Facial emotion recognition and its correlation with executive functions in bipolar I patients and healthy controls.

INTRODUCTION: The ability to recognize facial emotions is altered in patients with Bipolar Disorder (BD) during mood episodes and even in euthymia, while cognitive functioning is similarly impaired. This recognition is considered a fundamental skill for successful social interaction. However, it is unclear whether the ability to recognize facial emotions is correlated with the cognitive deficits observed in BD. OBJECTIVE: The objective of this study was to evaluate Facial Emotion Recognition (FER) and its correlation with executive function (EF) in BD I patients during mania, depression and euthymia compared to healthy controls. MATERIAL AND METHODS: A total of 110 patients with BD I, 18-40 years old were included (41 in manic episode; 31 in depressive episode and 38 euthymic). Patients were assessed for FER and EF (Wisconsin card sorting test - WCST), along with 96 healthy volunteers (18-40 years old) recruited from the University of São Paulo. RESULTS: The results showed that BD I patients had lower FER performance compared to controls on fear subtests, happiness, the surprise test, and FER total scores. Moreover, BD I manic patients showed poorer performance for EF compared to controls. Six out of the seven variables of the WCST correlated with FER in both healthy controls and BD euthymic subjects but not in BD patients during mood episodes. CONCLUSION: Cognitive deficits and difficulties recognizing facial emotions are present in all mood episodes in BD I patients, even during remission. Although FER is not considered a cognitive domain, these results suggest that, along with EF, it has a complementary function. Hence, further studies should investigate this issue in larger samples and verify whether these similarities also occur at a neurobiological level.

Gender effects of the COMT Val 158 Met genotype on verbal fluency in healthy adults.

Cognitive performance in healthy individuals is associated with gender differences in specific tests; a female advantage has been demonstrated in language tests, whereas a male advantage has been demonstrated in spatial relation examinations. The prefrontal cortex (PFC) mediates important cognitive domains and is influenced by dopamine (DA) activity. The single nucleotide polymorphism (SNP) rs4680 in the catechol­O­methyltransferase (COMT) gene results in an amino acid substitution from valine (Val) to methionine (Met). The Met allele has been demonstrated to decrease COMT enzyme activity and improve PFC cognitive function. COMT regulates DA activity in the PFC and exhibits gender effects. The aim of the present study was to investigate the gender­specific effects of the COMT genotype on cognition in healthy young adults. Seventy­six healthy subjects were genotyped for COMT rs4680 and submitted to an extensive range of neuropsychological tests assessing aspects of PFC function. The COMT Met allele influenced the performance of executive function. The results revealed gender effects of the COMT rs4680 Met allele on verbal fluency, with positive effects in males and negative effects in females. This suggested that DA activity affects cognitive function in different ways, according to gender.

The ARIQUELI study: potentiation of quetiapine in bipolar I nonresponders with lithium versus aripiprazole.

BACKGROUND: The treatment of bipolar disorder (BD) remains a challenge due to the complexity of the disease. Current guidelines represent an effort to assist clinicians in routine practice but have several limitations, particularly concerning long-term treatment. The ARIQUELI (efficacy and tolerability of the combination of lithium or aripiprazole in young bipolar non or partial responders to quetiapine monotherapy) study aims to evaluate two different augmentation strategies for quetiapine nonresponders or partial responders in acute and maintenance phases of BD treatment. METHODS/DESIGN: The ARIQUELI study is a single-site, parallel-group, randomized, outcome assessor-blinded trial. BD I patients according to the DSM-IV-TR, in depressive, manic/hypomanic or mixed episode, aged 18 to 40 years, are eligible. After diagnostic assessments, patients initiated treatment in phase I with quetiapine. Nonresponders or partial responders after 8 weeks are allocated into one of two groups, potentiated with either lithium (0.5 to 0.8 mEq/l) or aripiprazole (10 or 15 mg). Patients will be followed up for 8 weeks in phase I (acute treatment), 6 months in phase II (continuation treatment) and 12 months in phase III (maintenance treatment). Outcome assessors are blinded to the treatment. The primary outcome is the evaluation of changes in mean scores on the CGI-BP-M between baseline and the endpoint at the end of each study phase. DISCUSSION: The ARIQUELI study is currently in progress, with patients undergoing acute treatment (phase I), potentiation (phase II) and maintenance (phase III). The study will be extended until January 2015. Trials comparing lithium and aripiprazole with potentiate treatment in young BD I nonresponders to quetiapine in monotherapy can provide relevant information on the safety of these drugs in clinical practice. Long-term treatment is an issue of great importance and should be evaluated further through more in-depth studies given that BD is a chronic disease. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01710163.

COMT Met (158) modulates facial emotion recognition in bipolar I disorder mood episodes.

BACKGROUND: One of the many cognitive deficits reported in bipolar disorder (BD) patients is facial emotion recognition (FER), which has recently been associated with dopaminergic catabolism. Catechol-O-methyltransferase (COMT) is one of the main enzymes involved in the metabolic degradation of dopamine (DA) in the prefrontal cortex (PFC). The COMT gene polymorphism rs4680 (Val158Met) Met allele is associated with decreased activity of this enzyme in healthy controls. The objective of this study was to evaluate the influence of Val158Met on FER during manic and depressive episodes in BD patients and in healthy controls. MATERIALS AND METHODS: 64 BD type I patients (39 in manic and 25 in depressive episodes) and 75 healthy controls were genotyped for COMT rs4680 and assessed for FER using the Ekman 60 Faces (EK60) and Emotion Hexagon (Hx) tests. RESULTS: Bipolar manic patients carrying the Met allele recognized fewer surprised faces, while depressed patients with the Met allele recognized fewer "angry" and "happy" faces. Healthy homozygous subjects with the Met allele had higher FER scores on the Hx total score, as well as on "disgust" and "angry" faces than other genotypes. CONCLUSION: This is the first study suggesting that COMT rs4680 modulates FER differently during BD episodes and in healthy controls. This provides evidence that PFC DA is part of the neurobiological mechanisms of social cognition. Further studies on other COMT polymorphisms that include euthymic BD patients are warranted. Clinicaltrials.gov identifier: NCT00969.