Anja S. Euser

Differences in attention to food and food intake between overweight/obese and normal-weight females under conditions of hunger and satiety.

Starting from an addiction model of obesity, the present study examined differences in attention for food-related stimuli and food intake between overweight/obese and normal-weight women under conditions of hunger and satiety. Twenty-six overweight/obese (BMI: 30.00+/-4.62) and 40 normal-weight (BMI: 20.63+/-1.14) females were randomly assigned to a condition of hunger or satiety. Three indexes of attention were employed, all including pictures of food items: an eye-tracking paradigm (gaze direction and duration), a visual probe task (reaction times), and a recording of electrophysiological brain activity (amplitude of the P300 event-related potential). In addition, the acute food intake of participants was assessed using a bogus taste task. In general, an attentional bias towards food pictures was found in all participants. No differences between groups or conditions were observed in the eye-tracking data. The visual probe task revealed an enhanced automatic orientation towards food cues in hungry versus satiated, and in overweight/obese versus normal-weight individuals, but no differences between groups or conditions in maintained attention. The P300 amplitude showed that only in normal-weight participants the intentional allocation of attention to food pictures was enhanced in hunger versus satiety. In hungry overweight/obese participants, the P300 bias for food pictures was not clearly present, although an increased food intake was observed especially in this group. In conclusion, various attention-related tasks yielded various results, suggesting that they measure different underlying processes. Strikingly, overweight/obese individuals appear to automatically direct their attention to food-related stimuli, to a greater extent than normal-weight individuals, particularly when food-deprived. Speculatively, hungry overweight/obese individuals also appear to use cognitive strategies to reduce a maintained attentional bias for food stimuli, perhaps in an attempt to prevent disinhibited food intake. However, in order to draw firm conclusions, replication studies are needed.

The P300 event-related brain potential as a neurobiological endophenotype for substance use disorders: a meta-analytic investigation.

Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed.

Determinants of Physiological and Perceived Physiological Stress Reactivity in Children and Adolescents

Aims Abnormal physiological stress reactivity is increasingly investigated as a vulnerability marker for various physical and psychological health problems. However, studies are inconsistent in taking into account potential covariates that may influence the developing stress system. We systematically tested determinants (individual, developmental, environmental and substance use-related) of physiological and perceived physiological stress reactivity. We also examined the relation between physiological and perceived physiological stress reactivity. Method In a stratified sample of 363 children (7–12 years) and 344 adolescents (13–20 years) from the general population, we examined cortisol, heart rate, respiratory sinus arrhythmia and perceived physiological stress reactivity to a psychosocial stress procedure. Results Using multivariate linear regression models, we found that individual, developmental, environmental and substance use-related factors were related to each of the stress response indices. These determinant factors were different for each of the stress reactivity indices, and different in children versus adolescents. Perceived physiological stress reactivity predicted cortisol reactivity in adolescents only. All other relations between perceived physiological and physiological stress reactivity were not significant. Conclusions As physiological stress variables are often examined as vulnerability markers for the development of health problems, we maintain that it is essential that future studies take into consideration factors that may account for found relations. Our study provides an overview and indication of which variables should be considered in the investigation of the relation between physiological stress indices and illness.

Diminished error-related brain activity as a promising endophenotype for substance-use disorders: evidence from high-risk offspring

One of the core features of individuals with a substance‐use disorder (SUD) is the reduced ability to successfully process errors and monitor performance, as reflected by diminished error‐related negativities (ERN). However, whether these error‐related brain abnormalities are caused by chronic substance use or rather predates it remains unclear. The present study elucidated whether hypoactive performance monitoring represents an endophenotypic vulnerability marker for SUD by using a high‐risk paradigm. We assessed the behavioral components of error‐processing, as well as the amplitude of the ERN in the event‐related brain potential (ERP) during performance of the Eriksen Flanker Task among high‐risk adolescents of parents with a SUD (HR; n = 28) and normal‐risk controls (NR; n = 40). Results revealed that HR offspring were characterized by a higher prevalence of internalizing symptoms and more frequent cannabis use, the latter having a significant influence on the ERN. Interestingly, risk group uniquely predicted the negativity amplitude in response to error trials above and beyond confounding variables. Moreover, we found evidence of smaller ERN amplitudes in (cannabis use‐naïve) HR offspring, reflecting impaired early processing of error information and suboptimal performance monitoring, whereas no robust group differences were found for overall behavioral performance. This effect was independent of an overall reduction in brain activity. Taken together, although we cannot rule out alternative explanations, the results of our study may provide evidence for the idea that diminished error‐processing represents a promising endophenotype for SUD that may indicate a vulnerability to the disorder.

Alcohol and tobacco use and heart rate reactivity to a psychosocial stressor in an adolescent population

BACKGROUND Few studies have investigated physiological stress (re)activity in relation to substance use, especially in adolescents. Using substances is one way to stimulate physiological arousal, therefore inherent hypo-arousal may be associated with substance use in adolescents. The purpose of this study was to examine the relation of autonomic nervous system (ANS) activity with alcohol and tobacco use in adolescents. METHODS ANS activity and perceived stress during a social stress procedure were examined in relation to substance use. 275 Dutch adolescents from a general population study provided complete data. Heart rate was recorded continuously during a pre-task rest period, a stressful task period and a post-task recovery period. Alcohol and tobacco use were self-reported. RESULTS Adolescents who consumed a medium and high number of alcoholic drinks per week (more than two) exhibited lower heart rates during the entire stress procedure as compared to those who consumed a low number of alcoholic drinks. Adolescents who smoked every day portrayed blunted heart rate reactivity to stress as compared to adolescents who smoked less frequently or not at all. Perceived stress was not related to alcohol or tobacco use. CONCLUSIONS Overall lower heart rate in adolescents who drank more and blunted heart rate reactivity to stress in those who used tobacco every day may indicate inherent hypo-arousal of the ANS system in those vulnerable to use substances more often. These adolescents may actively seek out substances in order to achieve a more normalized state of arousal.

Blunted feedback processing during risky decision making in adolescents with a parental history of substance use disorders.

Risky decision making, a hallmark phenotype of substance use disorders (SUD), is thought to be associated with deficient feedback processing. Whether these aberrations are present prior to SUD onset or reflect merely a consequence of chronic substance use on the brain remains unclear. The present study investigated whether blunted feedback processing during risky decision making reflects a biological predisposition to SUD. We assessed event-related potentials elicited by positive and negative feedback during performance of a modified version of the Balloon Analogue Risk Task (BART) among high-risk adolescents with a parental history of SUD (HR; n = 61) and normal-risk controls (NR; n = 91). HR males made significantly more risky and faster decisions during the BART than did NR controls. Moreover, HR adolescents showed significantly reduced P300 amplitudes in response to both positive and negative feedback as compared to NR controls. These differences were not secondary to prolonged substance use exposure. Results are discussed in terms of feedback-specific processes. Reduced P300 amplitudes in the BART may reflect poor processing of feedback at the level of overall salience, which may keep people from effectively predicting the probability of future gains and losses. Though conclusions are tentative, blunted feedback processing during risky decision making may represent a promising endophenotypic vulnerability marker for SUD.

Youth in the Netherlands Study (JOiN): study design

BackgroundAdolescence is a critical developmental period regarding exposure to substances. Therefore, it is important to be able to identify those adolescents who are most vulnerable to substance abuse in the (near) future. The JOiN study was specifically designed to examine two endophenotypes of adolescent substance use in a normal risk (NR) and high risk (HR) sample of adolescents: (1) behavioural disinhibition, and (2) individual differences in stress sensitivity.MethodsThe NR adolescents were part of a longitudinal general population study at the Erasmus Medical Center in Rotterdam, the Netherlands of children and adolescents initially aged 6 to 18 years old. Three assessment waves have been nearly completed, and data are available of N = 711 participants for stress sensitivity measures, and of a subsample of N = 110 for electroencephalography (EEG) measures. Added to this study, HR adolescents who had at least one parent with a substance use disorder and who were treated by an outpatient clinic of a primary addiction care provider were approached via their parent(s). In total, N = 83 adolescents formed this HR sample. NR and HR adolescents participated in standardized stress procedure and EEG procedures in our laboratory. Questionnaires were filled out on background variables, behavioural and emotional problems, and substance use, and a diagnostic interview was conducted with adolescents and parents to assess psychopathology symptoms. DNA was collected through saliva or blood samples.DiscussionThe design of the JOiN study is optimal for examining the predictive role of endophenotypes of adolescent substance use. The combination of different methods, i.e. stress physiology, electrophysiology, genetics, and questionnaire data from several informants on a range of behaviours and environmental factors enables the investigation of the multifactorial nature of adolescent substance use.

Cortisol levels in children of parents with a substance use disorder

BACKGROUND Children of parents with a substance use disorder (CPSUDs) are at increased risk for the development of substance use disorders later in life, and therefore may manifest vulnerability markers for these disorders at a higher level than children from the general population. Our aim was to examine hypothalamic-pituitary-adrenal (HPA) axis activity as a potential vulnerability marker in CPSUDs as compared to healthy controls. We further examined whether having experienced more adverse life events (ALEs) accounted for differences in cortisol levels between CPSUDs and controls. METHODS 83 CPSUDs were matched to 83 controls on the basis of age, sex and socioeconomic status. Salivary cortisol was assessed at four time points during a normal day and at six time points during a psychosocial stress procedure, during which perceived stress was also measured. We implemented piecewise multilevel growth curve modeling to examine group differences in diurnal and stress-evoked cortisol levels. RESULTS Diurnal cortisol levels of CPSUDs did not differ from those of controls. Only stress-evoked cortisol levels at onset of the experiment were explained by group status, such that CPSUDs exhibited lower cortisol levels at onset of the stress procedure. CPSUDs reported experiencing significantly more ALEs, yet number of ALEs was not related to cortisol levels. CPSUDs furthermore reported less perceived stress than controls at onset of the procedure. CONCLUSIONS HPA axis dysregulation may be a vulnerability marker for substance use disorders, as CPSUDs show blunted activation in anticipation of stress. These blunted cortisol levels were not the result of having experienced more stressful experiences during their lifetimes, thus might reflect an inborn vulnerability to substance use disorders.

Blunted Heart Rate Response as a Potential Endophenotype of Substance Use Disorders: Evidence from High-Risk Youth

Background Children of parents with a substance use disorder (CPSUD) are at increased risk for developing problematic substance use later in life. Endophenotypes may help to clarify the mechanism behind this increased risk. However, substance use and externalizing symptoms may confound the relation between dysregulated physiological stress responding and familial risk for substance use disorders (SUDs). Methods We examined whether heart rate (HR) responses differed between CPSUDs and controls. Participants (aged 11–20 years) were CPSUDs (N = 75) and controls (N = 363), semi-matched on the basis of sex, socioeconomic status, and ethnicity. HR was measured continuously during a psychosocial stress procedure. Substance use and externalizing symptoms were self-reported and mother-reported, respectively. Results A piecewise, mixed-effects model was fit for HR across the stress procedure, with fixed effects for HR reactivity and HR recovery. CPSUDs showed a blunted HR recovery. CPSUDs reported drinking more frequently, were more likely to use tobacco daily, were more likely to report ever use of cannabis and used cannabis more frequently, and exhibited more externalizing symptoms. These variables did not confound the relation between familial risk for SUDs and a blunted HR recovery. Conclusion Our findings suggest dysregulated autonomic nervous system (ANS) responding in CPSUDs and contribute to the accumulating evidence for ANS dysregulation as a potential endophenotype for SUDs.

Multifactorial determinants of target and novelty-evoked P300 amplitudes in children of addicted parents

Background Although P300 amplitude reductions constitute a persistent finding in children of addicted parents, relatively little is known about the specificity of this finding. The major aim of this study was to investigate the association between parental rearing, adverse life events, stress-reactivity, substance use and psychopathology on the one hand, and P300 amplitude in response to both target and novel distracter stimuli on the other hand. Moreover, we assessed whether risk group status (i.e., having a parental history of Substance Use Disorders [SUD]) uniquely contributed to P300 amplitude variation above and beyond these other variables. Methods Event-related potentials were recorded in high-risk adolescents with a parental history of SUD (HR;n=80) and normal-risk controls (NR;n=100) while performing a visual Novelty Oddball paradigm. Stress-evoked cortisol levels were assessed and parenting, life adversities, substance use and psychopathology were examined by using self-reports. Results HR adolescents displayed smaller P300 amplitudes in response to novel- and to target stimuli than NR controls, while the latter only approached significance. Interestingly, the effect of having a parental history of SUD on target-P300 disappeared when all other variables were taken into account. Externalizing problem behavior was a powerful predictor of target-P300. In contrast, risk group status uniquely predicted novelty-P300 amplitude reductions above and beyond all other factors. Conclusion Overall, the present findings suggest that the P300 amplitude reduction to novel stimuli might be a more specific endophenotype for SUD than the target-P300 amplitude. This pattern of results underscores the importance of conducting multifactorial assessments when examining important cognitive processes in at-risk adolescents.