Vjekoslav Peitl1,2, Mario Štefanović3, Ivona Orlović4, Jelena Culej3, Ana Rendulić4, Krunoslav Matešić5, Dalibor Karlović4,5. 1. Department of Psychiatry, University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia. vjekoslav.peitl@gmail.com. 2. Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia. vjekoslav.peitl@gmail.com. 3. Clinical Department of Chemistry, University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia. 4. Department of Psychiatry, University Hospital Centre Sestre Milosrdnice, Zagreb, Croatia. 5. Catholic University of Croatia, Ilica 242, 10000, Zagreb, Croatia.
Abstract
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.
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.
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