The role of COMT polymorphism in modulation of prefrontal activity during verbal fluency in bipolar disorder.

OBJECTIVE: Verbal fluency (VF) impairment is a strong predictor of social functioning in bipolar disorder (BPD). The enzyme catechol-O- methyltransferase (COMT) has a critical role in cognitive responses by modulating dopaminergic activity in the prefrontal cortex (PFC). Here, we investigated the role of COMT polymorphism (i) in VF performance as well as (ii) in modulation of PFC activity during a VF-task in euthymic BPD patients. METHODS: 30 subjects with remitted BPD-I and 23 healthy controls (HCs) were genotyped for COMT Val158Met (rs4680) polymorphism and were compared in a VF-task. PFC activity was measured by 24-Channel Functional Near Infrared Spectroscopy. RESULTS: Bipolar subjects displayed lower VF performance than HCs. During the VF-task, BPD-group displayed higher activity than HCs in the Brocca's area, Premotor-cortex and supplementary motor area (SMA). In the index group, Val/Met polymorphism was associated with higher activity in the left- frontopolar and dorsolateral PFC (DLPFC) during the VF-task. LIMITATIONS: Antipsychotic use may have interfered with the results. CONCLUSIONS: Increased activity in the Brocca's area may represent compensation of low VF performance, whereas hyperactivity in premotor-cortex and SMA may be associated with increased behavioral intention and/or restlessness in BPD. Higher activity in left-frontopolar and DLPC among Val/Met individuals compared to Met-homozygotes may represent less effective prefrontal dopaminergic signaling in Val/Met individuals with BPD.

Investigation of the cortical activity during episodic future thinking in schizophrenia: A functional near-infrared spectroscopy study.

Episodic future thinking (EFT) refers to mental simulation of possible future events, a process that mostly depends on episodic memory (EM). EFT impairment in schizophrenia was proposed to disturb continuity in self-functioning. Schizophrenia patients are also impaired in EM as well as executive functions (EFs). In the present study, we aimed to clarify the relationship between EFT and memory functions in schizophrenia by assessing (a) whether a group of individuals with schizophrenia (schizophrenia group [SG]) who have relatively intact long-term memory functions differ from healthy controls (control group [CG]) in terms of EFT performance, and (b) whether such difference is biologically represented in terms of cortical activity. We also aimed to clarify the role of EFs in EFT in 3 task conditions: past remembering with a single cue (PR), future imagination with a single cue (FI-1C), and future imagination with 3 given cues (FI-3C). Cortical activity was monitored by functional near-infrared spectroscopy. Although the two groups showed a comparable performance in the PR, the SG performed worse than the CG in the two future-imagination conditions. In the CG, mental flexibility predicted EFT, and EM predicted PR. No such relationship was observed in the SG. In the CG only, activity was higher in the FI-1C than the PR in the middle and superior temporal cortices. In the SG, activity in the rostral prefrontal cortex (rPFC) was negatively correlated with performance in FI-3C. These results suggest that EFT is still observed but not associated with EFs in individuals with schizophrenia having relatively intact memory functions. Altered activity in the rPFC may be associated with EFT impairment in schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The impact of CYP2C19 polymorphisms on citalopram metabolism in patients with major depressive disorder.

WHAT IS KNOWN AND OBJECTIVE: Genetic variations in drug-metabolizing enzyme genes change drug pharmacokinetics and response. CYP2C19 is a clinically important enzyme that metabolizes citalopram (CIT). The objective of this study was to determine CYP2C19 genetic polymorphisms and to evaluate the impact of these polymorphisms on the metabolism of citalopram in a sample of the Turkish population. We also assessed *17 polymorphism in healthy subjects in this population. METHODS: The CYP2C19 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism method (209 healthy individuals and 50 patients for CIT metabolism), and the plasma concentrations of CIT and demethylcitalopram (DCIT) were quantified by high-performance liquid chromatography. RESULTS AND DISCUSSION: The CYP2C19*1 and *17 allele frequencies for the patient group and the healthy group were 71·0%, 18·0% and 81·1%, 18·9%, respectively. There was no significant difference between the two groups (P > 0·05). The mean plasma concentrations and the mean dose-corrected (C/D) plasma levels of DCIT were significantly higher in patients with the CYP2C19*1/*1 genotype compared to patients with CYP2C19*1/*2 and CYP2C19*2/*2 genotypes (P < 0·05). Furthermore, the mean metabolic ratio (MR, CIT/DCIT) was also significantly higher in the CYP2C19*1/*2 + CYP2C19*2/*2 genotypes (P < 0·05). On the other hand, plasma CIT, DCIT concentrations and M/R value in the CYP2C19*1/*1 genotypes were no different to those of the CYP2C19*1/*17 genotypes (P > 0·05). WHAT IS NEW AND CONCLUSION: Our data suggest that CYP2C19*17 polymorphism does not have a significant effect on CIT metabolism. In contrast CYP2C19*2 polymorphism has a prominent role and is likely to contribute to interindividual variability in CIT metabolism in vivo at therapeutic doses.

Proton MR spectroscopy: higher right anterior cingulate N-acetylaspartate/choline ratio in Asperger syndrome compared with healthy controls.

BACKGROUND AND PURPOSE: One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS: NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by (1)H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17-38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS: Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = -2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = -1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = -1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS: Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores.