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Numerous studies have shown that problem gambling is characterised by lack of impulse control. However, they have often been conducted without considering the multifaceted nature of impulsivity and related psychological mechanisms. The current study aims to disentangle which impulsivity facets are altered in pathological gambling. Twenty treatment-seeking pathological gamblers (PGs) and 20 matched control participants completed a self-reported questionnaire measuring the various facets of impulsive behaviours (UPPS Impulsive Behaviour Scale), as well as two laboratory tasks assessing inhibitory control (the go-stop task) and tolerance for delayed rewards (single key impulsivity paradigm). Compared with matched controls, PGs exhibited higher urgency, lower premeditation, impairment in prepotent inhibition, and lower tolerance towards delayed rewards. Nevertheless, complementary profile analyses showed that impulsivity-related deficits found in PGs are highly heterogeneous, and that some PGs are neither impulsive in the impulsivity facets assessed nor impaired in the cognitive mechanisms measured. These findings underscore (1) the necessity to disentangle the construct of impulsivity into lower-order components and (2) that further studies should take into account, in addition to impulsivity-related mechanisms, other psychological factors potentially involved in pathological gambling., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: In bipolar disorder (BD), little is known about how deficits in neurocognitive functions such as decision-making are related to phase of illness. We predicted that manic, depressed, and euthymic bipolar patients (BPs) would display impaired decision-making, and we tested whether clinical characteristics could predict patients' decision-making performance., Methods: Subjects (N = 317; age range: 18-65 years) including 167 BPs (45 manic and 32 depressed inpatients, and 90 euthymic outpatients) and 150 age-, IQ-, and gender-matched healthy control (HC) participants, were included within three university psychiatric hospitals using a cross-sectional design. The relationship between predictor variables and decision-making was assessed by one-step multivariate analysis. The main outcome measures were overall decision-making ability on the Iowa Gambling Task (IGT) and an index of sensitivity to punishment frequency., Results: Manic, depressed, and euthymic BPs selected significantly more cards from the risky decks than HCs (p < .001, p < .01, and p < .05, respectively), with no significant differences between the three BD groups. However, like HCs, BPs preferred decks that yielded infrequent penalties over those yielding frequent penalties. In multivariate analysis, decision-making impairment was significantly (p < .001) predicted by low level of education, high depressive scores, family history of BD, use of benzodiazepines, and nonuse of serotonin and norepinephrine reuptake inhibitor (SNRI) antidepressants., Conclusions: BPs have a trait-related impairment in decision-making that does not vary across illness phase. However, some subtle differences between the BD groups in the individual deck analyses may point to subtle state influences on reinforcement mechanisms, in addition to a more fundamental trait impairment in risk-sensitive decision making., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Studies on emotional biases towards threat-related stimuli in schizophrenia and bipolar disorder have provided, so far, inconsistent results. The aim of the present study was to investigate emotional interference in acute schizophrenic and manic patients and its clinical correlates by using a card version of the Emotional Stroop Task designed with neutral, paranoid, depressive and manic words., Methods: Thirty paranoid schizophrenia patients, 30 manic patients and 60 healthy controls were compared on the Emotional Stroop Test. Response times (RT) were collected for each card. Interference indices were calculated by subtracting the RT for the neutral card from the RT for the depressive, paranoid and manic cards., Results: The schizophrenic and manic patient groups showed an increased interference effect when the emotional valence was relating to the disorder-specific psychopathology. In addition, the paranoid interference index correlated with positive symptoms in schizophrenic patients. By contrast, no correlation was evidenced between interference indices and mood symptoms in the manic group., Conclusions: Among schizophrenic patients, paranoid interference might be a state-related emotional abnormality associated with persecutory delusions. In mania, we suggest that emotional biases towards depressive as well as manic information might be trait features of the emotional hyperreactivity involved in the vulnerability to bipolar disorder., (Copyright © 2010 S. Karger AG, Basel.)

Objectives: Neuroimaging studies of bipolar disorder (BD) have provided evidence of brain functional abnormalities during both the states of mania and remission. However, the differences in brain function between these two states are still poorly known. In the current study, we aimed to use a longitudinal design to examine the functional changes associated with symptomatic remission from mania within the brain network underlying motor response inhibition., Methods: Using event-related functional magnetic resonance imaging (fMRI), 10 BD patients and 10 healthy subjects were imaged twice while performing a Go/NoGo task. Patients were in a manic state when they underwent the first scan and fully remitted during the second scan. A mixed-effect ANOVA was used to identify brain regions showing differences in activation change over time between the two groups., Results: The left amygdala was the only brain region to show a time-dependent change in activation that was significantly different between BD patients and healthy subjects. Further analyses revealed that this difference arose from the patient group, in which amygdala activation was decreased between mania and subsequent remission., Conclusions: This finding suggests that a decrease in left amygdala responsiveness is a critical phenomenon associated with remission from mania. It emphasizes the relevance of longitudinal approaches for identifying neurofunctional modifications associated with mood changes in BD.

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.

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.

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.

Objective: The emotional Stroop test evaluates the influence of the emotional valence of stimuli on cognitive inhibition processes. In subjects with psychiatric disorders, interference increases in this test when valence refers to their specific psychopathology. This study aims to develop a version of the emotional Stroop test adapted to paranoid schizophrenia and bipolar disorder., Method: The emotional valence and the number of times patients used 200 words related to schizophrenia and bipolar disorder psychopathology were assessed by 25 clinicians; then a principal component analysis was performed with an ascending hierarchical classification., Results: Words are distributed according to 2 factorial dimensions, emotionality and tonality, into 4 valence classifications: depressive, paranoid, manic, and neutral words. There were no differences in the lexical frequency of the words chosen to develop the test., Conclusions: The statistical validation of the emotional valence of words allows for the development of an emotional Stroop test adapted to exploring emotional bias in paranoid schizophrenia and bipolar disorder.

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.

The number of structural neuroimaging studies of bipolar disorder have increased during recent years, expanding the literature on the nature of cerebral abnormalities underlying this disorder. The purpose of this paper is to provide a selective review on the main issues concerning this literature. Consistent findings are higher rate of periventricular and deep subcortical white matter hyperintensites seen on MRI. Although there is strong evidence for links between hyper-intense lesions and age or cardio-vascular risk factors, some authors have observed the presence of these abnormalities early in the course of the illness. There are also frequent reports on ventricular enlargement, which has been described as mild and predominant in the right lateral ventricle. Total cerebral volume appears to be preserved. Whereas changes in total grey matter volume are uncertain, evidence suggests that reduced white matter volume reflects genetic factors predisposing to the disorder. Recent studies have reported volume changes in several cortical areas including the subgenual cingular, frontal and temporal cortices. Additionally, a number of reports described morphometric abnormalities in various subcortical structures, such as amygdala, basal ganglia and thalamus. Part of the variability in the morphometric abnormalities might be attributable to differences in clinical status and demographic characteristics of patient groups. Despite some inconsistencies across the studies, it emerges that abnormalities are asymmetrically distributed throughout the two cerebral hemispheres. When increase in volume is reported, it is preferentially localised in the left cerebral hemi-sphere and more specifically in prefrontal and temporal cortices and in amygdala. By contrast, when structural abnormalities concern the right cerebral hemisphere, they are identified as deficits. These latter results are in direct line with those of studies of mania following brain injuries, which report that these secondary mania result mainly from right cerebral lesions. It is also important to notice that most of the abnormalities concern both the cortical and subcortical level, ie frontal, striatal, thalamic and limbic regions. These abnormalities highlight the role in the pathophysiology of bipolar disorder of the loops involved in emotional information processing. The particular role of fronto-limbic loops in the phenomenology of bipolar disorder have been emphasised by recent data from functional neuroimaging studies.

The study was aimed at investigating the repercussions of deficiency in thyroid function with and without thyroid hormone (TH) replacement on the neurochemical entities which underly serotonin (5-HT) neutrotransmission, namely 5-HT1A, 5-HT2A receptors, 5-HT transporter and tryptophan hydroxylase (TPH) in the mature brain. Surgically thyroidectomized male Wistar rats received: (1) an iodine-free diet to produce severe hypothyroidism; (2) hormonal replacement with 15 microgram/kg/day of thyroxine (T4) for 21 days to normalize serum TH levels, or (3) hormonal replacement with 200 microgram/kg/day of T4 for 14 days to produce an excess of circulating THs. Sham-operated rats were used as controls. Neither hypothyroidism nor an excess in serum TH levels affected 3H-8-OH-DPAT binding to 5-HT1A receptors, 3H-citalopram binding to 5-HT transporter and TPH activity in various brain structures indicating that, in the mature brain, the presynaptic entities of 5-HT neurotransmission are resistant to large variations in TH levels. By contrast, hypothyroid rats had a significant decrease in Bmax of 3H-ketanserin binding to cortical 5-HT2A receptors compared to controls. Cortical 3H-ketanserin binding in thyroidectomized rats was normalized after replacement with low-dose T4. Excess serum TH levels in thyroidectomized rats did not produce any changes in cortical 5-HT2A receptors when compared to thyroidectomized rats with normalized TH levels. The present data suggest that the decrease in cortical 5-HT2A receptors is the main neurochemical event underlying the impairing effect of hypothyroidism on 5-HT neurotransmission.

Objectives: Chronic idiopathic urticaria is known to have psychogenic component with a triggering or favoring effect. Different tests or evaluation scales have been unable to identify a specific psychological profile. Erythrocyte-specific membrane transport of tyrptophan (TRP), the main plasma precursor of cerebral serotonin synthesis, controls, by a erythrocyte-specific storage and release mechanism, circulating TRP homeostasis. Bioavailability of circulating TRP is a factor controlling serotonin synthesis in the brain. An evaluation of the rate of TRP transfer could be a biochemical approach to chronic urticaria more informative than psychological tests., Patients and Methods: A kinetic study of L-TRP influx into circulating erythrocytes was conducted in 17 patients with chronic urticaria with no detectable cause and in 35 healthy controls. Blood samples were marked with 3H-TRP. Maximum L-TRP-specific influx (Vmax) was expressed in mumol/cell/min. The urticaria patients also underwent psychological testing to determine anxiety and depression scores using standardized scales (Hamilton)., Results: Mean Vmax was not significantly difference between the two groups. Vmax values were quite similar in all the control subjects but showed wide dispersion in the urticaria group. Three subgroups were found in the urticaria patients depending on Vmax: those with Vmax equivalent in control levels (+2 SD), those with Vmax less then 2 SD (29% of the patients) and those with Vmax greater than 2 SD of control levels (23% of the patients). Thus more than 50% of the urticaria patients had perturbed erythrocyte-specific L-TRP influx. The anxiety and depression scores obtained from the psychological evaluation were not correlated with Vmax., Discussion: Erythrocyte-specific TRP membrane transport, evaluated by Vmax. Would not appear to be perturbed in chronic urticaria. Even though the urticaria patients could be divided into three groups according to their Vmax, the mean value was not significantly different from that in controls. These findings do not allow a conclusion concerning a perturbation of bioavailability of plasmatic TRP and any possible central serotoninergic dysfunction in chronic urticaria.