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Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study.

ABSTRACT: Pharmacological treatment of mental disorders is currently decided based on "trial and error" strategy. Mitochondrial multifaceted dysfunction is assumed to be a major factor in the pathophysiology and treatment of schizophrenia (SZ) and bipolar disorder (BD). This study aimed to explore the feasibility of using a profile of mitochondrial function parameters as a tool to predict the optimal drug for an individual patient (personalized medicine). Healthy controls (n?=?40), SZ (n?=?48) and BD (n?=?27) patients were recruited. Mental and global state of the subjects, six mitochondrial respiration parameters and 14 mitochondrial function-related proteins were assessed in fresh lymphocytes following in-vitro or in-vivo treatment with five antipsychotic drugs and two mood-stabilizers. In healthy controls, hierarchal clustering shows a drug-specific effect profile on the different mitochondrial parameters following in-vitro exposure. Similar changes were observed in untreated SZ and BD patients with psychosis. Following a month of treatment of the latter patients, only responders showed a significant correlation between drug-induced in-vitro effect (prior to in-vivo treatment) and short-term in-vivo treatment effect for 45% of the parameters. Long- but not short-term psychotropic treatment normalized mitochondria-related parameters in patients with psychosis. Taken together, these data substantiate mitochondria as a target for psychotropic drugs and provide a proof of concept for selective mitochondrial function-related parameters as a predictive tool for an optimized psychotropic treatment in a given patient. This, however, needs to be repeated with an expanded sample size and additional mitochondria related parameters.

SUBMITTER: Bar-Yosef T

PROVIDER: S-EPMC7378204 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study.

Bar-Yosef Tamara T Hussein Wessal W Yitzhaki Ofer O Damri Odeya O Givon Limor L Marom Carmit C Gurman Vlada V Levine Joseph J Bersudsky Yuly Y Agam Galila G Ben-Shachar Dorit D

Scientific reports 20200723 1

Pharmacological treatment of mental disorders is currently decided based on "trial and error" strategy. Mitochondrial multifaceted dysfunction is assumed to be a major factor in the pathophysiology and treatment of schizophrenia (SZ) and bipolar disorder (BD). This study aimed to explore the feasibility of using a profile of mitochondrial function parameters as a tool to predict the optimal drug for an individual patient (personalized medicine). Healthy controls (n = 40), SZ (n = 48) and BD (n = ...[more]

PMID: 32703977

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Project description:BackgroundTreadmill training augmented with visual images projected on the belt's surface can help improve walking adaptability. Moreover, patient-tailored automatization and standardization can increase the feasibility of walking-adaptability therapy. We developed C-Gait, a treadmill protocol consisting of a baseline walking-adaptability assessment involving 7 putatively distinct walking-adaptability tasks and a decision algorithm, to automatically update training content and execution parameters to a patients' performance and perceived challenge.ObjectivesThe main objective was to examine the feasibility, acceptability, and clinical potential of C-Gait training. The secondary objective was to evaluate the validity of the baseline assessment.DesignThis was a longitudinal proof-of-concept study with pretraining, posttraining, and retention tests encompassing baseline assessment and walking-related clinical measures.MethodsTwenty-four healthy adults, 12 healthy older persons, and 28 patients with gait and/or balance deficits performed the baseline assessment; the gait deficit group received 10 C-Gait training sessions over a 5-week period. Baseline assessment scores and walking-related clinical measures served as outcome measures.ResultsC-Gait training exhibited significant progression in training content and execution, with considerable between-patient variation and minimal overruling by therapists. C-Gait training was well accepted and led to improvements in walking adaptability and general walking ability, which persisted after training cessation. Baseline assessment scores differed over groups and difficulty levels, had no-to-moderate correlations with walking-related clinical measures, and had limited correlations among walking-adaptability tasks.LimitationsC-Gait was evaluated in a small yet diverse cohort. More encompassing studies are required to further establish its apparent merits. The validity of treadmill-based walking-adaptability assessment against an overground standard remains to be established.ConclusionsC-Gait offers automatized, standardized, and patient-tailored walking-adaptability training that is feasible and well accepted, with good potential for improving task-specific and generic measures of walking.

Dataset Information

Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study.

Publications

Mitochondrial function parameters as a tool for tailored drug treatment of an individual with psychosis: a proof of concept study.

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