March 9, 2026
Vital Signs
Beyond Serotonin, What Causes Depression? 7 Habits to Boost Mood
Depression has long been framed as a chemical imbalance—a simple matter of serotonin too low, mood too low. But the rabbit hole goes much deeper.
Mental health, like other dimensions of the body—the gut, metabolism, and immunity—can suffer illness, according to internal medicine physician Dr. Austin Perlmutter.
“But now we’re starting to understand that all these systems are interconnected,” he said.
Perlmutter joined “Vital Signs” to highlight deeper, systemic causes of depression and avenues to pursue in order to optimize mental health.
For instance, emerging research suggests inflammation can induce depressive symptoms in real time; while metabolic dysfunction—including insulin resistance—may alter brain signaling. Even air pollution and indoor toxins appear linked to cognitive decline and mood disorders.
In terms of the immune system, Perlmutter points to how immune cells in the brain, known as microglia, respond to chronic stress and environmental signals, potentially reshaping mood and behavior.
“The photons that a person takes in through their eyes coming from that TV screen, can increase stress in the brain,” he said.
“When you rev up stress pathways in the brain chronically, that can actually activate the danger signal in the brain’s immune cells.”
Neuroplasticity is often used to explain how people “get stuck” in negative thought patterns of depression. Equally, this ability of the brain to “rewire itself” gives hope for getting “unstuck.” Perlmutter said this is one reason why exercise, and resistance training in particular, may rival traditional therapies in improving depression outcomes.
Meanwhile, the gut-brain axis—the two-way communication system between gut and brain—highlights the value of diet to mental health. The Mediterranean pattern diet, in particular, is linked to measurable improvements in depressive symptoms, while more restrictive approaches such as ketogenic diets remain under investigation.
Moreover, Perlmutter reminds us that everyday inputs—the air we breathe, the media we consume, the social isolation we tolerate—quietly program the brain over time.
In this respect, depression is not simply a brain disorder. It may be a whole-body signal—one shaped by metabolism, immunity, environment, and behavior—and one that demands a broader solution.
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Dr. Perlmutter hosts the Get the STUCK Out podcast
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Related/Referenced studies/reports:
The Nun Study: Insights from 30 years of aging and dementia research – PMC
Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks: Cell
Alzheimer’s disease is type 3 diabetes-evidence reviewed – PubMed
Exercise restores brain insulin sensitivity in sedentary adults who are overweight and obese
Exercise for depression – Clegg, AJ – 2026 | Cochrane Library
NCHS Data Brief ■ No. 443 ■ August 2022
Urban Nature Experiences Reduce Stress in the Context of Daily Life Based on Salivary Biomarkers
Health and societal effects from exposure to fragranced consumer products – ScienceDirect
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Vital Signs’ host, guests, and contributors offer general information on improving health and wellness. This is not intended as diagnosis or medical advice. You should consult your medical doctor or holistic doctor before enacting any suggested strategies for health and wellness improvement, including those aimed at preventing or treating specific diseases featured on this program.
The views expressed in this video are opinions of the host and guests, and do not necessarily reflect the views of The Epoch Times.
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