Genetic Influences on Synaptic Connectivity in Neuropsychiatric Disorders

The architecture and function of neuronal circuits are critically shaped by synaptic connectivity, a process governed by genetic programmes that direct synapse formation, maturation and plasticity. Variants in genes encoding synaptic scaffolding proteins, neurotransmitter receptors and epigenetic regulators have been linked to altered dendritic spine morphology, impaired neurotransmission and disrupted network synchrony in disorders such as schizophrenia, bipolar disorder and autism spectrum disorder. Both common polymorphisms and rare high-impact mutations can perturb the balance between excitatory and inhibitory inputs, leading to circuit-level dysfunction. Advances in genomic sequencing, human pluripotent stem cell models and in vivo imaging have begun to elucidate how risk loci influence postsynaptic specialisations, presynaptic release machinery and the dynamic remodelling of synapses in response to activity. This body of work has global significance, offering mechanistic insights that may guide the development of targeted interventions to restore synaptic integrity in affected individuals.

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Genetic Influences on Synaptic Connectivity in Neuropsychiatric Disorders publication trend

The graph below shows the total number of articles in genetic influences on synaptic connectivity in neuropsychiatric disorders across all publications each year (not limited to Nature Index journals).

Technical terms

Dendritic spine: Small membranous protrusion from a neuron's dendrite that typically receives excitatory synaptic input.

Synaptic plasticity: The ability of synapses to strengthen or weaken over time in response to changes in activity or experience.

Copy number variant (CNV): A structural genomic alteration in which sections of DNA are duplicated or deleted, affecting gene dosage.

Histone methyltransferase: Enzyme that adds methyl groups to histone proteins, modulating chromatin structure and gene expression.

References

1. Schizophrenia-Like Behaviors Arising from Dysregulated Proline Metabolism Are Associated with Altered Neuronal Morphology and Function in Mice with Hippocampal PRODH Deficiency. Aging and Disease (2023).
2. DiGeorge syndrome critical region gene 2 (DGCR2), a schizophrenia risk gene, regulates dendritic spine development through cell adhesion. Cell & Bioscience (2023).
3. Loss-of-function variants in the schizophrenia risk gene SETD1A alter neuronal network activity in human neurons through the cAMP/PKA pathway. Cell Reports (2022).