Mental illness may start with power failures inside brain cells rather than chemical imbalances between them. Harvard psychiatrist Dr. Bruce Cohen spent nearly five decades uncovering how disrupted energy production drives conditions like schizophrenia, bipolar disorder, and Alzheimer’s disease. His team grows living brain cells from patient samples using stem cell technology, revealing metabolic defects that appear before symptoms emerge. Brain cells from people with psychiatric disorders show inherent problems generating energy and connecting. These discoveries challenge decades of neurotransmitter-focused theories and point toward prevention strategies that could stop illness before it starts. Dr. Cohen’s research suggests future treatments might target cellular power systems instead of just adjusting brain chemistry.
Growing Brain Cells From Patients Changes Everything
Scientists can now create brain cells from anyone by reprogramming their skin or blood cells. Induced pluripotent stem cell technology takes mature cells and turns them back into stem cells capable of becoming any cell type, including neurons. Dr. Cohen’s laboratory pioneered using this approach to study psychiatric disorders. His team collects samples from patients with schizophrenia, bipolar disorder, or Alzheimer’s disease, then grows their brain cells in laboratory dishes.
Brain cells grown this way carry the same genetic information as the patient’s own neurons. When researchers examine these cells, they find problems that exist independent of environment, medication, or life experiences. Cells from people with major psychiatric conditions display metabolic abnormalities even when grown under identical conditions to cells from healthy individuals. These defects represent inherent vulnerabilities present from birth or early development.
Dr. Cohen describes these advances as giving researchers leads they lacked 40 years ago. Before stem cell technology, scientists could only study postmortem brain tissue or living brains through limited imaging techniques. Now they can watch patient-derived neurons grow, connect, and function in real time. They can test how these cells respond to different treatments and measure their energy production at the cellular level.
Energy Crisis at the Cellular Level
Brains consume more energy than any other organ relative to their size. Neurons require constant fuel to maintain electrical signals, pump ions across membranes, and communicate with thousands of neighboring cells. Mitochondria serve as cellular power plants, converting nutrients into ATP (adenosine triphosphate), the energy currency cells use for all their work.
Dr. Cohen’s research documents widespread disturbances in how brain cells from psychiatric patients generate and use energy. Mitochondrial function appears compromised in cells from people with schizophrenia, bipolar disorder, and late-onset Alzheimer’s disease. These organelles cannot produce sufficient ATP or cannot produce it efficiently. Energy shortfalls affect every aspect of neuron function.
Low energy availability impairs how neurons grow, form connections, and maintain synapses. Cells struggling to meet energy demands cannot properly regulate their internal environment. Calcium levels swing too high or too low. Oxidative stress increases as damaged mitochondria leak toxic molecules. Neurons become vulnerable to additional stresses that healthy cells would easily withstand. Over time, these energy problems contribute to symptom emergence and disease progression.
Seymour Kety, who mentored Dr. Cohen early in his career, was the first person to measure energy use in living human brains. He won the Lasker Prize for that work. Decades later, his intellectual descendant returned to questions about brain energy metabolism with molecular tools Kety never imagined.
Beyond Dopamine and Serotonin
Psychiatry spent decades focused on neurotransmitters as the root cause of mental illness. The dopamine hypothesis dominated schizophrenia research. Serotonin imbalance became the accepted explanation for depression. Medications targeted these chemical messengers, blocking or boosting their signals. While drugs help many patients, they don’t cure illness and often lose effectiveness over time.
Dr. Cohen’s early work challenged oversimplified neurotransmitter theories. His team discovered that antipsychotic drug effectiveness correlated with how much medication reached the brain, not just which receptors it hit. All antipsychotic medications interact with multiple receptor types at therapeutic doses, not just dopamine D2 receptors as commonly believed. Drug effects proved far more complex than single-target models suggested.
Metabolic research extends this complexity further. Neurotransmitter systems depend on adequate energy supplies to function properly. Neurons must generate ATP to synthesize neurotransmitters, package them into vesicles, release them at synapses, and pump them back into cells. Energy deficits compromise every step of neurotransmitter signaling. Fixing energy production might correct multiple downstream problems simultaneously rather than adjusting one chemical messenger at a time.
Brain cells from psychiatric patients show developmental abnormalities affecting both neurons and glial support cells. Multiple metabolic pathways show defects. Synaptic structures form incorrectly. All these factors interact to determine overall illness risk. No single cause produces schizophrenia or bipolar disorder. Instead, numerous genetic and developmental factors combine, many affecting cellular energy systems.
Dimensional Thinking Replaces Category Boxes
Dr. Cohen advocates abandoning diagnostic categories like schizophrenia in favor of dimensional approaches that describe symptom patterns. His first psychiatric patient received a diagnosis of schizoaffective disorder, a label that bothered him even as a medical student. Categories feel clean and definite, but they don’t match biological reality or clinical presentation.
Current diagnostic systems (DSM and ICD) rely on expert consensus rather than evidence. They perpetuate century-old models that place people into rigid boxes. Patients with psychotic disorders vary enormously in their symptoms, course of illness, and treatment response. Forcing them into categories like schizophrenia or bipolar disorder loses important individual details.
Dimensional models describe patients along continuums of positive symptoms (hallucinations, delusions), negative symptoms (social withdrawal, flat affect), mood dysregulation, and cognitive impairment. Clinicians already evaluate patients this way in practice. Recording these dimensions provides richer, more accurate descriptions than categorical labels. Research cohorts become more homogeneous when grouped by symptom dimensions rather than diagnostic categories.
Terms like schizophrenia carry stigma and outdated assumptions. Dr. Cohen argues for replacing such labels with scientifically accurate alternatives. Evidence-based dimensional systems would improve diagnostic precision, reduce prejudice, and better guide treatment decisions across diverse healthcare settings worldwide.
Prevention Becomes Possible
Psychotic disorders rarely appear before adolescence. Alzheimer’s disease typically emerges in older. These delays create windows for preventive intervention. If scientists can identify metabolic abnormalities present from birth or early development, they might correct problems before symptoms ever manifest.
Brain cells from patients show inherent defects that exist independent of disease duration or medication exposure. Some of these abnormalities may prove modifiable through targeted treatments. Boosting mitochondrial function, correcting specific metabolic pathways, or supporting cellular energy production could reduce illness risk in vulnerable individuals.
Dr. Cohen’s current research focuses on identifying mechanisms that determine substantial portions of illness risk. His team combines genomic analysis, brain imaging, and cellular modeling to create complete pictures of how psychiatric disorders develop. Multiple research groups worldwide pursue similar goals, accelerated by increasingly accessible stem cell technology and genomic tools.
Prevention represents a shift from managing symptoms after they appear to protecting brain health before illness strikes. Families with strong histories of schizophrenia or bipolar disorder could benefit from screening and early intervention. Biomarkers based on cellular metabolism might identify at-risk individuals years before symptoms begin. Targeted treatments could modify disease trajectory or prevent illness entirely.
Leadership Beyond the Laboratory
Dr. Cohen’s impact extends past research discoveries. As McLean Hospital President and Psychiatrist-in-Chief from 1997 to 2005, he rescued the institution from financial crisis. Partners HealthCare (now Mass General Brigham) considered closing McLean and relocating its research elsewhere. Dr. Cohen presented the case for maintaining the hospital and was offered the presidency.
He guided McLean to financial health by cutting bureaucracy, supporting frontline staff, and establishing over 30 new clinical and research programs. Research funding doubled. Patient care reached record levels. Educational training expanded. Scientific rigor combined with compassionate leadership transformed a struggling hospital into a thriving center of excellence.
Waverley Place, a peer-run center supporting people with mental illness living in communities, exemplifies his values-driven approach. Programs don’t need to generate revenue if they serve the institutional mission and societal needs. Dr. Cohen balanced financial sustainability with commitment to helping vulnerable populations.
His leadership philosophy emphasizes supporting people doing direct work rather than building administrative hierarchies. Reducing barriers lets talented staff accomplish more. Trusting frontline workers to make good decisions produces better outcomes than top-down micromanagement. These principles apply to healthcare institutions worldwide struggling with resource constraints while maintaining quality care.
Personal Journey Shapes Scientific Vision
Anxiety and shyness limited some of Dr. Cohen’s professional opportunities. He speaks candidly about these challenges, offering rare vulnerability from a prominent researcher. Success comes through perseverance and dedication rather than the absence of difficulty. Young scientists facing similar obstacles can find encouragement in his honesty.
His father modeled medical dedication as a beloved internist who saw patients early each morning, maintained office practice, and returned to check on hospitalized patients each evening. Family dinners happened at 7 pm every night. Evenings included reading together, listening to music, and studying. Weekends brought trips, theater, concerts, and golf. The balance between intense work and family connection shaped Dr. Cohen’s approach to career and life.
Marriage of over 55 years provides steady support throughout his career. Family remains central to his identity beyond professional achievements. Great science often grows from human connections extending far beyond laboratory walls. Personal experiences, intellectual curiosity, meaningful relationships, and commitment to helping others all contributed to his scientific trajectory.
Directions for Mental Health Treatment
Dr. Cohen expresses optimism about psychiatric research while recognizing societal challenges ahead. Technologies in cellular reprogramming and genomic analysis transform what scientists can discover about mental illness. Methods once available only at elite institutions now spread worldwide through international initiatives and open-access publishing.
He advocates for supporting unconventional ideas and new investigators. Funding agencies too often restrict support to predictable, incremental research. Breakthroughs require risk-taking and creativity. Science advances fastest when innovation can flourish regardless of geographic location or institutional prestige.
Genomic Press and similar organizations promote truly inclusive, collaborative discovery by removing financial barriers to research publication and access. Important findings reach global audiences without paywalls. Scientists worldwide can build on each other’s work without restriction. Open science accelerates progress toward effective treatments for conditions affecting millions.
Psychiatric research stands at a turning point. Energy metabolism discoveries, stem cell technologies, dimensional diagnostic models, and prevention strategies together promise a new era. Mental healthcare could shift from symptom management after illness appears to protecting brain health before problems start. Precision treatments tailored to individual metabolic profiles might replace one-size-fits-all approaches. These changes won’t happen overnight, but foundations now exist for true transformation.
My Personal RX on Protecting Your Brain’s Energy Systems
Brain health depends on cellular energy production more than we ever understood. Dr. Cohen’s research shows mental illness often begins with mitochondrial dysfunction and metabolic defects present from birth or early development. While we wait for targeted therapies based on these discoveries, everyone can support their brain’s power supply through daily choices. Mitochondria need specific nutrients to function properly. Genetic vulnerabilities increase risk, but environmental factors influence whether illness actually develops. Supporting mitochondrial function might reduce risk or delay symptom onset in vulnerable individuals. Nobody can prevent all mental illness, but optimizing cellular energy production gives your brain its best chance at health.
- Support Your Gut-Brain Metabolism: Gut health affects brain energy production through inflammation and nutrient absorption. MindBiotic provides probiotics, prebiotics, and Ashwagandha KSM 66 to reduce systemic inflammation that impairs mitochondrial function and brain cell metabolism.
- Eat for Mitochondrial Health: Brain cells need specific nutrients for energy production. Mindful Meals cookbook offers 100+ doctor-approved recipes rich in B vitamins, CoQ10, magnesium, and antioxidants that support cellular power plants and protect against oxidative damage.
- Exercise Boosts Cellular Energy: Physical activity stimulates mitochondrial biogenesis, creating new power plants inside cells. Aim for 150 minutes of moderate exercise weekly to increase brain cell energy capacity.
- Stabilize Blood Sugar Levels: High blood sugar damages mitochondria and reduces energy production efficiency. Eat balanced meals with protein, healthy fats, and fiber to maintain steady glucose levels throughout the day.
- Get Quality Sleep Every Night: Deep sleep allows brain cells to repair mitochondrial damage and clear metabolic waste. Poor sleep accelerates mitochondrial dysfunction and increases psychiatric disorder risk.
- Manage Chronic Stress Daily: Stress hormones increase oxidative stress that damages mitochondrial membranes. Practice meditation, deep breathing, or activities that lower cortisol to protect cellular energy systems.
- Consider CoQ10 Supplementation: Coenzyme Q10 supports mitochondrial electron transport chains that generate ATP. Talk with your doctor about supplementation, especially if you have a family history of psychiatric disorders.
- Avoid Mitochondrial Toxins: Excessive alcohol, certain medications, and environmental toxins damage mitochondria. Minimize exposure to substances that impair cellular energy production.
Source:
Cohen, B. M. (2025). Bruce M. Cohen: An eclectic life and a multidisciplinary approach to the complex determinants and diverse presentations of psychiatric disorders. Genomic Psychiatry :, 1–5. https://doi.org/10.61373/gp025k.0104
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