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Contains fulltext : 241983.pdf (Publisher’s version ) (Closed access) 2 p.

Contains fulltext : 215849.pdf (Publisher’s version ) (Closed access) Background: Childhood adversity is known to influence personality development. Studies suggest that distinct types of childhood adversities have differential effects on personality dimensions. However, different types of adversity often co-occur, and personality dimensions are strongly interconnected. Objective: The aim of this study was to use a network approach to analyze the interrelationships between different types of childhood adversity and diverse personality dimensions integratively. Participants and setting: We used previously collected data on 142 alcohol dependent patients and 102 healthy controls. Methods: The participants completed the Interview for Traumatic Events in Childhood, the Parental Acceptance and Rejection Questionnaire and the Temperament and Character Inventory. Outcomes on the subscales of these instruments were included in the network analysis. Results: The resulting network showed strong connections between different types of childhood adversity, and between the different temperaments and characters of personality. Childhood adversity, mainly physical abuse and maternal rejection, was connected to most personality dimensions, except for reward dependence. Physical abuse showed the highest centrality measures, indicating a central, important role in the network. Conclusions: These findings confirm that different types of childhood adverse experiences often co-occur, and suggest that specifically physical and emotional abuse, and maternal rejection might play a prominent role in shaping personality. 11 p.

Contains fulltext : 167100.pdf (Publisher’s version ) (Closed access) Drug use is often associated with risky and unsafe behavior. However, the acute effects of cocaine and cannabis on performance monitoring processes have not been systematically investigated. The aim of the current study was to investigate how administration of these drugs alters performance monitoring processes, as reflected in the error-related negativity (ERN), the error positivity (Pe) and post-error slowing. A double-blind placebo-controlled randomized three-way crossover design was used. Sixty-one subjects completed a Flanker task while EEG measures were obtained. Subjects showed diminished ERN and Pe amplitudes after cannabis administration and increased ERN and Pe amplitudes after administration of cocaine. Neither drug affected post-error slowing. These results demonstrate diametrically opposing effects on the early and late phases of performance monitoring of the two most commonly used illicit drugs of abuse. Conversely, the behavioral adaptation phase of performance monitoring remained unaltered by the drugs.

Rationale Long-term cannabis and cocaine use has been associated with impairments in reversal learning. However, how acute cannabis and cocaine administration affect reversal learning in humans is not known. Objective In this study, we aimed to establish the acute effects of administration of cannabis and cocaine on valence-dependent reversal learning as a function of DRD2 Taq1A (rs1800497) and COMT Val108/158Met (rs4680) genotype. Methods A double-blind placebo-controlled randomized 3-way crossover design was used. Sixty-one regular poly-drug users completed a deterministic reversal learning task under the influence of cocaine, cannabis, and placebo that enabled assessment of both reward- and punishment-based reversal learning. Results Proportion correct on the reversal learning task was increased by cocaine, but decreased by cannabis. Effects of cocaine depended on the DRD2 genotype, as increases in proportion correct were seen only in the A1 carriers, and not in the A2/A2 homozygotes. COMT genotype did not modulate drug-induced effects on reversal learning. Conclusions These data indicate that acute administration of cannabis and cocaine has opposite effects on reversal learning. The effects of cocaine, but not cannabis, depend on interindividual genetic differences in the dopamine D2 receptor gene. Electronic supplementary material The online version of this article (doi:10.1007/s00213-015-4141-5) contains supplementary material, which is available to authorized users.

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage.

Substance abuse has often been associated with alterations in response inhibition in humans. Not much research has examined how the acute effects of drugs modify the neurophysiological correlates of response inhibition, or how these effects interact with individual variation in trait levels of impulsivity and novelty seeking. This study investigated the effects of cocaine and cannabis on behavioural and event-related potential (ERP) correlates of response inhibition in 38 healthy drug using volunteers. A double-blind placebo-controlled randomized three-way crossover design was used. All subjects completed a standard Go/NoGo task after administration of the drugs. Compared with a placebo, cocaine yielded improved accuracy, quicker reaction times and an increased prefrontal NoGo-P3 ERP. Cannabis produced opposing results; slower reaction times, impaired accuracy and a reduction in the amplitude of the prefrontal NoGo-P3. Cannabis in addition decreased the amplitude of the parietally recorded P3, while cocaine did not affect this. Neither drugs specifically affected the N2 component, suggesting that pre-motor response inhibitory processes remain unaffected. Neither trait impulsivity nor novelty seeking interacted with drug-induced effects on measures of response inhibition. We conclude that acute drug effects on response inhibition seem to be specific to the later, evaluative stages of response inhibition. The acute effects of cannabis appeared less specific to response inhibition than those of cocaine. Together, the results show that the behavioural effects on response inhibition are reflected in electrophysiological correlates. This study did not support a substantial role of vulnerability personality traits in the acute intoxication stage.

Contains fulltext : 167132.pdf (Publisher’s version ) (Open Access) Cannabis use history as predictor of neurocognitive response to cannabis intoxication remains subject to scientific and policy debates. The present study assessed the influence of cannabis on neurocognition in cannabis users whose cannabis use history ranged from infrequent to daily use. Drug users (N = 122) received acute doses of cannabis (300 mug/kg THC), cocaine HCl (300 mg) and placebo. Cocaine served as active control for demonstrating neurocognitive test sensitivity. Executive function, impulse control, attention, psychomotor function and subjective intoxication were significantly worse after cannabis administration relative to placebo. Cocaine improved psychomotor function and attention, impaired impulse control and increased feelings of intoxication. Acute effects of cannabis and cocaine on neurocognitive performance were similar across cannabis users irrespective of their cannabis use history. Absence of tolerance implies that that frequent cannabis use and intoxication can be expected to interfere with neurocognitive performance in many daily environments such as school, work or traffic.

Rationale Accumulating evidence indicates that the cognitive effects of dopamine depend on the subtype of dopamine receptor that is activated. In particular, recent work with animals as well as current theorizing has suggested that cognitive flexibility depends on dopamine D2 receptor signaling. However, there is no evidence for similar mechanisms in humans. Objectives We aim to demonstrate that optimal dopamine D2 receptor signaling is critical for human cognitive flexibility. Methods To this end, a pharmacological pretreatment design was employed. This enabled us to investigate whether effects of the dopamine receptor agonist bromocriptine on task-set switching were abolished by pretreatment with the D2 receptor antagonist sulpiride. To account for individual (genetic) differences in baseline levels of dopamine, we made use of a common variable number of tandem repeat (VNTR) polymorphism in the 3′-untranslated region of the dopamine transporter gene, DAT1. Results Bromocriptine improved cognitive flexibility relative to placebo, but only in subjects with genetically determined low levels of dopamine (n = 27). This beneficial effect of bromocriptine on cognitive flexibility was blocked by pretreatment with the selective dopamine D2 receptor antagonist sulpiride (n = 14). Conclusions These results provide strong evidence in favor of the hypothesis that human cognitive flexibility implicates dopamine D2 receptor signaling. Electronic supplementary material The online version of this article (doi:10.1007/s00213-011-2340-2) contains supplementary material, which is available to authorized users.

Aims Detection of errors is crucial for efficient goal-directed behaviour. The ability to monitor behaviour is found to be diminished in patients with substance dependence, as reflected in decreased error-related brain activity, i.e. error-related negativity (ERN). The ERN is also decreased in other psychiatric disorders with impaired response inhibition, such as attention-deficit hyperactivity disorder and borderline personality disorder, but increased in anxiety disorders. The objective of the current study was to assess error monitoring in alcohol-dependent patients in relation to psychiatric comorbidity. We expected decreased error monitoring in alcohol-dependent patients with impulse control disorders and increased error monitoring in anxious alcohol-dependent patients. Design In a case-control design alcohol-dependent patients were compared with healthy controls. Setting and participants A consecutive series of 29 male alcohol-dependent patients, between 18 and 55 years of age, applying for in-patient detoxification were recruited at Novadic Kentron Center for Addiction Treatment. Fifteen age-matched healthy controls were recruited through advertisements in regional newspapers. Measurements Event-related potentials were recorded while performing a speeded choice-reaction task, from which ERN amplitudes were calculated. Axis-I and -II psychiatric comorbidity were assessed using the MINI International Neuropsychiatric Interview and the Structured Interview for DSM-IV Personality disorders. All participants completed the Temperament and Character Inventory and Profile of Mood States. Findings ERN amplitudes were increased for alcohol-dependent patients compared to healthy controls, particularly in patients with comorbid anxiety disorders. Conclusions Increased error monitoring in alcohol-dependent patients, particularly those with comorbid anxiety disorders, is in contrast with previous studies that suggested decreased error monitoring to be a general feature in substance use disorders. Psychiatric disorders co-occurring with alcohol dependence, such as anxiety disorders, may indicate subpopulations of alcohol-dependent patients, with distinct neurobiological and genetic characteristics, possibly requiring different treatment strategies.

Contains fulltext : 71365.pdf (Publisher’s version ) (Closed access) The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of gamma-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

The neurobiological knowledge on the potentially new diagnostic entity “posttraumatic stress disorder with secondary psychotic features” (PTSD-SP) is reviewed. Studies published between 1980 and 2006 were traced focussing on adult patients suffering from this “syndrome”. Studies on cortisol, corticotrophin releasing hormone, dopamine beta-hydroxylase, smooth pursuit eye movements and psychopharmacology are described and potential pathophysiological mechanisms briefly discussed. More research is needed to validate the nosological status of PTSD-SP in order to promote neurobiological research and adequate therapeutic interventions.

The aim of this study was to examine whether patients with borderline personality disorder (BPD) have deficits in cognitive inhibition as measured with an anti-saccade eye task similar to patients with schizophrenia (Sz). Furthermore, we investigated whether these inhibition errors were more prominent among BPD patients with psychotic-like symptoms than among BPD patients without these symptoms.An anti-saccade task was administered in 32 BPD patients (among them, 20 had with psychotic-like symptoms), 21 patients with recent onset schizophrenia (Sz), and 25 healthy controls (HC). The percentage inhibition errors in the anti-saccade task were the primary outcome variable, in addition, the percentage of anticipatory errors was measured.Sz patients showed more inhibition errors than HC and BPD (p.001 and p.05 resp.), whereas BPD patients scored in between Sz and HC. The difference with HC was significant as well (p.05). BPD patients with psychotic-like symptoms showed more inhibition errors than BPD patients without these symptoms (p.05). BPD patients showed more anticipatory errors than HC (p.001), whereas Sz patients did not (p.26).The data demonstrate that inhibition deficits, as measured with anti-saccadic eye movement task, may be characteristic among BPD patients and in a larger extent in patients with psychotic-like symptoms. This inhibition deficit was distinct from a general predisposition to response impulsively as measured by anticipatory errors, which was found in the whole group of BPD patients. Psychotic-like symptoms may be an important target dimension for future BPD research and treatment.

Contains fulltext : 58623.pdf (Publisher’s version ) (Closed access) Peripheral benzodiazepine receptor (PBR) density in blood platelets and plasma allopregnanolone concentration in humans were determined following acute stress as represented by PhD examination. Fifteen healthy PhD students participated. Heart rate, blood pressure, plasma allopregnanolone, plasma cortisol, and PBR density were measured at different time points. Allopregnanolone and cortisol concentration and PBR density were significantly increased during examination. A positive correlation between allopregnanolone and PBR density was found.

Item does not contain fulltext RATIONALE: A deregulation in concentrations of the neurosteroids (allo)pregnanolone and 3alpha,5alpha-tetrahydrodeoxycorticosterone (3alpha,5alpha-TH DOC) has been found in depressed patients. These levels normalize following treatment with selective serotonin reuptake inhibitors (SSRIs). Furthermore, administration of the neurosteroid dehydroepiandrosterone (DHEA) to depressed patients is associated with an improvement in the symptoms of depression. OBJECTIVE: The aim of the present review is to clarify the mechanisms whereby neurosteroids, particularly allopregnanolone and DHEA, are involved in depression and to discuss the effect of SSRIs on allopregnanolone concentration. METHODS: Literature on preclinical and clinical research has been analyzed in relation to the pathophysiology of depression. RESULTS: Decreased plasma and cerebrospinal fluid concentrations of allopregnanolone in depressed patients increase to normal levels following effective psychopharmacological treatment. This might either be a physiological aspect of improvement in the symptoms of depression or a pharmacologically induced alteration. Several findings support the hypothesis of an antidepressant effect of allopregnanolone. These include an antidepressant effect demonstrated in an animal model of depression and a suppressing effect on corticotropin-releasing hormone (CRH) and arginine-vasopressin (AVP) gene expression. SSRIs increase levels of allopregnanolone, but this effect is not confined to this class of drugs alone. The beneficial effect of DHEA administration in depressed patients might result from its sigma 1 receptor-mediated enhancement of noradrenaline and serotonin neurotransmission, antiglucocorticoid effects, and cognition enhancing effects. CONCLUSIONS: Indirect genomic (allopregnanolone) and non-genomic (allopregnanolone and DHEA) mechanisms are involved in the neurosteroidogenic pathophysiology of depression. Clinical studies in homogeneous groups of non-pharmacologically treated depressed patients are required to elucidate this relationship further.

Objective: This study was designed to compare the efficacy of three two-phase pharmacological treatment strategies for inpatients with DSM-IV-TR major depressive disorder with psychotic features. Method: During phase I, 122 patients participated in a 7 week double-blind eight center study comparing imipramine (dose adjusted to target plasma levels of 200300 ng/ml), venlafaxine (maximum 375 mg/day) and venlafaxine-quetiapine (maximum 375 mg/day; 600 mg/day). Four centers participated in phase II. In phase II, for patients without treatment response or with partial response, lithium was added to phase I pharmacotherapy. Lithium dose was adjusted to a target serum level of 0.6-1.0 mmol/l. Final evaluation of remission and response was made after 4 weeks of lithium addition. Results: Since only 15 patients were included in phase II, evaluation of the twophase treatment strategies was impossible, and lithium addition was evaluated as an open study. Lithium addition appeared remarkably effective, since 9 of 15 (60%) attained remission, defined as a final Hamilton Depression Rating Scale (HAM-D) score≤ 7. The same number of patients achieved response (HAM-D reduction ≥ 50%). All 9 remitters had a sustained remission during a four-month follow-up period. Conclusion: Lithium addition appears to be remarkably effective in psychotic depression, but these data from an open study are insufficient evidence for this treatment to be considered evidence based. Trial registration: http://www.controlled-trials.com/isrctn/trial ISRCTN36607067 An open study of lithium addition in refractory psychotic depression 109

Contains fulltext : 136142.pdf (Publisher’s version ) (Open Access) BACKGROUND: Chronic fatigue syndrome (CFS) is still an enigmatic disorder. CFS can be regarded as a complex disorder with tremendous impact on lives of CFS-patients. Full recovery without treatment is rare.A somatic explanation for the fatigue is lacking. There is clinical and experimental evidence implicating enhanced serotonergic neurotransmission in CFS. Genetic studies and imaging studies support the hypothesis of upregulated serotonin system in CFS.In line with the hypothesis of an increased serotonergic state in CFS, we performed a randomised clinical trial investigated the effect of 5-HT3 receptor antagonism in CFS. No benefit was found of the 5-HT3 receptor antagonist ondansetron compared to placebo.To further investigate the involvement of serotonin in CFS we performed a placebo controlled cross over pilot study investigating the effect of Acute Tryptophan Depletion. FINDINGS: Five female CFS-patients who met the US Center for Disease Control and Prevention criteria for CFS were recruited. There were two test days, one week apart. Each participant received placebo and ATD. To evaluate the efficacy of the ATD procedure tryptophan and the large neutral amino acids were measured. The outcome measures were fatigue severity, concentration and mood states.ATD resulted in a significant plasma tryptophan to large neutral amino acid ratio reduction of 96%. There were no significant differences in fatigue-, depression and concentration between the placebo- and ATD condition. CONCLUSIONS: These first five CFS-patients did not respond to the ATD procedure. However, a much larger sample size is needed to draw final conclusions on the hypothesis of an increased serotonergic state in the pathophysiology of CFS. TRIAL REGISTRATION: ISRCTN07518149.

Rationale The neurotransmitter dopamine plays a key role in cognitive functions that are associated with fronto-striatal circuitry and has been implicated in many neuropsychiatric disorders. However, there is a large variability in the direction and extent of dopaminergic drug effects across individuals. Objectives We investigated whether individual differences in dopaminergic drug effects on human fronto-striatal functioning are associated with individual differences in white matter tracts. Methods The effects of the dopamine receptor agonist bromocriptine were assessed using functional magnetic resonance imaging in 22 healthy volunteers in a placebo-controlled, double-blind, within-subject design. Human psychopharmacology and functional neuroimaging were combined with functional connectivity analyses and structural connectivity analyses to establish a link between dopaminergic drug effects on fronto-striatal function and fronto-striatal anatomy. Results We demonstrate that bromocriptine alters functional signals associated with attention switching in the basal ganglia. Crucially, individual differences in the drug’s effect on these signals could be predicted from individual differences in fronto-striato-thalamic white matter tracts, as indexed by diffusion tensor imaging. Anatomical fronto-striatal connectivity also predicted drug effects on switch-related functional connectivity between the basal ganglia and the prefrontal cortex. Conclusions These data reinforce the link between dopamine, cognition and the basal ganglia and have implications for the individual tailoring of dopaminergic drug therapy based on anatomical fronto-striatal connection strength. Electronic supplementary material The online version of this article (doi:10.1007/s00213-013-3000-5) contains supplementary material, which is available to authorized users.

Understanding the cognitive sequela of repeated cocaine use is a growing area of research and is crucial to the development of cognitive models of addiction. We systematically reviewed all available placebo-controlled and case-controlled studies on the acute and long-term effects of cocaine on cognitive functioning. In order to compare the magnitude of cognitive effects across cognitive domains we conducted several meta-analyses on a subset of data from long-term effect studies. Studies on acute cocaine administration suggest enhancement of response inhibition and psychomotor speed, while all other domains appear to be unaffected or not investigated adequately. Long-term effects of cocaine show a wide array of deteriorated cognitive functions, indicating that long term cocaine use is characterized by a general cognitive impairment across functions, rather than by specific cognitive deficits. Literature on long-term cocaine effects is more substantial than literature on acute effects. This comprehensive review outlines possible dissociations and similarities of acute vs. long-term cocaine effects in the human brain. Atherosclerosis after cocaine exposure may underlie cognitive dysfunction, suggesting involvement of multiple brain areas. Acute drug studies are important to the future development of addiction models. (C) 2013 Elsevier Ltd. All rights reserved.

The Self-Expression and Control Scale (SECS), constructed to investigate the role of anger expression and anger control in somatic and mental diseases, was administered to patients with recurrent suicide attempts. The psychometric properties of the SECS proved to be highly acceptable and comparable with the psychometric properties of the instrument administered to a community sample. Suicide attempters scored higher on trait anger, higher on the internalization of anger and lower on both control of the internalization and the externalization of anger than controls in a community sample. Additionally, suicide attempters with a diagnosis of borderline personality disorder scored higher on the externalization of anger, and lower on both control of the internalization and the externalization of anger than suicide attempters without this diagnosis. Finally, the subgroup of patients with a psychiatric diagnosis of a“recurrent deliberate self-harm” scored higher on the internalization of anger than other patients with recurrent suicide attempts. These results show that the SECS is able to make a distinction between several subgroups of suicide attempters, and between suicide attempters and persons in a community sample with respect to the expression and control of anger. As such, the SECS can give indication for optimal psychotherapeutic treatment.

The circadian activity rhythm was assessed over a one-week period using a wrist-worn activity monitor in 59 patients with a history of recurrent suicide attempts. In 40 of these patients a second recording was made 6 months later. Platelet serotonin (5-HT) and monoamine oxidase-B activity (MAO) were measured. Suicidal ideation, borderline personality disorder and impulsiveness were associated with the absence of a clear 24-hour periodicity in motor activity. Depressive mood and hopelessness were associated with a less regular bed-in time and a lower daytime activity. Platelet 5-HT as well as MAO correlated negatively with the amplitude of the circadian activity rhythm. Our results support the suggested link between suicidality, altered circadian activity and serotonergic function.

Contains fulltext : 99871.pdf (Publisher’s version ) (Open Access) Background: Psychopathy is a severe personality disorder often leading to violent and disruptive antisocial behavior. Efficient and proper social behavior crucially relies on monitoring of one's own as well as others' actions, but the link between antisocial behavior in psychopathy and action monitoring in a social context has never been investigated. Methods: Event-related potentials were used to disentangle monitoring of one's own and others' correct and incorrect actions in psychopathic subjects (n = 18) and matched healthy control subjects (n = 18). The error-related negativity (ERN) was investigated following own and other's responses in a social flanker task. Results: Although both groups showed similar event-related potentials in response to own actions, amplitudes after the observation of others' action-outcome were greatly reduced in psychopathy. More specifically, the latter was not unique to observed errors, because the psychopathic group also showed reduced brain potentials after the observation of correct responses. In contrast, earlier processing of observed actions in the motor system, as indicated by the lateralized readiness potential, was unimpaired. Conclusions: Monitoring of own behavior is not affected in psychopathy, whereas processing of the outcome of others' actions is disturbed. Specifically, although psychopathic individuals do not have a problem with initial processing of the actions of others, they have problems with deeper analyses of the consequences of the observed action, possibility related to the reward value of the action. These results suggest that aspects of action monitoring in psychopathy are disturbed in social contexts and possibly play a central role in the acquisition of abnormal social behavior. 7 p.

Detection of errors is crucial for efficient goal-directed behaviour. The ability to monitor behaviour is found to be diminished in patients with substance dependence, as reflected in decreased error-related brain activity, i.e. error-related negativity (ERN). The ERN is also decreased in other psychiatric disorders with impaired response inhibition, such as attention-deficit hyperactivity disorder and borderline personality disorder, but increased in anxiety disorders. The objective of the current study was to assess error monitoring in alcohol-dependent patients in relation to psychiatric comorbidity. We expected decreased error monitoring in alcohol-dependent patients with impulse control disorders and increased error monitoring in anxious alcohol-dependent patients.In a case-control design alcohol-dependent patients were compared with healthy controls.A consecutive series of 29 male alcohol-dependent patients, between 18 and 55 years of age, applying for in-patient detoxification were recruited at Novadic Kentron Center for Addiction Treatment. Fifteen age-matched healthy controls were recruited through advertisements in regional newspapers.Event-related potentials were recorded while performing a speeded choice-reaction task, from which ERN amplitudes were calculated. Axis-I and -II psychiatric comorbidity were assessed using the MINI International Neuropsychiatric Interview and the Structured Interview for DSM-IV Personality disorders. All participants completed the Temperament and Character Inventory and Profile of Mood States.ERN amplitudes were increased for alcohol-dependent patients compared to healthy controls, particularly in patients with comorbid anxiety disorders.Increased error monitoring in alcohol-dependent patients, particularly those with comorbid anxiety disorders, is in contrast with previous studies that suggested decreased error monitoring to be a general feature in substance use disorders. Psychiatric disorders co-occurring with alcohol dependence, such as anxiety disorders, may indicate subpopulations of alcohol-dependent patients, with distinct neurobiological and genetic characteristics, possibly requiring different treatment strategies.

Item does not contain fulltext BACKGROUND: Anhedonia and lack of motivation are core symptoms of major depressive disorder (MDD). Neuroimaging studies in MDD patients have shown reductions in reward-related activity in terminal regions of the mesolimbic dopamine (DA) system, such as the ventral striatum. Monoamines have been implicated in both mesolimbic incentive processing and the mechanism of action of antidepressant drugs. However, not much is known about antidepressant effects on mesolimbic incentive processing in humans, which might be related to the effects on anhedonia. METHODS: To investigate the short-term effects of antidepressants on reward-related activity in the ventral striatum, we investigated the effect of the combined serotonin-norepinephrine reuptake inhibitor duloxetine. Healthy volunteers underwent functional magnetic resonance imaging in a randomized, double-blind, placebo-controlled, crossover study. After taking duloxetine (60 mg once a day) or placebo for 14 days, participants completed a monetary incentive delay task that activates the ventral striatum during reward anticipation. RESULTS: Our results (n = 19) show enhanced ventral striatal responses after duloxetine administration compared with placebo. Moreover, this increase in ventral striatal activity was positively correlated with duloxetine plasma levels. CONCLUSIONS: This is the first study to demonstrate that antidepressants augment neural activity in mesolimbic DA incentive processing circuits in healthy volunteers. These effects are likely caused by the increase in monoamine neurotransmission in the ventral striatum. Our findings suggest that antidepressants may alleviate anhedonia by stimulating incentive processing.

Contains fulltext : 109655.pdf (Publisher’s version ) (Closed access) OBJECTIVE: There is substantial symptomatic overlap between attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) in adults, but the nature of the relationship between these disorders needs further clarification. The role of temperament and character traits in the differentiation of classes of patients with similar ADHD and BPD symptom profiles was examined and possible pathways between early temperament and future ADHD and/or BPD were hypothesized. METHODS: Structured diagnostic interviews were conducted in 103 female patients to assess current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition symptoms of ADHD and BPD, and parent interviews were used to assess ADHD symptoms in childhood. Classes of subjects with homogeneous symptom profiles were identified using latent class analysis. Temperament and character traits were assessed using the Temperament and Character Inventory of Cloninger et al; scores were then compared across the latent classes. RESULTS: Latent class analysis revealed 4 mutually exclusive classes of patients: 1 with only ADHD symptoms; 1 with BPD symptoms and ADHD symptoms of hyperactivity; 1 with BPD symptoms and ADHD symptoms of inattention, hyperactivity, and impulsivity; and 1 with BPD symptoms and ADHD symptoms of inattention and hyperactivity. High Novelty Seeking was found in all classes except for the class with symptoms of BPD and only the hyperactivity aspect of ADHD. The highest Novelty Seeking temperament scores were found in that class of patients with both symptoms of BPD and symptoms in all areas of ADHD. High Harm Avoidance, low Cooperativeness, and low Self-directedness were specifically related to classes containing BPD symptoms. CONCLUSIONS: Classes of ADHD and BPD symptoms are associated with specific temperament and character configurations. Novelty Seeking was associated with the inattention symptoms of ADHD. An outspoken Novelty Seeking temperament suggests vulnerability for the development of ADHD and co-occurring BPD. Contrary to patients with combined ADHD and BPD symptoms, patients with only symptoms of ADHD showed normal character development and thus an absence of a personality disorder. Assessment of temperament and character traits can improve our understanding of the complex relationship between ADHD and BPD. 01 januari 2012

Contains fulltext : 90744.pdf (Publisher’s version ) (Open Access) BACKGROUND: Because the effects of susceptibility genes on alcohol use may differ as a function of age throughout adolescence and young adulthood, prospective study designs, in addition to cross-sectional ones are needed in genetic association studies. The short, low activity allele of a polymorphism (5-HTTLPR) in the serotonin transporter gene (SLC6A4) has been related to alcohol dependence. In the current study we tested whether 5-HTTLPR genotype was associated with adolescent alcohol use both cross-sectionally and longitudinally. METHODS: Non-regular drinkers (n=202) were selected from Dutch, nationwide sample of adolescents (mean age 13.4 at baseline) who were assessed across five annual waves. Latent growth curve modeling was applied to examine individual development of alcohol use over time, by estimating the initial level of alcohol use at Wave 2 (intercept), and the rate of change in alcohol use across time (slope). RESULTS: The 5-HTTLPR short allele predicted adolescent's growth (slope) in alcohol use over time. Adolescents with the 5-HTTLPR short allele showed larger increase in alcohol consumption than those without the 5-HTTLPR short allele. 5-HTTLPR genotype was not related to the initial level (intercept) of alcohol consumption. In all analyses we controlled for sex and personality. CONCLUSIONS: To gain more insight into the etiological role of genetic determinants of adolescent alcohol use, developmental approaches that distinguish between onset and continuation of drinking should be applied.

Contains fulltext : 90665.pdf (Publisher’s version ) (Closed access) The information provided by parents is indispensable for the early identification of psychopathology; for this reason, developmentally appropriate, reliable, and valid questionnaires are needed to gather their information. This study was designed to examine the utility of the Infant Toddler Social Emotional Assessment (ITSEA), a parent-report questionnaire covering a wide range of behavior and emotional problems and competencies, in preschoolers referred for child psychiatric evaluation. The fathers and mothers of 85 children (23.2% girls; age 15-57 months) with autism spectrum, externalizing, or internalizing disorders completed the ITSEA, the Child Behavior Checklist (CBCL/2-3 and 4-18 versions), and the child domain of the Parenting Stress Index (PSI). The ITSEA showed good interrater reliability between parents, and validity was supported by significant correlations with corresponding CBCl and PSI domains. Evidence supporting the validity of the ITSEA for psychopathology was mixed across scales, with good diagnostic accuracy at the level of the broader psychiatric syndromes being achieved by the combination of subscales within the Externalizing. Internalizing, and Competence domains. The value of the ITSEA lies in the ability to systematically evaluate a wide range of problem behaviors and competencies. The ITSEA may be useful to create profiles of children's functioning in preschoolers referred for psychiatric assessment.

Contains fulltext : 87295.pdf (Publisher’s version ) (Closed access) BACKGROUND: Data about follow-up after acute pharmacological treatment of psychotic depression are scarce. METHODS: A 4 month open follow-up was done, preferentially with same medication as during acute treatment, of patients (n=59) with DSM-IV-TR major depressive disorder with psychotic features, aged 18 to 65 years, who had completed as responders an acute double-blind 7 week trial with imipramine, venlafaxine or venlafaxine plus quetiapine. Main outcome measures were Hamilton Rating Scale for Depression and Clinical Global Impression Scale. RESULTS: Six patients dropped out during the 4 month follow-up. Almost all patients (86.4%; 51/59) remained responder while remission rate increased from 59.3% (35/59) to 86.8% (46/53), independent of treatment. Relapse rate was low (3.8%; 2/53). Tolerability was good. Weight increased with all treatments. LIMITATIONS: Limitations were the limited sample size and consequent limited statistical power. The treatment during follow-up was not double-blind. CONCLUSIONS: Continuation treatment with the same medication that was effective in the acute treatment trial, remained effective during the 4 month follow-up in many patients leading to further improvement, and was well tolerated. 01 juni 2010

Contains fulltext : 76957.pdf (Publisher’s version ) (Closed access) Contains fulltext : 76958.pdf (Publisher’s version ) (Closed access) Background - One of the most recognizable features of psychopathy is the reduced ability to successfully learn and adapt overt behavior. This might be due to deficient processing of error information indicating the need to adapt controlled behavior. Methods - Event-related potentials (ERPs) and behavioral components of error-monitoring processes were investigated in 16 individuals with psychopathy and in 18 healthy subjects. A letter version of the Eriksen flanker task was used in two conditions. The first condition (normal condition) required participants to press one of two buttons depending on the identity of the target stimulus. The second condition (signaling condition) required them to signal each time they had committed an error by making a second press on a signaling button. Early stages of error monitoring were investigated by using the error-related negativity (ERN/Ne) and post-error slowing as indexes. Later stages were explored by examining the error positivity (Pe) and signaling rates. Results - Both groups showed similar ERN amplitudes and amounts of post-error slowing. The psychopathic group exhibited both reduced Pe amplitudes and diminished error-signaling rates compared with the control group. Conclusions - Individuals with psychopathy show intact early error processing and automatic behavioral adaptation but have deficits in later stages of error processing and controlled behavioral adaptation. This is an indication that individuals with psychopathy are unable to effectively use error information to change their behavior adequately. Key Words: Automatic processing; behavioral adaptation; error positivity; error-related negativity; error signaling; psychopathy 7 p.

Item does not contain fulltext Dopamine neurotransmission has been a key player in attempts to identify genetic factors involved in alcohol dependence. The dopamine transporter terminates dopaminergic neurotransmission, making the gene encoding the transporter (SLC6A3/DAT1) an attractive candidate in clinical studies on alcohol dependence. We conducted a systematic review of 18 studies examining associations between polymorphisms in DAT1 and alcohol dependence. The DAT1 variable number tandem repeat, the most frequent studied polymorphism in DAT1, did not show a direct association with alcohol dependence in general. Several, but not all, studies found that the DAT1 variable number tandem repeat (9-repeat allele) was associated with alcohol-withdrawal symptoms, such as seizures and delirium tremens. We discuss shortcomings, such as lack of power and disregarding moderating variables, as well as future challenges of gene association studies.

The neurobiological knowledge on the potentially new diagnostic entity "posttraumatic stress disorder with secondary psychotic features" (PTSD-SP) is reviewed. Studies published between 1980 and 2006 were traced focussing on adult patients suffering from this "syndrome". Studies on cortisol, corticotrophin releasing hormone, dopamine beta-hydroxylase, smooth pursuit eye movements and psychopharmacology are described and potential pathophysiological mechanisms briefly discussed. More research is needed to validate the nosological status of PTSD-SP in order to promote neurobiological research and adequate therapeutic interventions.

Contains fulltext : 52610.pdf (Publisher’s version ) (Open Access) Progesterone, or rather its neuroactive metabolite allopregnanolone, modulates amygdala activity and thereby influences anxiety. Cognition and, in particular, memory are also altered by allopregnanolone. In the present study, we investigated whether allopregnanolone modulates memory for biologically salient stimuli by influencing amygdala activity, which in turn may affect neural processes in other brain regions. A single progesterone dose was administered orally to healthy young women in a double-blind, placebo-controlled, crossover design, and participants were asked to memorize and recognize faces while undergoing functional magnetic resonance imaging. Progesterone decreased recognition accuracy without affecting reaction times. The imaging results show that the amygdala, hippocampus, and fusiform gyrus supported memory formation. Importantly, progesterone decreased responses to faces in the amygdala and fusiform gyrus during memory encoding, whereas it increased hippocampal responses. The progesterone-induced decrease in neural activity in the amygdala and fusiform gyrus predicted the decrease in memory performance across subjects. However, progesterone did not modulate the differential activation between subsequently remembered and subsequently forgotten faces in these areas. A similar pattern of results was observed in the fusiform gyrus and prefrontal cortex during memory retrieval. These results suggest that allopregnanolone impairs memory by reducing the recruitment of those brain regions that support memory formation and retrieval. Given the important role of the amygdala in the modulation of memory, these results suggest that allopregnanolone alters memory by influencing amygdala activity, which in turn may affect memory processes in other brain regions.

Contains fulltext : 52599.pdf (Publisher’s version ) (Closed access) Allopregnanolone is a known GABA(A) receptor agonist not previously given to men, or to women using oral contraceptives (OC). The effects of metabolites of sex hormones on the GABA(A) receptor are different between men and women. OC are known to change GABA(A) receptor subunit composition. These factors might play a role in the differential effect of allopregnanolone in men and women, and in women with or without OC. To study the sedative effect of and sensitivity to allopregnanolone in men and in women with OC, nine healthy men (mean age 24.6 years) and nine healthy women on OC (mean age 21.8 years) were given three, increasing, intravenous dosages (0.015, 0.03, and 0.045 mg/kg) of allopregnanolone. Saccadic eye velocity (SEV), subjective ratings, and electroencephalography (EEG) were used to evaluate the response to allopregnanolone. Repeated blood samples for analyses of serum allopregnanolone levels were drawn throughout the study day. Allopregnanolone decreased SEV more in women than in men, and increased subjective ratings of 'sedation'. The results in women on OC are similar to earlier results in women without OC. Subjective ratings of 'contentedness' decreased in men but increased in women. Serum levels of allopregnanolone were more highly increased in men compared to women. Other pharmacokinetic parameters were not different between sexes. On the EEG, beta power increased in men. In conclusion, men and women on OC reacted differently to allopregnanolone.

Contains fulltext : 55668.pdf (Publisher’s version ) (Closed access) Patients with borderline personality disorder (BPD) are characterized by marked impulsive behaviour. The impulsive response style of patients with BPD may be associated with diminished action monitoring, which can be investigated by measuring the error-related negativity (ERN). The ERN is an ERP component generated in the anterior cingulate cortex (ACC) following erroneous responses. Behavioural and ERP measurements were obtained during performance on a speeded two-choice reaction task in a group of patients with BPD (N = 12) and in a group of age-matched controls (N = 12). The ERP results showed that ERN amplitudes were reduced for patients with BPD, as were the P300 amplitudes after late feedback. The behavioural results confirmed a more impulsive response style for the BPD group, reflected in larger RT differences between correct and incorrect responses and in an increase in erroneous responses to the easy congruent stimuli. Additionally, analyses on post-error congruency effects demonstrated that controls adjusted their behaviour following errors, but patients with BPD did not. The attenuated ERNs indicate reduced action monitoring in patients with BPD. This suggests that the ACC, or the action-monitoring network it is part of, is not functioning optimally. Due to this reduced action monitoring, patients with BPD do not learn from their errors as well as controls. Consequently, they do not adjust their behaviour when necessary and thus maintain their impulsive response style. 10 p.

Contains fulltext : 54636.pdf (Publisher’s version ) (Closed access) Humans need to monitor their actions continuously to detect errors as fast as possible and to adjust their performance to prevent future errors. This process of action monitoring can be investigated by measuring the error-related negativity (ERN), an ERP component elicited immediately after an error. In the current study, we investigated action monitoring after administration of the classic antipsychotic haloperidol (2.5 mg), the atypical antipsychotic olanzapine (10 mg), and the antidepressant paroxetine (20 mg), a selective serotonin reuptake inhibitor. Healthy volunteers (N = 14) were administered the three compounds and placebo in a randomized, double-blind, single-dose, four-way cross-over design. All participants performed a speeded two-choice reaction task, while event-related potentials and behavioral measurements were obtained. Both haloperidol and olanzapine significantly reduced ERN amplitudes. After paroxetine, the ERN was not different from placebo. N2 congruency effects were not affected by treatment condition. Only olanzapine demonstrated behavioral effects, namely a slowing of responses, an increase in error rates, and the absence of performance adjustments. The attenuated ERNs after the dopamine antagonist haloperidol are in line with the presumed role of dopamine in action monitoring. Haloperidol is thought to block dopaminergic signaling, thus reducing ERN amplitudes. On the other hand, the effects of olanzapine are mainly caused by its sedative side effects, leading to a decline in motivation and appraisal of errors. Finally, the absence of any effects after paroxetine suggests that serotonin transmission does not play a direct role in regulating mechanisms related to action monitoring. 8 p.

Contains fulltext : 57834.pdf (Publisher’s version ) (Closed access) RATIONALE: Action monitoring has been studied extensively by means of measuring the error-related negativity (ERN). The ERN is an event-related potential (ERP) elicited immediately after an erroneous response and is thought to originate in the anterior cingulate cortex (ACC). Although the ACC has a central role in the brain, only a few studies have been performed to investigate directly the effects of drugs on action monitoring. A recent theory argues that the mesencephalic dopamine system carries an error signal to the ACC, where it generates the ERN. METHODS: ERPs and behavioral measurements were obtained from 12 healthy volunteers performing an Eriksen Flankers task. On each of the 4 test days, the stimulant D-amphetamine, the sedative lorazepam, the antidepressant mirtazapine, or a placebo was orally administered in a double-blind, four-way crossover design. RESULTS: The indirect dopamine agonist amphetamine led to a strong enlargement of ERN amplitudes without affecting reaction times. Lorazepam and mirtazapine both showed slowing of responses, but only lorazepam led to reduced ERN amplitudes. CONCLUSIONS: Administration of amphetamine leads to stimulated action monitoring, reflected in increased ERN amplitudes. This result provides evidence for dopaminergic involvement in action monitoring and is in line with differences in ERN amplitude found in neuropsychiatric disorders also suggesting dopaminergic involvement. The different effects for lorazepam and mirtazapine are probably caused by the neurobiological characteristics of these two types of sedation. Action monitoring is suppressed after administration of lorazepam, because the GABAergic pathways directly inhibit ACC functioning, whereas the histaminergic pathways of mirtazapine do not innervate the ACC directly.

The influence of selective attention on P50 gating - the decline of the amplitude of the P50 component of the auditory evoked potential (AEP) to the second of a pair of clicks - was examined. Three conditions were presented in counterbalanced order to 29 18-47 year-old healthy volunteers: a baseline condition, in which the double click was presented and no specific task was required, an attention condition in which attention to the clicks was required, and a distraction condition in which paired clicks were presented during rehearsal time of a reversed digit span task. P50 gating, as measured with ratio and difference scores, did not differ across the three conditions. However, the amplitude of the N100 showed an increase in the attention condition compared to the two nonattention conditions, supporting the validity of our task manipulations. The data on P50 demonstrate that P50 gating is not affected by attentional manipulations. ispartof: Journal of Psychophysiology vol:17 issue:1 pages:23-29 status: published

Item does not contain fulltext RATIONALE: () 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy") has been shown to cause long term damage to serotonergic cerebral neurons in animals. The neurotoxic effects in humans are less clear and little is known about the functional consequences, although some studies suggest memory impairment. Given the widespread use of MDMA, our lack of knowledge raises concerns. OBJECTIVE: We investigated, in humans, the relation between past use of ecstasy and cognitive performance as well as serotonergic function. Methods: Two groups of 21 males with moderate and heavy recreational use of MDMA, respectively, and a control group of 20 males without use of MDMA were compared. All were from the same subculture. Reaction time, direct recall, and recognition were assessed. Serotonergic function was measured by the neuro-endocrine response to a placebo-controlled, crossover challenge with dexfenfluramine. RESULTS: Ecstasy users showed a broad pattern of statistically significant, but clinically small, impairment of memory and prolonged reaction times. Heavy users were affected stronger than moderate users. Release of cortisol but not of prolactin after dexfenfluramine administration was significantly reduced in both groups of ecstasy users compared with the controls. Analyses of covariance showed that likely confounding variables including recent exposure to ecstasy, psychosocial profiles and use of other drugs did not explain the differences found between the groups. CONCLUSIONS: These results provide further evidence that use of ecstasy may be associated with impairment of memory and of serotonergic function. These findings are compatible with neurotoxicity of ecstasy as shown in animals.

Depressive mood and impulsive-aggressive behavior are relevant to suicidal behavior and have been associated with decreased central serotonergic function. Impulsive behavior and aggression have also been related to abnormal glucose metabolism. To investigate these relationships further, blood serotonin (5-HT), blood glucose measures (glycated hemoglobin (HbA 1C ) and fructosamine) and self-reported depressive symptoms and anger were repeatedly measured, during a 1-year follow-up, in 106 patients who had recently attempted suicide for at least a second time. A major DSM-III-R Axis I diagnosis or use of antidepressants were reasons for exclusion. Intra-individual variations in blood 5-HT were inversely correlated with variations in depressive mood, self-depreciation, and anger, and positively with variations in fructosamine. Intra-individual variations of HbA 1C or fructosamine were not correlated with mood. Mean blood 5-HT levels per patient were positively correlated with mean scores of depression and self-depreciation. The contrast between the intra-individual and the inter-individual correlations may reflect a difference between short- vs. long-term effects. The results do support an association between serotonergic function and mood, but not between glucose metabolism and mood, in recurrent suicide attempters.

This study examined the relationship between borderline and impulsive personality traits on the one hand, and monoamine function on the other in 15 women with bulimia nervosa and 15 women with recurrent suicidal behavior. Platelet serotonin (5-HT) and platelet monoamine oxidase (MAO) activity were used as peripheral measures of monoaminergic function. All suicide attempters were diagnosed as having a borderline personality disorder, whereas this diagnosis was less frequent in bulimics. Bulimics with borderline comorbidity resembled recurrent suicide attempters with borderline personality disorder more closely in both psychological (anger, impulsive behavior) and biochemical characteristics (platelet 5-HT) than bulimics without borderline personality disorder. Platelet 5-HT was higher in patients with borderline personality than in normal female controls and was positively correlated with the disposition to experience anger. Impulsive personality traits were consistently negatively correlated with platelet MAO activity. Our findings support the subdivision of bulimics according to the presence of borderline or "multi-impulsive" personality disorder.

Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.

A group of 127 patients with esophageal cancer treated with radiotherapy at different dose levels was retrospectively analysed. It was found that 70.5% of the patients showed improvement of dysphagia and that 54% remained palliated with respect to food passage until their death. The two major prognostic variables with respect to the palliative effect on dysphagia as well as survival were the passage score and the radiation dose. Patients with severe dysphagia (PASS 0 or 1) had a median actuarial DFI and SURV of 3.7 and 6.4 months, respectively, in contrast to 16.0 and 8.7 months for patients who were able to use (semi)solid food (PASS 2 and 3). The median actuarial DFI and SURV of patients treated with a relatively low dose (less than 50 Gy in 5 weeks) were 2.5 and 4.8 months, respectively, compared to 10.1 and 8.3 months, respectively, for patients treated with a relatively high dose.