Years of research have shown that depression is a complex condition with no single cause. Instead, it emerges from a dynamic mix of biological, psychological, and environmental influences. In many cases, several factors intertwine to trigger its onset. For instance, a person with a genetic vulnerability to depression might not experience symptoms until they face a significant life event, like the loss of a loved one or prolonged stress.

Understanding the diverse causes of depression helps inform treatment. At Spearhead Health, we take a personalized, whole-person approach that includes therapy, medication (if appropriate), lifestyle support, and compassionate care so you can heal from the inside out. Here’s what current science tells us about the genetic link to depression.

There Is No One “Depression Gene”

Despite early hopes of finding a single gene responsible for depression, research has shown that depression is polygenic, meaning it involves multiple genes, each contributing a small amount to overall risk. These genes may influence how your brain regulates mood, responds to stress, and processes emotions.

For example, one of the most studied genes in depression research is 5-HTTLPR, which affects how serotonin is transported in the brain. Some early studies suggested that people with a certain variation of this gene were more likely to develop depression after stressful life events. However, later research has produced mixed results.

While 5-HTTLPR may play a role, it’s not the sole factor, and it doesn’t act alone. Depression is far too complex to be pinned on a single genetic variant. In fact, one large-scale study published in Nature Genetics found more than 100 gene variants associated with depression. However, none of them alone cause the disorder; they only slightly increase the risk.

Genes Interact with the Environment

It’s also important to know that genes have the potential to interact with the environment. This means that even if you inherit genes associated with depression, that does not guarantee you’ll develop it. Mental health is shaped by both genetics (nature) and environmental factors (nurture).

Life experiences, such as childhood trauma, chronic stress, substance use, or major loss, can “switch on” certain genetic tendencies. This is known as gene-environment interaction or epigenetics, where environmental influences affect how genes are expressed.

What About an Imbalance of Brain Chemicals?

For many years, depression was widely believed to be caused mainly by a chemical imbalance, especially a lack of serotonin, a neurotransmitter involved in mood regulation. This led to the popularity of SSRIs (Selective Serotonin Reuptake Inhibitors) like Prozac and Zoloft, which increase serotonin in the brain.

However, current research shows that depression is much more complex—and it’s much more than just chemistry. Multiple neurotransmitters are involved in depression, including dopamine, norepinephrine, and GABA. Therefore, simply increasing serotonin levels isn’t enough to treat depression.

Additionally, brain circuitry, such as the function and structure of the prefrontal cortex, amygdala, and hippocampus, can also influence depression. Inflammation and immune system activity can also increase depressive symptoms in some people.

What This Means for Treatment

Understanding that depression is influenced by many small genetic factors plus life experiences helps shift the focus from blame to healing. It also supports the move toward personalized mental health care, where treatment is tailored to each person’s biology, history, and environment.

At Spearhead Health, we explore your full mental health profile, including your genetic background, personal challenges, and emotional needs, to develop an individualized care plan. Whether through therapy, medication, nutrition, or lifestyle changes, our goal is to support long-term recovery and resilience.

Depression Treatment: You’re More Than Your Genes

While genetics may increase the risk for depression, they don’t define your destiny. Mental health is dynamic, and with the right support, healing is possible for anyone, regardless of family history or genetic makeup. If you or someone you love is struggling with depression, contact Spearhead Health at (310) 561-1704 to learn how we can support your journey toward wellness and recovery.