Association between Insertion-Deletion Polymorphism of the Angiotensin-Converting Enzyme Gene and Treatment Response to Antipsychotic Medications: A Study of Antipsychotic-Naïve First-Episode Psychosis Patients and Nonadherent Chronic Psychosis Patients

Abstract

We investigated whether a functional insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE) influenced antipsychotic treatment. At baseline, and after 8 weeks of treatment with various antipsychotic medications, we assessed patients’ Positive and Negative Syndrome Scale (PANSS) scores, PANSS factors, and metabolic-syndrome-related parameters (fasting plasma lipid and glucose levels, and body mass index). A total of 186 antipsychotic-naïve first-episode psychosis patients or nonadherent chronic psychosis individuals (99 males and 87 females) were genotyped by polymerase chain reaction analysis. The ACE-I/D polymorphism was significantly associated with changes in PANSS psychopathology only (p < 0.05). Compared to ACE-II homozygous males, ACE-DD homozygous and ACE-ID heterozygous males manifested significantly greater decreases in PANSS positive score, PANSS excitement factor, and PANSS cognitive factor. ACE-DD homozygous females manifested higher decreases in PANSS depression factor compared to ACE-II homozygous and ACE-ID heterozygous females. The polymorphism’s effect size was estimated as moderate to strong, while its contribution to the PANSS psychopathology ranged from ~5.4 to 8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicate that ACE-I/D polymorphism had a statistically significant but weak gender-specific impact on psychopathology data, and showed no association between ACE-I/D polymorphism and metabolic-syndrome-related parameters.

ACE Insertion/Deletion Gene Polymorphisms with DM Type II and Metabolic Syndrome among Sample of Jordanians

“…Abouelfath et al [44,45] highlighted the etiological role of ACE I/D polymorphisms in MetS and its components progress, additionally, DD polymorphism and D allele were shown to be protective against MetS development among adult Moroccan population and in Chilean subjects. In an Indonesian study, the frequent polymorphism among patients with DM type II was the DD variant and no association was found between ACE I/D polymorphisms and MetS & its related parameters [46,47]. This discrepancy in the results regarding the distribution frequency of ACE I/D gene polymorphisms, alleles and their participation in the development in DM type II, MetS and its related components could be attributed the ethnic variations among different population.…”

Angiotensin‐converting enzymes as druggable features of psychiatric and neurodegenerative disorders

“…For antipsychotic‐naïve first episode psychosis patients, an increase in ACE activity was also seen after 2 months of treatment with atypical antipsychotic risperidone compared to pre‐treatment, but only for the D/D genotype subgroup (Nani, Dal Mas, et al, 2020). In such drug‐naïve first episode psychosis patients, the D/D genotype was associated with reduced psychopathology symptoms, as assessed using the Positive and Negative Syndrome Scale (PANSS) scores, with patients with I/D or D/D also showing a greater reduction in a range of symptoms following antipsychotic medication (Nadalin et al, 2022). Conversely, other studies have also found evidence that carrying at least one D‐allele provides protection against SCZ, either generally (Crescenti et al, 2009) or specifically in women (Mazaheri & Saadat, 2015), while this polymorphism was not associated with SCZ in a Croatian population, but with a significant impact of the polymorphism on the clinical expression of the illness (Nadalin et al, 2012).…”