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Contains fulltext : 240462.pdf (Publisher’s version ) (Open Access) Abundant evidence shows that early-life stress (ELS) predisposes for the development of stress-related psychopathology when exposed to stressors later in life, but the underlying mechanisms remain unclear. To study predisposing effects of mild ELS on stress sensitivity, we examined in a healthy human population the impact of a history of ELS on acute stress-related changes in corticolimbic circuits involved in emotional processing (i.e., amygdala, hippocampus, ventromedial prefrontal cortex; vmPFC). Healthy young male participants (n=120) underwent resting-state functional magnetic resonance imaging (fMRI) in two separate sessions (stress induction versus control). The Childhood Trauma Questionnaire (CTQ) was administered to index self-reported ELS, and stress induction was verified using salivary cortisol, blood pressure, heart rate, and subjective affect. Our findings show that self-reported ELS was negatively associated with baseline cortisol, but not with the acute stress-induced cortisol response. Critically, individuals with more self-reported ELS exhibited an exaggerated reduction of functional connectivity in corticolimbic circuits under acute stress. A mediation analysis showed that the association between ELS and stress-induced changes in amygdala-hippocampal connectivity became stronger when controlling for basal cortisol. Our findings show, in a healthy sample, that the effects of mild ELS on functioning of corticolimbic circuits only become apparent when exposed to an acute stressor, and may be buffered by adaptations in hypothalamic-pituitary-adrenal axis function. Overall, our findings might reveal a potential mechanism whereby even mild ELS might confer vulnerability to exposure to stressors later in adulthood. 20 p.

Contains fulltext : 194468.pdf (Publisher’s version ) (Open Access) Aggression replacement training (ART) is widely used to reduce aggression. Results regarding its effectiveness, however, are inconclusive regarding adults and specific populations displaying severe aggression. The current open uncontrolled treatment study aimed at assessing the social skills and anger control modules of the ART to reduce aggression in forensic psychiatric outpatients (FPOs). Furthermore, characteristics associated with treatment outcome and dropout were examined. The results suggested that aggression changed during the ART. In addition, higher baseline levels of trait aggression were associated with greater reductions of aggression, whereas more cognitive distortions were associated with less reduction. Treatment dropouts were characterized by higher levels of psychopathic traits, proactive aggression, and more weekly substance use. As there was a considerable amount of dropout; it is important to assess risk of dropping out of treatment and, subsequently, improve treatment motivation. This might enhance treatment adherence which may lead to a more successful reduction of aggression. 19 p.

Purpose Low levels of subjective wellbeing in prisoners may relate to mental health problems and difficulties in reintegration after imprisonment. The development of subjective wellbeing during imprisonment is mostly unclear. The purpose of this paper is to explore this development in a longitudinal study in association with mental disorders and socioeconomic factors. Design/methodology/approach Subjective wellbeing was assessed via a visual analogue scale and retrieved at admission to remand prison and then again after four and eight weeks. Changes in subjective wellbeing between time-points were analyzed taking into account mental disorders and socioeconomic factors, which were assessed by use of the Mini International Neuropsychiatric Interview – Plus and the Camberwell Assessment of Need – Forensic Version, respectively. Findings On average, subjective wellbeing declined directly after remand prison admission, but differences between individuals were found. At remand prison admission, subjective wellbeing significantly improved rather than declined in prisoners with alcohol and substance use disorders, housing problems, unemployment prior to incarceration and in relatively older prisoners. Other related factors did not add significance to this model. In contrast, during remand imprisonment subjective wellbeing displayed an overall increase. For this increase, no predicting factors were found. However, prisoners with an antisocial personality disorder are more at risk of experiencing a decrease in wellbeing during remand imprisonment. Originality/value In general, the Dutch prison system appears not to result in a decrease in subjective wellbeing in prisoners suffering from a mental disorder during remand imprisonment.

Brain serotonin (5-HT) plays a key role in aggressive behaviours and related psychopathologies, but its precise mechanism of action remains elusive. Genetic animal models may provide a tool to elucidate the relationship between aggression and serotonin. The present study showed that tryptophan hydroxylase 2 (Tph2) knockout (KO) rats, which exhibit profoundly diminished extracellular serotonin levels, display increased aggressiveness compared to their Tph2 wildtype (WT) counterparts. However, the level of aggression in Tph2 KO rats did not equal that of feral wild type Groningen (WTG) rats. To investigate whether enhanced 5-HT

Item does not contain fulltext Effective interactions between patients and staff have been associated with positive ward climate and therapeutic effects, but also pose a challenge in high secure forensic psychiatric settings. The goal of this study was to gain more insight into i) the characteristics that play a role in how staff members perceive the interpersonal style of patients, and ii) whether these perceptions are related to patients' evaluation of ward climate and satisfaction with daily staff. Staff members (n=69), rated the interpersonal style of 102 male patients. Satisfaction with daily staff and ward climate were rated by 45 patients. Results show that patient characteristics (primary diagnosis, patient age, disruptive behavior, recent problems with symptoms of major mental disorder and recent problems with treatment or supervision response) were related to how staff perceived the interpersonal style (i.e., affiliation and control) of patients. Furthermore, the level of affiliation was positively related to patients’ satisfaction with daily staff. Patients that were seen as more controlling by staff were less satisfied with the safety on their ward (as a factor of ward climate). The results indicate that perception of patients' interpersonal style entails patient related information and can be relevant for staff to use in their work. 8 p.

Contains fulltext : 162797.pdf (Publisher’s version ) (Open Access) The dopamine beta-hydroxylase (DbetaH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 mug/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes. 10 p.

Objectives Neuropsychiatric symptoms (NPS) are highly prevalent in dementia, but effective pharmacotherapy without important side effects is lacking. This study aims to assess the efficacy and safety of oral tetrahydrocannabinol (THC) in the treatment of NPS in dementia. Design Randomized, double-blind, placebo-controlled, repeated crossover trial, consisting of six treatment blocks of 2 weeks each. Setting Two hospital sites in The Netherlands, September 2011 to December 2013. Participants Patients with dementia and clinically relevant NPS. Intervention Within each block THC (0.75 mg twice daily in blocks 1–3 and 1.5 mg twice daily in blocks 4–6) and placebo were administered in random order for 3 consecutive days, followed by a 4-day washout. Measurements Primary outcome was change in Neuropsychiatric Inventory (NPI) score. Analyses were performed intention-to-treat. Data from all subjects were used without imputation. Sample size required for a power of 80% was 20 patients, because of repeated crossover. Results 22 patients (15 men, mean age 76.4 [5.3] years) were included, of whom 20 (91%) completed the trial. THC did not reduce NPI compared to placebo (blocks 1–3: 1.8, 97.5% CI: −2.1 to 5.8; blocks 4–6: −2.8, 97.5% CI: −7.4 to 1.8). THC was well tolerated, as assessed by adverse event monitoring, vital signs, and mobility. The incidence of adverse events was similar between treatment groups. Four non-related serious adverse events occurred. Conclusions This is the largest randomized controlled trial studying the efficacy of THC for NPS, to date. Oral THC did not reduce NPS in dementia, but was well tolerated by these vulnerable patients, supporting future higher dosing studies.

Background: Prospective memory is the ability to recall intended actions or events at the right time or in the right context. While cannabis is known to impair prospective memory, the acute effect of cocaine is unknown. In addition, it is not clear whether changes in prospective memory represent specific alterations in memory processing or result from more general effects on cognition that spread across multiple domains such as arousal and attention. Aims: The main objective of the study was, therefore, to determine whether drug-induced changes in prospective memory are memory specific or associated with more general drug-induced changes in attention and arousal. Methods: A placebo-controlled, three-way, cross-over study including 15 regular poly-drug users was set up to test the influence of oral cocaine (300 mg) and vaporised cannabis (300+150 ‘booster’ µg/kg bodyweight) on an event-based prospective memory task. Attentional performance was assessed using a divided attention task and subjective arousal was assessed with the Profile of Mood States questionnaire. Results: Results showed that cocaine enhanced prospective memory, attention and arousal. Mean performance of prospective memory and attention, as well as levels of arousal were lowest during treatment with cannabis as compared with placebo and cocaine as evinced by a significantly increased trend across treatment conditions. Prospective memory performance was only weakly positively associated to measures of attention and arousal. Conclusion: Together, these results indicate that cocaine enhancement of prospective memory performance cannot be fully explained by parallel changes in arousal and attention levels, and is likely to represent a direct change in the neural network underlying prospective memory.

Contains fulltext : 194467.pdf (Publisher’s version ) (Open Access) Aggression Replacement Training (ART) is widely used to reduce aggression and is considered to be effective although there are also inconsistent results. Studies investigating the effectiveness of ART do not focus on neurocognitive characteristics. Focusing on these aspects would result in enhanced understanding of underlying mechanisms of ART. The current open uncontrolled treatment study assessed whether neurocognitive characteristics were associated with change in aggression during the social skills and anger control modules of ART among forensic psychiatric outpatients. Furthermore, differences between treatment dropouts and completers and change in these characteristics during ART were examined. A reduction of trait aggression, cognitive distortions, and social anxiety was observed. Neurocognitive characteristics were not associated with change in aggression, could not distinguish treatment completers from dropouts, and did not change after ART. It is suggested that new paradigms should be developed which take into account the social context in which these impairments appear. 20 p.

Some drugs of abuse may produce dissociative symptoms, but this aspect has been understudied. We explored the dissociative potential of three recreational drugs (3,4-methylenedioxymethamphetamine (MDMA), cannabis, and cocaine) during intoxication and compared their effects to literature reports of dissociative states in various samples. Two placebo-controlled studies were conducted. In Study 1 (N=16), participants received single doses of 25, 50, and 100 mg of MDMA, and placebo. In Study 2 (N=21), cannabis (THC 300 mu g/kg), cocaine (HCI 300 mg), and placebo were administered. Dissociative symptoms as measured with the Clinician-Administered Dissociative States Scale (CADSS) significantly increased under the influence of MDMA and cannabis. To a lesser extent, this was also true for cocaine. Dissociative symptoms following MDMA and cannabis largely exceeded those observed in schizophrenia patients, were comparable with those observed in Special Forces soldiers undergoing survival training, but were lower compared with ketamine-induced dissociation. Cocaine produced dissociative symptoms that were comparable with those observed in schizophrenia patients, but markedly less than those in Special Forces soldiers and ketamine users. Thus, MDIVIA and cannabis can produce dissociative symptoms that resemble dissociative pathology. The study of drug induced dissociation is important, because it may shed light on the mechanisms involved in dissociative psychopathology. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Contains fulltext : 180429.pdf (Publisher’s version ) (Open Access) Deficits in multiple neuropsychological domains and specific personality profiles have been observed in attention-deficit/hyperactivity disorder (ADHD). In this study we investigated whether personality traits are related to neurocognitive profiles in adults with ADHD. Neuropsychological performance and Five Factor Model (FFM) personality traits were measured in adults with ADHD (n = 133) and healthy controls (n = 132). Three neuropsychological profiles, derived from previous community detection analyses, were investigated for personality trait differences. Irrespective of cognitive profile, participants with ADHD showed significantly higher Neuroticism and lower Extraversion, Agreeableness, and Conscientiousness than healthy controls. Only the FFM personality factor Openness differed significantly between the three profiles. Higher Openness was more common in those with aberrant attention and inhibition than those with increased delay discounting and atypical working memory / verbal fluency. The results suggest that the personality trait Openness, but not any other FFM factor, is linked to neurocognitive profiles in ADHD. ADHD symptoms rather than profiles of cognitive impairment have associations with personality traits. 7 p.

Item does not contain fulltext Oral tetrahydrocannabinol (THC) is currently studied for its possible efficacy on dementia-related neuropsychiatric symptoms (NPS), but might lead to increased risk of falling. This was a randomised, double-blind, crossover study to evaluate the effects of THC on mobility in dementia patients. Eighteen community-dwelling patients ( Mage=77 years) received 1.5 mg of oral THC twice daily and placebo, in random order, for three days, separated by a four-day washout. Balance and gait were assessed using SwayStarTM and GAITRiteTM within two hours after administration, in two consecutive intervention periods, under the following conditions: standing with eyes open (EO) and eyes closed (EC), preferred speed walking with and without a cognitive dual task. THC significantly increased sway during standing EC (roll angle 0.32[+/-0.6] degrees , p=0.05; pitch angle 1.04[+/-1.5] degrees , p=0.009; pitch velocity 1.96[+/-3.3] degrees /s, p=0.02), but not during standing EO. During preferred speed walking, THC increased stride length (4.3[+/-5.4] cm, p=0.005) and trunk sway (pitch angle 1.18[+/-1.6] degrees , p=0.005). No effects were observed during dual task walking. No differences in the number and type of adverse events were found, and no falls occurred after administration of THC. This study showed that 3 mg of THC per day has a benign adverse event profile regarding mobility and was well tolerated by community-dwelling dementia patients.

Contains fulltext : 126635.pdf (Publisher’s version ) (Closed access) Resting-state studies in depressed patients have revealed increased connectivity within the default mode network (DMN) and task-positive network (TPN). This has been associated with heightened rumination, which is the tendency to repetitively think about symptoms of distress. Here, we performed a pharmacological neuroimaging study in healthy volunteers to investigate whether short-term antidepressant administration could reduce DMN connectivity. We recorded resting-state functional magnetic resonance imaging (fMRI) scans in twenty-three healthy volunteers after two week intake of the combined serotonin-norepinephrine reuptake inhibitor (SNRI) duloxetine in a double-blind, placebo-controlled, crossover study. Duloxetine improved mood in part as a result of increased resilience to the mood-worsening effects of scanning and reduced DMN and TPN connectivity. Within the DMN, duloxetine reduced connectivity between the medial prefrontal cortex (MPFC) and the lateral parietal cortex (LPC) and uncoupled the MPFC from the dorsolateral prefrontal cortex (DLPFC). Within the TPN, duloxetine uncoupled the intraparietal sulcus (IPS) from the inferior occipital gyrus. These results show that two-week antidepressant administration reduces DMN and TPN connectivity in healthy volunteers, which may contribute to their antidepressant effects in depression.

Contains fulltext : 213997.pdf (Publisher’s version ) (Open Access) Previous research showed that the disposition to react with disproportionate aggression in adults is influenced by an interaction between a variant in the X-chromosomal monoamine oxidase A gene (MAOA) and early traumatic events. Such studies have often focused on a single type of trauma, whereas we know that experiencing multiple trauma types is associated with more detrimental consequences. The differential susceptibility hypothesis suggests that individuals who are most susceptible to adversity, are also most likely to benefit from supportive experiences in childhood. Differences in susceptibility are thought to be partly genetically driven. In the present study we explored whether a genotype of MAOA linked to lower expression of the gene (MAOA-L) modified the effect of multiple types of trauma on aggression and/or altered responsiveness to treatment among adults with severe aggression. Forensic psychiatric outpatients (FPOs) (N=150) receiving treatment for aggression regulation problems were recruited. Traumatic events and aggression were measured using self-report. FPOs with multiple trauma types and those with the MAOA-L allele reported more severe levels of aggression. No interaction effects between MAOA genotype and trauma emerged. There were no differences in response to the intervention between FPOs with and without the MAOA-L variant, whereas FPOs with a single type of trauma showed the slowest reduction of aggression. FPOs with multiple types of trauma reported the highest levels of aggression over the course of treatment. Future research is needed to elucidate this association in further detail. The current study emphasized the importance of early recognition of early traumatic events. 9 p.

Contains fulltext : 115407.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with major depressive disorder (MDD) display impairments in recollection, which have been explained by both hippocampal and prefrontal dysfunction. Here, we used an event-related fMRI design, to dissociate hippocampal and prefrontal contributions to the neural processes involved in recollection success and recollection attempt early in the course of MDD. METHODS: To disentangle state- and trait-effects of depression, we included 20 medication-naive patients with a first depressive episode, 20 medication-free patients recovered from a first episode, and 20 matched, healthy controls in an event-related fMRI study using a source recollection paradigm. RESULTS: Group comparisons revealed that during the acute state of depression there is an increase in left prefrontal activity related to recollection attempt, while there were no differences in neural correlates of successful recollection. CONCLUSIONS: Our results indicate that in the early course of depression, depressive state is associated with increased left prefrontal activation during the attempt to recollect source information suggesting an increased need for executive control during recollection in MDD. In this sample of first-episode MDD patients we found no evidence for hippocampal dysfunction.

Individuals with aggression regulation disorders tend to attribute hostility to others in socially ambiguous situations. Previous research suggests that this "hostile attribution bias" is a powerful cause of aggression. Facial expressions form important cues in the appreciation of others' intentions. Furthermore, accurate processing of facial expressions is fundamental to normal socialization. However, research on interpretation biases in facial affect is limited. It is asserted that a hostile interpretation bias (HIB) is likely to be displayed by individuals with an antisocial (ASPD) and borderline personality disorder (BPD) and probably also with an intermittent explosive disorder (IED). However, there is little knowledge to what extent this bias is displayed by each of these patient groups. The present study investigated whether a HIB regarding emotional facial expressions was displayed by forensic psychiatric outpatients (FPOs) and whether it was associated with ASPD and BPD in general or, more specifically, with a disposition to react with pathological aggression. Participants of five different groups were recruited: FPOs with ASPD, BPD, or IED, non-forensic patients with BPD (nFPOs-BPD), and healthy, non-aggressive controls (HCs). Results suggest that solely FPOs with ASPD, BPD, or IED exhibit a HIB regarding emotional facial expressions. Moreover, this bias was associated with type and severity of aggression, trait aggression, and cognitive distortions. The results suggest that a HIB regarding facial expressions is an important characteristic of pathological aggressive behavior. Interventions that modify the HIB might help to reduce the recurrence of aggression. Aggr. Behav. 43:386-397, 2017. © 2017 Wiley Periodicals, Inc.

Drugs that alter dopamine transmission have opposite effects on reward and punishment learning. These opposite effects have been suggested to depend on dopamine in the striatum. Here, we establish for the first time the neurochemical specificity of such drug effects, during reward and punishment learning in humans, by adopting a coadministration design. Participants (N = 22) were scanned on 4 occasions using functional magnetic resonance imaging, following intake of placebo, bromocriptine (dopamine-receptor agonist), sulpiride (dopamine-receptor antagonist), or a combination of both drugs. A reversal-learning task was employed, in which both unexpected rewards and punishments signaled reversals. Drug effects were stratified with baseline working memory to take into account individual variations in drug response. Sulpiride induced parallel span-dependent changes on striatal blood oxygen level-dependent (BOLD) signal during unexpected rewards and punishments. These drug effects were found to be partially dopamine-dependent, as they were blocked by coadministration with bromocriptine. In contrast, sulpiride elicited opposite effects on behavioral measures of reward and punishment learning. Moreover, sulpiride-induced increases in striatal BOLD signal during both outcomes were associated with behavioral improvement in reward versus punishment learning. These results provide a strong support for current theories, suggesting that drug effects on reward and punishment learning are mediated via striatal dopamine.

Item does not contain fulltext BACKGROUND: The inability of individuals with Alcohol Use Disorders (AUD) to recognize and describe their feelings and cravings may be due to alexithymia. Previous researches have shown evidence for a negative influence of alexithymia on treatment outcomes in patients with AUD. Therefore, it was hypothesized that high alexithymic patients with AUD would benefit less from cognitive behavioral therapy (CBT) compared with low alexithymic patients. METHODS: One hundred alcohol-dependent inpatients (DSM IV) were assessed with the Mini International Neuropsychiatric Interview for psychiatric disorders, the Toronto Alexithymia Scale (TAS-20), and the European Addiction Severity Index (EuropASI). Baseline alexithymia, as a categorical and continuous variable, was used to compare or relate baseline demographic and addiction characteristics, time in treatment, abstinence, and differences in addiction severity at 1-year follow-up. Analyses were performed using chi(2) test, analysis of variance or Kruskal-Wallis, paired t-tests or Wilcoxon's signed rank tests, multivariate logistic, and linear regression models, as appropriate. RESULTS: The prevalence of high alexithymia (TAS-20 > 61) was 45%. The total TAS-20 score correlated negatively with years of education (r = -.21; p = .04) and positively with the psychiatry domain of the EuropASI (r = .23; p = .04). Alexithymia showed no relation to abstinence, time in treatment, or change in severity of alcohol-related problems on the EuropASI. CONCLUSION: High alexithymic patients with AUD do benefit equally from inpatient CBT-like treatment as low alexithymic patients with AUD. SCIENTIFIC SIGNIFICANCE: Multimethod alexithymia assessments with an observer scale have been advised to judge the relationship with resulting outcome in CBT. 01 juli 2012

Item does not contain fulltext BACKGROUND: Hyperreactivity and impaired sensory gating of the acoustic startle response in alcohol dependence has been suggested to reflect a residual effect of previous detoxifications, increasing the severity of subsequent withdrawal episodes. Previous studies on the acoustic startle only included early-onset alcohol-dependent patients. The observed abnormalities may therefore also be specific for this subtype of alcohol dependence. We investigated the acoustic startle response in alcohol-dependent patients and healthy controls and hypothesized that (i) early-onset alcohol-dependent patients show increased acoustic startle responses compared with late-onset alcohol-dependent patients and healthy controls, and (ii) the duration of alcohol dependence or the number of prior detoxifications would not explain the differences in the acoustic startle between early- and late-onset alcohol dependence. METHODS: The acoustic startle reflex was assessed in detoxified, male alcohol-dependent patients (N = 83) and age-matched healthy male controls (N = 86). Reflex eye blink responses to an auditory startle stimulus were measured by means of electromyographic recordings over the right orbicularis oculi muscle. Reflex amplitudes and levels of prepulse inhibition (PPI) were analyzed. RESULTS: There was no association between number of previous withdrawals and the startle response or PPI. Early-onset alcohol-dependent patients showed higher acoustic startle amplitudes compared with late-onset alcohol-dependent patients and healthy controls [75/105 dB: F(2, 166) = 9.2, p < 0.001; 85/105 dB: F(2, 166) = 12.1, p < 0.001; 95 dB: F(2, 166) = 8.2, p < 0.001; 105 dB: F(2, 166) = 9.7, p < 0.001], and there were no differences in PPI. CONCLUSIONS: Increased acoustic startle response in detoxified early-onset alcohol-dependent patients may reflect a trait marker specifically involved in early-onset alcohol dependence. The findings of the current study do not support the hypothesis that the increased startle response is a residual state marker. 01 juni 2012

Item does not contain fulltext It is unknown how antidepressants reverse mood-congruent memory bias, a cognitive core factor causing and maintaining depression. Using a double-blind, placebo-controlled, cross-over design, we investigated the effect of a short-term treatment (14 days) with the dual reuptake inhibitor duloxetine on neural correlates of mood-congruent and mood-incongruent memory formation and retrieval in healthy volunteers who underwent a sad mood induction procedure. Duloxetine did not affect acute mood state or memory performance, but interacted with brain processes mediating mood-congruent memory. It decreased activity related to successful memory formation for mood-congruent and -incongruent items in a set of brain regions comprising the putamen and the middle frontal gyrus, as well as the middle and the anterior cingulate cortex. Duloxetine specifically increased amygdala activity related to successful memory retrieval for mood-incongruent items. Here we show that short-term administration of duloxetine affects the neural correlates of emotional memory formation and retrieval in a set of brain regions whose processing is related to affective state and its regulation. While duloxetine suppressed the neural correlates of emotional memory formation in general, it specifically enhanced amygdala processes associated with mood-incongruent memory retrieval. This pattern of results shows how an antidepressant may reduce emotional memory formation and reverse mood-congruent processing biases at retrieval.

Contains fulltext : 96622.pdf (Publisher’s version ) (Closed access) Episodic memory impairment is considered to be a core cognitive deficit of Major Depressive Disorder (MDD) and has motivated a line of research investigating the role of the amygdala and the hippocampus in depression. While functional neuroimaging studies have focused on memory for emotional but not for neutral stimuli, in order to probe amygdala function, structural imaging studies have tied episodic memory to hippocampal function. We therefore investigated the neural correlates of episodic memory formation for neutral stimuli in 20 patients with a first depressive episode, 20 patients recovered from a first episode and 20 healthy controls. Because there is evidence that the amygdala exhibits hyperactive responses even to neutral stimuli in depressed subjects, we specifically explored the potential role of the amygdala in forming episodic memories with neutral content. Both patient groups showed stronger subsequent memory effects in the amygdala when compared to controls, in the absence of any differences in hippocampal activity between groups. Patients with a first episode of MDD showed increased activity related to episodic memory formation in a fronto-limbic network. These state-related activations may be related to a compensatory mechanism, which is supported by the absence of any differences in memory performance between groups. These findings represent initial evidence for a neurocognitive trait or vulnerability marker of depression-amygdala involvement in episodic memory formation of neutral stimuli.

Contains fulltext : 87624.pdf (Publisher’s version ) (Closed access) OBJECTIVE: It remains unclear whether unipolar psychotic depression should be treated with an antidepressant and an antipsychotic or with an antidepressant alone. METHOD: In a multi-center RCT, 122 patients (18-65 years) with DSM-IV-TR psychotic major depression and HAM-D-17 > or = 18 were randomized to 7 weeks imipramine (plasma-levels 200-300 microg/l), venlafaxine (375 mg/day) or venlafaxine-quetiapine (375 mg/day, 600 mg/day). Primary outcome was response on HAM-D-17. Secondary outcomes were response on CGI and remission (HAM-D-17). RESULTS: Venlafaxine-quetiapine was more effective than venlafaxine with no significant differences between venlafaxine-quetiapine and imipramine, or between imipramine and venlafaxine. Secondary outcomes followed the same pattern. CONCLUSION: That unipolar psychotic depression should be treated with a combination of an antidepressant and an antipsychotic and not with an antidepressant alone, can be considered evidence based with regard to venlafaxine-quetiapine vs. venlafaxine monotherapy. Whether this is also the case for imipramine monotherapy is likely, but cannot be concluded from the data. 01 maart 2010

Contains fulltext : 88956.pdf (Publisher’s version ) (Closed access) Brain-derived neurotrophic factor (BDNF) is involved in memory and the pathophysiology of various neuropsychiatric disorders. A single nucleotide polymorphism in the human BDNF gene (Val66Met) affects memory, and influences Alzheimer's disease and depression vulnerability in a sex-specific manner. Recent animal studies suggest that BDNF mediates memory for emotional experiences in the amygdala, but it is currently unknown whether BDNF Val66Met influences memory processing in the amygdala. Here, we investigated its effect on the successful encoding and recognition of biologically salient stimuli. Forty-seven healthy volunteers memorized and recognized faces while their brain activity was measured with event-related functional MRI. No significant differences in memory performance were observed between Val homozygotes and Met allele carriers. The imaging results demonstrated BDNF genotype x sex interactions in the amygdala during memory formation, and in the prefrontal cortex and posterior cingulate cortex during memory retrieval. Subsequent tests showed a larger contribution of these brain regions to successful encoding and retrieval in male Met allele carriers than male Val homozygotes, whereas no significant differences were observed in females. These results provide preliminary evidence that the BDNF Val66Met polymorphism influences specific mnemonic operations underlying encoding and retrieval of salient stimuli, and suggest less efficient memory processing in male Met allele carriers. Furthermore, the sex-specific genotype effects may contribute to sex-specific effects of BDNF Val66Met on depression vulnerability.

Contains fulltext : 81790.pdf (Publisher’s version ) (Closed access) BACKGROUND: Psychomotor slowing is regarded as an important clinical phenomenon in schizophrenia and simple graphic tasks consistently revealed deficits in the (implicit) planning and execution of motor actions in patients with chronic schizophrenia. The aim of the present study is to test the hypothesis that such deficits are already present in patients with recent-onset schizophrenia. METHODS: Psychomotor performance and several aspects of movement planning were analyzed in 36 patients with recent-onset schizophrenia and a group of 33 matched healthy controls. Participants were required to draw patterns varying in complexity in three different figure-copying tasks, match and draw simple symbols in the Digit Symbol Substitution Test (DSST) and connect target circles with varying orientations in a newly developed Line Sequencing Task. RESULTS: Relative to the controls, the patients showed significantly longer initiation times when the patterns in the copying tasks became more complex, suggesting increased difficulty in movement planning. Overall, they were not slowed in the execution stages. In the cognitively more demanding DSST, the patients were significantly slowed in both the initiation and movement phases. Moreover, they selected less optimal movement directions in the Line Sequencing Task. CONCLUSIONS: Psychomotor planning deficits are already present in the early stages of schizophrenia and involve deficient planning but intact motor action. Planning difficulties can be detected in motor sequences as well. The results indicate that the cognitive deficit in schizophrenia also affects the implicit planning of very simple movements.

Contains fulltext : 77274.pdf (Publisher’s version ) (Closed access) BACKGROUND: Reduced metabolic activity in frontal brain regions, and reduced striatal dopamine receptor densities have been shown in alcohol dependent patients. Little is known on functional changes in the fronto-striatal-thalamic dopaminergic neurocircuitry in these patients. The objective of this study was to assess sensitivity of prefrontal dopamine receptors in alcohol dependent patients. EXPERIMENTAL PROCEDURES: Male alcohol dependent patients (N=40) and healthy controls (N=39) performed an AX-continuous performance test before and after administration of the DA agonist apomorphine (0.005 mg/kg). RESULTS: At baseline alcohol dependent patients were slower and less accurate compared to healthy controls. After administration of apomorphine, performance improved in alcohol dependent patients and deteriorated in healthy controls. CONCLUSIONS: Reduced cognitive performance in alcohol dependent patients compared with healthy controls may indicate dopamine dysfunctioning at the prefrontal level. Improvement of cognitive performance in alcohol dependent patients after administration of apomorphine and deterioration in healthy controls provides evidence for an inverted U-shape relation between dopaminergic functioning and cognitive performance. 6 p.

Contains fulltext : 77468.pdf (Publisher’s version ) (Closed access) BACKGROUND: The amygdala and hippocampus play a key role in the neural circuitry mediating depression. It remains unclear how much structural and functional changes of amygdala and hippocampus reflect the acute state of depression or an underlying neurobiological trait marker of depression. METHODS: High-resolution anatomical images were acquired in 20 medication-naive major depressive disorder (MDD) patients with a current first episode, 20 medication-free patients recovered from a first episode of MDD, and 20 healthy control subjects that were matched for age, gender, and level of education. Manual volumetry of amygdala and hippocampus was performed on coronal images. Volumetric measurements of brain volume and intracranial volume were acquired with automatic segmentation procedures. RESULTS: Both amygdalae were significantly enlarged in currently depressed patients, whereas there was no significant difference between recovered patients and control subjects. The amygdala enlargement correlated positively with the severity of depressive state but with no other clinical or neuropsychological variable. The hippocampal volume did not differ between groups. CONCLUSIONS: A state related increase of amygdala volume can be detected early in the course of MDD. Neurotoxic effects might account for the fact that state-related amygdala enlargement has not been found in recurrent depression with relative long illness duration.

The Reactive Proactive Questionnaire (RPQ) was originally developed to assess reactive and proactive aggressive behavior in children. Nevertheless, some studies have used the RPQ in adults. This study examines the reliability of the RPQ within an adult sample by investigating whether reactive and proactive aggression can be distinguished at a variable- and person-based level. Male adults from forensic samples (N = 237) and from the general population (N = 278) completed the RPQ questionnaire. Variable-based approaches, including factor analyses, were conducted to verify the two-factor model of the RPQ and to examine alternative factor solutions of the 23 items. Subsequently, a person-based approach, i.e., Latent Class Analysis (LCA), was executed to identify homogeneous classes of subjects with similar profiles of aggression in the observed data. The RPQ proved to have sufficient internal consistency. Multiple-factor models were examined, but the original two-factor model was statistically and theoretically considered as most solid and in line with previous research. The multi-level LCA identified three different classes of aggression severity (class 1 showed low aggressive behavior; class 2 subjects displayed modest aggression levels; and class 3 exhibited the highest level of aggressive behavior). In addition, class 1 and 2 showed more reactive than proactive aggression, whereas class 3 displayed comparable levels of reactive/proactive aggression. The RPQ appears to have clinical relevance for adult populations in the way that it can distinguish severity levels of aggression. Before the RPQ is implemented in adult populations, norm scores need to be developed. Aggr. Behav. 43:155-162, 2017. © 2016 Wiley Periodicals, Inc.

Objective: To study the efficacy and safety of low-dose oral tetrahydrocannabinol (THC) in the treatment of dementia-related neuropsychiatric symptoms (NPS). Methods: This is a randomized, double-blind, placebo-controlled study. Patients with dementia and clinically relevant NPS were randomly assigned to receive THC 1.5 mg or matched placebo (1:1) 3 times daily for 3 weeks. Primary outcome was change in Neuropsychiatric Inventory (NPI), assessed at baseline and after 14 and 21 days. Analyses were based on intention-to-treat. Results: Twenty-four patients received THC and 26 received placebo. NPS were reduced during both treatment conditions. The difference in reduction from baseline between THC and placebo was not significant (mean difference NPI total : 3.2, 95% confidence interval [CI] −3.6 to 10.0), nor were changes in scores for agitation (Cohen-Mansfield Agitation Inventory 4.6, 95% CI −3.0 to 12.2), quality of life (Quality of Life–Alzheimer9s Disease −0.5, 95% CI −2.6 to 1.6), or activities of daily living (Barthel Index 0.6, 95% CI −0.8 to 1.9). The number of patients experiencing mild or moderate adverse events was similar (THC, n = 16; placebo, n = 14, p = 0.36). No effects on vital signs, weight, or episodic memory were observed. Conclusions: Oral THC of 4.5 mg daily showed no benefit in NPS, but was well-tolerated, which adds valuable knowledge to the scarce evidence on THC in dementia. The benign adverse event profile of this dosage allows study of whether higher doses are efficacious and equally well-tolerated. Classification of evidence: This study provides Class I evidence that for patients with dementia-related NPS, low-dose THC does not significantly reduce NPS at 21 days, though it is well-tolerated.

Item does not contain fulltext Trait impulsivity has been linked to addiction in humans. It has been suggested that drug users with high trait impulsivity levels are more sensitive to subjective drug intoxication. This study assessed whether subjective response to drugs differs between drug users with normal or high levels of trait impulsivity. Regular drug users (N = 122) received doses of cocaine HCl, cannabis, and placebo in a three-way crossover study. Their mood, dissociative state, and psychedelic symptoms were measured with subjective rating scales (CADDS, Bowdle, POMS). Trait impulsivity was assessed with the Barratt Impulsiveness Scale. Cannabis increased dissociation and psychedelic state, as well as fatigue, confusion, depression and anxiety, and decreased arousal, positive mood, vigor, friendliness, and elation. Cocaine increased dissociation, psychedelic state, vigor, friendliness, elation, positive mood, anxiety and arousal, while decreasing fatigue. Only a few subjective items revealed a drug x trait impulsivity interaction, suggesting that psychedelic symptoms were most intense in high impulsivity subjects. Trait impulsiveness ratings were negatively correlated with ratings of vigor (r = -.197) and positively correlated with ratings of loss of thought control (r = .237) during cannabis intoxication. It is concluded that a broad association between trait impulsivity and psychedelic subjective drug experience appears to be absent. 11 p.

Introduction:Alcohol dependence and anxiety disorders often co-occur. Yet, the effect of co-morbid anxiety disorders on the alcohol relapse-risk after treatment is under debate. This study investigated the effect of co-morbid anxiety disorders on relapse rates in alcohol dependence. We hypothesized that co-morbid anxiety disorders would be particularly predictive for early relapse, but not late relapse.Subjects and methods:In a prospective design, male alcohol dependent patients (n = 189) were recruited from an inpatient detoxification clinic. Psychiatric diagnoses and personality traits were assessed using the Mini International Neuropsychiatric Interview for psychiatric disorders and the Temperament and Character Inventory. The addiction severity index was used to assess addiction severity and follow-up.Results:One year after detoxification, 81 patients (53%) relapsed and nine patients (7%) were deceased, due to alcohol related causes. Co-morbid anxiety disorder, marital status, addiction severity, in particular legal problems, and harm avoidance predicted relapse. Anxiety disorders specifically predicted early relapse.Conclusion:Alcohol dependence is a severe mental disorder, with high relapse rates and high mortality. Alcohol dependent patients with co-morbid anxiety disorders are particularly prone to relapse during the first three months of treatment. These patients may therefore require additional medical and psychological attention.

Item does not contain fulltext There is a lack of detailed information on the role of substance use disorders (SUD) as a substantial factor in offences and treatment in forensic psychiatric patients. The aim of this study was to get a better understanding of these specifics. Clinical records of 193 male patients admitted to a Dutch forensic psychiatric hospital were scrutinized on anamnestic, diagnostic and risk assessment data. One of the central findings was that the prevalence of SUDs was high. Patients with an SUD had a more extensive criminal history, unstable and deviant lifestyle and higher risk of violent behavior than patients without a substance use disorder. No differences were found in duration of treatment, aggressive incidents and leave. Another important finding was that a distinction could be made between patients with substance use as a primary criminogenic risk factor and patients with substance use as a secondary risk factor. Although substance use is identified as a general risk factor, this study supports the idea of sub categorization of patients with an SUD and emphasizes the need for a different treatment approach. Further study is needed to identify specific treatment approaches, based on more differentiated profiles of these patients. 5 p.

Item does not contain fulltext RATIONALE: Knowing how commonly used drugs affect performance monitoring is of great importance, because drug use is often associated with compromised behavioral control. Two of the most commonly used recreational drugs in the western world, 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") and ethanol (alcohol), are also often used in combination. The error-related negativity (ERN), correct-related negativity (CRN), and N2 are electrophysiological indices of performance monitoring. OBJECTIVES: The present study aimed to investigate how ethanol, MDMA, and their co-administration affect performance monitoring as indexed by the electrophysiological correlates. METHODS: Behavioral and EEG data were obtained from 14 healthy volunteers during execution of a speeded choice-reaction-time task after administration of ethanol, MDMA, and combined ethanol and MDMA, in a double-blind, placebo-controlled, randomized crossover design. RESULTS: Ethanol significantly reduced ERN amplitudes, while administration of MDMA did not affect the ERN. Co-administration of MDMA and ethanol did not further impair nor ameliorate the effect of ethanol alone. No drug effects on CRN nor N2 were observed. DISCUSSION: A decreased ERN following ethanol administration is in line with previous work and offers further support for the impairing effects of alcohol intoxication on performance monitoring. This impairment may underlie maladaptive behavior in people who are under influence. Moreover, these data demonstrate for the first time that MDMA does not affect performance monitoring nor does it interact with ethanol in this process. These findings corroborate the notion that MDMA leaves central executive functions relatively unaffected.

Objective: The amplitude and latency of the P300 may be associated by variations in dopaminergic genes. The current study was conducted to determine whether functional variants of the catechol-O-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) gene were associated with P300 amplitude and latency in an auditory oddball task. Methods: The P300 ERP was assessed by a two-tone auditory oddball paradigm in a large sample of 320 healthy volunteers. The Val108/158Met polymorphism (rs4680) of the COMT gene and the -1021C>T polymorphism (rs1611115) of the DBH gene were genotyped. P300 amplitude and latency were compared across genotype groups using analysis of variance. Results: There were no differences in demographic characteristics in subjects for genotypic subgroups. No genotype associations were observed for the P300 amplitude and latency on frontal, central and parietal electrode positions. Conclusions: COMT Val108/158Met and DBH -1021C>T polymorphisms do not show evidence of association with characteristics of the P300 ERP in an auditory oddball paradigm in healthy volunteers. Significance: We failed to find evidence for the association between dopaminergic enzymatic polymorphisms and the P300 ERP in healthy volunteers, in the largest study undertaken to date. (C) 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland All rights reserved.

Item does not contain fulltext Optimal behavior depends on the ability to assess the predictive value of events and to adjust behavior accordingly. Outcome processing can be studied by using its electrophysiological signatures-that is, the feedback-related negativity (FRN) and the P300. A prominent reinforcement-learning model predicts an FRN on negative prediction errors, as well as implying a role for the FRN in learning and the adaptation of behavior. However, these predictions have recently been challenged. Notably, studies so far have used tasks in which the outcomes have been contingent on the response. In these paradigms, the need to adapt behavioral responses is present only for negative, not for positive feedback. The goal of the present study was to investigate the effects of positive as well as negative violations of expectancy on FRN amplitudes, without the usual confound of behavioral adjustments. A reversal-learning task was employed in which outcome value and outcome expectancy were orthogonalized; that is, both positive and negative outcomes were equally unexpected. The results revealed a double dissociation, with effects of valence but not expectancy on the FRN and, conversely, effects of expectancy but not valence on the P300. While FRN amplitudes were largest for negative-outcome trials, irrespective of outcome expectancy, P300 amplitudes were largest for unexpected-outcome trials, irrespective of outcome valence. These FRN effects were interpreted to reflect an evaluation along a good-bad dimension, rather than reflecting a negative prediction error or a role in behavioral adaptation. By contrast, the P300 reflects the updating of information relevant for behavior in a changing context. 10 p.

Genetic factors and childhood adverse experiences contribute to the vulnerability to alcohol dependence. However, empirical data on the interplay between specific genes and adverse experiences are few. The COMT Val158Met and DRD2/ANKK1 Taq1A genotypes have been suggested to affect both stress sensitivity and the risk for alcohol dependence. This study tested the hypothesis that genetic variation in COMT Val158Met and DRD2/ANKK1 Taq1A interacts with childhood adverse experiences to predict alcohol dependence. Male abstinent alcohol-dependent patients (n = 110) and age-matched healthy male controls (n = 99) were genotyped for the COMT Val158Met and the DRD2/ANKK1 Taq1A genotypes. Childhood adverse events were measured using three self-report questionnaires. Alcohol dependence severity, age of onset and duration of alcohol dependence were analyzed as secondary outcome measures. Statistical analysis involved logistic regression analysis and analysis of variance. Alcohol-dependent patients reported increased childhood adversity. The interaction between childhood adversity and the COMT Val158Met genotype added significantly to the prediction model. This gene-environment interaction was confirmed in the analysis of the secondary outcome measures, i.e. alcohol dependence severity, age of onset and duration of alcohol dependence. The DRD2/ANKK1 Taq1A genotype was not related to alcohol dependence, nor did it interact with childhood adversity in predicting alcohol dependence. This study provides evidence for a gene-environment interaction in alcohol dependence, in which an individual's sensitivity to childhood adverse experience is moderated by the COMT genotype. Exposed carriers of a low-activity Met allele have a higher risk to develop severe alcohol dependence than individuals homozygous for the Val allele.

Contains fulltext : 102824.pdf (Publisher’s version ) (Open Access) Psychopathy (PP) is associated with marked abnormalities in social emotional behaviour, such as high instrumental aggression (IA). A crucial but largely ignored question is whether automatic social approach-avoidance tendencies may underlie this condition. We tested whether offenders with PP show lack of automatic avoidance tendencies, usually activated when (healthy) individuals are confronted with social threat stimuli (angry faces). We applied a computerized approach-avoidance task (AAT), where participants pushed or pulled pictures of emotional faces using a joystick, upon which the faces decreased or increased in size, respectively. Furthermore, participants completed an emotion recognition task which was used to control for differences in recognition of facial emotions. In contrast to healthy controls (HC), PP patients showed total absence of avoidance tendencies towards angry faces. Interestingly, those responses were related to levels of instrumental aggression and the (in)ability to experience personal distress (PD). These findings suggest that social performance in psychopaths is disturbed on a basic level of automatic action tendencies. The lack of implicit threat avoidance tendencies may underlie their aggressive behaviour. 6 p.

BackgroundDepressed individuals demonstrate a poorer ability to recognize the emotions of others, which could contribute to difficulties in interpersonal behaviour. This emotion recognition deficit appears related to the depressive state and is particularly pronounced when emotions are labelled semantically. Here, we investigated its neural basis by comparing emotion recognition processing between depressed, recovered and healthy individuals.MethodMedication-naive patients with a first major depressive episode, medication-free patients who had recovered from a first episode, and a group of matched healthy individuals participated. They were requested to identify the emotion of angry and fearful face stimuli, either by matching them to other emotional faces on a perceptual basis or by matching them to a semantic label, while their brain activity was measured with functional magnetic resonance imaging.ResultsThe depressed individuals performed worse than recovered and healthy individuals on the emotion-labelling but not the emotion-matching task. The labelling deficit was related to increased recruitment of the right amygdala, left inferior frontal gyrus and anterior cingulate cortex.ConclusionsDeficits in semantic labelling of negative emotions are related to increased activation in specific brain regions and these abnormalities are mood state-dependent. These results indicate that accessing semantic knowledge about negative information triggers increased amygdala and left inferior frontal gyrus processing, which subsequently impairs task-relevant behaviour. We propose that this may reflect the activation of negative schemas.

Introduction: In Western societies a considerable percentage of young people expose themselves to the combination of 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”). Cannabis (main active compound D9-tetrahydrocannabinol or THC) is frequently co-used with ecstasy (Parrott et al., 2007). Despite the prevalence of co-administration of MDMA and THC, the effects of combined use of these substances on behaviour in humans have so far not been investigated. The aim of the present study was to assess the acute effects of (co-) administration of MDMA and THC (the main psychoactive compound of cannabis) on pharmacokinetics, psychomotor performance, memory and subjective experience over time. Methods: We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (12 male, 4 female) between the ages of 18 and 27. MDMA (100 mg) was given orally, THC (4, 6, and 6 mg, interval of 90 minutes) was vaporized and inhaled. Outcome measures were assessed repeatedly, i.e. before MDMA administration and at 15, 60, 105, 150, 240 and 300 minutes post drug administration, with the exception of the 18 word list memory task, which was performed 120 minutes after drug administration. Repeated measures consisted of blood sampling for analysis of study drug kinetics and assessments of postural stability (body sway), psychomotor function (eye movements and the Rotor Pusuit Task), memory (18 word list and N-back task), and subjective effects (VAS). Results: Body sway was increased, i.e. postural position was impaired, in all drug conditions compared to placebo. THC alone as well as co-administration of THC plus MDMA increased body sway compared to the MDMA alone condition. Eye movements were unaffected by THC, MDMA increased the peak velocity of eye movements. The Rotor Pursuit task (see Figure 1) performance was significantly impaired in the THC condition and the MDMA plus THC condition compared to the placebo and MDMA condition. MDMA alone did not affect the Rotor Pursuit task. Immediate recall of words was impaired in all drug conditions compared to placebo. Delayed recall and delayed recognition did not show a significant main effect of drug administration. The effects of (co-administration) of THC on the N-back working memory task were time- and dose dependent, where THC generally induced a robust but short-lived impairment of working memory. N-back performance was unaffected in the MDMA condition. Co-administration of THC and MDMA enhanced separate subjective drug effects: ratings of 'drug strength', 'internal and external perception', and 'feeling high' were increased compared to the MDMA condition. Conclusion: These results suggest that THC may exert much of its cognitive impairment via a common mechanism of reduced alertness. The stimulant effects of MDMA may attenuate this effect, but could not overcome THC induced impairments in the current study. Overall, THC induced more robust cognitive impairment compared to MDMA. Co-administration of THC with MDMA increased desired subjective drug effects and drug strength compared to the MDMA condition, which may explain the widespread use of this combination.

BackgroundPsychopathy (PP) is associated with a performance deficit in a variety of stimulus–response and stimulus–reinforcement learning paradigms. We tested the hypothesis that failures in error monitoring underlie these learning deficits.MethodWe measured electrophysiological correlates of error monitoring [error-related negativity (ERN)] during a probabilistic learning task in individuals with PP (n=13) and healthy matched control subjects (n=18). The task consisted of three graded learning conditions in which the amount of learning was manipulated by varying the degree to which the response was predictive of the value of the feedback (50, 80 and 100%).ResultsBehaviourally, we found impaired learning and diminished accuracy in the group of individuals with PP. Amplitudes of the response ERN (rERN) were reduced. No differences in the feedback ERN (fERN) were found.ConclusionsThe results are interpreted in terms of a deficit in initial rule learning and subsequent generalization of these rules to new stimuli. Negative feedback is adequately processed at a neural level but this information is not used to improve behaviour on subsequent trials. As learning is degraded, the process of error detection at the moment of the actual response is diminished. Therefore, the current study demonstrates that disturbed error-monitoring processes play a central role in the often reported learning deficits in individuals with PP.

Contains fulltext : 87910.pdf (Publisher’s version ) (Closed access) In Western societies, a considerable percentage of young people use 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'). The use of alcohol (ethanol) in combination with ecstasy is common. The aim of the present study was to assess the acute psychomotor and subjective effects of (co-) administration of MDMA and ethanol over time and in relation to the pharmacokinetics. We performed a four-way, double blind, randomized, crossover, placebo-controlled study in 16 healthy volunteers (nine men, seven women) between the ages of 18 and 29. MDMA (100 mg) was given orally while blood alcohol concentration was maintained at pseudo-steady state levels of approximately 0.6 per thousand for 3 h by a 10% intravenous ethanol clamp. MDMA significantly increased psychomotor speed but did not affect psychomotor accuracy and induced subjective arousal. Ethanol impaired both psychomotor speed and accuracy and induced sedation. Coadministration of ethanol and MDMA improved psychomotor speed but impaired psychomotor accuracy compared with placebo and reversed ethanol-induced sedation. Pharmacokinetics and pharmacodynamics showed maximal effects at 90-150 min after MDMA administration after which drug effects declined in spite of persisting MDMA plasma concentration, with the exception of ethanol-induced sedation, which manifested itself fully only after the infusion was stopped. In conclusion, results show that subjects were more aroused when intoxicated with both substances combined compared with placebo, but psychomotor accuracy was significantly impaired. These findings may have implications for general neuropsychological functioning as this may provide a sense of adequate performance that does not agree with a significant reduction in psychomotor accuracy. 01 februari 2010

Contains fulltext : 77272.pdf (Publisher’s version ) (Open Access) Background Remarkably, little attention has been paid to the role of intimate partners and their drinking behavior in relation to adolescent alcohol use. In the current study, we examined associations between adolescent alcohol use and romantic partners’ drinking behavior. Methods A total of 428 families, consisting of both parents and two adolescents (aged 13.4 and 15.2 at Time 1) participated in a prospective study with four annual waves. Correlations and multivariate regressions were used to examine (1) similarity in drinking behaviors of adolescents and intimate partners, (2) whether alcohol use of partners prospectively predicts adolescent alcohol consumption, and (3) whether adolescents who consume alcohol select partners over time who show similar drinking behaviors. Results (1) Frequency of alcohol consumption of adolescents and of their romantic partners correlated significantly. (2) Alcohol use of partners was not predictive of adolescent alcohol consumption over time, if previous levels of alcohol consumption were taken into account. (3) Adolescents acquired partners with similar drinking behaviors. Gender effects were found; adolescent girls, but not boys, were more likely to become involved with partners who also frequently consumed alcohol. Conclusions Regarding alcohol consumption, adolescents and their intimate partners were relatively similar in alcohol use. This resemblance is best explained by adolescents’ selection of future partner on the basis of alcohol consumption. Less indication was found for influence effects, perhaps due to the transient nature of most adolescent romantic relationships.

Contains fulltext : 80307.pdf (Publisher’s version ) (Closed access) This study assessed the acute physiologic effects over time of (co)administration of Delta9-tetrahydrocannabinol (Delta9-THC) (the main psychoactive compound of cannabis) and 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") in 16 healthy volunteers. Pharmacokinetics and cardiovascular, temperature, and catecholamine responses were assessed over time. Both single-drug conditions robustly increased heart rate, and coadministration showed additive effects. MDMA increased epinephrine and norepinephrine concentrations, whereas THC did not affect the catecholamine response. Coadministration of MDMA and THC attenuated the increase of norepinephrine concentrations relative to administration of MDMA alone. These results show that THC mediates heart rate increase independent of sympathetic (catecholaminergic) activity, probably through direct cannabinoid receptor type 1 (CB(1)) agonism in cardiac tissue. Furthermore, THC coadministration did not prevent MDMA-induced temperature increase, but it delayed the onset and prolonged the duration of temperature elevation. These effects may be of particular relevance for the cardiovascular safety of ecstasy users who participate in energetic dancing in nightclubs with high ambient temperature.

Contains fulltext : 80229.pdf (Publisher’s version ) (Closed access) MDMA (3,4-methylenedioxymethamphetamine or "ecstasy") is a recreationally used drug with remarkable and characteristic prosocial effects. In spite of abundant attention in the scientific literature, the mechanism of its prosocial effects has not been elucidated in humans. Recently, research in animals has suggested that the neuropeptide oxytocin may induce these effects. In a double blind, randomized, crossover, and placebo-controlled study in 15 healthy volunteers we assessed blood oxytocin and MDMA concentrations and subjective prosocial effects after oral administration of 100 mg MDMA or placebo. MDMA induced a robust increase of blood oxytocin concentrations and an increase of subjective prosocial feelings. Within subjects, the variations in these feelings were significantly and positively correlated with variation in oxytocin levels, and the correlations between these feelings and oxytocin were significantly stronger than those between these feelings and blood MDMA levels. MDMA induces oxytocin release in humans, which may be involved in the characteristic prosocial effects of ecstasy.

Contains fulltext : 71542.pdf (Publisher’s version ) (Closed access) The present study examined whether parental problem drinking affected parenting (i.e., behavioral control, support, rule-setting, alcohol-specific behavioral control), and whether parental problem drinking and parenting affected subsequent adolescent alcohol use over time. A total of 428 families, consisting of both parents and two adolescents (mean age 13.4 and 15.2 years at Time 1) participated in a three-wave longitudinal study with annual waves. A series of path analyses were conducted using a structural equation modeling program (Mplus). Results demonstrated that, unexpectedly, parental problem drinking was in general not associated with parenting. For the younger adolescents, higher levels of both parenting and parental problem drinking were related to lower engagement in drinking over time. This implies that shared environment factors (parenting and modeling effects) influence the development of alcohol use in young adolescents. When adolescents grow older, and move out of the initiation phase, their drinking behavior may be more affected by other factors, such as genetic susceptibility, and peer drinking.

Contains fulltext : 56024.pdf (Publisher’s version ) (Closed access) The study investigated whether four specified drugs would show similar patterns on tests considered to measure sedation. In addition, their drug-effect patterns on sedation and memory performance were compared to determine whether the sedative effects could be differentiated from the memory effects. Two double-blind, placebo-controlled, crossover studies, each with 16 healthy volunteers, were performed, one testing lorazepam (2.5 mg) and mirtazapine (15 mg) and the other olanzapine (10 mg) and haloperidol (2.5 mg). Subjective sedation was assessed by means of visual analogue scales (VAS) and objective sedation using a simple-reaction-time (SRT) task and a choice-reaction-time (CRT) task, code substitution (symbol digit substitution test (SDST)) and the peak velocity of saccadic eye movements (SEM). A verbal memory test (VMT) was administered to evaluate memory capacity. Apart from haloperidol, all drugs proved to impair performance on all five sedation indices. Contrary to the VAS, the objective measures yielded different response profiles. Two types of drug-effect patterns emerged: one for greater impairments in response speed (SRT, SEM) and one for greater impairments in information processing (CRT, SDST). Lorazepam and olanzapine impeded memory performance, whereas mirtazapine did not. With the use of standardized scores it proved possible to differentiate between the size of the effects of the drugs on the sedation and memory tests. To accurately assess the level and nature of sedation and to differentiate sedation from memory impairments different types of sedation measures are required. Besides studying the subjective effects, it is recommended to also test psychomotor responses and information processing speed. 9 p.

Contains fulltext : 49563.pdf (Publisher’s version ) (Closed access) This review of the literature aims to identify the acute effects of MDMA (ecstasy) in healthy volunteers. The wide range of relevant but methodologically diverse tests was .rst grouped into clusters to allow an evaluation of tests that would otherwise have been excluded due to their low frequency of utilization. The following three types of tests were evaluated: (1) functional tests quantifying executive, attention, visual, motor, visuomotor and auditory functions, (2) phenomenological tests assessing personal, subjective experiences, and (3) physiological measures reflecting neurophysiological, endocrine and physiological parameters. MDMA showed robust effects on most of the phenomenological and physiological tests. Functional tests were scarce, preventing any meaningful conclusions to be drawn from their evaluation other than that these tests should be incorporated into future acute-effect studies. A striking dosenresponse relationship appeared for cardiovascular effects. At doses below 1.0 mg/kg MDMA no change was observed relative to placebo while above this dose all studies reported significant increases. Furthermore, pupil size, plasma cortisol and plasma prolactin levels proved responsive to MDMA administration. The reported subjective effects of MDMA matched the entactogenic profile. Although interest in the action of MDMA is considerable, the existing knowledge about the cognitive effects of MDMA in humans is still rather limited and further research into the drug's effects is recommended, also in view of potential therapeutic uses of the drug.

Contains fulltext : 54702.pdf (Publisher’s version ) (Closed access) Mental fatigue is a common phenomenon that either results from sustained mental effort or that is comorbid to a range of psychological and somatic disorders. Important symptoms of mental fatigue comprise cognitive and attentional difficulties, which have adverse effects on task performance and on everyday activities. Yet, little is known about the neurocognitive mechanisms that underlie these effects. In the current study, we explore whether sensorimotor gating is one of the cognitive mechanisms that is disturbed under fatigue. To test this, we compare prepulse inhibition (PPI) between fatigued (n = 11) and non-fatigued participants (n = 9). Fatigue was induced by 90 min of cognitively demanding work. Results showed that, compared to the non-fatigue group, fatigued participants displayed significantly reduced levels of PPI after the manipulation. These findings are linked to theories about compromised cognitive control under fatigue and to recent ideas about the role of dopamine in fatigue as well as in the regulation of PPI. 7 p.

Contains fulltext : 47330.pdf (Publisher’s version ) (Closed access) Although additional dosages of benzodiazepines in long-term users of benzodiazepines are common, it is unknown whether these additional dosages resort any effect. The effects of an additional 20-mg dosage oxazepam were assessed in a double-blind, balanced-order, crossover randomized study comparing 16 long-term users of oxazepam (patients) with 18 benzodiazepine-naive controls (controls). The effects of 10 and 30 mg oxazepam were assessed at pretest and 2.5 hours after drug administration on: (a) saccadic eye movements as proxy for the sedative effect, (b) acoustic startle response (ASR) as proxy for the anxiolytic effects, (c) memory, (d) reaction time tasks, and (e) subjective measurements. Dose-related effects were found in patients on the peak velocity of saccadic eye movement and on response probability, respectively peak amplitude of the ASR. Comparison with controls, however, suggests that in patients the sedative effects might be mixed up with suppression of sedative withdrawal symptoms, whereas patients were as sensitive as benzodiazepine-naive controls for the effects of an additional dosage on the ASR. Neither 10 nor 30 mg oxazepam challenge affected the reaction time tasks in patients, whereas controls show a dose-related impairment. The memory impairing effects, however, did not differ significantly between patients and controls. In contrast to controls, patients could not discriminate between a 10- and 30-mg dosage as assessed by visual analogue scales and the STAI-DY-1, which might indicate a placebo effect in the 10-mg challenge in patients. We conclude that additional dosages of oxazepam still exert pronounced effects after daily use for more than 10 years.

Item does not contain fulltext We previously reported that a single dose of the serotonin receptor agonist meta-chlorophenylpiperazine increased the peak velocity of saccadic eye movements and decreased low-frequency electroencephalographic activity. METHODS: We administered a single dose of the serotonin releaser dexfenfluramine in a double blind, placebo controlled randomised cross-over design and measured saccadic eye movements and EEG every hour up to 6 h. Subjects were 62 males (18-30 years) with a history of no, moderate or heavy use of ecstasy tablets. RESULTS: Dexfenfluramine increased saccadic peak velocity and decreased alpha, delta and theta electroencephalographic activity, the latter predominantly in heavy users of ecstasy. CONCLUSIONS: This study supports the idea that saccadic peak velocity and EEG can be useful endpoints of a serotonergic challenge. This could be an important anatomical extension of these end-points, which until now were limited to the effect on hypothalamic serotonergic projections.

Item does not contain fulltext RATIONALE: Typical users of 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") are polydrug users, combining MDMA with alcohol or cannabis [most active compound: delta-9-tetrahydrocannabinol (THC)]. OBJECTIVES: The aim of the present study was to investigate whether co-administration of alcohol or THC with MDMA differentially affects ongoing electroencephalogram (EEG) oscillations compared to the administration of each drug alone. METHODS: In two separate experiments, 16 volunteers received four different drug conditions: (1) MDMA (100 mg); (2) alcohol clamp (blood alcohol concentration = 0.6 per thousand) or THC (inhalation of 4, 6 and 6 mg, interval of 1.5 h); (3) MDMA in combination with alcohol or THC; and (4) placebo. Before and after drug administration, electroencephalography was recorded during an eyes closed resting state. RESULTS: Theta and alpha power increased after alcohol intake compared to placebo and reduced after MDMA intake. No interaction between alcohol and MDMA was found. Significant MDMA x THC effects for theta and lower-1-alpha power indicated that the power attenuation after the combined intake of MDMA and THC was less than the sum of each drug alone. For the lower-2-alpha band, the intake of MDMA or THC alone did not significantly affect power, but the intake of combined MDMA and THC significantly decreased lower-2-alpha power. CONCLUSIONS: The present findings indicate that the combined intake of MDMA and THC, but not of MDMA and alcohol, affects ongoing EEG oscillations differently than the sum of either one drug alone. Changes in ongoing EEG oscillations may be related to the impaired task performance that has often been reported after drug intake.