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INTRODUCTION: Attention deficit/hyperactivity disorder (ADHD) with co-occurring substance use disorder (SUD) is associated with poor treatment outcomes. Two randomized controlled trials, utilizing robust doses of stimulants, demonstrated a significant effect on treatment outcomes in patients with ADHD/SUD. This study aimed to investigate differences in executive functioning and explore the dose-dependent effect of OROS-methylphenidate (MPH) in patients with comorbid ADHD and amphetamine use disorder (ADHD+AMPH) and patients with ADHD only. METHODS: Three groups (ADHD+AMPH, ADHD only, and healthy controls) were assessed repeatedly with a neuropsychological test battery. An exploratory within-subject single-blinded design was employed where the ADHD only group received a maximum dose of 72 mg OROS-MPH, the ADHD+AMPH group a maximum dose of 180 mg, whereas the healthy subjects did not receive any study medication. Both ADHD groups received the same dose titration up to 72 mg OROS-MPH. RESULTS: The ADHD+AMPH group demonstrated a significantly poorer motor inhibition and spatial working memory and reported more severe ADHD symptoms compared to the ADHD only group. 180 mg OROS-MPH was associated with a significant improvement in executive functioning in the dual diagnosis group. However, the exploratory study design and recruitment issues do not allow for any conclusion to be drawn regarding the effect of 180 mg OROS-MPH. CONCLUSION: Patients with ADHD+AMPH present with more severe neurocognitive deficits compared to ADHD only. The effect of 180 mg OROS-MPH on cognition in patients with ADHD+AMPH was inconclusive. Future studies should consider recruitment issues and high drop-out rates in this study population.

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Background: Intellectual disability (ID) is a disorder with unknown aetiology in many cases. Maternal alcohol use is a known risk factor for ID, but less is known about the importance of maternal and paternal substance use disorder (SUD) and risk of ID in offspring. Methods: Data from multiple nationwide registers were used to create a cohort of children born from January 01, 1978 to December 31, 2002. All participants were born in Sweden, had available parental identification information and did not emigrate or die before age 12 (n = 1,940,820). Logistic regression modelling was performed with exposure defined as having a parent who received any SUD diagnosis, including alcohol use disorder (AUD) and drug use disorder (DUD). The outcome was registration of diagnosis of any form of ID. First, we analysed the risk of ID if parental SUD was registered prior to childbirth with stepwise adjustment of multiple covariates. Second, the effect of timing of SUD diagnosis in relation to childbirth was analysed. Findings: Of 37,410 offspring with parental SUD registered prior to birth, 3.0% (n = 1110) had any form of ID compared to 1.2% (n = 23,168) of those 1,903,410 individuals without parental SUD prior birth. Parental SUD prior birth was associated with an increased risk of any form of ID (Odds Ratio [OR]: 2.3 [2.2-2.5]), with ORs similar for maternal (OR: 2.3 [2.1-2.5]) and paternal SUD (OR: 2.3 [2.1-2.5]). These ORs were reduced but remained statistically significant after adjusting for parental education, migration, psychiatric comorbidity, and co-parent SUD (OR parental SUD: 1.6 [1.5-1.8]; OR maternal SUD: 1.4 [1.2-1.5]; OR paternal SUD: 1.6 [1.5-1.7]). Parental SUD was associated with increased risk of ID in offspring irrespective of timing of diagnosis, but if mothers or fathers were diagnosed with AUD during pregnancy (OR maternal AUD: 5.0 [3.1-8.2]; OR paternal AUD: 2.8 [2.2-3.6]), the risk was significantly greater than if the AUD diagnosis was first registered after childbirth (OR maternal AUD: 1.9 [1.8-2.0]; OR paternal AUD: 1.6 [1.6-1.7]). Interpretation: Both paternal and maternal SUD were associated with an increased risk of ID in offspring, with greatest risk observed when AUD was diagnosed during pregnancy. Possible mechanisms may involve shared genetic and environmental factors, including toxic effects from alcohol intake. These findings have clinical implications in suggesting that parental SUD in either parent represents a possibly modifiable risk factor to consider when developing prevention, diagnostics and treatment programs for children with ID. Funding: Stockholm County Council, the Research Council of the Swedish Alcohol Retailing Monopoly, Fredrik and Ingrid Thurings stiftelse, Academy of Finland, the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare, Nordforsk by the Nordic Council of Ministers and the Polish Medical Research Agency.

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BACKGROUND: Amphetamine use disorder (AMPH) and attention deficit-hyperactivity disorder (ADHD) often co-occur and are associated with poor treatment outcomes. Elevated impulsivity is a core feature in both disorders. Little is known however about the specific neurocognitive profile regarding different facets of impulsivity, and specifically impulsive choice, in comorbid populations. METHODS: Three groups (ADHD + AMPH, ADHD only and healthy controls (HC)) were assessed with self-reported impulsivity and cognitive tasks of impulsive choice, operationalized as delay aversion (DA) and reflection impulsivity. RESULTS: Twenty-nine participants with comorbid ADHD + AMPH, 25 participants with ADHD only and 116 HC completed screening, including self-rating scales, and cognitive testing. 20, 16 and 114 participants completed computerized cognitive tasks in the ADHD + AMPH group, ADHD group and HC group, respectively. The ADHD + AMPH group reported significantly higher motor, attentional and non-planning impulsiveness, and showed a significantly higher degree of impulsive choice, compared to both groups. There were no differences in task-related impulsiveness between ADHD only and HC. CONCLUSIONS: The current findings suggest that individuals with ADHD + AMPH have overall elevated levels of impulsivity compared to individuals with ADHD only. In addition, that ADHD + AMPH is specifically associated with impairments in task-related impulsive choice, which was not found in ADHD only compared to HC. The neurocognitive profile in this specific patient group may represent a need for more systematic screening within healthcare settings in order to develop effective and targeted treatment for comorbid patients. TRIAL REGISTRATION: EudraCT, 2012-004298-20.

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BACKGROUND: Parental substance abuse (SA) of alcohol and drugs is associated with offspring mortality, including sudden infant death syndrome (SIDS), in infancy, but research on cause-specific mortality and mortality in later childhood is scarce. METHODS: Using population-based register data on all births in Sweden in 1973-2013 (N = 4.2 million) and Cox regressions, we examined the associations of mother's and father's SA registered between 2 years before and 12 years after the child birth with offspring all-cause and cause-specific mortality in infancy and childhood. RESULTS: Parental SA was associated with increased offspring all-cause and natural-cause mortality in infancy, but not in the neonatal period, and with external-cause mortality in ages 1-9. Risk of SIDS was 130-280% higher in infants with parental SA compared to infants with no parental SA. Adjusting for parental socioeconomic and immigrant status and severe psychiatric disorders, paternal SA was associated with 66% higher mortality due to communicable diseases and infections in infancy, and both maternal and paternal SA were associated with 40-174% higher mortality due to accidents in infancy and in ages 1-9. The associations between parental SA and offspring mortality were similar for male and female offspring. CONCLUSIONS: Child mortality is rare in contemporary Sweden, and parental SA has variable associations with elevated offspring mortality throughout the first 10 years of life, excluding the neonatal period, which is indicative of insufficient recognition of children at risk. Preventive measures should be long-term and targeted to both parental and offspring behaviour.

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BACKGROUND: Alcohol use disorder (AUD) is associated with deficits in social cognition, but the relationship between harmful alcohol use and the processes underlying interactive social behavior is still unknown. We hypothesized that prosocial decision making is reduced in AUD and that individual differences in the underlying processes are key to better understanding these reductions. METHODS: In one laboratory study (Swedish participants, n = 240) and one confirmatory online study (American participants, n = 260), we compared young adults with AUD with age-, gender-, and education-matched healthy control subjects on 6 facets of prosocial decision making. We used standardized behavioral economic tasks, namely the dictator game, ultimatum game, trust game, and third-party game. To better understand the expected differences in prosociality, we evaluated attention by tracking eye gaze, decision response time, clinical symptoms, and social cognition. RESULTS: Altruism (lab study: p = .007; online study: p < .001), fairness (lab study: p = .003; online study: p = .007), and reciprocal trust (lab study: p = .007; online study: p = .039) were reduced in individuals with AUD compared with healthy control subjects, whereas trust and third-party punishment and compensation were comparable in both studies. Reduced prosociality was associated with attending to the selfish response option, faster response time, and moral attitudes, while being dissociated from both psychiatric symptoms and drinking history in AUD. CONCLUSIONS: Individuals with AUD have trait-related reductions in prosocial decision making that do not vary with drinking history or psychiatric symptom load. These reductions were confined to one-to-one interactions accompanied by differences in attention, decision time, and moral attitudes.

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BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits but little is known to what degree this is caused by genetically influenced traits, i.e. endophenotypes, present before the onset of the disorder. The aim of the current study was to investigate to what degree family history (FH) of AUD is associated with cognitive functions. METHODS: Case-control cross-sectional study at an outpatient addiction research clinic. Treatment-seeking AUD patients (n = 106) were compared to healthy controls (HC; n = 90), matched for age and sex. The HC group was further subdivided into AUD FH positive (FH+; n = 47) or negative (FH-; n = 39) based on the Family Tree Questionnaire. Participants underwent psychiatric and substance use assessments, completed the Barratt Impulsiveness Scale and performed a comprehensive battery of neuropsychological tests assessing response inhibition, decision making, attention, working memory, and emotional recognition. RESULTS: Compared to HC, AUD patients exhibited elevated self-rated impulsivity (p < 0.001; d = 0.62), as well as significantly poorer response inhibition (p = 0.001; d = 0.51), attention (p = 0.021; d = 0.38) and information gathering in decision making (p = 0.073; d = 0.34). Similar to AUD patients, FH+ individuals exhibited elevated self-rated impulsivity (p = 0.096; d = 0.46), and in addition significantly worse future planning capacity (p < 0.001; d = 0.76) and prolonged emotional recognition response time (p = 0.010; d = 0.60) compared to FH-, while no other significant differences were found between FH+ and FH-. CONCLUSIONS: Elevated impulsivity, poor performance in future planning and emotional processing speed may be potential cognitive endophenotypes in AUD. These cognitive domains represent putative targets for prevention strategies and treatment of AUD.

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BACKGROUND AND AIMS: Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed medications for patients with anxiety/depression. These patients often have problems with substance use, but it remains unclear whether the risk of substance misuse is influenced by SSRI treatment. We aimed to determine whether SSRI treatment is associated with a decreased risk of acute substance misuse-related outcomes. DESIGN: Cohort study following individuals through Swedish nation-wide registers between July 2005 and December 2013 and comparing the risk of substance misuse outcomes during periods on- versus off-treatment within the same individual. SETTING: Swedish general population. PARTICIPANTS: Individuals with a newly dispensed prescription of SSRIs between July 2006 and December 2013 and an ICD-10 diagnosis of anxiety/depressive disorder before the first treatment initiation. The cohort included 146 114 individuals (60.7% women). MEASUREMENTS: Substance misuse outcomes included ICD-10 diagnoses of acute intoxications (F10.0-F19.0), accidental poisonings by alcohol or drugs (X41-X42, X45-X46) and substance-related criminal offenses. FINDINGS: The absolute rate of substance misuse increased sharply before the onset of SSRI treatment and decreased after treatment initiation. Stratified Cox regression models showed an elevated risk [hazard ratio (HR) = 1.70, 95% confidence interval (CI) = 1.62-1.78] of substance misuse outcomes during a 1-month period preceding treatment initiation, compared with the reference period of more than 1 month before treatment start. The on-treatment estimates (1-30 days, HR = 1.29, 95% CI = 1.23-1.37; 31-120 days, HR = 1.30, 95% CI = 1.24-1.35; and > 120 days, HR = 1.24, 95% CI = 1.18-1.30 after treatment initiation] were consistently lower than the 1-month pre-treatment estimate, but still elevated compared with the reference period. CONCLUSIONS: For people with anxiety/depression, the risk of substance misuse appears to be particularly elevated immediately before initiating selective serotonin reuptake inhibitor (SSRI) treatment, which may reflect the emergence or worsening of substance use problems concurrently with anxiety/depression. SSRI treatment appears to be associated with a lower risk of substance misuse compared with the 1-month period preceding treatment initiation, but causality remains uncertain.

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BACKGROUND: Impulsivity is associated with several psychiatric disorders, including substance use disorders (SUD) and attention deficit hyperactivity disorder (ADHD). A widely used questionnaire to assess impulsivity is the Barratt Impulsiveness Scale (BIS), and the aim of the current study was to evaluate the psychometric properties of the Swedish version of the BIS (swe-BIS). METHODS: The original BIS was translated to Swedish and back-translated by an authorized translator. The swe-BIS was administered to healthy controls (n = 113), patients with alcohol use disorder (n = 97), amphetamine use disorder (n = 37) and attention deficit hyperactive disorder (ADHD; n = 26). A subset of subjects (n = 62) completed the swe-BIS twice within 1 week. Psychometric evaluation of the swe-BIS included assessment of different indices of reliability (internal consistency, test-retest and agreement) and validity (response processess, divergent and convergent). Confirmatory factor analyses (CFA) were performed to assess several indices of model fit in five different models based on previously suggested subscales. RESULTS: Cronbach's alpha for all swe-BIS items in the full sample was 0.89, ranging from 0.78-0.87 within the different subgroups. The Pearson test-retest correlation for total score was 0.78 (p < 0.001), with greater test-retest correlations within compared to across different subscales. The Bland-Altman plot indicated high level of agreement between test and retest. The healthy individuals had lower swe-BIS score compared to the patients (t(267.3) = - 8.6; p < 0.001), and the swe-BIS total score was also significantly different between each of the four participant groups (p < 0.01 for all group comparisons). Furthermore, swe-BIS had greater correlations with impulsivity related scales compared to non-impulsivity related scales. The CFA analyses indicated that while no suggested model showed an optimal fit, the best model fit indices was found for the 3-factor model. CONCLUSIONS: The swe-BIS was found to have good to excellent psychometric properties with respect to the assessed indices of reliability and validity, supporting use of the scale in clinical research in both healthy individuals and patients with SUD and ADHD.

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BACKGROUND: Alcohol use disorder (AUD) is to a high degree heritable, and in clinical practice it is common to assert presence of alcohol abuse family history (FH) in treatment-seeking AUD patients. Patients with AUD also exhibit cognitive deficits, including elevated impulsivity and impairments in executive functions (EF), but less is known regarding the relation between FH and these cognitive domains. The aim of the current study was to investigate if alcohol abuse FH in AUD patients is associated with a specific cognitive profile. METHODS: Patients with AUD (n = 197) from Sweden (n = 106) and Belgium (n = 91) were recruited. Self-rated impulsivity was assessed by the Barratt Impulsiveness Scale (BIS). EF assessed were response inhibition (stop signal task), attention (rapid visual processing task), and working memory (digit span). A series of linear regression models were run to explore the effect of FH on cognitive outcomes. RESULTS: A FH of alcohol abuse was associated with elevated score in self-rated impulsivity assessed by the BIS, with the greatest effect on the subscale of nonplanning. There was no statistically significant association between FH and any of the other neuropsychological task outcomes. CONCLUSION: Presence of alcohol abuse FH within AUD patients could be a marker of higher impulsivity, which may have clinical implications regarding diagnostic evaluation and treatment.

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AIMS: To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors. DESIGN: A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins). SETTING AND PARTICIPANTS: A total of 3 004 401 people born in Sweden between 1951 and 1998. MEASUREMENTS: The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses. FINDINGS: In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI) = 4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI = -0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI = 5.17-5.18; grades: 0.09, 95% CI = 0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI = 4.15-4.20; grades: -0.83, 95% CI = -0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI = 4.59-4.60; grades: -0.38, 95% CI = -0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors. CONCLUSIONS: There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.

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INTRODUCTION: Alcohol dependence (AD) is associated with a dysregulated mesolimbocortical dopamine system-a pathway which is also implicated in both reward and cognition. The monoamine stabilizer (-)-OSU6162 (OSU) is a novel pharmacological compound with the ability to reduce ethanol intake and ethanol seeking in long-term drinking rats as well as reducing alcohol craving in AD patients. Dopaminergic drugs can both impair and improve cognitive functions, and the aim of the current study was to investigate the effect of OSU treatment on cognitive functioning in AD patients. METHOD: In a randomized double-blind placebo-controlled study, 56 individuals with AD received 14 days of OSU or placebo treatment. Neuropsychological tasks from the Cambridge Automated Neuropsychological Test Battery (CANTAB®) and other tasks were used to evaluate treatment effect on executive function/impulsivity, working memory, attention, emotional recognition, and divergent thinking. RESULTS: Treatment with OSU did not impair neuropsychological function in any of the cognitive domains investigated (all p > 0.1). In fact, OSU treatment did, compared to placebo, improve future planning ability (F(1,46) = 6.9; p = 0.012; Cohen's d = 0.54), verbal divergent thinking (F(1,44) = 10.1; p = 0.003; d = 0.96), and response time for emotional recognition (F(1,47) = 6.7; p = 0.013; d = 0.44). CONCLUSION: OSU treatment did not cause short-term cognitive side effects, further supporting the potential of OSU as a clinically feasible pharmacological treatment in AD patients. OSU treatment might improve future planning, verbal divergent thinking, and emotional recognition latency, which in turn may have a beneficial impact on alcohol use outcomes. Future studies are needed to confirm these preliminary findings.

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BACKGROUND: Alcohol use disorder (AUD) is associated with cognitive deficits such as impaired executive functions, which are hypothesized to contribute to the progression of the disease and worsen treatment outcome. Training of working memory (WM) to improve cognitive functions and thereby reduce alcohol use has been proposed as a novel treatment strategy. METHODS: Patients with AUD (n = 50) who were recruited to an outpatient addiction clinic were randomized to receive 5 weeks of active WM training or control training. Participants had weekly follow-up visits, and all cognitive training sessions were done online at home. Primary outcomes were WM function and change in self-reported heavy drinking. Secondary outcomes were craving, other drinking outcomes, and performance on a range of neuropsychological tasks from the Cambridge Neuropsychological Test Automated Battery. RESULTS: The active training group demonstrated a significantly greater improvement in verbal WM compared with the control group. No statistically significant effect of training was found on the primary drinking outcome, but a trend was observed indicating that WM training reduces the number of drinks per drinking occasion. WM training had no statistically significant effect on any of the other neuropsychological tasks. CONCLUSIONS: Cognitive training can improve WM function in individuals with AUD, suggesting that such interventions are feasible to administer in this patient population. The results do not support an effect of WM training on heavy drinking or transfer effects to other cognitive domains. Future studies should evaluate WM training as an adjunct to evidence-based treatments for AUD to assess potential synergistic effects.

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INTRODUCTION: Craving is a clinically important feature of alcohol use disorders (AUD), representing a diagnostic criterion as well as a target for treatment. The Desire for Alcohol Questionnaire (DAQ) is a widely used scale to measure craving. The aim of the current study was to evaluate the psychometric properties of a Swedish version of the Shortened-DAQ. METHOD: The English DAQ was translated into Swedish and back translated to English. Individuals with a diagnosis of AUD (n=118) participated in a laboratory experiment comprising presentation of alcohol and non-alcohol cues, as well as consumption of an alcoholic drink, with the aim of exploring changes in the craving responses following pharmacological treatment for AUD. Subjective craving across the experimental conditions was recorded using Shortened-DAQ and a Visual Analogue Scale (VAS). The psychometric analysis of the Shortened-DAQ investigated some important aspects of reliability, validity and the factor solution using principal components analysis. RESULTS: Cronbach's alphas were above 0.8 across all sessions, the test-retest correlations were statistically significant. In the alcohol cue session the Shortened-DAQ total score was significantly greater compared to the non-alcohol cue session, and correlated significantly with the VAS craving item across all sessions. The principal component analysis resulted in two significant factors comprised of (1) Alcohol desire and reinforcement and (2) Ability to control drinking. No difference in psychometric properties between treatment and placebo groups were found. CONCLUSION: In future clinical studies on alcohol craving responses in Swedish patients with AUD, we suggest the use of the Swedish Shortened-DAQ, due to its comparably swift administration and overall acceptable psychometric properties.

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Alcohol dependence (AD) and aggression-impulsivity are both associated with increased suicide risk. There is a need to evaluate clinical tools in order to improve suicide risk assessment of AD patients. The present study consisted of 95 individuals with a diagnosis of AD, consecutively admitted for addiction treatment, compared with 95 healthy controls. Suicidal risk was assessed together with exposure of violence and impulsivity. AD patients reported significantly higher rates of exposure to violence in childhood, as measured by the Karolinska Interpersonal Violence Scale (KIVS), compared to HC. Within the AD group, individuals with history of suicidal ideation and suicidal behavior reported higher levels of violence experience compared to AD individuals without such history. AD patients with previous suicidal ideation scored higher on self-reported impulsivity as assessed by the Barratt Impulsivity Scale (BIS). Our main finding was that experience of trauma and expression of violent behavior, coupled with increased impulsivity are associated with an elevated suicide risk in AD patients. Future longitudinal studies assessing these traits are needed to evaluate their potential role in identifying AD patients at risk of future suicide.

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Alcohol dependence is associated with a dysregulated dopamine system modulating reward, craving and cognition. The monoamine stabilizer (-)-OSU6162 (OSU6162) can counteract both hyper- and hypo-dopaminergic states and we recently demonstrated that it attenuates alcohol-mediated behaviors in long-term drinking rats. The present Phase II exploratory human laboratory study investigated to our knowledge for the first time the effects of OSU6162 on cue- and priming-induced craving in alcohol dependent individuals. Fifty-six alcohol dependent individuals were randomized to a 14-day-treatment period of OSU6162 or placebo after their baseline impulsivity levels had been determined using the Stop Signal Task. On Day 15, participants were subjected to a laboratory alcohol craving test comprised of craving sessions induced by: i) active - alcohol specific cues, ii) neutral stimuli and iii) priming - intake of an alcoholic beverage (0.20g ethanol/kg bodyweight). Subjective ratings of alcohol craving were assessed using the shortened version of the Desire for Alcohol Questionnaire and visual analog scales (VAS). OSU6162 treatment had no significant effect on cue-induced alcohol craving, but significantly attenuated priming-induced craving. Exploratory analysis revealed that this effect was driven by the individuals with high baseline impulsivity. In addition, OSU6162 significantly blunted the subjective liking of the consumed alcohol (VAS). Although the present 14-day-treatment period, showed that OSU6162 was safe and well tolerated, this exploratory human laboratory study was not designed to evaluate the efficacy of OSU6162 to affect alcohol consumption. Thus a larger placebo-controlled efficacyclinical trial is needed to further investigate the potential of OSU6162 as a novel medication for alcohol dependence.

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Recent studies indicate that emotional processes, mediated by the ventromedial prefrontal cortex (VMPC), are of great importance for moral judgment. Neurological patients with VMPC dysfunction have been shown to generate increased utilitarian moral judgments, i.e. are more likely to endorse emotionally aversive actions in order to maximize aggregate welfare, when faced with emotionally salient personal moral dilemmas. Patients with alcohol dependence (AD) also exhibit impairments in functions mediated by the prefrontal cortex, but whether they exhibit increased utilitarian moral reasoning has not previously been investigated. The aim of this study was to investigate moral judgment in AD patients (n = 20) compared to healthy controls (n = 20) matched by sex, age and education years. Each subject responded to a battery of 50 hypothetical dilemmas categorized as non-moral, moral impersonal and moral personal. They also responded to a questionnaire evaluating explicit knowledge of social and moral norms. Results confirmed our hypothesis that AD patients generated increased utilitarian moral judgment compared to controls when faced with moral personal dilemmas. Crucially, there was no difference in their responses to non-moral or impersonal moral dilemmas, nor knowledge of explicit social and moral norms. One possible explanation is that damage to the VMPC, caused by long term repeated exposure to alcohol results in emotional dysfunction, predisposing to utilitarian moral judgment. This work elucidates a novel aspect of the neuropsychological profile of AD patients, namely a tendency to generate utilitarian moral judgment when faced with emotionally salient moral personal dilemmas.

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A 45-year-old man with bipolar disease type I and post-traumatic frontal lobe lesions following a previous psychotic episode was hospitalised after having stopped taking aripiprazole (15 mg/day) and lithium (126 mg twice/daily). He presented with hypomania, psychosis, verbal unresponsiveness and disorientation. He engaged in compulsive onanism in public which resulted in the restriction of his freedom, suggesting impulse control disorder (ICD). Electroencephalogram showed no epileptiform activity. Brain CT-scan showed post-traumatic bifrontal and left occipital lesions. Viral and bacterial serologies were normal. Lithium was initially reinstated (same dose), but it was aripiprazole reinstatement at a lower dose (10 mg) that made his condition rapidly improve within 24-36 h. Aripiprazole is a partial dopamine D2-receptor antagonist that blocks dopamine at higher dopamine concentrations and augments/releases prefrontal cortex dopamine at lower concentrations. The rapid recovery suggests stabilisation of dopamine levels in the frontal lobes and that ICD may be modified by aripiprazole treatment.

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