discriminative ability. In addition, poor functional outcomes were not entirely dependent on the development of psychosis, because 40.3% and 45.5% of nonconverters at clinical high risk had poor social and role outcomes, respectively.Results from this study support the increasing emphasis on functional decline as a critically important outcome that parallels conversion to psychosis and suggest that both psychosis and long-term functional disability are equally important targets for prevention. Reduced neurocognitive performance, functional impairments, and nonpositive attenuated symptoms at baseline were associated with an increased risk of poor functional outcomes in our sample. Poor functional outcomes were not entirely dependent on positive symptoms and the development of psychosis, further highlighting the need for intervention at this early stage of development for those who do and do not convert to a full-blown psychotic disorder.

Project description:Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the 'normativeness' of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.

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Mitochondrial function in individuals at clinical high risk for psychosis.

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Mitochondrial function in individuals at clinical high risk for psychosis.

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