Combinatorial approaches for treating neuropsychiatric social impairment

Abstract

Social behaviour is an essential component of human life and deficits in social function are seen across multiple psychiatric conditions with high morbidity. However, there are currently no FDA-approved treatments for social dysfunction. Since social cognition and behaviour rely on multiple signalling processes acting in concert across various neural networks, treatments aimed at social function may inherently require a combinatorial approach. Here, we describe the social neurobiology of the oxytocin and endocannabinoid signalling systems as well as translational evidence for their use in treating symptoms in the social domain. We leverage this systems neurobiology to propose a network-based framework that involves pharmacology, psychotherapy, non-invasive brain stimulation and social skills training to combinatorially target trans-diagnostic social impairment. Lastly, we discuss the combined use of oxytocin and endocannabinoids within our proposed framework as an illustrative strategy to treat specific aspects of social function. Using this framework provides a roadmap for actionable treatment strategies for neuropsychiatric social impairment. This article is part of the theme issue 'Interplays between oxytocin and other neuromodulators in shaping complex social behaviours'.

Keywords: combinatorial; endocannabinoids; oxytocin; social behaviour; social cognition.

Figure 1.

Target regions for network-based combinatorial treatment strategies. Selected treatment modalities act at overlapping and distinct brain regions to drive activity in networks that influence social behaviour. Regions in which these treatment modalities have shown the ability to drive social effects include subregions of the prefrontal cortex (dorsolateral prefrontal cortex (dlPFC), vlPFC, inferior frontal cortex (IFC) and medial prefrontal cortex (mPFC)), as well as the anterior cingulate cortex (ACC), superior temporal sulcus (STS), temporoparietal junction (TPJ) and amygdala. We propose that different modalities can be combined using their profile in this framework in order to achieve more specific treatment of social symptoms. This figure was made with Biorender. (Online version in colour.)

Figure 2.

Target trans-diagnostic domains for the treatment of social impairment. Deficits in social behaviour occur in many psychiatric conditions, including depression, anxiety, schizophrenia and ASD. A transdiagnostic model that targets domains of social function rather than a specific diagnosis will provide a mechanistically based approach for developing combined treatment strategies. We propose the following trans-diagnostic social domains: (a) social anxiety, (b) attachment processes, (c) reward processes that reinforce social engagement, (d) recognition of social cues and (e) mentalization of ongoing social dynamics. We provide examples of putative combination approaches utilizing endocannabinoids, oxytocin, non-invasive brain stimulation (NIBS), psychotherapy and social skills training. (Online version in colour.)