Researchers in Greece studied 163 people with schizophrenia to understand why some patients respond better to antipsychotic medications than others. They looked at five different genetic variations that affect how the body processes certain vitamins and chemicals in the brain. The study found that specific genetic differences, especially one called MTR, combined with vitamin B12 levels, may predict how well antipsychotic drugs will work for reducing hallucinations and delusions. This research suggests that doctors might one day use genetic testing to personalize treatment plans for people with psychotic disorders, though more research is needed to confirm these findings.

The Quick Take

  • What they studied: Whether five specific genetic variations affect how well antipsychotic medications work and how severe symptoms are at the start of treatment
  • Who participated: 163 people in Greece diagnosed with schizophrenia or other psychotic disorders, including some who had taken antipsychotics before and some who hadn’t
  • Key finding: A genetic variation called MTR rs1805087 was linked to better improvement in hallucinations and delusions, especially when patients had healthy vitamin B12 levels. Another variation (COMT rs4680) was connected to more severe negative symptoms initially but better improvement in depression.
  • What it means for you: In the future, genetic testing combined with vitamin B12 checks might help doctors predict which antipsychotic treatment will work best for individual patients. However, this is early-stage research and shouldn’t change current treatment decisions without talking to your doctor.

The Research Details

This was a prospective observational study, meaning researchers followed patients forward in time and observed what happened naturally without controlling the treatment. They recruited 163 patients with schizophrenia or related psychotic disorders and tested their DNA for five specific genetic variations. These genetic variations affect how the body handles B vitamins (folate and B12) and certain brain chemicals. Researchers measured patients’ symptoms at the beginning using standard rating scales, then checked again after four weeks of treatment with antipsychotic medications that the patients’ doctors had already prescribed.

The genetic variations studied were in genes that control one-carbon metabolism (the body’s process for managing B vitamins and creating important molecules) and catecholamine degradation (how the brain breaks down dopamine and similar chemicals). The researchers compared whether different versions of these genes were associated with how severe symptoms were initially and how much improvement patients showed after four weeks.

Understanding which genetic variations predict treatment response is important because antipsychotic medications work very differently from person to person. Some patients improve dramatically while others see little benefit, and side effects vary widely. If doctors could predict treatment response using genetic testing, they could choose the most effective medication faster, reducing the time patients suffer with untreated symptoms and avoiding unnecessary side effects from ineffective drugs.

This study has moderate reliability. Strengths include prospective design (following patients forward in time), use of standardized symptom rating scales, and focus on a real-world clinical setting. Limitations include the relatively small sample size (163 patients), which means findings may not apply to larger populations. The study also didn’t collect information about patients’ diets or B vitamin intake, which could affect results. Additionally, some patients had previously taken antipsychotics, which could influence how they respond to new treatment. The findings are described as ’nominal’ for some genetic variations, meaning they’re suggestive but not statistically strong.

What the Results Show

The MTR rs1805087 genetic variation showed the strongest association with treatment response. Patients who carried certain versions of this gene showed greater improvement in positive symptoms (hallucinations and delusions) over four weeks, particularly when they had adequate vitamin B12 levels. This suggests that the combination of this genetic variation and sufficient B12 may be important for predicting how well antipsychotics will work.

The COMT rs4680 genetic variation had two interesting effects. Patients with a specific version of this gene showed more severe negative symptoms (like reduced motivation and emotional expression) at the beginning of treatment. However, these same patients showed better improvement in depression symptoms after four weeks. This suggests the gene affects different aspects of mental health in different ways.

The AS3MT genetic variation showed a weaker association with improvement in positive symptoms, but only in patients with lower vitamin B12 levels. This is the opposite pattern from MTR, suggesting that B12 levels may be a key factor in how these genetic variations affect treatment response.

Two other genetic variations studied (MTHFR and MTRR) showed no significant associations with treatment response or baseline symptoms in this group of patients.

The research highlights the importance of vitamin B12 levels as a factor that interacts with genetic variations to influence treatment outcomes. Patients with higher B12 levels showed different treatment responses based on their MTR genetic variation, while those with lower B12 levels showed different patterns with the AS3MT variation. This suggests that B12 status should be considered alongside genetic testing when predicting antipsychotic response. The study also found that depression symptoms improved more in patients with the COMT rs4680 variation, which is a positive finding for this subgroup.

This research builds on previous studies suggesting that genes involved in B vitamin metabolism and brain chemical processing affect antipsychotic response. The finding that MTR variation predicts treatment response is relatively novel and adds to growing evidence that one-carbon metabolism genes play a role in psychotic disorder treatment. The COMT findings align with previous research showing this gene affects dopamine levels and psychiatric symptoms. However, the specific combinations of genetic variations and B12 levels identified here need confirmation in larger studies before being used clinically.

The study has several important limitations. The sample size of 163 patients is relatively small, which means the findings may not apply to larger, more diverse populations. The researchers didn’t collect detailed information about patients’ diets, B vitamin intake, or homocysteine levels (a marker of B vitamin metabolism), which could have affected results. Some patients had previously taken antipsychotics, which could influence how they respond to new treatment. The study only followed patients for four weeks, so it’s unclear whether these genetic associations predict longer-term treatment response. Finally, the study was conducted in Greece, so results may not apply equally to other ethnic groups with different genetic backgrounds.

The Bottom Line

Current recommendation (moderate confidence): Continue using standard clinical approaches to antipsychotic treatment selection. Future potential (low confidence): Genetic testing combined with vitamin B12 level checks may eventually help personalize antipsychotic selection, but this needs confirmation in larger studies before routine clinical use. If you have schizophrenia or a related condition, discuss with your psychiatrist whether genetic testing might be appropriate for your situation, but don’t expect it to be standard practice yet.

People with schizophrenia or related psychotic disorders should be aware of this research, as it may eventually improve how their treatment is selected. Family members and caregivers may also find this information helpful for understanding treatment decisions. Psychiatrists and mental health professionals should monitor this research area as it develops. People without psychotic disorders don’t need to apply these findings to themselves.

If genetic testing becomes available for antipsychotic selection, benefits would likely appear within 4-8 weeks of starting the appropriate medication, based on this study’s timeframe. However, full symptom improvement typically takes 8-12 weeks or longer. This research is still in early stages, so it may take 3-5 years before genetic testing becomes a standard part of antipsychotic treatment planning.

Want to Apply This Research?

  • Track positive symptoms (hallucinations, delusions, disorganized thinking) and negative symptoms (motivation, emotional expression, social engagement) weekly using a simple 1-10 scale. Also note any dietary changes or B vitamin supplementation, as these may interact with genetic factors affecting treatment response.
  • If your doctor mentions genetic testing for antipsychotic response, ensure you also get your vitamin B12 levels checked. If you’re deficient, work with your doctor on supplementation. Keep detailed records of which medications you’ve tried and your response to each, as this information becomes more valuable if genetic testing is used to guide future treatment.
  • Use the app to track symptom changes weekly for at least 8-12 weeks after starting or changing antipsychotic medication. Create a timeline showing which medications you’ve used and your response to each. If genetic testing becomes available, save your results in the app and correlate them with your symptom tracking data to see if the predictions match your actual experience.

This research is preliminary and should not change current antipsychotic treatment decisions. Antipsychotic medication selection should always be made in consultation with a qualified psychiatrist who knows your complete medical history. Genetic testing for antipsychotic response is not yet standard clinical practice and should only be considered under medical supervision. If you have schizophrenia or a related psychotic disorder, continue taking prescribed medications as directed and discuss any treatment concerns with your healthcare provider. This article is for educational purposes only and is not a substitute for professional medical advice.