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NEW YORK (Reuters Health) – Three proxies for insulin resistance each may predict incident major depressive disorder, according to new research.

Combined with findings from other studies, these new data suggest that treating so-called pre-diabetes might help prevent some cases of depression, researchers write in The American Journal of Psychiatry.

“For physicians of any sort, or any medical healthcare providers who deal with patients who are overweight or have any issues with glucose control, a very simple guideline is to ask them upfront about their mood, and manage them – follow them – with the idea that they might become depressed,” Dr. Natalie Rasgon, crestor therapy first professor of Psychiatry and Obstetrics and Gynecology at Stanford University School of Medicine, in California, told Reuters Health by phone.

“The premise is that if we were to resolve the metabolic dysfunction of pre-diabetes, that would, in turn, mitigate the risk of developing depression,” she said.

Dr. Rasgon and her colleagues examined data from 601 individuals in the control group of the Netherlands Study of Depression and Anxiety (NESDA), an ongoing longitudinal study. These participants had no history of depression or anxiety.

Over the nine years that the study has been running so far, 14% of the control group developed major depressive disorder. Those who did were more likely to have one or more of three proxy measurements that can signify insulin resistance, or pre-diabetes.

Adjusting for age, sex, education, physical activity, harmful alcohol use and smoking status, the highest risk of depression was seen in people with a high ratio of triglycerides to high-density lipoprotein (hazard ratio, 1.89; 95% confidence interval, 1.15 to 3.11).

Fasting plasma glucose levels in the pre-diabetes range of 100 to 125 mg/dL was associated with a 37% risk increase (HR, 1.37; 95% CI, 1.05 to 1.77), and obesity, as measured by waist circumference, was associated with an 11% increase (HR, 1.11; 95% CI, 1.01 to 1.21).

Analysis of a sub-group of participants who did not have any of the three predictors of depression at the start of the study, but who had developed one or more at a two-year follow-up, found that only pre-diabetes had a statistically significant link to depression, at an adjusted hazard ratio of 2.66 (95% CI, 1.13 to 6.27).

“These results are exciting and consistent with the notion that bidirectional relationships exist between metabolic dysfunction and psychiatric illnesses,” said Dr. Mandakh Bekhbat, a neuroscientist at Emory University’s Department of Psychiatry and Behavioral Sciences, in Atlanta, who was not involved in the research. “Replication of the findings will be crucial in depression, and it is worth exploring whether results hold trans-diagnostically across other psychiatric illnesses with known metabolic abnormalities.”

“Understanding the mechanisms of how systemic insulin resistance may translate to fairly specific neurotransmitter and neural circuit changes known to underlie depression will be a huge step forward,” she told Reuters Health by email.

In support of their hypothesis that treating insulin resistance could prevent the onset of depression, Dr. Rasgon and her colleagues cite research suggesting that the insulin-sensitizing drug pioglitazone has an effect on depression.

“It has been shown to improve people in a current episode of depression,” Dr. Kathleen Watson, who also worked on the study, told Reuters Health by phone.

The problem is that pioglitazone has at least two possible methods of lessening depression: it improves insulin resistance and it reduces inflammation, she added.

“So, we don’t know exactly how it works,” said Dr. Watson, also with Stanford. “But there is the potential that if you reverse the insulin resistance, or even the pre-diabetes, that you could see an improvement in mood.”

SOURCE: The American Journal of Psychiatry, online September 22, 2021.

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