Oxytocin Enhances an Amygdala Circuit Associated with Negative Symptoms in Schizophrenia: A Single-Dose, Placebo-Controlled, Crossover, Randomized Control Trial Articles uri icon

authors

  • Abram, Samantha V.
  • DE COSTER, LIZE
  • Roach, Brian J.
  • Mueller, Bryon A.
  • Van Erp, Theo G.M.
  • Calhoun, Vince D.
  • Preda, Adrian
  • Lim, Kelvin O.
  • Turner, Jessica A.
  • Ford, Judith M.
  • Mathalon, Daniel H.
  • Woolley, Joshua D.

publication date

  • October 2019

start page

  • 661

end page

  • 669

issue

  • 3

volume

  • 46

International Standard Serial Number (ISSN)

  • 0586-7614

Electronic International Standard Serial Number (EISSN)

  • 1745-1701

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.

keywords

  • expressive negative symptoms; functional connectivity; resting-state; temporal lobe