Biological Lens of Mental Health

In an earlier post, we discussed five lenses for thinking about mental health: biological, psychological, social, consumer, and cultural. These lenses are just different perspectives, different ways of looking at the same topic. These perspectives all feed into our understanding of this thing called "mental health."

The biological model starts with the simple premise that the brain is a physical organ, and like any physical organ, it can be affected by genetics, chemistry, injury, illness, and development. This was not always the dominant way of thinking about mental health. For most of Western history, mental suffering was understood through moral or religious frames. After all, even the word “psyche”, from which we get psychology and psychiatry, often means “soul.” Any deviation from accepted norms of behavior and functioning was a spiritual crisis, a failure of character, evidence of sin or divine punishment. Any treatment or care for these conditions, such as it was, happened in churches, families, and eventually asylums.

It wasn’t until the early 20th century that we begin to see real changes in how mental health was conceptualized. The field of psychology really began to develop in the late 1800s, and erupted after the world wars. Psychology was being studied across broad domains, and many different approaches were being explored. Psychoanalysis, developed by Freud and his successors, took a prominent role in clinical and cultural settings when discussing mental health. They pushed out the religious and moral framing and offered a new explanatory language for mental health, focusing on unconscious conflict, early developmental experience, repression, and the dynamics of the inner life. The problem was still fundamentally one of the “psyche”, located in the mind and its history. The brain, as a physical organ, barely entered the conversation.

That began to change in the late 1950s. Psychiatric medications were showing positive treatment effects on symptoms for the first time. Before this, psychiatric interventions fell largely into attempts at sedation and control, whether through lobotomies, electroconvulsive therapy, or sedatives. Chlorpromazine reduced psychotic symptoms in ways nothing before it had, and the first antidepressants were showing real effects on severe depression.

The American Psychiatric Association followed this shift in its own Diagnostic and Statistical Manual (DSM). It is worth noting that while the DSM is used in medical and clinical settings, it is as much a cultural document as a scientific one. The standards reflected in it are shaped by the culture, politics, and institutions influencing its production. A clear example is how homosexuality was classified as a mental disorder until advocacy and education led to its removal in 1973 (if you want the full story, Alix Spiegel told it beautifully in This American Life episode 204, "81 Words”). In 1980, the DSM-III was published and shifted away from a Freudian, psychoanalytic framework toward one focused on observable symptoms. This made psychiatric diagnosis more compatible with pharmaceutical research, insurance reimbursement, and the broader medical establishment. DSM-III opened the door for the biological model to become psychiatry's dominant framework.

The 1990s accelerated everything. Fluoxetine (Prozac) had arrived in 1988, and a broader class of antidepressants called SSRIs (selective serotonin reuptake inhibitors) followed. These were working for most patients, and they were better tolerated and safer to use than earlier antidepressants. They were also heavily marketed directly to consumers in the United States. Marketing has to tell a complex story quickly, while persuading people to take action. The marketing of these drugs honed in on the idea that depression and anxiety were caused by a chemical imbalance in the brain and that the medication corrected that imbalance.

The chemical imbalance explanation was simple and memorable. It aligned with cultural expectations; when there is a disease, you take a pill to cure it. This explanation became embedded in popular culture, and it even shaped the way that the scientific and medical communities discussed depression and depression treatment. Some prominent psychiatrists repeated it in public comments and clinical settings. The American Psychiatric Association told the public in its own materials that differences in certain brain chemicals may contribute to depression. Influential research papers and textbooks endorsed versions of the serotonin theory between 1990 and 2010.

The problem is that the science never supported the claim. Researchers Jonathan Leo and Jeffrey Lacasse, writing in the journal Society in 2008, documented how the chemical imbalance story spread through media and public discourse well beyond anything the research literature actually established. The major assumption of the theory is that there is a correct or normal level of serotonin, or other brain chemicals, that should be in “balance” or at correct levels. But, there isn't. Unlike blood glucose or thyroid hormones, we have no established baseline for brain serotonin, or dopamine, or other neurotransmitters and brain chemicals. The analogy to a chemical imbalance or deficiency, likening depression to something like anemia, has no real biological foundation. In 2022, Joanna Moncrieff and colleagues at University College London published a comprehensive umbrella review in Molecular Psychiatry examining decades of serotonin research across multiple areas of inquiry. They found no consistent evidence that people with depression have lower serotonin levels or reduced serotonin activity compared to people without depression. The entire framing around why psychiatric medicine works doesn’t hold up.

That doesn’t mean that antidepressants don’t work, though. For many people they are genuinely helpful. What the research suggests is that we may not have fully understood why they work. If we alter brain chemistry, people may feel better. But that doesn’t mean they had lower levels to begin with, or that the lower levels caused the depression. The medication addresses a symptom, but it doesn’t answer any questions about etiology.

Just because the chemical imbalance explanation is overly simple and incorrect, doesn’t mean that we rule out the biological influence on mental health. Our “psyche”, our “mind” as a process that produces thoughts and consciousness, is undoubtedly connected to our biological selves. It does not exist independently or outside our bodies. Research continuously supports the notion that things that are good for our brains and bodies, generally are good for our mental health. Wickham and colleagues (2020), studying sleep, physical activity, and diet in over a thousand young adults, found all three predicted mental health outcomes. They found that sleep quality was the strongest predictor of depressive symptoms and overall well-being.

Genetics research has also established that heritability plays a role in mental health conditions. Schizophrenia, bipolar disorder, and major depression all run in families, and twin studies have estimated heritability for schizophrenia as high as 80% (International Schizophrenia Consortium, 2009). But finding specific genes for mental health issues isn’t a simple task, and may not even be the right approach. Most conditions involve what researchers call polygenic risk, that hundreds or thousands of genetic variants each contribute a small amount, instead of one or two genes that cause large effects. As the saying goes “genes load the gun, the environment pulls the trigger.” (Bray, 1998). Environment, experience, and circumstance matter enormously in whether any genetic risks ever become actualized.

That last point connects to one of the more interesting developments in biological research called epigenetics. Epigenetics studies how environmental factors (stress, trauma, poverty, early childhood experiences) can alter how genes are expressed without changing the underlying DNA sequence itself. A person can carry a genetic predisposition and never develop a condition, depending on what they encounter in their life. Peedicayil (2023), reviewing the literature in Biomedicines, found that factors including poverty, migration, trauma, and prenatal stress all interact with the genome through epigenetic mechanisms to influence the development of psychiatric disorders. This research sits at the border of the biological and social lenses, which is part of what makes it significant. Two people can experience the same things, but may have genetic predispositions to how it is processed and expressed in their genes.

Neuroplasticity is another interesting aspect of the biological lens. Research is showing how the brain changes structurally over time in response to experiences, both good and bad. Chronic stress is associated with measurable changes in the hippocampus and prefrontal cortex, areas involved in memory, emotion regulation, and decision-making. Andrade (2011), writing in the Indian Journal of Psychiatry, summarizes that depression may be better understood as a disorder of brain structure and adaptation than as a state of chemical imbalance. Both antidepressant medications and psychotherapy have been found to produce measurable changes in brain structure, which raises interesting questions about mechanism that we will return to in later posts.

Inflammation is an area of active and growing inquiry. A number of studies have found elevated levels of inflammatory markers in people with depression, and some researchers are exploring whether immune system activity plays a role in the development of mood disorders. Roohi and colleagues (2021), reviewing the evidence in the Journal of Neuroinflammation, found associations between cytokine levels and depression, though the research is still working out questions of cause, effect, and which patients this applies to. This is promising but not settled science.

Where does the biological model stand today? It has gotten more sophisticated, and more humble, at the same time. The brain is physical, it is affected by genetics and environment and experience, and understanding its biology matters for understanding mental health. The stories that dominated public conversation for thirty years, the chemical imbalance, the serotonin deficiency, were a significant oversimplification. The research that replaced it is more open about what it doesn't know, and more open to the idea that biology and environment are not separate stories.

So, the biological lens is extremely important. From it we get medications that help people function, research that has reduced stigma, and a growing understanding of how the brain and body interact with our mental lives. The specific explanations we were handed in the 1990s turned out to be incomplete, partly because that is how science works, mostly because that is how marketing works. But medications are extremely helpful, even if we don’t fully understand why or through which mechanism. And the biological lens still has many interesting areas of research: why two people with similar neurobiology can have vastly different mental health outcomes, or why the therapeutic relationship produces measurable changes in brain structure, or how poverty and trauma get encoded through generations.

But biology doesn’t answer all our questions. Biology will never fully answer why meaning matters to recovery, why social connection predicts health outcomes as strongly as smoking or physical health factors, why the same trauma lands differently depending on culture and community, or why a person's sense of identity shapes what symptoms they develop and how they understand them. These are different types of questions, and they lead us to other lenses and perspectives.

Citations:

Andrade, C. (2011). Antidepressant treatment in unipolar depression: Neuroplasticity as a putative mechanism. Indian Journal of Psychiatry, 53(1), 80–83. https://pmc.ncbi.nlm.nih.gov/articles/PMC3025168/

Bray, M. S. (1998). Quoted in context of gene-environment interaction. [Note: the "genes load the gun" phrase is widely attributed but difficult to pin to a single citable source — Bray 1998 is one attribution but it circulates as a folk saying in the literature. We should either drop the attribution or I can search for the most defensible citation.]

International Schizophrenia Consortium. (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature, 460, 748–752. https://www.nature.com/articles/nature08185

Leo, J., & Lacasse, J. R. (2008). The media and the chemical imbalance theory of depression. Society, 45(1), 35–45.

Moncrieff, J., Cooper, R. E., Stockmann, T., Amendola, S., Hengartner, M. P., & Horowitz, M. A. (2022). The serotonin theory of depression: A systematic umbrella review of the evidence. Molecular Psychiatry. https://doi.org/10.1038/s41380-022-01661-0

Peedicayil, J. (2023). Epigenetic approaches to psychiatric disorders. Biomedicines, 11(4), 1143. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10136093/

Roohi, E., Jaafari, N., & Hashemian, F. (2021). On inflammatory hypothesis of depression: What is the role of IL-17? Journal of Neuroinflammation, 18, 45. https://link.springer.com/article/10.1186/s12974-021-02100-7

Wickham, S. R., Amarasekara, N. A., Bartonicek, A., & Conner, T. S. (2020). The big three health behaviors and mental health and well-being among young adults: A cross-sectional investigation of sleep, exercise, and diet. Frontiers in Psychology, 11, 579205. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758199/