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Oxytocin may curb negative symptoms in schizophrenia

October 24, 2019

By David Douglas

NEW YORK (Reuters Health) - The hypothalamic neuropeptide oxytocin's effects on the amygdala may impact processes implicated in the negative symptoms of schizophrenia and may help normalize its function, according to a randomized controlled trial.

"Administration of a single dose of oxytocin alters a brain circuit related to expressive deficits in schizophrenia," Dr. Samantha V. Abram explained in an email to Reuters Health.

In a paper online October 9 in Schizophrenia Bulletin, Dr. Abram of the University of California, San Francisco, and colleagues note that available antipsychotic medications typically fail to reduce negative symptoms such as deficits in motivation, social interaction and experience of pleasure.

Oxytocin, they go on to point out, is a promising treatment given its role in complex social behaviors mediated by the amygdala. The researchers used a double-blind, placebo-controlled, crossover design to test the effects of a single intranasal dose of the agent on amygdala resting-state functional connectivity (rsFC).

In an initial study involving 22 patients and 24 healthy controls, the team found that in patients compared to controls, oxytocin increased rsFC between the amygdala and left middle temporal gyrus, superior temporal sulcus and angular gyrus (MTG/STS/AngG).

The patients also showed hypo-connectivity in this circuit compared with controls. The researchers found that "patients with higher baseline symptoms had the most connectivity recovery from (oxytocin), indicating (oxytocin) treatment may have a greater impact for more symptomatic patients."

Given the "modest" initial sample size, the researchers replicated their findings in 183 patients and 178 controls. Exploratory analyses in this sample showed that lower amygdala-to-left-MTG/STS/AngG connectivity was related to worse expressive deficits.

These findings, Dr. Abram concluded, have "important implications for the development of novel and feasible treatments aimed at alleviating negative symptoms."

However, the researchers concede that they did not measure symptoms after oxytocin administration and thus "cannot determine if acutely altering this circuit's rsFC actually improves certain negative symptoms."

Future studies, they add, "should investigate whether oxytocin-induced normalization of this circuit leads to improvement in certain negative symptoms."

Dr. Stephen R Marder, director of the VA Desert Pacific Mental Illness Research, Education, and Clinical Center Los Angeles, told Reuters Health by email that the findings "may provide a path for developing treatments for negative symptoms." He was not involved in the study.


Schizophr Bull 2019.

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