J.-M. Azorin

Lack of insight may predict impaired decision making in manic patients.

OBJECTIVES The tendency to engage in risky behaviours is a core feature of the manic episodes of bipolar disorder. The aim of this study was to establish whether this characteristic can be quantified with a laboratory measure of decision making [the Iowa Gambling Task (IGT)] and to determine clinical correlates of the IGT performance in mania. METHODS Inpatients with acute mania (n = 45) and healthy volunteers (n = 45) were assessed on the IGT. Affective symptomatology was assessed with the Young Mania Rating Scale and Hamilton Depression Rating Scale, and item scores were subjected to factor analysis. Multivariate regression was used to assess clinical predictors of impaired decision making in the manic patients. RESULTS On the IGT, manic patients selected more cards from the risky decks than healthy controls, and showed little capacity to learn from incurred losses. In a multivariate analysis, impaired decision making ability in the manic patients was significantly predicted by a symptom factor associated with lack of insight. CONCLUSIONS Manic patients clearly show defects in decision making, which are strongly related to their lack of insight. Neural circuitry supporting effective decision making, including the ventromedial prefrontal cortex and somatosensory cortex, may be implicated in the pathophysiology of acute mania.

Bilateral decrease in ventrolateral prefrontal cortex activation during motor response inhibition in mania

Mania has been frequently associated with impaired inhibitory control. The present study aimed to identify brain functional abnormalities specifically related to motor response inhibition in mania by using event-related fMRI in combination with a Go/NoGo task designed to control for extraneous cognitive processes involved in task performance. Sixteen manic patients and 16 healthy subjects, group-matched for age and sex, were imaged while performing a warned equiprobable Go/NoGo task during event-related fMRI. Between-group differences in brain activation associated with motor response inhibition were assessed using analyses of covariance. Although no significant between-group differences in task performance accuracy were observed, patients showed significantly longer response times on Go trials. After controlling for covariates, the only brain region that differentiated the two groups during motor response inhibition was the ventrolateral prefrontal cortex (VLPFC), where activation was significantly decreased in both the right and left hemispheres in manic patients. Our data suggest that response inhibition in mania is associated with a lack of engagement of the bilateral VLPFC, which is known to play a primary role in the suppression of irrelevant responses. This result might give clues to understanding the pathophysiology of disinhibition and impulsivity that characterize mania.

Blunted activation in right ventrolateral prefrontal cortex during motor response inhibition in schizophrenia

OBJECTIVES Previous functional magnetic resonance imaging (fMRI) studies have reported abnormal brain activation in individuals with schizophrenia during performance of motor inhibition tasks. We aimed to clarify brain functional abnormalities related to motor response inhibition in schizophrenia by using event-related fMRI in combination with a Go-NoGo task designed to control for non-inhibitory cognitive processes involved in task performance. METHOD We studied 21 schizophrenic patients and 21 healthy subjects, group-matched for age, sex, and performance accuracy on a Go-NoGo task during event-related fMRI. The task was designed so that Go and NoGo events were equally probable. Between-group activation differences were assessed using ANCOVAs with response time and IQ as covariates of non-interest. RESULTS Compared to healthy subjects, schizophrenic patients exhibited a significant decrease in activation during motor response inhibition in the right ventrolateral prefrontal cortex (VLPFC) only. There were no areas of increased brain activation in patients compared to healthy subjects. CONCLUSIONS Schizophrenic patients demonstrate a blunted activation in the right VLPFC, a region known to play a critical role in motor response inhibition. Further research should ascertain the contribution of the VLPFC dysfunction to the impulsive behavior observed in schizophrenia.

Impulsivity and neural correlates of response inhibition in schizophrenia.

BACKGROUND The clinical picture of schizophrenia is frequently worsened by manifestations of impulsivity. However, the neural correlates of impulsivity in this disorder are poorly known. Although impulsivity has been related to disturbances of the neural processes underlying response inhibition, no studies have yet examined the relationship between these processes and psychometric measures of impulsivity in schizophrenia. This was the aim of the current investigation. METHOD Event-related functional magnetic resonance imaging in conjunction with a Go/NoGo task was employed to probe the neural activity associated with response inhibition in 26 patients with schizophrenia and 30 healthy comparison subjects. All participants also completed the Barratt Impulsiveness Scale - version 11 (BIS-11). Voxel-wise regression analyses were used to examine the relationship between the BIS-11 score and brain activation during response inhibition in each group. RESULTS Patients with schizophrenia were more impulsive than healthy subjects, as indicated by higher BIS-11 scores. Patients, but not healthy subjects, were found to display a positive correlation between these scores and cerebral activation associated with response inhibition. This correlation involves a unique cluster localized within the right ventrolateral prefrontal cortex (VLPFC), a key node of the brain network subserving response inhibition. CONCLUSIONS We evidenced in patients with schizophrenia that greater BIS-11 scores are associated with greater activation within the right VLPFC during response inhibition. This finding suggests that the efficiency of this brain region to process inhibitory control is reduced in the more impulsive patients.

Reduced brain activation in euthymic bipolar patients during response inhibition: An event-related fMRI study

Deficits in inhibitory control have been reported in euthymic bipolar disorder patients. To date, data on the neuroanatomical correlates of these deficits are exclusively related to cognitive inhibition. This study aimed to examine the neural substrates of motor inhibitory control in euthymic bipolar patients. Groups of 20 patients with euthymic bipolar disorder and 20 demographically matched healthy subjects underwent event-related functional magnetic resonance imaging while performing a Go-NoGo task. Between-group differences in brain activation associated with motor response inhibition were assessed by using random-effects analyses. Although euthymic bipolar patients and healthy subjects performed similarly on the Go-NoGo task, they showed different patterns of brain activation associated with response inhibition. Specifically, patients exhibited significantly decreased activation in the left frontopolar cortex and bilateral dorsal amygdala compared with healthy subjects. There were no brain regions that were significantly more activated in patients than in healthy subjects. The findings suggest that euthymic bipolar patients have deficits in their ability to engage the left frontopolar cortex and bilateral dorsal amygdala during response inhibition. Further research should ascertain the role that such deficits may play in the emergence of impulsive behaviors that characterize bipolar disorder.

Lithium might be associated with better decision-making performance in euthymic bipolar patients ☆

Bipolar disorder is associated with impaired decision-making. Little is known about how treatment, especially lithium, influences decision-making abilities in bipolar patients when euthymic. We aimed at testing for an association between lithium medication and decision-making performance in remitted bipolar patients. Decision-making was measured using the Iowa Gambling Task in 3 groups of subjects: 34 and 56 euthymic outpatients with bipolar disorder, treated with lithium (monotherapy and lithium combined with anticonvulsant or antipsychotic) and without lithium (anticonvulsant, antipsychotic and combination treatment), respectively, and 152 matched healthy controls. Performance was compared between the 3 groups. In the 90 euthymic patients, the relationship between different sociodemographic and clinical variables and decision-making was assessed by stepwise multivariate regression analysis. Euthymic patients with lithium (p=0.007) and healthy controls (p=0.001) selected significantly more cards from the safe decks than euthymic patients without lithium, with no significant difference between euthymic patients with lithium and healthy controls (p=0.9). In the 90 euthymic patients, the stepwise linear multivariate regression revealed that decision-making was significantly predicted (p<0.001) by lithium dose, level of education and no family history of bipolar disorder (all p≤0.01). Because medication was not randomized, it was not possible to discriminate the effect of different medications. Lithium medication might be associated with better decision-making in remitted bipolar patients. A randomized trial is required to test for the hypothesis that lithium, but not other mood stabilizers, may specifically improve decision-making abilities in bipolar disorder.

P01-61 - Impaired decision-making in the 3 phases of bipolar disorder : a trait-related deficit

Introduction Bipolar disorder (BD) is associated with impaired psychosocial behaviours. Little is known about deficits in neurocognitive functions like decision-making possibly related both to these behaviours and to the nature of the disorder. Objectives To determine whether decision-making impairments exist in manic (M), depressed (D) and euthymic (E) bipolar patients (BP) and to determine whether illness and course-of-illness characteristics can predict participants’ performance Methods A power analysis was conducted. A total of 315 subjects, including 45 M and 32 D inpatients and 90 E outpatients with BD I, medicated, and 150 Healthy Controls (HC), age, IQ and gender-matched, were included. Decision-making ability and sensitivity to punishment frequency were assessed with the Iowa Gambling Task (IGT). Results On the IGT, MBP (p Conclusions BP clearly show defects in decision-making predicted by course-of-illness illness characteristics. Impaired decision-making might be a trait-related neurocognitive deficit in BD and partly explain impaired psychosocial behaviours of BP.