Targeting impulsivity in Parkinson's disease using atomoxetine.

Noradrenergic dysfunction may play a significant role in cognition in Parkinson's disease due to the early degeneration of the locus coeruleus. Converging evidence from patient and animal studies points to the role of noradrenaline in dopaminergically insensitive aspects of the parkinsonian dysexecutive syndrome, yet the direct effects of noradrenergic enhancement have not to date been addressed. Our aim was to directly investigate these, focusing on impulsivity during response inhibition and decision making. To this end, we administered 40 mg atomoxetine, a selective noradrenaline re-uptake inhibitor to 25 patients with Parkinson's disease (12 female /13 male; 64.4 ± 6.9 years old) in a double blind, randomized, placebo controlled design. Patients completed an extensive battery of neuropsychological tests addressing response inhibition, decision-making, attention, planning and verbal short term memory. Atomoxetine improved stopping accuracy on the Stop Signal Task [F(1,19) = 4.51, P = 0.047] and reduced reflection impulsivity [F(1,9) = 7.86, P = 0.02] and risk taking [F(1,9) = 9.2, P = 0.01] in the context of gambling. The drug also conferred effects on performance as a function of its measured blood plasma concentration: it reduced reflection impulsivity during information sampling [adjusted R(2) = 0.23, F(1,16) = 5.83, P = 0.03] and improved problem solving on the One Touch Stockings of Cambridge [adjusted R(2) = 0.29, F(1,17) = 8.34, P = 0.01]. It also enhanced target sensitivity during sustained attention [F(1,9) = 5.33, P = 0.046]. The results of this exploratory study represent the basis of specific predictions in future investigations on the effects of atomoxetine in Parkinson's disease and support the hypothesis that targeting noradrenergic dysfunction may represent a new parallel avenue of therapy in some of the cognitive and behavioural deficits seen in the disorder.

Cue-induced craving increases impulsivity via changes in striatal value signals in problem gamblers.

Impulsive behavior such as steep temporal discounting is a hallmark of addiction and is associated with relapse. In pathological gamblers, discounting may be further increased by the presence of gambling-related cues in the environment, but the extent to which the gambling relatedness of task settings affects reward responses in gambling addiction is debated. In the present study, human problem gamblers made choices between immediate rewards and individually tailored larger-but-later rewards while visual gambling-related scenes were presented in the background. N = 17 participants were scanned using fMRI, whereas N = 5 additional participants completed a behavioral version of the task. Postscan craving ratings were acquired for each image, and behavioral and neuroimaging data were analyzed separately for high- and low-craving trials (median split analysis). Discounting was steeper for high versus low craving trials. Neuroimaging revealed a positive correlation with model-based subjective value in midbrain and striatum in low-craving trials that was reversed in high-craving trials. These findings reveal a modulation of striatal reward responses in gamblers by addiction-related cues, and highlight a potentially important mechanism that may contribute to relapse. Cue-induced changes in striatal delayed reward signals may lead to increased discounting of future rewards, which might in turn affect the likelihood of relapse.

Selective serotonin reuptake inhibition modulates response inhibition in Parkinson's disease.

Impulsivity is common in Parkinson's disease even in the absence of impulse control disorders. It is likely to be multifactorial, including a dopaminergic 'overdose' and structural changes in the frontostriatal circuits for motor control. In addition, we proposed that changes in serotonergic projections to the forebrain also contribute to response inhibition in Parkinson's disease, based on preclinical animal and human studies. We therefore examined whether the selective serotonin reuptake inhibitor citalopram improves response inhibition, in terms of both behaviour and the efficiency of underlying neural mechanisms. This multimodal magnetic resonance imaging study used a double-blind randomized placebo-controlled crossover design with an integrated Stop-Signal and NoGo paradigm. Twenty-one patients with idiopathic Parkinson's disease (46-76 years old, 11 male, Hoehn and Yahr stage 1.5-3) received 30 mg citalopram or placebo in addition to their usual dopaminergic medication in two separate sessions. Twenty matched healthy control subjects (54-74 years old, 12 male) were tested without medication. The effects of disease and drug on behavioural performance and regional brain activity were analysed using general linear models. In addition, anatomical connectivity was examined using diffusion tensor imaging and tract-based spatial statistics. We confirmed that Parkinson's disease caused impairment in response inhibition, with longer Stop-Signal Reaction Time and more NoGo errors under placebo compared with controls, without affecting Go reaction times. This was associated with less stop-specific activation in the right inferior frontal cortex, but no significant difference in NoGo-related activation. Although there was no beneficial main effect of citalopram, it reduced Stop-Signal Reaction Time and NoGo errors, and enhanced inferior frontal activation, in patients with relatively more severe disease (higher Unified Parkinson's Disease Rating Scale motor score). The behavioural effect correlated with the citalopram-induced enhancement of prefrontal activation and the strength of preserved structural connectivity between the frontal and striatal regions. In conclusion, the behavioural effect of citalopram on response inhibition depends on individual differences in prefrontal cortical activation and frontostriatal connectivity. The correlation between disease severity and the effect of citalopram on response inhibition may be due to the progressive loss of forebrain serotonergic projections. These results contribute to a broader understanding of the critical roles of serotonin in regulating cognitive and behavioural control, as well as new strategies for patient stratification in clinical trials of serotonergic treatments in Parkinson's disease.

Impulsiveness in professional fighters.

Sports involving repeated head trauma are associated with risk of neurodegenerative disorders such as chronic traumatic encephalopathy (CTE). Among the behavioral manifestations of CTE is increased impulsiveness. Here, the authors investigate the relationship between impulsiveness and exposure to head trauma in a large group of active professional fighters. Fighters tended to report less impulsiveness than did non-fighting control respondents. Overall, greater fight exposure was associated with higher levels of a specific form of impulsiveness, although there were differences between mixed martial arts fighters and boxers. Fight exposure was associated with reduction in volume of certain brain structures, and these changes were also associated with impulsiveness patterns. Longitudinal studies of professional fighters are important to understand the risk for neuropsychiatric problems.

Emotional and behavioral dyscontrol after traumatic brain injury.

Emotional and behavioral dyscontrol are relatively common neuropsychiatric sequelae of traumatic brain injury and present substantial challenges to recovery and community participation. Among the most problematic and functionally disruptive of these types of behaviors are pathologic laughing and crying, affective lability, irritability, disinhibition, and aggression. Managing these problems effectively requires an understanding of their phenomenology, epidemiology, and clinical evaluation. This article reviews these issues and provides clinicians with brief and practical suggestions for the management of emotional and behavioral dyscontrol.

Depression, impulsiveness, sleep, and memory in past and present polydrug users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy).

RATIONALE: Ecstasy (3,4-methylenedioxymethamphetamine, MDMA) is a worldwide recreational drug of abuse. Unfortunately, the results from human research investigating its psychological effects have been inconsistent. OBJECTIVES: The present study aimed to be the largest to date in sample size and 5HT-related behaviors; the first to compare present ecstasy users with past users after an abstinence of 4 or more years, and the first to include robust controls for other recreational substances. METHODS: A sample of 997 participants (52 % male) was recruited to four control groups (non-drug (ND), alcohol/nicotine (AN), cannabis/alcohol/nicotine (CAN), non-ecstasy polydrug (PD)), and two ecstasy polydrug groups (present (MDMA) and past users (EX-MDMA). Participants completed a drug history questionnaire, Beck Depression Inventory, Barratt Impulsiveness Scale, Pittsburgh Sleep Quality Index, and Wechsler Memory Scale-Revised which, in total, provided 13 psychometric measures. RESULTS: While the CAN and PD groups tended to record greater deficits than the non-drug controls, the MDMA and EX-MDMA groups recorded greater deficits than all the control groups on ten of the 13 psychometric measures. Strikingly, despite prolonged abstinence (mean, 4.98; range, 4-9 years), past ecstasy users showed few signs of recovery. Compared with present ecstasy users, the past users showed no change for ten measures, increased impairment for two measures, and improvement on just one measure. CONCLUSIONS: Given this record of impaired memory and clinically significant levels of depression, impulsiveness, and sleep disturbance, the prognosis for the current generation of ecstasy users is a major cause for concern.

The relation between poor sleep, impulsivity and aggression in forensic psychiatric patients.

Psychiatric disorders are often associated with disturbed sleep. Poor sleep can attenuate emotional control, including the regulation of aggression, and thus, may increase the risk of impulsive, aggressive acts. This cross-sectional study aimed to investigate the potential contribution of sleep problems to subjective and objective aggressiveness and impulsivity in a forensic psychiatric population. Questionnaires on sleep quality (Pittsburgh Sleep Quality Index), chronic severe insomnia (Sleep Diagnosis List), aggressiveness (Aggression Questionnaire) and impulsivity (Barratt Impulsiveness Scale-11) were completed by 96 forensic psychiatric inpatients, admitted to two forensic facilities in the Netherlands. To obtain more objective measurements of aggression and impulsivity, observational scores on a professional instrument to assess the risk of future aggression (Historical Clinical Future-30) and reported aggressive incidents were collected from files. Results showed that a worse sleep quality and higher insomnia scores were significantly associated with self-reported aggression and impulsivity, clinician-rated hostility and involvement in aggressive incidents within the facility. Whether a participant was professionally judged as impulsive could not be predicted by sleep quality or the insomnia score. To a large extent the results of this study support the hypothesis that poor sleep is related to impulsive, aggressive behavior in forensic psychiatric patients. It is worthwhile to examine the protective effect of treatment of sleep difficulties on aggressive reactivity in (forensic) psychiatric populations.

The value of impulsivity to define subgroups of addicted individuals differing in personality dysfunction, craving, psychosocial adjustment, and wellbeing: a latent class analysis.

High impulsivity is common to substance and gambling addictions. Despite these commonalities, there is still substantial heterogeneity on impulsivity levels within these diagnostic groups, and variations in impulsive levels predict higher severity of symptoms and poorer outcomes. We addressed the question of whether impulsivity scores can yield empirically driven subgroups of addicted individuals that will exhibit different clinical presentations and outcomes. We applied latent class analysis (LCA) to trait (UPPS-P impulsive behavior scale) and cognitive impulsivity (Stroop and d2 tests) scores in three predominantly male addiction diagnostic groups: Cocaine with Personality Disorders, Cocaine Non-comorbid, and Gambling and analyzed the usefulness of the resulting subgroups to differentiate personality beliefs and relevant outcomes: Craving, psychosocial adjustment, and quality of life. In accordance with impulsivity scores, the three addiction diagnostic groups are best represented as two separate classes: Class 1 characterized by greater trait impulsivity and poorer cognitive impulsivity performance and Class 2 characterized by lower trait impulsivity and better cognitive impulsivity performance. The two empirically derived classes showed significant differences on personality features and outcome variables (Class 1 exhibited greater personality dysfunction and worse clinical outcomes), whereas conventional diagnostic groups showed non-significant differences on most of these measures. Trait and cognitive impulsivity scores differentiate subgroups of addicted individuals with more versus less severe personality features and clinical outcomes.

Reward, interrupted: Inhibitory control and its relevance to addictions.

There are broad individual differences in the ability to voluntarily and effortfully suppress motivated, reward-seeking behaviors, and this review presents the hypothesis that these individual differences are relevant to addictive disorders. On one hand, cumulative experience with drug abuse appears to alter the molecular, cellular and circuit mechanisms that mediate inhibitory abilities, leading to increasingly uncontrolled patterns of drug-seeking and -taking. On the other, native inter-individual differences in inhibitory control are apparently a risk factor for aspects of drug-reinforced responding and substance use disorders. In both cases, the behavioral manifestation of poor inhibitory abilities is linked to relatively low striatal dopamine D2-like receptor availability, and evidence is accumulating for a more direct contribution of striatopallidal neurons to cognitive control processes. Mechanistic research is now identifying genes upstream of dopamine transmission that mediate these relationships, as well as the involvement of other neurotransmitter systems, acting alone and in concert with dopamine. The reviewed research stands poised to identify new mechanisms that can be targeted by pharmacotherapies and/or by behavioral interventions that are designed to prevent or treat addictive behaviors and associated behavioral pathology. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

Impulsive and compulsive behaviors among Danish patients with Parkinson's disease: prevalence, depression, and personality.

INTRODUCTION: Dopaminergic medication administered to ameliorate motor symptoms of Parkinson's disease is associated with impulse control disorders, such as pathological gambling, hypersexuality, compulsive buying, and binge eating. Studies indicate a prevalence of impulse control disorders in Parkinson's disease of 6-16%. OBJECTIVE: To estimate the prevalence of impulsive and compulsive behaviors among Danish patients with Parkinson's disease and to explore the relation of such behavioral disorders to depression and personality. METHODS: 490 patients with Parkinson's disease (303 males), identified through the National Danish Patient Registry, were evaluated with: 1) the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease; 2) the Geriatric Depression Scale; and 3) the NEO-Personality Inventory. RESULTS: 176 (35.9%) patients reported impulsive and compulsive behaviors sometime during Parkinson's disease (current symptoms in 73, 14.9%). Hereof, 114 (23.3%) reported multiple behavioral symptoms. Patients with behavioral symptoms were significantly younger, were younger at PD onset, had longer disease duration, displayed more motor symptoms, and received higher doses of dopaminergic medication than patients without behavioral symptoms. Furthermore, they reported significantly more depressive symptoms and scored significantly higher on neuroticism and lower on both agreeableness and conscientiousness than patients without behavioral symptoms. CONCLUSION: A history of impulsive and compulsive behaviors are common in Danish patients with Parkinson's disease and have clinical correlates that may allow identification of patients at risk for developing these behaviors.

Baseline impulsive choice predicts the effects of nicotine and nicotine withdrawal on impulsivity in rats.

Impulsive choice, a form of impulsivity, is associated with tobacco smoking in humans. Trait impulsivity may be a vulnerability factor for smoking, or smoking may lead to impulsive behaviors. We investigated the effects of 14-day nicotine exposure (6.32mg/kg/day base, subcutaneous minipumps) and spontaneous nicotine withdrawal on impulsive choice in low impulsive (LI) and high impulsive (HI) rats. Impulsive choice was measured in the delayed reward task in which rats choose between a small immediate reward and a large delayed reward. HI and LI rats were selected from the highest and lowest quartiles of the group before exposure to nicotine. In non-selected rats, nicotine or nicotine withdrawal had no effect on impulsive choice. In LI rats, chronic nicotine exposure decreased preference for the large reward with larger effects at longer delays, indicating increased impulsive choice. Impulsive choices for the smaller immediate rewards continued to increase during nicotine withdrawal in LI rats. In HI rats, nicotine exposure and nicotine withdrawal had no effect on impulsive choice, although there was a tendency for decreased preference for the large reward at short delays. These results indicate that nicotine- and nicotine withdrawal-induced increases in impulsive choice depend on trait impulsivity with more pronounced increases in impulsive choice in LI compared to HI subjects. Increased impulsivity during nicotine exposure may strengthen the addictive properties of nicotine and contribute to compulsive nicotine use.

Serotonin at the nexus of impulsivity and cue reactivity in cocaine addiction.

Cocaine abuse and addiction remain great challenges on the public health agendas in the U.S. and the world. Increasingly sophisticated perspectives on addiction to cocaine and other drugs of abuse have evolved with concerted research efforts over the last 30 years. Relapse remains a particularly powerful clinical problem as, even upon termination of drug use and initiation of abstinence, the recidivism rates can be very high. The cycling course of cocaine intake, abstinence and relapse is tied to a multitude of behavioral and cognitive processes including impulsivity (a predisposition toward rapid unplanned reactions to stimuli without regard to the negative consequences), and cocaine cue reactivity (responsivity to cocaine-associated stimuli) cited as two key phenotypes that contribute to relapse vulnerability even years into recovery. Preclinical studies suggest that serotonin (5-hydroxytryptamine; 5-HT) neurotransmission in key neural circuits may contribute to these interlocked phenotypes well as the altered neurobiological states evoked by cocaine that precipitate relapse events. As such, 5-HT is an important target in the quest to understand the neurobiology of relapse-predictive phenotypes, to successfully treat this complex disorder and improve diagnostic and prognostic capabilities. This review emphasizes the role of 5-HT and its receptor proteins in key addiction phenotypes and the implications of current findings to the future of therapeutics in addiction. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.

Impulsivity and alcohol demand in relation to combined alcohol and caffeine use.

Problematic alcohol use among college students continues to be a prominent concern in the United States, including the growing trend of consuming caffeinated alcoholic beverages (CABs). Epidemiologically, CAB use is associated with incremental risks from drinking, although these relationships could be due to common predisposing factors rather than specifically due to CABs. This study investigated the relationship between CAB use, alcohol misuse, and person-level characteristics, including impulsive personality traits, delayed reward discounting, and behavioral economic demand for alcohol use. Participants were 273 regularly drinking undergraduate students. Frequency of CAB use was assessed over the past month. A multidimensional assessment of impulsivity included the UPPS-P questionnaire, which measures positive and negative urgency, premeditation (lack thereof), perseverance (lack thereof), and sensation seeking (Lynam, Smith, Whiteside, & Cyders, 2007), and a validated questionnaire-based measure of delayed reward discounting. Demand was assessed via a hypothetical alcohol purchase task. Frequency of CAB consumption was significantly higher in men than in women and was also associated with higher impulsivity on the majority of the UPPS-P subscales, steeper delayed reward discounting, and greater demand for alcohol. Significant correlations between CAB use and both alcohol demand and lack of premeditation remained present after including level of alcohol misuse in partial correlations. In a hierarchical linear regression incorporating demographic, demand, and impulsivity variables, CAB frequency continued to be a significant predictor of hazardous alcohol use. These results suggest that although there are significant associations between CAB consumption and gender, impulsivity, and alcohol demand, CAB use continues to be associated with alcohol misuse after controlling for these variables.

An intrinsic connectivity network approach to insula-derived dysfunctions among cocaine users.

BACKGROUND: Addiction is a complex phenotype, though it consistently includes characteristics of impulsivity. A number of brain regions are suggested to be involved in cocaine addiction, including the insula, which serves diverse functions including interoceptive awareness and integration of neural signals from sensory, subcortical and frontal regions. Malfunction of this integration links impulsive behavior to the insula. OBJECTIVES: This study examines intrinsic connectivity of the insula in chronic cocaine users to investigate abnormal insular circuitry, its role in cocaine addiction, and relationships to measure of impulsivity. METHODS: Cocaine-dependent individuals (n = 33) and healthy controls (n = 32) completed a resting-state fMRI scan. An intrinsic connectivity network (ICN) approach generated metrics of mean network connectivity and inter-network connectivity from fMRI data. Metrics pertaining to ICNs involving insula and other structures repeatedly involved in addiction (e.g. striatum) were selected for analysis, which included the capacity to discriminate groups. Relationships between group discriminating connectivity metrics and behavioral impulsivity were examined. RESULTS: Models demonstrated group prediction accuracy up to 75%. Accuracy of 69% was obtained by a parsimonious model of six inter-network connectivity metrics. The inter-network connectivity between an ICN involving the anterior insula and ACC, and an ICN involving the striatum, was significantly weaker in cocaine users relative to controls. The degree of reduced inter-network connectivity was significantly related to greater non-planning impulsivity in cocaine users. CONCLUSIONS: Aberrant insula-derived intrinsic connectivity patterns are observed in cocaine users and include dysfunctions in insula to striatal connectivity, which is furthermore linked to increased impulsivity pertaining to forethought.

Prevalence of neurobehavioral, social, and emotional dysfunction in patients treated for childhood craniopharyngioma: a systematic literature review.

BACKGROUND: Craniopharyngiomas (CP) are locally invasive and frequently recurring neoplasms often resulting in neurological and endocrinological dysfunction in children. In addition, social-behavioral impairment is commonly reported following treatment for childhood CP, yet remains to be fully understood. The authors aimed to further characterize the prevalence of neurobehavioral, social, and emotional dysfunction in survivors of childhood craniopharyngiomas. MATERIALS AND METHODS: A systematic literature review was conducted in PubMed to identify studies formally assessing neurobehavioral, social, and emotional outcomes in patients treated for CP prior to 18 years of age. Studies published between the years 1990-2012 that reported the primary outcome (prevalence of neurobehavioral, social, emotional/affective dysfunction, and/or impaired quality of life (QoL)) in ≥ 10 patients were included. RESULTS: Of the 471 studies screened, 11 met inclusion criteria. Overall neurobehavioral dysfunction was reported in 51 of 90 patients (57%) with available data. Social impairment (i.e. withdrawal, internalizing behavior) was reported in 91 of 222 cases (41%). School dysfunction was reported in 48 of 136 patients (35%). Emotional/affective dysfunction was reported in 58 of 146 patients (40%), primarily consisting of depressive symptoms. Health related quality of life was affected in 49 of 95 patients (52%). Common descriptors of behavior in affected children included irritability, impulsivity, aggressiveness, and emotional outbursts. CONCLUSIONS: Neurobehavioral, social, and emotional impairment is highly prevalent in survivors of childhood craniopharyngioma, and often affects quality of life. Thorough neurobehavioral/emotional screening and appropriate counseling is recommended in this population. Additional research is warranted to identify risk factors and treatment strategies for these disorders.

Levodopa infusion improves impulsivity and dopamine dysregulation syndrome in Parkinson's disease.

BACKGROUND: Impulsivity and dopamine dysregulation syndrome are frequent complications of treatment in Parkinson's disease (PD). METHODS: We assessed the effect of jejunal levodopa infusion (JLI) on behavioral symptoms in 8 PD patients with motor complications and severe impulsivity and dopamine dysregulation syndrome (DDS), which had not be controlled before by adjusting oral medications. The infusion was delivered during 15 hours (daily dose 1007.2 ± 302.5 mg) and stopped at night time. Patients were reassessed after 25 ± 9 weeks of treatment with a stable dose of jejunal l-dopa. RESULTS: Off periods and dyskinesias decreased by 27% and 20,7% respectively, compared to baseline. DDS and all types of impulse control disorders (ICDs) improved in all patients, with nearly complete symptom resolution. Punding improved in all 5 patients but disappeared completely in only 1. CONCLUSIONS: Our experience suggests that l-dopa infusion has a positive effect on both motor complications and behavioral disorders. This treatment approach deserves further controlled studies.

Decision-making, reward-seeking behaviors and dopamine agonist therapy in restless legs syndrome.

STUDY OBJECTIVES: To assess whether the frequency of impulse control disorders (ICDs), addictive behaviors, impulsivity, and impairment of decision-making task performance under ambiguous and risky conditions were present in patients with restless legs syndrome (RLS) and whether changes could be related to dopaminergic medications. DESIGN: Case-control prospective study. SETTING: Academic Sleep Disorders Center. PARTICIPANTS: Of the 149 participants, there were 39 who were drug free with primary RLS, 50 who were taking dopamine agonists (DA), and 60 control subjects. Participants were assessed with a clinical interview screening for ICDs, augmentation syndrome, impulsivity, depression, and addictive behaviors. All participants completed two decision-making tasks, one under an ambiguous condition (Iowa Gambling Task) and the other under a risky condition (Game of Dice Task). Drug-free patients with RLS underwent 1 night of polysomnography recording. MEASUREMENTS AND RESULTS: Seventy percent of patients were treated with pramipexole (median dose, 0.36 mg), and 30% with ropinirole (median dose, 0.75 mg). Median duration of DA intake was 11 mo (range, 1-72 mo). No differences were found on impulsivity scores, ICDs, and substance addiction between drug-free patients or those taking DA, or control subjects. Patients with RLS reported more depressive symptoms than control subjects, but without differences between patients taking or not taking DA. Drug-free and treated patients demonstrated reduced performances on the Iowa Gambling Task but not on the Game of Dice Task compared to control subjects, with no differences between patients taking medications and those who were not. No association was found between decision-making task performances, or polysomnographic and clinical variables. CONCLUSION: Impulse control disorders, impulsivity, and substance addiction were infrequent in drug-free patients with restless legs syndrome or those treated with a low dose of dopamine agonists. However, patients with restless legs syndrome, either drug free or taking dopamine agonists, had preferences toward risky choices on the Iowa Gambling Task, which led to negative consequences in the long run, a condition potentially leading to further development of impulse control disorders.

Impulsivity in bipolar disorder: relationships with neurocognitive dysfunction and substance use history.

OBJECTIVES: Impulsivity is a core feature in bipolar disorder. Although mood symptoms exacerbate impulsivity, self-reports of impulsivity are elevated, even during euthymia. Neurocognitive processes linked to impulsivity (e.g., attention, inhibition) are also impaired in patients with bipolar disorder, and a high frequency of comorbidities associated with impulsivity, such as substance use disorders, further highlights the clinical relevance of this dimension of the illness. Our objective was to assess the relationship between impulsivity and cognition in bipolar disorder. METHODS: We evaluated impulsivity in 98 patients with bipolar disorder and its relationship with symptoms, cognition, and substance use history. We assessed self-reports of trait impulsivity [Barrett Impulsiveness Scale (BIS)] and impulsive behaviors on the Iowa Gambling Task (IGT). A comprehensive clinical and neurocognitive battery was also completed. Patients were compared with 95 healthy controls. RESULTS: Patients with bipolar disorder had higher scores versus healthy controls on all BIS scales. Performance on the IGT was significantly impaired and patients showed a tendency toward more erratic choices. Depressive symptoms were positively correlated with trait impulsivity and with an increased tendency to attend more readily to losses versus gains on the IGT. We found no significant associations between impulsivity and neurocognition in the full bipolar sample; however, when sub-grouped based on substance abuse history, significant relationships were revealed only in subjects without a substance abuse history. CONCLUSIONS: Our data support prior reports of increased trait impulsivity and impairment on behavioral tasks of impulsiveness in bipolar disorder and suggest a differential relationship between these illness features that is dependent upon history of substance abuse.

Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture.

BACKGROUND: Families of children with attention deficit hyperactivity disorder (ADHD) report more negative family relationships than families of children without ADHD. Questions remain as to the role of genetic factors underlying associations between family relationships and children's ADHD symptoms, and the role of children's ADHD symptoms as an evocative influence on the quality of relationships experienced within such families. Utilizing the attributes of two genetically sensitive research designs, the present study examined associations between biologically related and nonbiologically related maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. The combined attributes of the study designs permit assessment of associations while controlling for passive genotype-environment correlation and directly examining evocative genotype-environment correlation (rGE); two relatively under examined confounds of past research in this area. METHODS: A cross-sectional adoption-at-conception design (Cardiff IVF Study; C-IVF) and a longitudinal adoption-at-birth design (Early Growth and Development Study; EGDS) were used. The C-IVF sample included 160 mothers and children (age 5-8 years). The EGDS sample included 320 linked sets of adopted children (age 6 years), adoptive-, and biologically related mothers. Questionnaires were used to assess maternal ADHD symptoms, parenting practices, child impulsivity/activation, and child ADHD symptoms. A cross-rater approach was used across measures of maternal behavior (mother reports) and child ADHD symptoms (father reports). RESULTS: Significant associations were revealed between rearing mother ADHD symptoms, hostile parenting behavior, and child ADHD symptoms in both samples. Because both samples consisted of genetically unrelated mothers and children, passive rGE was removed as a possible explanatory factor underlying these associations. Further, path analysis revealed evidence for evocative rGE processes in the longitudinal adoption-at-birth study (EGDS) from biologically related maternal ADHD symptoms to biologically unrelated maternal hostile parenting through early disrupted child behavior (impulsivity/activation), with maternal hostile parenting and disrupted child behavior associated with later child ADHD symptoms, controlling for concurrent adoptive mother ADHD symptoms. CONCLUSIONS: Results highlight the importance of genetically influenced child ADHD-related temperamental attributes on genetically unrelated maternal hostility that in turn links to later child ADHD symptoms. Implications for intervention programs focusing on early family processes and the precursors of child ADHD symptoms are discussed.

Pre-attentive information processing and impulsivity in bipolar disorder.

Early responses to stimuli can be measured by sensory evoked potentials (EP) using repeated identical stimuli, S1 and S2. Response to S1 may represent efficient stimulus detection, while suppression of response to S2 may represent inhibition. Early responses to stimuli may be related to impulsivity. We compared EP reflecting stimulus detection and inhibition in bipolar disorder and healthy controls, and investigated relationships to impulsivity. Subjects were 48 healthy controls without family histories of mood disorder and 48 with bipolar disorder. EP were measured as latencies and amplitudes for auditory P50 (pre-attentional), N100 (initial direction of attention) and P200 (initial conscious awareness), using a paired-click paradigm, with identical stimuli 0.5 s apart. Impulsivity was measured by questionnaire and by laboratory tests for inability to suppress responses to stimuli or to delay response for a reward. Analyses used general linear models. S1 amplitudes for P50, N100, and P200, and gating of N100 and P200, were lower in bipolar disorder than in controls. P50 S1 amplitude correlated with accurate laboratory-task responding, and S2 amplitude correlated with impulsive task performance and fast reaction times, in bipolar disorder. N100 and P200 EP did not correlate with impulsivity. These findings were independent of symptoms, treatment, or substance-use history. EPs were not related to questionnaire-measured or reward-based impulsivity. Bipolar I disorder is characterized by reduced pre-attentional and early attentional stimulus registration relative to controls. Within bipolar disorder, rapid-response impulsivity correlates with impaired pre-attentional response suppression. These results imply specific relationships between ERP-measured response inhibition and rapid-response impulsivity.