Researchers at the University of Sydney have found that weight gain most commonly occurs in atypical depression, a distinct biological subtype of the disorder with specific genetic risks and treatment responses. The results of the study were published in Biological Psychiatry (BioPsy).

The analysis was based on data from the large-scale Australian Genetics of Depression Study, which included nearly 15,000 individuals with depressive disorders. Participants provided DNA samples and detailed information about their symptoms and treatment experiences.

The findings showed that weight gain in depression is not random—it is associated with a particular biological subtype of the condition. In atypical depression, the regulation of appetite and circadian rhythms is disrupted, increasing the likelihood of body weight gain.

Genetic analysis revealed that individuals with this form of depression have a distinct profile of inherited risks. In addition to depression, this group more frequently exhibited a predisposition to attention deficit hyperactivity disorder (ADHD), bipolar disorder, and metabolic disturbances, all of which may contribute to weight gain.

These characteristics were also reflected in treatment outcomes. Patients with atypical depression reported less improvement with commonly prescribed antidepressants—SSRIs and SNRIs—and more often experienced side effects.

“Atypical depression requires a different therapeutic approach, as standard treatment regimens may not only be less effective but could also exacerbate symptoms related to changes in body weight,” the researchers concluded.