Identifying and targeting abnormal mitochondrial localization associated with psychosis

Area of Science:

• Cell biology
• Neuroscience
• Pharmacology

Background:

• Novel therapeutics are crucial for psychiatric conditions.
• Cell-based assays offer a method to identify therapeutic candidates.
• Understanding cellular phenotypes in psychiatric disorders is key.

Purpose of the Study:

• To develop and validate a cell-based assay for identifying novel psychiatric therapeutics.
• To investigate mitochondrial positioning in peripheral cells of psychiatric patients.
• To screen for compounds and genes impacting the identified cellular phenotype.

Main Methods:

• Imaging peripheral skin fibroblasts from 168 psychiatric patients.
• Staining cells for DNA, actin, and mitochondria.
• Quantifying mitochondrial distance from the cell border.
• Querying cell databases for compounds/genes affecting the phenotype.

Main Results:

• Mitochondria were significantly farther from the cell border in patients experiencing psychosis (schizophrenia, bipolar disorder, schizoaffective disorder).
• A non-significant trend for reversed mitochondrial positioning was observed in major depression.
• Several compounds and genes were identified that modulate the psychosis-associated mitochondrial phenotype.

Conclusions:

• A novel cell-based assay using mitochondrial positioning shows promise for psychiatric drug discovery.
• This assay can be used for virtual and physical screening of therapeutic candidates.
• The findings support the development of novel mechanism therapeutics for psychiatric conditions.