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Oxytocin Enhances an Amygdala Circuit Associated With Negative Symptoms in Schizophrenia: A Single-Dose,
Samantha V Abram1,2,3, Lize De Coster4, Brian J Roach2,3
1Sierra Pacific Mental Illness Research Education and Clinical Centers, San Francisco VA Medical Center, and the University of California, San Francisco, CA.
Abstract:
Negative symptoms are core contributors to vocational and social deficits in schizophrenia (SZ). Available antipsychotic medications typically fail to reduce these symptoms. The neurohormone oxytocin (OT) is a promising treatment for negative symptoms, given its role in complex social behaviors mediated by the amygdala. In sample 1, we used a double-blind, placebo-controlled, crossover design to test the effects of a single dose of intranasal OT on amygdala resting-state functional connectivity (rsFC) in SZ (n = 22) and healthy controls (HC, n = 24) using a whole-brain corrected approach: we identified regions for which OT modulated SZ amygdala rsFC, assessed whether OT-modulated circuits were abnormal in SZ relative to HC on placebo, and evaluated whether connectivity on placebo and OT-induced connectivity changes correlated with baseline negative symptoms in SZ. Given our modest sample size, we used a second SZ (n = 183) and HC (n = 178) sample to replicate any symptom correlations. In sample 1, OT increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) in SZ compared to HC. Further, SZ had hypo-connectivity in this circuit compared to HC on placebo. More severe negative symptoms correlated with less amygdala-to-left-MTG/STS/AngG connectivity on placebo and with greater OT-induced connectivity increases. In sample 2, we replicated the correlation between amygdala-left-MTG/STS/AngG hypo-connectivity and negative symptoms, finding a specific association with expressive negative symptoms. These data suggest intranasal OT can normalize functional connectivity in an amygdala-to-left-MTG/STS/AngG circuit that contributes to negative symptoms in SZ.
Insights
Intranasal oxytocin (OT) may improve negative symptoms in schizophrenia by normalizing amygdala connectivity. This treatment shows promise for addressing social and vocational deficits in patients with schizophrenia.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- Negative symptoms significantly impair social and vocational functioning in schizophrenia (SZ).
- Current antipsychotic medications are largely ineffective against these core negative symptoms.
- Oxytocin (OT), a neurohormone involved in social behavior, is being investigated as a potential treatment for negative symptoms.
Purpose of the Study:
- To investigate the effects of intranasal oxytocin (OT) on amygdala resting-state functional connectivity (rsFC) in individuals with schizophrenia (SZ).
- To determine if OT modulates SZ amygdala rsFC and if these circuits are abnormal in SZ compared to healthy controls (HC).
- To examine the correlation between functional connectivity, OT treatment, and the severity of negative symptoms in SZ.
Main Methods:
- A double-blind, placebo-controlled, crossover study design was employed in two independent samples of SZ and HC.
- Resting-state functional connectivity (rsFC) was analyzed using whole-brain corrected approaches.
- Intranasal OT administration and its effects on amygdala connectivity were assessed in relation to negative symptom severity.
Main Results:
- Intranasal OT increased amygdala-to-left middle temporal gyrus, superior temporal sulcus, and angular gyrus (MTG/STS/AngG) rsFC in SZ compared to HC.
- Individuals with SZ exhibited reduced amygdala-left MTG/STS/AngG connectivity compared to HC on placebo.
- Greater severity of negative symptoms correlated with reduced baseline connectivity and increased OT-induced connectivity changes in this circuit.
Conclusions:
- Intranasal oxytocin (OT) shows potential to normalize amygdala-based functional connectivity in schizophrenia.
- The amygdala-left MTG/STS/AngG circuit is implicated in the pathophysiology of negative symptoms in SZ.
- OT may represent a novel therapeutic strategy for improving negative symptoms and associated deficits in schizophrenia.
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