ReviewBrain, behavior and evolution2025
Inhibitory Systems in Brain Evolution: Pathways of Vulnerability in Neurodevelopmental Disorders.
Review in Brain, behavior and evolution, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Prenatal maternal immune activation triggers lasting cell-specific transcriptomic dysregulation in the amygdala of primate offspring.Molecular psychiatry · 2026Article
- Extra-axial cerebrospinal fluid volumes from 6 to 24 months of age are associated with poorer executive function at school-age in children with and without autism.Journal of neurodevelopmental disorders · 2026Article
- Early life shifts in cortical inhibitory-excitatory balance underlies sensitive periods and skill development.Frontiers in cellular neuroscience · 2026Article
- Evolutionary neuroeconomic adaptations of fast-spiking neurons in the human neocortex.Frontiers in synaptic neuroscience · 2026Review
- A single-cell transcriptomic atlas of developing inhibitory neurons reveals expanding and contracting modes of diversification.bioRxiv : the preprint server for biology · 2025Article
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Authors and funding
4 authors.
Funding
Abstract
backgroundThe evolution of the primate brain has been characterized by the reorganization of key structures and circuits underlying derived specializations in sensory systems, as well as social behavior and cognition. Among these, expansion and elaboration of the prefrontal cortex has been accompanied by alterations to the connectivity and organization of subcortical structures, including the striatum and amygdala, underlying advanced aspects of executive function, inhibitory behavioral control, and socioemotional cognition seen in our lineages. At the cellular level, the primate brain has further seen an increase in the diversity and number of inhibitory GABAergic interneurons. A prevailing hypothesis holds that disruptions in the balance of excitatory to inhibitory activity in the brain underlies the pathophysiology of many neurodevelopmental and psychiatric disorders. SUMMARY: This review highlights the evolution of inhibitory brain systems and circuits and suggests that recent evolutionary modifications to GABAergic circuitry may provide the substrate for vulnerability to aberrant neurodevelopment. We further discuss how modifications to primate and human social organization and life history may shape brain development in ways that contribute to neurodivergence and the origins of neurodevelopmental disorders. KEY MESSAGES: Many brain systems have seen functional reorganization in the mammalian, primate, and human brain. Alterations to inhibitory circuitry in frontostriatal and frontoamygdalar systems support changes in social behavior and cognition. Increased complexity of inhibitory systems may underlie vulnerabilities to neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Changes observed in Williams syndrome may further elucidate the mechanisms by which alterations in inhibitory systems lead to changes in behavior and cognition. Developmental processes, including altered neuroimmune function and age-related vulnerability of inhibitory cells and synapses, may lead to worsening symptomatology in neurodevelopmental and psychiatric disorders.
backgroundThe evolution of the primate brain has been characterized by the reorganization of key structures and circuits underlying derived specializations in sensory systems, as well as social behavior and cognition. Among these, expansion and elaboration of the prefrontal cortex has been accompanied by alterations to the connectivity and organization of subcortical structures, including the striatum and amygdala, underlying advanced aspects of executive function, inhibitory behavioral control, and socioemotional cognition seen in our lineages. At the cellular level, the primate brain has further seen an increase in the diversity and number of inhibitory GABAergic interneurons. A prevailing hypothesis holds that disruptions in the balance of excitatory to inhibitory activity in the brain underlies the pathophysiology of many neurodevelopmental and psychiatric disorders. SUMMARY: This review highlights the evolution of inhibitory brain systems and circuits and suggests that recent evolutionary modifications to GABAergic circuitry may provide the substrate for vulnerability to aberrant neurodevelopment. We further discuss how modifications to primate and human social organization and life history may shape brain development in ways that contribute to neurodivergence and the origins of neurodevelopmental disorders. KEY MESSAGES: Many brain systems have seen functional reorganization in the mammalian, primate, and human brain. Alterations to inhibitory circuitry in frontostriatal and frontoamygdalar systems support changes in social behavior and cognition. Increased complexity of inhibitory systems may underlie vulnerabilities to neurodevelopmental and psychiatric disorders, including autism and schizophrenia. Changes observed in Williams syndrome may further elucidate the mechanisms by which alterations in inhibitory systems lead to changes in behavior and cognition. Developmental processes, including altered neuroimmune function and age-related vulnerability of inhibitory cells and synapses, may lead to worsening symptomatology in neurodevelopmental and psychiatric disorders.
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