Chemokine receptors and cortical interneuron dysfunction in schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Developmental Biology

Background:

• Schizophrenia involves prefrontal cortex GABA neuron alterations, particularly in parvalbumin and somatostatin subtypes.
• Deficits in GAD67 and Lhx6 suggest prenatal developmental disturbances affecting these GABA neurons.
• Chemokine receptors CXCR4 and CXCR7 are crucial for the migration of these specific GABA neuron populations.

Purpose of the Study:

• To investigate the association between CXCR4 and CXCR7 mRNA levels and GABA-related markers in the prefrontal cortex of schizophrenia patients.
• To explore potential prenatal developmental disruptions in GABAergic circuitry in schizophrenia.

Main Methods:

• Quantitative PCR was used to measure CXCR4 and CXCR7 mRNA levels in the prefrontal cortex of 62 schizophrenia patients and 62 healthy controls.
• Analysis included subjects previously characterized for parvalbumin, somatostatin, GAD67, and Lhx6 markers.
• Gene expression was also assessed in antipsychotic-exposed monkeys.

Main Results:

• Schizophrenia subjects showed significantly elevated CXCR7 mRNA (+29%) and a trend for increased CXCR4 mRNA (+14%).
• Antipsychotic-exposed monkeys did not exhibit similar alterations in CXCR4/CXCR7 mRNA levels.
• In schizophrenia, higher CXCR7 mRNA inversely correlated with GAD67, parvalbumin, somatostatin, and Lhx6 mRNA levels.

Conclusions:

• Elevated CXCR7 and CXCR4 mRNA in schizophrenia may represent a compensatory response to prenatal insults affecting GABA neuron development.
• These findings highlight the role of chemokine signaling in the prenatal origins of cortical GABA neuron dysfunction in schizophrenia.