Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 26 September 2022 / Approved: 28 September 2022 / Online: 28 September 2022 (03:12:20 CEST)

A peer-reviewed article of this Preprint also exists.

Nadalin, S.; Dević Pavlić, S.; Peitl, V.; Karlović, D.; Zatković, L.; Ristić, S.; Buretić-Tomljanović, A.; Jakovac, H. 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. Int. J. Mol. Sci. 2022, 23, 12180. Nadalin, S.; Dević Pavlić, S.; Peitl, V.; Karlović, D.; Zatković, L.; Ristić, S.; Buretić-Tomljanović, A.; Jakovac, H. 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. Int. J. Mol. Sci. 2022, 23, 12180.

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 ~5.4–8.7%, with the lowest contribution observed for PANSS positive score changes and the highest for PANSS depressive factor changes. Our results indicated 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.

Keywords

angiotensin-converting enzyme (ACE); antipsychotic medication; polymorphism, insertion/deletion; treatment response

Subject

Medicine and Pharmacology, Psychiatry and Mental Health

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