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Cited by 46Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry

Open access
Ford, Charles L, Young, Larry J·2021·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2020.11.007PMC PMC8160019
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Abstract

The recent advancements of social behavioral neuroscience are unprecedented. Through manipulations targeting neural circuits, complex behaviors can be switched on and off, social bonds can be induced, and false memories can be “incepted.” Psychiatry, however, remains tethered to concepts and techniques developed over half a century ago, including purely behavioral definitions of psychopathology and chronic, brain-wide pharmacological interventions. Drawing on recent animal and human research, we outline a circuit-level approach to the social brain and highlight studies demonstrating the translational potential of this approach. We conclude by suggesting ways both clinical practice and translational research can apply circuit-level neuroscientific knowledge to advance psychiatry, including adopting neuroscience-based nomenclature, stratifying patients into diagnostic subgroups based on neurobiological phenotypes, and pharmacologically enhancing psychotherapy.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that circuit-level social neuroscience, especially oxytocin-related circuits, can move psychiatry beyond behavioral diagnoses and brain-wide pharmacology. It synthesizes rodent and human findings to propose neuroscience-based nomenclature, patient stratification by neurobiological phenotype, and pharmacologically enhanced psychotherapy.

Key findings

Circuit manipulations in rodents can switch complex social behaviors: activating or inhibiting galanin-positive medial preoptic area neurons inhibited infanticidal behavior, increased pup grooming, increased parental motivation, and inhibited male-male aggression; activating a ventral CA1 social engram with foot shock “incepted” a false fear memory; and stimulating PFC-to-NAc projections induced pair-bonding in prairie voles without mating. Human oxytocin pathway gene expression is highest in olfactory bulbs and pallidum, high in hypothalamus, thalamus, caudate, and putamen, and moderately elevated in amygdala, anterior cingulum, and hippocampus; a meta-analysis of 82 studies including 3950 subjects found the amygdala most likely to be modulated by intranasal oxytocin (IN-OT). IN-OT often normalizes amygdala activity/connectivity in psychiatric cohorts; in PTSD, females showed increased right basolateral amygdala–right anterior cingulate connectivity and males showed decreased right centromedial amygdala–right ventromedial PFC connectivity, with IN-OT restoring functional connectivity to healthy-control levels and decreasing anxiety/nervousness. Six weeks of IN-OT in ASD patients rescued social reciprocity deficits and enhanced task-dependent anterior cingulate–PFC connectivity, but well-powered IN-OT ASD trials have shown replication failures.

Methods

This is a narrative review/perspective, not a primary empirical study; it synthesizes selected animal and human research on the social brain and oxytocin. No primary sample, systematic search strategy, or formal meta-analysis conducted by the authors is described. The main analysis is conceptual synthesis and translational proposal, drawing on cited rodent circuit studies, human genetics/fMRI/IN-OT studies, and clinical trial evidence.

Limitations

The paper states that most human research is noninvasive, limiting mechanistic insight; that IN-OT results are highly heterogeneous, effect sizes are small, and questions remain about crossing the blood-brain barrier and diffusing to subcortical structures; and that replication failures in well-powered IN-OT ASD trials urge caution. Evident from the text: as a narrative review, it does not report systematic inclusion criteria, risk-of-bias assessment, or quantitative synthesis, and its proposed clinical applications are largely conceptual rather than tested in this paper.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.conb.2020.11.007

Cites

73 of 73 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 96 cited sources checked · 0 supported · 0 flagged

  • Interpretationreasoning

    The homogeneous repertoire of psychiatric pharmaceuticals is ill-matched for treating heterogeneous psychiatric disorders.

    “This homogeneous repertoire of pharmaceuticals is ill-matched for treating heterogeneous psychiatric disorders.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The majority of “new” psychiatric pharmaceuticals are variations of old drugs with marginal improvements rather than drugs with novel mechanisms of action.
  • Interpretationreasoning

    Two patients may share the same diagnosis while having only a single symptom in common.

    “Two patients may therefore share the same diagnosis while having only a single symptom in common”
    Quote in the paperSubstantial claim
    • Rests on an assumption: Depression is diagnosed behaviorally by the presence of at least five of nine possible symptoms and is typically treated with selective serotonin reuptake inhibitors (SSRIs).
  • Premisecitation

    In rodents, monogamous pair bond formation can be biased.

    “monogamous pair bond formation can be biased [3]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Amadei EA, Johnson ZV, Jun Kwon Y, Shpiner AC, Saravanan V, Mays WD, Ryan SJ, Walum H, Rainnie DG, Young LJ,: Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles. Nature 2017, 546: 297– 301. 28562592 PMC5499998 source

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  • Premisecitation

    In rodents, distinct parental behaviors can be switched on and off.

    “distinct parental behaviors can be switched on and off [4**]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4**]

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  • Interpretationnone given

    Progress in treating psychiatric disorders has largely stalled since the advent of modern psychopharmacology in the 1950s and 1960s.

    “Mental illness is a leading cause of global disease burden, yet progress in treating psychiatric disorders has largely stalled since the advent of modern psychopharmacology in the 1950s and 1960s.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 25
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Premisecitation

    Divergent behavioral presentations often have different neurobiological etiologies and responses to treatment.

    “yet divergent behavioral presentations often have different neurobiological etiologies and responses to treatment [1,2**].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1,2**]

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  • May combine two claims.

    Premisecitation

    The medial and basolateral amygdala both project to the hippocampus, which expresses oxytocin receptors and is necessary for social recognition and memory formation.

    “The medial and basolateral amygdala both project to the hippocampus, which expresses oxytocin receptors and is necessary for social recognition and memory formation [5,11].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [5] Okuyama T, Kitamura T, Roy DS, Itohara S, Tonegawa S: Ventral CA1 neurons store social memory. Science 2016, 353: 1536– 1541. 27708103 PMC5493325 source

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    • cites [11] Freeman SM, Young LJ: Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications. J Neuroendocrinol 2016, 28. PMC4886472 26940141 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In sensory pathways, oxytocin signaling increases the salience of social stimuli by modulating neuron excitability and facilitates the flow of social information across the brain.

    “In sensory pathways, oxytocin signaling increases the salience of social stimuli by modulating neuron excitability and facilitates the flow of social information across the brain [15].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [15] Johnson ZV, Walum H, Xiao Y, Riefkohl PC, Young LJ: Oxytocin receptors modulate a social salience neural network in male prairie voles. Hormones and behavior 2017, 87: 16– 24. 27793769 PMC5207344 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rodents, olfactory information is transmitted to the medial amygdala, where oxytocin-dependent signaling is necessary for social recognition.

    “In rodents, olfactory information is transmitted to the medial amygdala, where oxytocin-dependent signaling is necessary for social recognition [10,19].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Walum H, Young LJ: The neural mechanisms and circuitry of the pair bond. Nat Rev Neurosci 2018, 19: 643– 654. 30301953 PMC6283620 source

      Not checked in the free run.

    • cites [19] Gangopadhyay P, Chawla M, Monte OD, Chang SWC: Prefrontal-Amygdala Circuits in Social Decision-Making. Nat Neurosci 2020, in press. PMC7899743 33169032

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  • May combine two claims.

    Premisecitation

    Inhibiting or stimulating PFC-to-NAc projections of D1 dopamine receptor-expressing neurons impaired or restored social recognition memories in mice.

    “Inhibiting or stimulating the PFC-to-NAc projections of D1 dopamine receptor-expressing neurons impaired or restored, respectively, social recognition memories in mice [25]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Xing B, Mack NR, Guo K, Zhang Y, Ramirez B, Yang S, Lin L, Wang DV, Li Y, Gao W: A subpopulation of prefrontal cortical neurons is required for social memory. Biol Psychiatry 2020, In press. PMC7867585 33190846

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  • May combine two claims.

    Premisecitation

    Activating or inhibiting specific subsets of galanin-positive neurons in the medial preoptic area inhibited infanticidal behavior in males and increased pup grooming in females via projections to periaqueductal gray.

    “By activating or inhibiting specific subsets of galanin-positive neurons in the medial preoptic area, Kohl et al. [4**] inhibited infanticidal behavior in males and increased pup grooming in females (projections to periaqueductal gray)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [4**]

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  • May combine two claims.

    Premisecitation

    Hippocampus projects back to basolateral amygdala and NAc, where oxytocinergic, dopaminergic, and serotonergic innervation from the hypothalamic paraventricular nucleus, ventral tegmental area, and dorsal raphe nucleus are necessary for social reward learning.

    “The hippocampus projects back to basolateral amygdala and nucleus accumbens (NAc), where oxytocinergic, dopaminergic, and serotonergic innervation from the hypothalamic paraventricular nucleus, ventral tegmental area, and dorsal raphe nucleus, respectively, are necessary for social reward learning [21,22].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Hung LW, Neuner S, Polepalli JS, Beier KT, Wright M, Walsh JJ, Lewis EM, Luo L, Deisseroth K, Dölen G,: Gating of social reward by oxytocin in the ventral tegmental area. Science 2017, 357: 1406– 1411. 28963257 PMC6214365 source

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    • cites [22] Dölen G, Darvishzadeh A, Huang KW, Malenka RC: Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 2013, 501: 179– 184. 24025838 PMC4091761 source

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  • May combine two claims.

    Premisecitation

    Cntnap2 knockout mice show deficits in social behavior and reduced numbers of oxytocin neurons.

    “Cntnap2 knockout mice show deficits in social behavior and reduced numbers of oxytocin neurons”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Peñagarikano O, Lázaro MT, Lu XH, Gordon A, Dong H, Lam HA, Peles E, Maidment NT, Murphy NP, Yang XW,: Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism. Sci Transl Med 2015, 7: 271ra278. PMC4498455 25609168 source

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  • May combine two claims.

    Premisecitation

    Results across IN-OT studies are highly heterogeneous and vary based on the population and context of the study.

    “However, results across studies are highly heterogeneous and vary based on the population and context of the study.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [39] Grace SA, Rosseii SL, Heinrichs M, Kordsachia C, Labuschagne I: Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology 2018, 96: 6– 24. 29879563 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    The noninvasive nature of most human research limits its mechanistic insights.

    “The noninvasive nature of most human research limits its mechanistic insights.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Chemogenetic stimulation of oxytocin neurons or pharmacologically-evoked release of endogenous oxytocin rescues social deficits in Cntnap2 knockout mice.

    “while chemogenetic stimulation of oxytocin neurons or pharmacologically-evoked release of endogenous oxytocin rescues the deficits [29].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [29] Peñagarikano O, Lázaro MT, Lu XH, Gordon A, Dong H, Lam HA, Peles E, Maidment NT, Murphy NP, Yang XW,: Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism. Sci Transl Med 2015, 7: 271ra278. PMC4498455 25609168 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Quintana et al. mapped the mRNA of oxytocin pathway genes throughout human brains and found the highest expression in olfactory bulbs and pallidum, high expression in hypothalamus, thalamus, caudate, and putamen, and more moderately elevated expression in amygdala, anterior cingulum, and hippocampus.

    “Quintana et al. [31] mapped the mRNA of oxytocin pathway genes throughout human brains and found the highest expression in olfactory bulbs and pallidum, high expression in hypothalamus, thalamus, caudate, and putamen, and more moderately elevated expression in amygdala, anterior cingulum, and hippocampus.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Quintana DS, Rokicki J, van der Meer D, Alnæs D, Kaufmann T, Córdova-Paiomera A, Dieset I, Andreassen OA, Westiye LT: Oxytocin pathway gene networks in the human brain. Nat Commun 2019, 10: 668. 30737392 PMC6368605 source

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    Premisecitation

    Divergent responses to IN-OT are associated with OXTR polymorphisms, gender, personality traits, attachment style, and underlying psychopathology.

    “Divergent responses to IN-OT have been associated with OXTR polymorphisms, gender, personality traits, attachment style, and underlying psychopathology [39,40].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [39] Grace SA, Rosseii SL, Heinrichs M, Kordsachia C, Labuschagne I: Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies. Psychoneuroendocrinology 2018, 96: 6– 24. 29879563 source

      Not checked in the free run.

    • cites [40] Andari E, Huriemann R, Young LJ: A Precision Medicine Approach to Oxytocin Trials. Curr Top Behav Neurosci 2018, 35: 559– 590. 28812273 PMC5815942 source

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  • May combine two claims.

    Interpretationcitation

    Oxytocin systems in humans and animals are similar in their anatomical distribution, interaction with other neurotransmitter systems, and role in regulating socioemotional processes.

    “These data suggest the oxytocin systems in humans and animals are similar in their anatomical distribution, interaction with other neurotransmitter systems, and role in regulating socioemotional processes.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Hypermethylation at specific sites in OXTR is associated with autism spectrum disorders and with distinct ASD behavioral phenotypes.

    “Hypermethylation at specific sites in OXTR is associated not only with autism spectrum disorders (ASD), but with distinct ASD behavioral phenotypes [37*].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37*]

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  • May combine two claims.

    Interpretationcitation

    Recent human work using genetic analyses, fMRI, and intranasal oxytocin administration supports the circuit-level conception of the social brain emerging from animal research and provides insight into the heterogeneity of human populations.

    “However, recent work using genetic analyses, fMRI, and intranasal oxytocin (IN-OT) administration supports the circuit-level conception of the social brain emerging from animal research and provides insight into the heterogeneity of human populations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Despite promising results of augmenting psychotherapy for PTSD with IN-OT, no studies have been reported for ASD.

    “Despite the promising results of augmenting psychotherapy for PTSD with IN-OT [59], no studies have been reported for ASD”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Flanagan JC, Sippel LM, Wahlquist A, Moran-Santa Maria MM, Back SE: Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. J Psychiatr Res 2018, 98: 64– 69. 29294429 PMC5800951 source

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  • May combine two claims.

    Premisecitation

    In these PTSD subjects, IN-OT restored functional connectivity to levels observed in healthy controls and decreased subjective experiences of anxiety and nervousness.

    “In these subjects, IN-OT restored functional connectivity to levels observed in healthy controls and also decreased subjective experiences of anxiety and nervousness.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Koch SB, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M: Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder. Neuropsychopharmacology 2016, 41: 2041– 2051. 26741286 PMC4908648 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In pair-bonded men, IN-OT enhances the perceived attractiveness of their female partners' faces but not that of other equally attractive female faces.

    “Similarly, in pair-bonded men, IN-OT enhances the perceived attractiveness of their female partners’ faces but not that of other equally attractive female faces [43]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Scheele D, Wille A, Kendrick KM, Stoffel-Wagner B, Becker B, Güntürkün O, Maier W, Huriemann R: Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proc Natl Acad Sci U S A 2013, 110: 20308– 20313. 24277856 PMC3864312 source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Psychiatry is mired in the psychopharmacological techniques of the 1950s.

    “Psychiatry is mired in the psychopharmacological techniques of the 1950s”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    To date, most research on IN-OT interventions for ASD has involved administrations independent of context.

    “to date, most research on IN-OT interventions for ASD has involved administrations independent of context.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    As pharmacology-based and psychotherapy-based interventions are independently capable of modulating circuit-level neural activity, pharmacologically-enhanced psychotherapy would seem an obvious opportunity to target specific circuits more effectively and potentially reduce the need for chronic pharmacological therapy.

    “As pharmacology-based and psychotherapy-based interventions are independently capable of modulating circuit-level neural activity, pharmacologically-enhanced psychotherapy would seem an obvious opportunity to target specific circuits more effectively and potentially reduce the need for chronic pharmacological therapy [58].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [58] Sartori SB, Singewald N: Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders. Pharmacol Ther 2019, 204: 107402. 31470029 source

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  • May combine two claims.

    Interpretationcitation

    Oxytocin-enhanced therapy would have the combined benefits of increasing the salience of information coming from the therapist, promoting synaptic plasticity, and facilitating learning by modulating circuit-level neural activity.

    “Oxytocin-enhanced therapy would have the combined benefits of increasing the salience of information coming from the therapist [63,64], promoting synaptic plasticity [65], and facilitating learning by modulating circuit-level neural activity [37*,66].”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [63] Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA: Oxytocin enhances brain function in children with autism. Proc Natl Acad Sci U S A 2013, 110: 20953– 20958. 24297883 PMC3876263 source

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    • cites [64] Shamay-Tsoory SG, Abu-Akel A: The Social Salience Hypothesis of Oxytocin. Biol Psychiatry 2016, 79: 194– 202. 26321019 source

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    • cites [65] Rajamani KT, Wagner S, Grinevich V, Harony-Nicolas H: Oxytocin as a Modulator of Synaptic Plasticity: Implications for Neurodevelopmental Disorders. Front Synaptic Neurosci 2018, 10: 17. 29970997 PMC6018411 source

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    • cites [37*,66]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    In one study using resting state fMRI, females with PTSD displayed increased connectivity between the right basolateral amygdala and right anterior cingulate cortex while males with PTSD displayed decreased activity between the right centromedial amygdala and right ventromedial PFC.

    “In one study using resting state fMRI, females with PTSD displayed increased connectivity between the right basolateral amygdala and right anterior cingulate cortex while males with PTSD displayed decreased activity between the right centromedial amygdala and right ventromedial PFC [47].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [47] Koch SB, van Zuiden M, Nawijn L, Frijling JL, Veltman DJ, Olff M: Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder. Neuropsychopharmacology 2016, 41: 2041– 2051. 26741286 PMC4908648 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationnone given

    Clinical language that omits the neurobiological basis of diseases and treatments precludes the incorporation of neuroscientific precision into clinical practice.

    “clinical language that omits the neurobiological basis of diseases and treatments precludes the incorporation of neuroscientific precision into clinical practice.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Human studies highlight the neural heterogeneity of the population and demonstrate the potential of approaching the social brain, psychiatric disorders, and interventions from a circuit perspective.

    “Taken together, human studies highlight the neural heterogeneity of the population and further demonstrate the potential of approaching the social brain, psychiatric disorders, and interventions from a circuit perspective.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Recasting psychiatric conditions in terms of "misfiring circuits" rather than disorders of behavior might reduce stigma, a key barrier to seeking treatment.

    “Regarding patients, it’s worth considering that recasting psychiatric conditions in terms of “misfiring circuits” rather than disorders of behavior might reduce stigma, a key barrier to seeking treatment [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Schnyder N, Panczak R, Groth N, Schultze-Lutter F: Association between mental health-related stigma and active help-seeking: systematic review and meta-analysis. Br J Psychiatry 2017, 210: 261– 268. 28153928 source

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationnone given

    A circuit-based approach suggests immediate solutions for addressing the mismatch between the heterogeneity of psychiatric disorders and the homogeneity of both diagnoses and treatments.

    “A circuit-based approach also suggests immediate solutions for addressing the glaring mismatch between the heterogeneity of psychiatric disorders and the homogeneity of both diagnoses and treatments.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    A circuit-targeted approach to manipulating oxytocin signaling increases the feasibility of resetting transcriptional or translational abnormalities, altering the course of neurodevelopmental disorders through interventions during developmental sensitive periods, or reopening critical periods in adults to enable new social learning.

    “For instance, a circuit-targeted approach to manipulating oxytocin signaling increases the feasibility of resetting transcriptional or translational abnormalities [30*], altering the course of neurodevelopmental disorders through interventions during developmental sensitive periods [67], or reopening critical periods in adults to enable new social learning [68**].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [30*]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [67] DeMayo MM, Young LJ, Hickie IB, Song YJC, Guastella AJ: Circuits for social learning: A unified model and application to Autism Spectrum Disorder. Neurosci Biobehav Rev 2019, 107: 388– 398. 31560922 PMC6875617 source

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    • cites [68**]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisecitation

    Psychotherapy is an alternative and effective means of treating mental illness that alters activity within neural circuits by harnessing the brain's inherent capacity for experience-dependent plasticity.

    “Psychotherapy is an alternative and effective means of treating mental illness that alters activity within neural circuits by harnessing the brain’s inherent capacity for experience-dependent plasticity [57].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [57] Marwood L, Wise T, Perkins AM, Cleare AJ: Meta-analyses of the neural mechanisms and predictors of response to psychotherapy in depression and anxiety. Neurosci Biobehav Rev 2018, 95: 61– 72. 30278195 PMC6267850 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Six-weeks of IN-OT treatment in ASD patients rescued social reciprocity deficits and enhanced task-dependent functional connectivity between anterior cingulate cortex and PFC.

    “Six-weeks of IN-OT treatment in ASD patients rescued social reciprocity deficits and enhanced task-dependent functional connectivity between anterior cingulate cortex and PFC [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Watanabe T, Kuroda M, Kuwabara H, Aoki Y, Iwashiro N, Tatsunobu N, Takao H, Nippashi Y, Kawakubo Y, Kunimatsu A,: Clinical and neural effects of six-week administration of oxytocin on core symptoms of autism. Brain 2015, 138: 3400– 3412. 26336909 source

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  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    The potential of incorporating circuit-level approaches into the diagnosis and treatment of psychiatric disorders is no longer theoretical but manifestly evident.

    “As research on the social brain has demonstrated, the potential of incorporating circuit-level approaches into the diagnosis and treatment of psychiatric disorders is no longer theoretical – it is manifestly evident.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    There are questions surrounding IN-OT's ability to cross the blood-brain barrier and diffuse to subcortical structures.

    “and there are questions surrounding its ability to cross the blood-brain barrier and diffuse to subcortical structures [70,71]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [70] Yamamoto Y, Liang M, Munesue S, Deguchi K, Harashima A, Furuhara K, Yuhi T, Zhong J, Akther S, Goto H,: Vascular RAGE transports oxytocin into the brain to elicit its maternal bonding behaviour in mice. Commun Biol 2019, 2: 76. 30820471 PMC6389896 source

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    • cites [71] Higashida H, Hashii M, Tanaka Y, Matsukawa S, Higuchi Y, Gabata R, Tsubomoto M, Seishima N, Teramachi M, Kamijima T,: CD38, CD157, and RAGE as Molecular Determinants for Social Behavior. Cells 2019, 9. PMC7016687 31881755 source

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  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    We presently possess the technological capabilities and scientific understanding required to begin implementing circuit-level approaches in psychiatry.

    “Moreover, we presently possess the technological capabilities and scientific understanding required to begin implementing this approach.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Emerging technologies such as transcranial magnetic stimulation, deep brain stimulation, and focused ultrasound to circumvent the blood-brain barrier are enabling more targeted interventions.

  • Probably not a substantial claim: may not pass S2 (checkable), S4 (based).

    Interpretationreasoning

    The sooner circuit-level approaches are embraced, the sooner psychiatry can move beyond twentieth-century behavioral pharmacology and into twenty-first-century precision medicine.

    “The sooner circuit-level approaches are embraced, the sooner the field of psychiatry can move beyond twentieth-century behavioral pharmacology and into twenty-first-century precision medicine (Figure 2).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Circuit manipulations have proven efficacious in animal research.

    “the circuit manipulations that have proven so efficacious in animal research”
    Quote in the paperNot a substantial claim
36 of 36

  • The paper relies on this without support.

    The majority of “new” psychiatric pharmaceuticals are variations of old drugs with marginal improvements rather than drugs with novel mechanisms of action.

    “The majority of “new” psychiatric pharmaceuticals are variations of old drugs with marginal improvements rather than drugs with novel mechanisms of action.”

  • The paper relies on this without support.

    Depression is diagnosed behaviorally by the presence of at least five of nine possible symptoms and is typically treated with selective serotonin reuptake inhibitors (SSRIs).

    “For example, depression is diagnosed behaviorally by the presence of at least five of nine possible symptoms and is typically treated with selective serotonin reuptake inhibitors (SSRIs).”

  • The paper relies on this without support.

    SSRIs serve as first-line treatment for at least nine different diagnoses.

    “Furthermore, as first-line treatment for at least nine different diagnoses, SSRIs serve as a sort of modern-day panacea for a myriad of conditions ranging from depression and panic disorders to bulimia and premature ejaculation.”

  • The paper relies on this without support.

    Many psychiatric disorders manifest with disruptions in social cognition and behavior.

    “Many psychiatric disorders manifest with disruptions in social cognition and behavior”

  • The paper relies on this without support.

    In mammals, social information is first processed by sensory areas including olfactory bulb, superior colliculus, pulvinar, primary visual cortex, and primary auditory cortex.

    “In mammals, social information is first processed by sensory areas including olfactory bulb for olfaction; superior colliculus, pulvinar, and primary visual cortex for vision; and primary auditory cortex for hearing.”

  • The paper relies on this without support.

    Emerging technologies such as transcranial magnetic stimulation, deep brain stimulation, and focused ultrasound to circumvent the blood-brain barrier are enabling more targeted interventions.

    “emerging technologies like transcranial magnetic stimulation, deep brain stimulation, and the application of focused ultrasound to circumvent the blood-brain barrier are enabling more targeted interventions.”

  • The paper relies on this without support.

    Psychiatric precision will always lag behind neuroscientific precision due to ethical and technological constraints.

    “psychiatric precision will always lag behind neuroscientific precision due to ethical and technological constraints”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The incorporation of modern molecular genetic approaches into studies of alternative model organisms with diverse social systems is essential for gaining a complete understanding of oxytocin and vasopressin function in the brain, and thereby maximizing translational opportunities.

    “Finally, the incorporation of modern molecular genetic approaches into studies of alternative model organisms with diverse social systems is essential for gaining a complete understanding of OXT and AVP function in the brain, and thereby maximizing translational opportunities (19,174).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [19]

  • Oxytocin does not directly cause prosocial behaviour.

    “does not directly cause prosocial behaviour”

    From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [6]

  • Oxytocin enhances social salience rather than social behaviour.

    “oxytocin enhances social salience rather than social behaviour”

    From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [6]

  • For oxytocin administration to be therapeutic and influence behaviour, it must be paired with an appropriate social context.

    “for oxytocin administration to be therapeutic and influence behaviour, it must be paired with an appropriate social context2–6”

    From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [6]

  • Even in a therapeutic context, intranasal oxytocin is a suboptimal method for enhancing oxytocin signalling.

    “Even in a therapeutic context, intranasal oxytocin is a suboptimal method for enhancing oxytocin signalling.”

    From Refining oxytocin therapy for autism: context is key (2022) · cites this paper as [6]

Cites

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Authors
Ford, C. L., & Young, L. J.
Affiliations
Emory University (US)
Corresponding author
Young, Larry J
ORCID
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2021-06
Volume
68
Pages
1-8
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2020.11.007
PMC
PMC8160019
OpenAlex
W3110503640
Semantic Scholar
69fdda2ce6bb1522f109245885c53c2fcd460e74
Cited by
46
References
73
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 14 · 2021: 11
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (P50MH100023, P51OD011132, R01MH112788)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
social neuroscience, neural circuits, social brain, translational research, psychopathology, patient stratification, social bonding
MeSH terms
Cognitive Neuroscience, Animals, Brain, Humans, Neurosciences, Psychiatry

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