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Schizophrenia Genomics: Convergence on Synaptic Development, Adult Synaptic Plasticity, or Both?
Jeremy Hall1, Nicholas J Bray1
1MRC Centre for Neuropsychiatric Genetics & Genomics, Division of Psychological Medicine & Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; Neuroscience & Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.
Biological Psychiatry
|January 3, 2022
Summary
Schizophrenia genetic studies reveal synaptic dysfunction as a core cause. Interventions targeting synaptic health during development and adulthood may offer new treatment avenues.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Schizophrenia is a complex psychiatric disorder with hundreds of identified genetic risk loci.
- Understanding the biological basis of schizophrenia is crucial for developing effective treatments.
Purpose of the Study:
- To review recent genomic and functional data on schizophrenia.
- To explore the role of synaptic development and function in schizophrenia pathophysiology.
Main Methods:
- Genome-wide association studies (GWAS).
- Copy number variant (CNV) analysis.
- Exome sequencing.
- Functional genomics of brain development.
Main Results:
- Genomic data strongly implicates synaptic dysfunction in glutamatergic and GABAergic neurons.
- Synaptic connectivity disturbances begin prenatally and persist through adulthood.
- Specific genetic alleles confer risk by directly impacting adult synaptic function.
Conclusions:
- Synaptic dysfunction is central to schizophrenia pathophysiology.
- Interventions could focus on enhancing synaptic health during development.
- Targeted treatments to correct adult synaptic function are also promising.
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