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Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

ABSTRACT: Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics.

SUBMITTER: Machado AK

PROVIDER: S-EPMC4959649 | biostudies-other | 2016 Aug

REPOSITORIES: biostudies-other

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Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

Machado Alencar Kolinski AK Pan Alexander Yongshuai AY da Silva Tatiane Morgana TM Duong Angela A Andreazza Ana Cristina AC

Canadian journal of psychiatry. Revue canadienne de psychiatrie 20160509 8

Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell ...[more]

PMID: 27310240

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Project description:Family and genetic studies indicate overlapping liability for major depressive disorder and bipolar disorder. The purpose of the present study was to determine whether this shared genetic liability influences clinical presentation.A polygenic risk score for bipolar disorder, derived from a large genome-wide association meta-analysis, was generated for each subject of European-American ancestry (n = 1,274) in the Sequential Treatment Alternatives to Relieve Depression study (STAR*D) outpatient major depressive disorder cohort. A hypothesis-driven approach was used to test for association between bipolar disorder risk score and features of depression associated with bipolar disorder in the literature. Follow-up analyses were performed in two additional cohorts.A generalized linear mixed model including seven features hypothesized to be associated with bipolar spectrum illness was significantly associated with bipolar polygenic risk score [F = 2.07, degrees of freedom (df) = 7, p = 0.04]. Features included early onset, suicide attempt, recurrent depression, atypical depression, subclinical mania, subclinical psychosis, and severity. Post-hoc univariate analyses demonstrated that the major contributors to this omnibus association were onset of illness at age ? 18 years [odds ratio (OR) = 1.2, p = 0.003], history of suicide attempt (OR = 1.21, p = 0.03), and presence of at least one manic symptom (OR = 1.16, p = 0.02). The maximal variance in these traits explained by polygenic score ranged from 0.8% to 1.1%. However, analyses in two replication cohorts testing a five-feature model did not support this association.Bipolar genetic loading appeared to be associated with bipolar-like presentation in major depressive disorder in the primary analysis. However, the results were at most inconclusive because of lack of replication. Replication efforts were challenged by different ascertainment and assessment strategies in the different cohorts. The methodological approach described here may prove useful in applying genetic data to clarify psychiatric nosology in future studies.

Dataset Information

Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

Publications

Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

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