Could Brain Insulin Signaling Predict Depression Outcomes? Pilot MRI Study Points to a Potential Biomarker

CONFERENCE REPORTER

At the 2026 American Society of Clinical Psychopharmacology (ASCP) Annual Meeting in Miami, early pilot data suggested that impaired insulin signaling in the brain may help predict short-term depression outcomes, adding to growing evidence that metabolic dysfunction and psychiatric illness may be more biologically intertwined than traditionally appreciated.¹

Kateryna Maksyutynska, PhD, a postdoctoral research fellow at the Centre for Addiction and Mental Health, presented findings from a small neuroimaging pilot study (N=12) examining insulin action in the brain among adolescents 14-18 years of age with depression. The researchers assessed depression severity at baseline during MRI imaging and again 6 months later.

“What we found was that individuals who had maybe more impaired, or our take on impaired, insulin action in the brain predicted worse illness severity 6 months after,” Maksyutynska told Psychiatric Times. “They actually had increased depression severity score at that follow-up assessment.”

Although preliminary, the findings raise the possibility that disrupted brain insulin signaling could serve as a predictive biomarker for depression trajectory. According to Maksyutynska, the team has since secured funding for a larger follow-up study to determine whether the signal can be replicated in a broader cohort.

“This is a very small study, it’s a pilot trial,” she cautioned. “But I was very interested to see that we were actually able to predict short-term outcome.”

The research emerged from longstanding observations that metabolic disorders and depression frequently coexist and may influence one another bidirectionally. Patients with metabolic dysfunction appear to have elevated risk for depression, while individuals with depression often demonstrate higher rates of metabolic abnormalities.

“We’re trying to understand if there’s this maybe underlying biological mechanism that might be disrupted in both disorders,” Maksyutynska said. “That’s why we’re specifically looking at insulin action in the brain.”

The focus on insulin signaling is rooted in its broad neurologic and physiologic functions. Insulin activity in the brain has been associated with mood regulation, cognition, and metabolic processes, all of which have been implicated in depressive disorders.

“We know insulin action in the brain is related to a lot of processes that have been seen to be disrupted in depression,” she explained. “So things like regulating mood, cognitive function, metabolic function. That’s why we want to dig into it a little bit further in this project.”

For practicing psychiatrists, the work reinforces increasing calls to integrate metabolic assessment more routinely into psychiatric care. Rather than viewing psychiatric illness and metabolic dysfunction as isolated domains, Maksyutynska suggested clinicians may need to adopt a more unified framework.

“The fact that these 2 disorders, metabolic dysfunction specifically and depressive disorders, are so interlinked, it’s really difficult to look at them separately,” she said. “We have to kind of take a very holistic approach to it and move away from the more siloed health care systems.”

She added that metabolic screening may provide clinically relevant information beyond physical health monitoring alone.

“I think looking at a metabolic panel for individuals with psychiatric disorders is very important,” Maksyutynska told Psychiatric Times. “There’s been a lot of research looking at whether higher rates of metabolic dysfunction can predict worse clinical performance or worse illness severity.”

The discussion also touched on growing interest in repurposing metabolic treatments for psychiatric indications. Maksyutynska pointed to emerging evidence surrounding metformin, other antidiabetic agents, and even GLP-1 agents that have shown signals of benefit in psychiatric populations, although she emphasized that larger randomized controlled trials remain necessary before firm conclusions can be drawn.

“There have been positive findings in terms of improved illness severity and things like that,” she said. “But I think we do need some more evidence conducted in RCTs [randomized controlled trials] where the evidence comes from larger cohorts and better designed studies.”

Her laboratory is also examining whether similar metabolic-neuropsychiatric mechanisms may extend beyond depression into other diagnoses, including schizophrenia spectrum disorders.

“Our lab is looking at schizophrenia spectrum disorder specifically,” Maksyutynska added. “Seeing whether this is as effective in other psychiatric diagnoses as well would be very interesting.”

In ongoing work, the team is continuing to analyze additional neuroimaging modalities to refine how insulin action in the brain is measured and characterized.

“I’m working on analyzing some more neuroimaging data from the work that I’m going to be presenting tomorrow,” she said. “Looking whether our ability to measure insulin action in the brain has been effectively captured through other imaging modalities.

Dr Maksyutynska is a postdoctoral research fellow at the Centre for Addiction and Mental Health.

Reference

1. Maksyutynska K, Stogios N, Korran V,et al. Is Brain Insulin Action Implicated in the Biology of Depression? A Pilot Neuroimaging Study in Adolescents. Presented at the 2026 ASCP Annual Meeting; May 26-29, 2026; Miamia, Florida.