Insulin is the most overlooked hormone in mental health. It’s primary job is to direct fuel and when signaling breaks down, tissues can be overfed or underpowered.
The brain is an energy demanding organ, consuming 20% of the body’s energy despite making up a small fraction of its weight. Under normal circumstances, the brain relies heavily on glucose to meet demands. Is it really surprising, then, that disturbances in how the body produces, transports and uses fuel might influence mood, cognition, motivation and mental health. Metabolic psychiatry begins with this question.
Metabolic psychiatry is an emerging field doing just that. It reconceptualizes psychiatric disorders as conditions with significant metabolic underpinnings, rather than neurotransmitter imbalances. The field integrates genomics, mitochondrial biology and clinical information to both diagnose and treat.
There are several foundational areas of evidence that support this paradigm:
Mitochondrial dysfunction and impaired brain energy metabolism are observed across schizophrenia, BD and MDD including deficits in oxidative phosphorylation, increased ROS and tricarboxylic acid cycle disruption.
Insulin resistance
Some research has shown that olfactory neuronal cells from patients with schizophrenia and BD have shown reduced insulin receptor substrate signaling even in the absence of Diabetes.
Genes
A large genomic study found that MDD shares a metabolic genetic profile similar to type 2 Diabetes and coronary artery disease, while schizophrenia and BD show an opposite pattern. This suggests disorder specific metabolic etiology.
Metabolic profiling
There has been identified consistent dysregulation in amino acid metabolism, lipid signaling, energy homeostasis and oxidative stress pathways across disorders with specific signatures (eg glutathione disruption in schizophrenia).
So, what are the metabolic interventions in psychiatry under investigation?
Ketogenic diet
A pilot trial in patients with schizophrenia or BP with metabolic abnormalities showed 32% reduction in Brief Psychiatric Rating scores in schizophrenia, 31% improvment in Clinical Global Impression severity over 4 months. The proposed mechanisms include GABAergic tone, reduced glutamatergic excitotoxicity and bypassing cerebral glucose hypometabolism.
Targeted Metabolic Correction
It treatment refractory depression, metabolomic evaluation of CSF identified potentially treatable abnormalities in 47% of patients including cerebral folate deficiency. Supplementation with folate (B9) led to improvement in depression.
GLP-1s
A meta-analysis of 80 RCTs (>107,000) in JAMA Psychiatry found that GLP-1RAs were not associated with increased psychiatric adverse events and were associated with improvements in mental health. As a naturopathic doctor that specializes in mental health, I am weary. As many of my patients are tapering psych meds and have sensitive nervous systems.
In conclusion
Across these lines of evidence, a unifying picture begins to emerge: psychiatric illness may, in part, reflect a disorder of fuel utilization.
This is not a rejection of what we already know. The mind-body connection in mental health has long been recognized. Mental health is physical health: brain function arises from biology, and biology is inseparable from metabolism. Metabolic psychiatry deepens traditional models of psychiatry by asking what sustains the brain at the cellular level.
Neurotransmitters still matter, but they do not operate in isolation. They are built, regulated, and expressed within the context of cellular energy availability and metabolic signaling.
Metabolic psychiatry asks a simple but destabilizing question: what if we have been treating the downstream effects, while overlooking the systems that power the brain itself?
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