Several observational studies have reported the relationship between antihypertensive medication and psychiatric disorders. The dependence appears to be dependent on the drug class, but no strong evidence confirms this assumption. This study aims to estimate the effect of different antihypertensive drug classes on psychiatric disorders, like schizophrenia, major depressive disorder, and bipolar disorder.

 This two-sample Mendelian randomization study included a total of 40,675 patients with schizophrenia and 64,643 controls, 135, 458 patients with major depressive disorder and 344,901 controls, and 20,352 patients with bipolar disorder and 31,358 controls. The expression levels of antihypertensive drug target genes were considered, and the primary outcome of the study was the risk of psychiatric disorders.

 The findings suggested that a 1-SD lower expression of the angiotensin-converting enzyme (ACE) gene was in the blood resulted in lower systolic blood pressure of 4.0 mm Hg; however, it increased the risk of schizophrenia (odds ratio 1.75). The findings further indicated a concordant direction of association between ACE expression in the prefrontal cortex and ACE protein levels in the cerebral spinal fluids.  However, no associations were found between genetically estimated SBP and schizophrenia risk.

 The research concluded that there was an adverse association of lower ACE protein levels and messenger RNA with the risk of schizophrenia.