Genetic overlap between major depression and obesity in some patients

By Marilynn Larkin

NEW YORK (Reuters Health) – Patients with major depressive disorder who experience increases in appetite, weight, or both have a higher genetic risk for obesity-related traits such as high body-mass index (BMI) and elevated levels of leptin and inflammation, researchers suggest.

“As clinicians, we are well aware that depression is highly heterogeneous, and patients with the same diagnosis of major depressive disorder may present with very different symptom profiles,” Dr. Yuri Milaneschi of VU University Medical Center Amsterdam in the Netherlands told Reuters Health.

“It has been previously shown that the relationship with obesity and its biological alterations is stronger in certain subgroups of depressed patients, in particular in those reporting symptoms such as appetite increase, weight gain and fatigue,” he said by email.

“In the present study, we examined whether the specific connection between a subgroup of depressed patients and obesity-related alterations may emerge from a common genetic base.”

Dr. Milaneschi and colleagues analyzed data from September 2015 to May 2017 on more than 26,000 people of European ancestry (59% female) from 14 datasets in the Psychiatric Genomics Consortium. The data included 11,837 people with MDD and 14,791 controls.

Among those with MDD, about 45% were in the decreased appetite/weight (A/W) and about 15% in the increased A/W subgroups.

As reported in JAMA Psychiatry, online October 18, common genetic variants explained about 10% of the heritability in the two subgroups.

The increased A/W subgroup showed a strong, positive genetic correlation with BMI, whereas the decreased A/W subgroup showed an inverse correlation. Further, the increased A/W subgroup had a significantly higher polygenic risk for increased BMI (odds ratio, 1.18) and levels of C-reactive protein (OR, 1.08) and leptin (OR, 1.09).

Dr. Milaneschi said, “These results confirm that in certain patients with major depressive disorder, the connection with obesity may emerge from a common genetic background. Further studies are needed to identify the genes involved and whether they may have a direct causal role in the development of both depression and obesity.”

“Clinical implications lying much further away include the possibility of targeting the connecting mechanisms identified as a treatment for patients with comorbid depression and obesity,” he concluded.

Dr. Roseann Peterson of Virginia Commonwealth University in Richmond, author of a related editorial, told Reuters Health by email, “We now have evidence for shared genetic risk between BMI and depression with the atypical depression subtype features of increased weight and/or appetite.”

However, “replication is key,” she added. “We cannot extrapolate causality from (the study). Also, interpretation is limited to those of European descent, as other ancestries/ethnicities were not studied.”

“Important next steps are to establish causality and test for direction of effect (i.e., does BMI risk cause atypical depression features and vice versa?), which will guide prevention and treatment efforts for both obesity and major depression disorder,” she concluded.

Dr. James Gangwisch of Columbia University Medical Center in New York City said in an email to Reuters Health that the result “is not surprising given that a significant proportion of atypical depression has a seasonal pattern or is seasonal affective disorder.”

“Seasonal changes in mood, with seasonal affective disorder being on the extreme end of the spectrum, have been theorized to have evolved (from our hunter-gatherer ancestors) to promote weight gain and the conservation of energy to survive winter food shortages and cold temperatures,” he said by email.

“The findings point to the need to treat both depression and obesity,” he observed. “These two problems are likely to have a bidirectional relationship, and therefore treating one can have benefits for the other.”

SOURCES: http://bit.ly/2xUotR6 and http://bit.ly/2yvGswJ

JAMA Psychiatry 2017.

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