Long acting aripiprazole influences cognitive functions in recent onset schizophrenia.
RATIONALE
Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia.


OBJECTIVES
This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia.


METHODS
This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods.


RESULTS
Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (p<0.001) and subscale scores as well as cognitive parameters of delayed recall (p<0.03), attention (p<0.01), and executive functions in the form of less perseverations (p<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (p<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (p<0.01). Additionally, we also established a positive association between the COMT - MTHFR interaction and attention (p<0.02), as well as perseveration item belonging to executive functions (p<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores.


CONCLUSIONS
Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT's biomarker potential in terms of cognition in schizophrenia.
['Peitl|Vjekoslav|V|http://orcid.org/0000-0003-4163-6411', 'Štefanović|Mario|M|', 'Orlović|Ivona|I|', 'Culej|Jelena|J|', 'Rendulić|Ana|A|', 'Matešić|Krunoslav|K|', 'Karlović|Dalibor|D|']
D000293:Adolescent D000328:Adult D000483:Alleles D000068180:Aripiprazole D001288:Attention D002394:Catechol O-Methyltransferase D003071:Cognition D056344:Executive Function D005260:Female D005838:Genotype D006801:Humans D008297:Male D042965:Methylenetetrahydrofolate Reductase (NADPH2) D008875:Middle Aged D011110:Polymorphism, Genetic D012559:Schizophrenia D055815:Young Adult
Aripiprazole Cognition Schizophrenia Polymorphism, Genetic