Hippocampal Atrophy May Be Associated With Duration of Untreated Psychosis

being prepped for MRI
being prepped for MRI
Investigators sought to determine if reduction in brain volume occurs early in treatment along with the association to duration of untreated psychosis.

A longer duration of untreated psychosis is associated with an accelerated loss of hippocampal volume during the initial treatment of first-episode psychosis, according to a recent study published in JAMA Psychiatry.

The current study sought to determine if reduction in brain volume occurs early in treatment and whether it is associated with duration of untreated psychosis, by measuring hippocampal volumetric integrity of medication-naive patients experiencing their first episode of psychosis before and after initial antipsychotic treatments.

From March 5, 2013 to October 8, 2014, 71 medication-naive individuals with first-episode nonaffective psychosis (52 outpatients and 19 inpatients) were recruited from the Shanghai Mental Health Center’s early psychosis program. 

To make up a healthy control group, 73 individuals matched in age, sex, and education level who were also psychotropic medication-naive were recruited through advertisements. All study participants had completed 9 or more years of school and were between 16 and 40, right-handed, and without suicidal ideation or substance abuse. All participants received MRIs at baseline, and a total of 31 participants with first-episode psychosis and 32 control participants completed the study by undergoing assessment and imaging again 8 weeks later.

Study limitations include the 56% dropout rate of participants with first-episode psychosis, which could have led to higher ratings of symptom severity due to the larger number of hospitalized patients who completed the study. The homogenous study sample in regard to ethnicity/race and substance abuse may mean the results would not necessarily apply to more diverse populations. Also, without a placebo control, study investigators could not determine if hippocampal volumetric integrity reduction resulted from medication effect, illness progression, or both.

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At baseline, the left hippocampal volumetric integrity and right hippocampal volumetric integrity of participants with first-episode psychosis were significantly lower than left and right hippocampal volumetric integrities of the control group.  Further reduction in brain volume occurred from baseline to 8 weeks following antipsychotic treatment for participants with first-episode psychosis which correlated with duration of untreated psychosis.

Study investigators conclude that this association is “consistent with a persistent, possibly deleterious, effect of untreated psychosis on brain structure… [larger] longitudinal studies of longer duration are needed to examine the association between [duration of untreated psychosis], hippocampal volume, and clinical outcomes.”


Goff DC, Zeng B, Ardekani BA, et al. Association of hippocampal atrophy with duration of untreated psychosis and molecular biomarkers during initial antipsychotic treatment of first-episode psychosisJAMA Psychiatry. 2018; 75(4):370-378.