Obesity and depression are entwined, major genetic study reveals

Camille Bienvenu
Fri, 20 Oct 2017
Obesity and depression are entwined, major genetic study reveals
A new study has found important genetic ties between obesity and major depressive disorder (MDD) which could help further our understanding of the mechanics linking the two conditions together.

An increasing number of people who are depressed also show signs of having metabolic problems like type 2 diabetes or are carrying excess weight, and vice versa.

Convinced that there is a connection, scientists at Vrije University Medical Centre, in Amsterdam, have looked at variations in the sequence of genes of people with MDD and obesity to see if there were some similarities.

A comparative genetic analysis was performed on 26,628 male and female study participants of the Psychiatic GWAS Consortium research project, which included data on 11,837 diagnosed with MDD.

About fifteen percent of those with MDD reported increased appetite and upward weight fluctuations while depressed. Using a combination of molecular genetic techniques, the researchers homed in on gene variants that they all shared.

They found that they carried a number of variants associated with higher body mass indexes, elevated levels of the marker of inflammation C-reactive protein (CRP) and abnormal levels of leptin, a hormone regulating appetite and metabolism.

Statistically, an eighteen per cent of MDD patients with bodyweight issues were more genetically predisposed to having a high BMI; eight per cent were more prone to have high CRP levels; and nine per cent were more likely to have a disruption in leptin.

The researchers then proceeded to chart interactions between these genetic factors, metabolic changes and disease processes leading to MDD or obesity.

According to their estimations, MDD may start with generalised inflammation (as indicated by higher CRP) that "spreads" to the brain and impairs the production or signalling of hormones involved in the regulation of mood and metabolism.

High levels of CRP and other inflammatory cytokines could lead to an overactive hypothalamus, a part of the brain which governs the production of precursors to neurotransmitters (like serotonin) that are out of balance in depressive disorders.

The hypothalamus also controls the normal signalling of leptin, whose dysregulation has been associated with increased appetite and lower satisfaction after meals. And researchers discovered that a disrupted signalling of leptin influences mood regulation.

The relationship between obesity and depression appears to be what researchers call "bidirectional". Being overweight or obese may up the odds of depression and inversely, people who are obese have a higher propensity to depression.

However, there is evidence to suggest that small lifestyle changes such as exercising at any intensity for just one hour a week can greatly reduce the risk of future depression.

As depression and obesity are both on the rise, unlocking the connection between the two and developing therapies that address them simultaneously is of paramount importance.

The findings were published in the journal JAMA Psychiatry.
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