Atypical Depression Linked to Obesity

Pauline Anderson

June 05, 2014

Major depressive disorder (MDD) with atypical features, including increased appetite and hypersomnia, is linked to obesity and other measures of adiposity, new research shows.

According to investigators, this increased risk is not explained by sociodemographic or lifestyle factors or the use of medications that might influence weight.

In addition, the study showed that the elevated body mass index (BMI) in patients with atypical depression is not a temporary phenomenon but persists after depressive symptoms remit and is not attributable to new episodes.

The study, which is the first to assess prospectively the association between different subtypes of depression and weight changes, provides insights into the complex relationship between depression and obesity, according to lead study author Aurélie Lasserre, MD, Center for Psychiatric Epidemiology and Psychopathology, Department of Psychiatry, Lausanne University Hospital, Prilly, Switzerland.

And although it cannot inform clinical decisions, the study is useful in that it suggests that atypical features of depression may represent red flags about susceptibility to weight gain, she added.

"It's important to be aware of this problem and to follow the weight of patients, and it might be a good idea to avoid weight-increasing drugs" in those with atypical depression, Dr. Lasserre told Medscape Medical News.

The study was published online June 4 in JAMA Psychiatry.

Increased Inflammation?

The researchers used cohort studies designed to prospectively investigate mental disorders and cardiovascular risk factors in the general population. The sample was randomly selected from the residents of Lausanne, Switzerland, in 2003.

Dr. Aurélie Lasserre

The analysis included 3054 individuals aged 35 to 66 years (mean age, 49.7 years) who underwent a physical examination, a psychiatric evaluation about a year later, and regular physical evaluations during follow-up.

Researchers used diagnostic information from the French version of the Diagnostic Interview for Genetic Studies (DIGS), which is a semistructured interview. They assigned psychiatric diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). (The DSM-5 was not yet available).

As per the DSM-IV, atypical features require mood reactivity and at least 2 of the following: increased appetite or significant weight gain; hypersomnia; leaden paralysis; a long-standing pattern of interpersonal rejection sensitivity.

For melancholia, the DSM-IV requires either a loss of energy or a lack of mood reactivity and 3 of the following symptoms: depression that is regularly worse in the morning; early-morning awakening; psychomotor retardation or agitation; decreased appetite; excessive guilt.

The researchers divided MDD into 4 subgroups ― melancholic, atypical, combined, and unspecified ― and looked at the change of adiposity during a mean of 5.5 years. To assess adiposity, they used measurements of BMI, waist circumference, and fat mass (collected using electrical bioelectrical bioimpedance), as well as the incidence of obesity.

The study showed that at baseline, 7.6% of participants met criteria for MDD, and 36.7% reported at least 1 remitted major depressive episode (MDE) in the past. Of those with MDD, about 10% had atypical and melancholic episodes combined, 14% had atypical episodes, 29% had melancholic episodes, and 48% had unspecified episodes.

Of those taking antidepressants at baseline, about 75% were receiving selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs); fewer than 10% were receiving a tricyclic or tetracyclic drug.

During follow-up, the BMI of the whole sample increased by 2.6%. After adjusting for sociodemographic characteristics, only patients with the atypical subtype of MDD had a higher increase in adiposity than patients without major depression.

The increases remained statistically significant after also adjusting for comorbid anxiety; lifestyle factors, such as smoking, physical activity and alcohol consumption; and medication use, and after further adjustments for MDE during follow-up (β = 3.19, 95% confidence interval [CI], 1.50 - 4.88).

Increase in Waist Circumference

Even patients whose atypical depression had remitted were prone to increased BMI during the course of the study.

"We don't know why, but once they have a remitted episode, some people continue to eat more and take on weight," said Dr. Lasserre. "It might be that they still have some symptoms but don't completely meet the criteria for a depressive episode."

According to the authors, depression subtypes are likely associated with different biological correlates and with differential pathways to cardiovascular risk.

The finding that BMI increases even in those with remitted episodes of depression supports a potential obesity-related pathway from atypical depression to cardiovascular risk and other chronic diseases related to obesity, said the authors. Relevant mechanisms could include adipokine or alterations in the hypothalamic-pituitary-adrenal axis, but proinflammatory dysregulation might be a more likely route.

"More and more, researchers are thinking that atypical depression could increase inflammation," said Dr. Lasserre. However, in the end, "it's really not clear why some people have a higher appetite and others have less appetite; it may be a different type of depression," she said.

Waist circumference increased by 4.6% during the study follow-up. Again, the presence of atypical MDD at baseline predicted elevated waist circumference increases regardless of the number of variables accounted for (β = 2.44; 95% CI, 0.21 - 4.66 after all adjustments).

According to Dr. Lasserre, other research suggests that waist circumference (abdominal obesity) might be a better marker of cardiovascular risk than BMI.

Depression status at baseline was only predictive of the increase of body fat percentage in men. This could be because women naturally have a higher fat mass, said Dr. Lasserre. She cautioned that less is known about the relationship between fat mass and cardiovascular diseases than about the role of other weight measurements.

A limitation of the study was the delay between the initial physical and psychiatric evaluations, which could increase the risk for misclassification of episodes at the psychiatric baseline as remitted depressive episodes. Also, in those who refused a diagnostic interview, depressive episodes were evaluated during follow-up using a depression scale.

Not New

Commenting on the study for Medscape Medical News, Alan J. Gelenberg, MD, Shively/Tan professor and chair, Department of Psychiatry, Pennsylvania State University College of Medicine, in Hershey, said that the concept that certain types of depression affect appetite more than others is not new.

"This group of investigators just observed that if you have the atypical depression in which you eat too much, lo and behold, you get more of an increase in BMI," said Dr. Gelenberg.

The new study is perhaps more sophisticated than previous ones, but basically makes the same point, added Dr. Gelenberg. "If for whatever reason your depression has you consuming more food than me because with my depression I don't feel like eating, you're going to gain more weight and have all these other indices of weight gain ― BMI, fat mass, and so forth ― so you're going to have all the adverse consequences metabolically of that."

Essentially, said Dr. Gelenberg, experts do not really know what depression is.

"It just means that something's wrong, and different types of underlying biological abnormalities are probably involved. It's much like a fever where there are different bacteria, different viruses, and different nonpathogens that might cause the fever."

Dr. Gelenberg does not believe the study will be of much help to clinicians in making treatment decisions. For a patient with a depression that is making him or her want to eat more, "I provide some diet counseling and health-promoting advice, but mostly, as a psychiatrist, I'll try to help the patient combat the depression with the hope that when their depression gets better, that urge to eat will diminish."

Dr. Lasserre and Dr. Gelenberg report no relevant financial relationships.

JAMA Psychiatry. Published online June 4, 2014. Abstract


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