Lack of ‘feel good’ neurosteroid may contribute to depression or anxiety in anorexic or obese women

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Women who live with anorexia or obesity exhibit low levels of a neurosteroid that may explain why both conditions are associated with an increased risk for depression and anxiety, according to a small study published in the journal Neuropsychopharmacology.

The study found low levels of allopregnanolone (all), which has been tied to heightened rates of depression and anxiety. Similarly low levels of the allo, which is a metabolite of the hormone progesterone, have also been found in those living with post-traumatic stress disorder (PTSD).

According to the authors of the study, this is the first time researchers have examined the neurosteroid’s effect on mood in women with eating disorders or obesity. Previous research has indicated that up to half of all women with anorexia experience comorbid depression or anxiety, while 43% of obese adults live with depression.

Allo, sometimes called the “feel good” neurosteroid, functions by binding to receptors in the brain and enhancing the effect of the neurotransmitter gamma-aminobutyric acid (GABA). The result is an overall positive mood and feelings of well-being.

“Depression is an incredibly prevalent problem, especially in women, and also particularly at the extremes of the weight spectrum,” said study leader Dr. Karen Miller, professor of medicine at Harvard Medical School.

“The hope is that a greater understanding of mechanisms contributing to these disorders —including abnormalities in the regulation of hormones and their neuroactive metabolites — may lead to new targeted therapies in the future.”

For the study, the team evaluated 12 women with anorexia with amenorrhea (not having menstrual periods), whose body mass indices were less than 18.5, as well as 12 obese women with BMI at 25 or above. These participants were then compared against 12 normal-weight women with BMIs between 19 and 24.

None of the women involved in the study had ever received a clinical depression diagnosis or taken antidepressants.

Each participant gave blood samples and completed questionnaires designed to evaluate levels of depression and anxiety. The blood samples were evaluated using gas chromatography and mass spectrometry to identify the extremely low levels of sex hormones and metabolites in the blood, saliva, and brain tissue of the participants.

According to the published findings, women with anorexia or obesity all had blood levels of allo that were at least 50% lower than they were in women with normal BMI.

The researchers say the levels of allo in the participants correlated directly with the severity of their depression and anxiety symptoms reported in questionnaires.

“We are beginning to see more and more evidence that low allo levels are tightly linked to depression, anxiety, post-traumatic stress disorder, and other mood disorders,” said Dr. Graziano Pinna, associate professor of psychiatry in the University of Illinois at Chicago (UIC) College of Medicine and an author on the paper.

“To see that women with anorexia nervosa and obesity have low levels adds to the picture that the role of allo is under-recognized in mood disorders.”

The team also noted that progesterone levels were similarly low in women with anorexia or obesity. This may indicate that the low allo levels may be the result of improper functioning in enzymes associated with converting progesterone into allo.

“Women with anorexia nervosa had low progesterone because they were amenorrheic, and the other two groups also had low progesterone levels because their blood was taken in the follicular phase when progesterone is naturally low,” said Pinna.

“That we found that obese women had lower allo levels than normal weight participants adds to growing evidence that this steroid is involved in depression and anxiety regardless of how much progesterone is available to begin with.”

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