Gene ancestry linked to increased depression risk in Central Americans, Amish and Ashkenazi Jews

By LUCIENNE RONCO, PhD, Guest writer
Ver en español Ancestro Genético Vinculado a un Mayor Riesgo de Depresión en Centroamericanos, Amish y Judíos Ashkenazíes

Genetic research suggests that our ancestry may play a significant role in determining the risk of developing depression, with specific gene variations tied to mental health vulnerabilities in certain populations.

A gene known as MTHFR (methylenetetrahydrofolate reductase) has been identified as a key factor affecting brain chemistry. Certain variants of this gene, passed down through generations, may impair the body’s ability to produce essential brain chemicals — increasing the risk of depression, anxiety, and cognitive issues.

Individuals with ancestral ties to indigenous peoples of the Americas — including populations in North and Central America such as Mexico and Guatemala — as well as specific European groups such as the Amish and Ashkenazi Jews may be more likely to inherit these gene variants.

The issue lies in the function of the MTHFR protein, which helps convert folate (a form of vitamin B) into L-methylfolate (LMF). LMF is necessary for producing neurotransmitters such as serotonin and dopamine — key chemicals that regulate mood, focus and energy. When MTHFR activity is reduced due to genetic variants, the resulting drop in LMT can lead to a chemical imbalance, contributing to mental health disorders.

Low serotonin levels are strongly associated with depression. If the body can’t efficiently produce L-methylfolate, this could impair serotonin production and regulation.

Depression linked to MTHFR gene variants can present differently throughout life. In children, it might manifest as irritability or aggression. In teens, it can appear as withdrawal or low mood. In adults, it often affects energy, appetite and overall emotional well-being.

Treatments exist

Importantly, this form of depression may not respond to typical antidepressant medications. However, there is promising news: A simple genetic test can identify MTHFR gene activity. If a person is found to have the lower-activity version, they may benefit from taking L-methylfolate supplements, which directly supports serotonin and dopamine production even if a person has a low-activity variant of MTHFR.

Not everyone with an MTHFR variant will experience depression. The gene’s role in mental health is complex, but in cases where depression is resistant to treatment, testing for MTHFR may provide new answers and new hope.

As awareness grows, healthcare providers are encouraging patients with treatment-resistant depression to speak with their doctors about the potential role of genetics — and the power of personalized medicine.

Lucienne Ronco, PhD, is a scientist with decades of experience in translational science, drug discovery, biotechnology and pharmaceuticals. She earned her doctorate in biological chemistry at UCLA and did a postdoctoral fellowship in viral oncology and inflammation at Harvard Medical School. She currently serves as chief science officer at the FSHD Society. See her LinkedIn profile for more information.