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Longer duration of untreated psychosis linked to loss of brain volume

Longer duration of untreated psychosis was associated with accelerated hippocampal atrophy during initial antipsychotic treatment of first-episode schizophrenia, suggesting that psychosis may have persistent, negative effects on brain structure, according to finding published in JAMA Psychiatry.

“Several factors ... have been linked to early psychosis and could mediate an association between [duration of untreated psychosis] and hippocampal volume loss, but evidence from longitudinal studies is lacking,” Donald C. Goff, MD, department of psychiatry, New York University Langone Medical Center, and colleagues wrote. “Whereas the negative association of [duration of untreated psychosis] with clinical course is attenuated by the initiation of antipsychotic treatment, the evidence is mixed as to whether antipsychotics contribute to loss of brain volume or protect against it.”

The extent to which loss of brain volume early in psychosis treatment reflects an illness effect, a drug effect or both remains unknown, according to the researchers. Therefore, Goff and colleagues examined loss of hippocampal volume during the first 8 weeks of treatment for schizophrenia, its link to duration of untreated psychosis and molecular biomarkers related to hippocampal volume loss and duration of untreated psychosis.

At Shanghai Mental Health Center in China, researchers conducted a longitudinal study with age- and sex-matched healthy controls between Mar. 5, 2013, and Oct. 8, 2014. They assessed 71 patients with nonaffective first-episode psychosis treated with second-generation antipsychotics and 73 controls. They reassessed 31 participants with psychosis and 32 controls 8 weeks later, measuring hippocampal volumetric integrity (HVI), duration of untreated psychosis, 13 molecular biomarkers and 14 single-nucleotide polymorphisms from 12 candidate genes.

Participants in the first-episode psychosis group had lower baseline median left HVI (n = 57) compared with those in the control group (n = 54; P = .001). Left HVI decreased in 24 participants with psychosis at a median annualized rate of –.03791 throughout the 8 weeks of treatment, whereas left HVI increased in 31 controls at a rate of 0.00115 (P = .001). Furthermore, researchers observed an inverse association between the change in left hippocampal volume and duration of untreated psychosis (P = .002).

Although they observed similar results in the right HVI, the relationship between change in right HVI and duration of psychosis was not significant. According to the results of analyses that looked at left-side hippocampal volume only, left HVI was associated with molecular biomarkers of inflammation, oxidative stress, brain-derived neurotrophic factor, glial injury and those reflecting dopaminergic and glutamatergic transmission.

“We found significantly lower HVI at baseline in participants with [first episode psychosis] compared with healthy controls and additional HVI reduction during antipsychotic treatment that correlated with [duration of untreated psychosis], consistent with a persistent, possibly deleterious, effect of untreated psychosis on brain structure,” Goff and colleagues wrote. “Larger longitudinal studies of longer duration are needed to examine the association between [duration of untreated psychosis], hippocampal volume and clinical outcomes.” – by Savannah Demko

Disclosures: Goff reports support from Avanir Pharmaceuticals, the National Institute of Mental Health and Stanley Medical Research Institute. Please see the study for all other authors’ relevant financial disclosures.