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Appetite Changes Reflect Distinct Subgroups of Depression

July 05, 2018

By Will Boggs 

NEW YORK—In patients with depression, appetite increases or decreases reflect pathophysiologically distinct endocrine, metabolic and immune subgroups of the disorder, researchers report.

"I was surprised that by simply asking individuals whether their appetite went up or down during the course of their depression, we were able to identify significant differences in stress hormones, metabolism, and inflammatory markers circulating in the body," said Dr. W. Kyle Simmons from the Laureate Institute for Brain Research and The University of Tulsa, in Oklahoma.

"I was particularly intrigued, however, by the strong links we found between these changes that were happening in the body and the activity of brain regions that are important to sensing the body's energy state and responding to rewards," he told Reuters Health by email.

Changes in appetite and weight are important features of depression, with nearly half of patients experiencing depression-related decreases in appetite and approximately a third experiencing depression-related increases in appetite.

In an earlier functional MRI study, Dr. Simmons and colleagues found that depressed adults with appetite change showed marked differences in brain activity to food cues.

In the current study, they compared the relationships between peripheral endocrine, metabolic and immune signaling and brain activity to food cues between 23 depressed participants who experienced increased appetite and weight, 21 who experienced decreased appetite and weight, and 42 healthy controls.

The only significant relationship between bio-assay values and brain activity was a significant negative correlation between activity in the right posterior insula and the subjects' ghrelin levels.

Compared with the decreased-appetite group, the increased-appetite group had significantly lower nighttime salivary cortisol levels, higher insulin levels, higher insulin resistance, higher leptin levels and lower ghrelin levels.

Increased-appetite participants had higher levels of C-reactive protein and interleukin (IL-)1RA than did decreased-appetite participants and healthy controls and higher IL-6 levels than healthy controls, the team reports in Molecular Psychiatry, online June 13.

The researchers identified four notable associations between brain activity to food cues and cortisol, metabolic and inflammatory factors: (1) a strong negative correlation between cortisol and ventral striatum activity in the decreased-appetite group; (2) a positive correlation between insulin resistance and insula activity in the increased-appetite group; (3) among participants with the highest IL-6 levels, weak responses to food cues in the decreased-appetite group but strong responses to food cues in the increased-appetite group in both insula regions; and (4) a negative correlation between insulin resistance and parahippocampal gyrus response to food pictures in the increased-appetite group.

"I think there are at least two important implications of this research," Dr. Simmons said. "First, this work helps us understand how the endocrine, immune, and metabolic changes happening in the bodies of people with depression may lead to changes in brain activity that regulate appetite when they become depressed. Second, and perhaps most importantly, this work strongly supports the idea that there is more than one biological pathway into depression."

"For some people, depression may be relatively more associated with increased stress hormones - and those folks may experience appetite loss," he said. "For others with an increased appetite, depression may be associated with immune and metabolic dysregulation."

"In future studies, scientists may be able to use an easily observable behavioral symptom like appetite change to quickly select among depressed research participants who have different depression biologies," Dr. Simmons said. "Scientifically, this could be tremendously helpful."

The researchers note, "Addressing the causality of the relationships reported here will require subsequent studies in which mood and appetite are measured in the presence of interventions that alter activity in basic signaling pathways underlying responses to stress, inflammation, and cellular energy regulation."

Two of the nine authors of this report, including Dr. Simmons, are employees of Janssen Research and Development, LLC and are coinventors on a patent regarding appetite change and depression.


Mol Psychiatry 2018.

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