Mood disorders: research clarifies the impact of metabolism on the brain and cognitive functions

Mood disorders, including major depressive disorder and bipolar disorder, are among the leading causes of disability worldwide, with a significant impact also in Italy. Bipolar disorder, in particular, is characterized by alternating depressive episodes and phases of elevated mood and may be associated with cognitive impairment that persists even outside acute phases.

In recent years, research has moved beyond a purely psychiatric view of these conditions, recognizing that systemic biological factors, such as inflammation and metabolism, also play an important role.

The San Raffaele study involved 159 patients hospitalized for a depressive episode, diagnosed with either bipolar disorder or major depressive disorder. For each participant, metabolic parameters were assessed through:

• blood tests;
• neuroimaging data obtained via magnetic resonance imaging (MRI);
• cognitive performance evaluated using standardized tests.

The aim was to determine whether a relationship exists between metabolism, brain structure, and cognitive function, going beyond traditional approaches that consider these aspects separately.

The study was conducted at IRCCS Ospedale San Raffaele, involving the Division of Neuroscience, the Psychiatry and Clinical Psychobiology Unit, and the Mood Disorders Unit, within a highly integrated clinical and neuroscientific research setting.

The findings show that a less favorable metabolic profile is associated with poorer cognitive performance and structural changes in brain regions involved in memory and emotional regulation. This association is particularly pronounced in patients with bipolar disorder, while it appears less evident in major depression.

“In particular, insulin resistance and leptin levels are associated with volume reductions in brain regions involved in memory and emotion, as well as with less efficient cognitive functioning. In bipolar disorder,” explains Laura Raffaelli, “this relationship appears stronger, suggesting that metabolic alterations may impact patients’ cognitive functioning.”

“We integrated multiple levels of analysis (biological, structural, and cognitive) to provide a comprehensive view of the disease. Our results,” adds Elena Mazza, “indicate that these levels interact more closely than previously thought.”

These findings open new perspectives in understanding mood disorders and suggest the potential to develop therapeutic approaches in which the management of metabolic factors complements traditional psychiatric interventions.

Monitoring metabolic parameters may provide useful information not only about cardiovascular risk, but also about patients’ brain and cognitive functioning.

“This study reinforces the idea that in mood disorders the brain should be considered within a broader system that includes metabolism and other biological processes occurring in the human body,” concludes Francesco Benedetti. “Understanding these interactions is essential for developing comprehensive models of the disease and, ultimately, more targeted therapeutic interventions.”