Table 3. Pharmacogenetic studies showing the effect of catechol-O-methyltransferase genotype polymorphism in neurological and psychiatric disorders.

COMT: catechol-O-methyltransferase; Met: Methionine; MTHFR: methylenetetrahydrofolate reductase; A allele: adenine allele; CA: cytosine-adenine; MLIC: motor levodopa-induced complications; PD: Parkinson's disease; AG: adenine-guanine; GG: guanine-guanine; AA: adenine-adenine; LID: levodopa-induced dyskinesia; BDNF: brain-derived neurotrophic factor; DAT: dopamine transporter; Val: Valine; ECT: electroconvulsive therapy; tDCS: transcranial direct current stimulation; MMT: methadone maintenance treatment; TC: thymine-cytosine; CC: cytosine-cytosine

Author	Year of publication	Type of study	No. of subjects	Purpose of study	Results /conclusion
Peitl V et al. [31]	2021	Observational	98	To study how the long-acting aripiprazole influences cognitive functions in recent-onset schizophrenia.	COMT Met/Met genotype and COMT interaction with methylenetetrahydrofolate reductase (MTHFR) gene were found to have a positive association with attention and executive functioning.
Nikolac Perkovic M et al. [32]	2020	Observational	521	To study the association between catechol-O-methyltransferase (COMT) rs4680 and rs4818 haplotype with treatment response to olanzapine in patients with schizophrenia.	A significant therapeutic response to olanzapine was found in schizophrenia patients with the COMT rs4680 A allele and rs4680-rs4818 C-A haplotype.
Michałowska M et al. [33]	2020	Observational	136	To determine the association of gene polymorphisms with MLIC in Parkinson’s Disease (PD).	A positive association was found between a combination of AG BDNF, AG DAT, and GG COMT genotypes with MLIC.
Dos Santos EUD et al. [34]	2020	Observational	220	To study the impact of variants in several genes on the development of levodopa-induced dyskinesia (LID) in patients with idiopathic PD.	COMT LL genotype was seen to increase the chances of developing LID.
Zhao C et al. [35]	2020	Observational	150	To investigate the association of COMT genotype variants with variability in response to levodopa therapy in PD patients.	Single nucleotide polymorphisms other than rs4680 were found to have a possible association with variation in the daily dose of levodopa as well as susceptibility to the occurrence of dyskinesia after levodopa therapy.
Tang Z et al. [36]	2020	Meta-analysis	2845	To study the association between COMT gene Val108/158Met and antidepressive treatment response.	COMT rs4680 variant was found to be significantly associated with antidepressive treatment. Patients with the GG or AG + GG variants responded better to ECT than patients with AA genotype.
Brunoni AR et al. [37]	2020	Randomized control trial	195	To investigate whether neuroplasticity-associated SNPs like COMT gene and other gene variants affect the efficacy of tDCS or escitalopram therapy in major depression.	The results indicated non-significant dose-dependent effects of the Met allele and lower tDCS vs. placebo effects.
McClintock SM et al. [38]	2020	Randomized control trial	130	To assess the neurocognitive effects of transcranial direct current stimulation (tDCS) in unipolar and bipolar depression.	COMT and BDNF genotype polymorphisms were determined as potential moderators of neurocognitive effects. COMT rs4680 variant was found to affect verbal fluency outcomes.
Duan L et al. [39]	2020	Observational	820	To study the association of COMT gene polymorphisms with response to MMT among opioid-dependent patients.	Patients with the TC or CC genotypes of the rs933271 variant had a higher chance of responding to MMT.