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The Role of Synaptic Cell Adhesion Molecules and Associated Scaffolding Proteins in Social Affiliative Behaviors

  • Sara C. Taylor
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Sarah L. Ferri
    Affiliations
    Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
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  • Mahip Grewal
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Zoe Smernoff
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania

    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Maja Bucan
    Affiliations
    Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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  • Joshua A. Weiner
    Affiliations
    Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa

    Department of Biology, University of Iowa, Iowa City, Iowa
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  • Ted Abel
    Affiliations
    Iowa Neuroscience Institute, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa
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  • Edward S. Brodkin
    Correspondence
    Address correspondence to Edward S. Brodkin, M.D., University of Pennsylvania Department of Psychiatry, Perelman School of Medicine, Translational Research Laboratory, 125 South 31st Street, Room 2202, Philadelphia, PA 19104-3403.
    Affiliations
    Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
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Published:February 21, 2020DOI:https://doi.org/10.1016/j.biopsych.2020.02.012

      Abstract

      Social affiliative behaviors—engagement in positive (i.e., nonaggressive) social approach and reciprocal social interactions with a conspecific—comprise a construct within the National Institute of Mental Health Research Domain Criteria Social Processes Domain. These behaviors are disrupted in multiple human neurodevelopmental and neuropsychiatric disorders, such as autism, schizophrenia, social phobia, and others. Human genetic studies have strongly implicated synaptic cell adhesion molecules (sCAMs) in several such disorders that involve marked reductions, or other dysregulations, of social affiliative behaviors. Here, we review the literature on the role of sCAMs in social affiliative behaviors. We integrate findings pertaining to synapse structure and morphology, neurotransmission, postsynaptic signaling pathways, and neural circuitry to propose a multilevel model that addresses the impact of a diverse group of sCAMs, including neurexins, neuroligins, protocadherins, immunoglobulin superfamily proteins, and leucine-rich repeat proteins, as well as their associated scaffolding proteins, including SHANKs and others, on social affiliative behaviors. This review finds that the disruption of sCAMs often manifests in changes in social affiliative behaviors, likely through alterations in synaptic maturity, pruning, and specificity, leading to excitation/inhibition imbalance in several key regions, namely the medial prefrontal cortex, basolateral amygdala, hippocampus, anterior cingulate cortex, and ventral tegmental area. Unraveling the complex network of interacting sCAMs in glutamatergic synapses will be an important strategy for elucidating the mechanisms of social affiliative behaviors and the alteration of these behaviors in many neuropsychiatric and neurodevelopmental disorders.

      Keywords

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      • Erratum
        Biological PsychiatryVol. 88Issue 6
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          Erratum to: “The Role of Synaptic Cell Adhesion Molecules and Associated Scaffolding Proteins in Social Affiliative Behaviors,” by Taylor et al. (Biol Psychiatry 2020; 88:442–451); https://doi.org/10.1016/j.biopsych.2020.02.012 .
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