Neural disruption to theory of mind predicts daily social functioning in individuals at familial high-risk for schizophrenia

Abstract

Theory-of-mind (ToM) ability is foundational for successful social relationships, and dependent on a neurocognitive system, which includes temporoparietal junction and medial prefrontal cortex. Schizophrenia is associated with ToM impairments, and initial studies demonstrate similar, though more subtle deficits, in unaffected first-degree relatives, indicating that ToM deficits are a potential biomarker for the disorder. Importantly, the social consequences of ToM deficits could create an additional vulnerability factor for individuals at familial high risk (FHR). However, behavioral studies of ToM are inconsistent and virtually nothing is known about the neural basis of ToM in FHR or the relationship between ToM and social functioning. Here, FHR and non-FHR control participants underwent functional MRI scanning while reasoning about a story character's thoughts, emotions or physical appearance. Afterwards, participants completed a 28-day online 'daily-diary' questionnaire in which they reported daily social interactions and degree of ToM reasoning. FHR participants demonstrated less neural activity in bilateral temporoparietal junction when reasoning about thoughts and emotions. Moreover, across all participants, the degree of neural activity during ToM reasoning predicted several aspects of daily social behavior. Results suggest that vulnerability for schizophrenia is associated with neurocognitive deficits in ToM and the degree of deficit is related to day-to-day social functioning.

Keywords: fMRI; familial high risk; schizophrenia; social functioning; theory of mind.

Fig. 1

Results of the ROI analyses comparing neural activity for Thought > Appearance (top panel), Emotion > Appearance (middle panel) and Emotion > Thought (bottom panel) between non-FHR (red bars) and FHR (blue bars). *P < 0.05.

Fig. 2

Whole-brain random-effects analysis (one sample t-test) of the Person-Description task within non-FHR (red activations), FHR (blue activations) and their overlap (purple activations) for the Thought > Appearance (left panel), Emotion > Appearance (middle panel) and Emotion > Thought (right panel) contrasts. Maps are displayed at P < 0.001 corrected for multiple comparisons to P < 0.05 at the cluster-level.

Fig. 3

Scatter plots illustrating the relationship between neural activity and social functioning. Average ratings across 28 days for the daily-diary social functioning variables (perspective-taking in panel A; empathy in panel B; enjoyment of socializing in panel C) are plotted on the y-axis and contrast estimates from the ROIs are plotted on the x-axis. Possible scores on the social functioning variables range from 1 (not at all) to 5 (extremely). Red circles represent non-FHR; blue diamonds represent FHR.