Examining associations between brain morphology in late childhood and early alcohol or tobacco use initiation in adolescence: Findings from a large prospective cohort.

A prominent challenge in understanding neural consequences of substance use involves disentangling predispositional risk factors from resulting consequences of substance use. Existing literature has identified pre-existing brain variations as vulnerability markers for substance use throughout adolescence. As early initiation of use is an important predictor for later substance use problems, we examined whether pre-existing brain variations are associated with early initiation of use. In the Generation R Study, a prospective population-based cohort, brain morphology (gray matter volume, cortical thickness and surface area) was assessed at ages 10 and 14 using neuroimaging. In the second wave, participants reported on alcohol and tobacco use initiation. From a base study population (N = 3019), we examined the longitudinal (N = 2218) and cross-sectional (N = 1817) association between brain morphology of frontolimbic regions of interest known to be associated with substance use risk, and very early (age < 13) alcohol/tobacco use initiation. Additionally, longitudinal and cross-sectional associations were examined with a brain surface-based approach. Models were adjusted for age at neuroimaging, sex and relevant sociodemographic factors. No associations were found between brain morphology (ages 10 and 14) and early alcohol/tobacco use initiation (<13 years). Sex-specific analyses suggested a cross-sectional association between smaller brain volume and early initiated tobacco use in girls. Our findings are important for interpreting studies examining neural consequences of substance use in the general population. Future longitudinal studies are needed to specify whether these findings can be extended to initiation and continuation of alcohol/tobacco use in later stages of adolescence.

One-Year Follow-Up: Schema Therapy for Patients With Borderline Personality Disorder and Comorbid Alcohol Use Disorder.

This article describes the 1-year follow-up of a study into the effectiveness of Schema Therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol use disorder (AUD). In the original study, 20 of these patients participated in a multiple baseline case series design study. The results of the original study were promising (a significant decrease of BPD and AUD symptoms). The present study is aimed at examining the longer term benefits of ST for BPD and comorbid AUD. One year after the cessation of the investigational therapy, 17 of the original participants agreed to participate in this follow-up study. T- or Wilcoxon signed rank tests were performed to compare 1-year follow-up to start of therapy (baseline). The results suggest that the main therapeutic improvements were generally preserved at 1-year follow-up. These findings add to the idea that integrated ST for BPD and comorbid AUD might be effective, also in the long term. A randomized clinical trial is indicated to substantiate this idea.

Evidence for post-decisional conflict monitoring in delay discounting.

Choice impulsivity can be measured by offering a sequence of various binary choices between smaller, immediately available rewards and larger, later available rewards. An individual's delay discount (DD) rate reflects the aggregate decision-making tendency. Given the broad spectrum of disorders associated with a high DD rate, this may be an important transdiagnostic factor. This study aimed to establish whether post-decisional neurophysiological processes reflecting the presence of error monitoring are involved in delay discounting. A large sample (N = 97) was investigated, including 46 females and 51 males. The electroencephalogram (EEG) was recorded during the classic monetary choice questionnaire (MCQ-27). Error-related event-related potentials (ERPs) and event-related oscillations (EROs) following responses were analyzed. A modest relationship between error positivity (Pe) and DD rate was seen centro-parietal, with higher amplitude for low DD individuals after choosing immediate rewards. A robust association was found between DD rate and theta oscillation power increases. This was most prominent in low DD individuals after making an immediate reward choice. Theta power was positively associated with decision (reaction) time, suggesting an association between pre- and post-decisional conflict. No evidence was found for an error-related negativity (ERN) and delta oscillations. This study provides clear evidence for conflict monitoring as a post-decision process in delay discounting. Findings suggest that diminished theta band power bursts and lower Pe amplitude, observed after choosing an immediate reward, reflect the neurophysiological consequence and possibly the cause of steep delay discounting. High DD was characterized by prefrontal hypoactivation and appears to result from affective decision-making. Highlights.

Getting closer to social interactions using electroencephalography in developmental cognitive neuroscience.

The field of developmental cognitive neuroscience is advancing rapidly, with large-scale, population-wide, longitudinal studies emerging as a key means of unraveling the complexity of the developing brain and cognitive processes in children. While numerous neuroscientific techniques like functional magnetic resonance imaging (fMRI), functional near-infrared spectroscopy (fNIRS), magnetoencephalography (MEG), and transcranial magnetic stimulation (TMS) have proved advantageous in such investigations, this perspective proposes a renewed focus on electroencephalography (EEG), leveraging underexplored possibilities of EEG. In addition to its temporal precision, low costs, and ease of application, EEG distinguishes itself with its ability to capture neural activity linked to social interactions in increasingly ecologically valid settings. Specifically, EEG can be measured during social interactions in the lab, hyperscanning can be used to study brain activity in two (or more) people simultaneously, and mobile EEG can be used to measure brain activity in real-life settings. This perspective paper summarizes research in these three areas, making a persuasive argument for the renewed inclusion of EEG into the toolkit of developmental cognitive and social neuroscientists.

The effect of HD-tDCS on brain oscillations and frontal synchronicity during resting-state EEG in violent offenders with a substance dependence

Violence is a major problem in our society and therefore research into the neural underpinnings of aggression has grown exponentially. Although in the past decade the biological underpinnings of aggressive behavior have been examined, research on neural oscillations in violent offenders during resting-state electroencephalography (rsEEG) remains scarce. In this study we aimed to investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) on frontal theta, alpha and beta frequency power, asymmetrical frontal activity, and frontal synchronicity in violent offenders.Fifty male violent forensic patients diagnosed with a substance dependence were included in a double-blind sham-controlled randomized study. The patients received 20 minutes of HD-tDCS two times a day on five consecutive days. Before and after the intervention, the patients underwent a rsEEG task.Results showed no effect of HD-tDCS on the power in the different frequency bands. Also, no increase in asymmetrical activity was found. However, we found increased synchronicity in frontal regions in the alpha and beta frequency bands indicating enhanced connectivity in frontal brain regions as a result of the HD-tDCS-intervention.This study has enhanced our understanding of the neural underpinnings of aggression and violence, pointing to the importance of alpha and beta frequency bands and their connectivity in frontal brain regions. Although future studies should further investigate the complex neural underpinnings of aggression in different populations and using whole-brain connectivity, it can be suggested with caution, that HD-tDCS could be an innovative method to regain frontal synchronicity in neurorehabilitation. (AU)

The effect of HD-tDCS on brain oscillations and frontal synchronicity during resting-state EEG in violent offenders with a substance dependence.

Violence is a major problem in our society and therefore research into the neural underpinnings of aggression has grown exponentially. Although in the past decade the biological underpinnings of aggressive behavior have been examined, research on neural oscillations in violent offenders during resting-state electroencephalography (rsEEG) remains scarce. In this study we aimed to investigate the effect of high-definition transcranial direct current stimulation (HD-tDCS) on frontal theta, alpha and beta frequency power, asymmetrical frontal activity, and frontal synchronicity in violent offenders. Fifty male violent forensic patients diagnosed with a substance dependence were included in a double-blind sham-controlled randomized study. The patients received 20 minutes of HD-tDCS two times a day on five consecutive days. Before and after the intervention, the patients underwent a rsEEG task. Results showed no effect of HD-tDCS on the power in the different frequency bands. Also, no increase in asymmetrical activity was found. However, we found increased synchronicity in frontal regions in the alpha and beta frequency bands indicating enhanced connectivity in frontal brain regions as a result of the HD-tDCS-intervention. This study has enhanced our understanding of the neural underpinnings of aggression and violence, pointing to the importance of alpha and beta frequency bands and their connectivity in frontal brain regions. Although future studies should further investigate the complex neural underpinnings of aggression in different populations and using whole-brain connectivity, it can be suggested with caution, that HD-tDCS could be an innovative method to regain frontal synchronicity in neurorehabilitation.

Schema therapy for patients with borderline personality disorder and comorbid alcohol dependence: A multiple-baseline case series design study.

This study tested the effectiveness of schema therapy (ST) for borderline personality disorder (BPD) and comorbid alcohol dependence (AD). Twenty patients participated in a case series study with multiple baselines. The baseline phase consisted of treatment as usual. It was followed by a case conceptualization phase, an experiential techniques phase and a behavioural change phase. Patients showed a significant decrease in BPD and AD symptoms; change was mainly accomplished in the experiential techniques phase, with medium to large effect sizes. Three months after termination of therapy, 68% of the patients had remitted from BPD, and the number of drinking days decreased clearly. This study shows that, although treatment is challenging in this group of patients, meaningful change can be obtained in patients with BPD and AD using ST.

A randomized controlled trial to pilot the efficacy of a computer-based intervention with elements of virtual reality and limited therapist assistance for the treatment of post-traumatic stress disorder.

Although well-established therapies exist for post-traumatic stress disorder (PTSD), barriers to seek mental health care are high. Technology-based interventions may play a role in improving the reach of efforts to treat, especially when therapist availability is low. The goal of the current randomized controlled trial was to pilot the efficacy of a computer-based trauma intervention with elements of virtual reality (VR; 3MR system) and limited therapist involvement for the treatment of PTSD in a childhood sexual abuse (CSA) and war veteran sample and to compare this to "treatment as usual" (TAU). TAU consisted of evidence-based approaches such as imaginal exposure, EMDR, or narrative exposure therapy. A total of 44 patients with PTSD were included and randomly assigned to 12 sessions of 3MR intervention or TAU (completer n 3MR = 12, TAU = 18). Several measures (PCL-5, BDI-II, OQ-45-2, and the M.I.N.I. 5.0.0.) were administered to measure symptoms of PTSD and depression and scores of overall well-being at pre, post, and a three-month follow-up measurement. Analyses suggest that symptoms of PTSD and depression in the 3MR condition decreased, and overall well-being increased between pre and post measurements. Results did not indicate any clear differences between the treatment conditions over time which suggests that treatment gains of the 3MR intervention seem no less than those of TAU. Finally, both treatment conditions produced similar remission rates of PTSD and depression. Therefore, the 3MR intervention could possibly constitute an appropriate treatment alternative. The small sample size as well as evident drop-out rates in the 3MR condition (45%) do warrant further research. The procedures of this study were approved by the Medical Ethical Research Committee (MERC) of the Erasmus Medical Center in Rotterdam (MEC-NL46279.078.13) and pre-registered via ClinicalTrials.gov (Protocol Record CI1-12-S028-1).

Association of Maternal Tobacco Use During Pregnancy With Preadolescent Brain Morphology Among Offspring.

Importance: Maternal tobacco use during pregnancy has been associated with various health consequences, including suboptimal neurodevelopment in offspring. However, the effect of prenatal exposure to maternal smoking on child brain development has yet to be elucidated. Objective: To investigate the association between maternal smoking during pregnancy and offspring brain development in preadolescence as well as the mediating pathways. Design, Setting, and Participants: This prospective, population-based cohort study was embedded in the Generation R Study, Rotterdam, the Netherlands. The Generation R Study was launched in 2002, with follow-up ongoing. Child brain morphology was assessed at 9 to 11 years of age (ie, 10-12 years between exposure and outcome assessment). Data analysis was performed from March 1, 2021, to February 28, 2022, and at the time of manuscript revision. Participants included the singleton children of pregnant women residing in the study area with an expected date of delivery between April 1, 2002, and January 31, 2006; 2704 children with information on maternal smoking during pregnancy and structural neuroimaging at 9 to 11 years of age were included. A subsample of 784 children with data on DNA methylation at birth was examined in the mediation analysis. Exposures: Information on maternal smoking during pregnancy was collected via a questionnaire in each trimester. As a contrast, paternal smoking was assessed at recruitment. Main Outcomes and Measures: Brain morphology, including brain volumes and surface-based cortical measures (thickness, surface area, and gyrification), was assessed with magnetic resonance imaging. For mediation analysis, DNA methylation at birth was quantified by a weighted methylation risk score. Results: The 2704 participating children (1370 [50.7%] girls and 1334 [49.3%] boys) underwent brain imaging assessment at a mean (SD) age of 10.1 (0.6) years. Compared with nonexposed children (n = 2102), exposure to continued maternal smoking during pregnancy (n = 364) was associated with smaller total brain volume (volumetric difference [b] = -14.5 [95% CI, -25.1 to -4.0] cm3), cerebral gray matter volume (b = -7.8 [95% CI, -13.4 to -2.3] cm3), cerebral white matter volume (b = -5.9 [95% CI, -10.7 to -1.0] cm3), and surface area and less gyrification. These associations were not explained by paternal smoking nor mediated by smoking-associated DNA methylation patterns at birth. Children exposed to maternal smoking only in the first trimester (n = 238) showed no differences in brain morphology compared with nonexposed children. Conclusions and Relevance: The findings of this cohort study suggest that continued maternal tobacco use during pregnancy was associated with lower brain volumes and suboptimal cortical traits of offspring in preadolescence, which seemed to be independent of shared family factors. Tobacco cessation before pregnancy, or as soon as pregnancy is known, should be recommended to women for optimal brain development of their offspring.

Brain morphology predictors of alcohol, tobacco, and cannabis use in adolescence: A systematic review.

In the last decade, extensive research has emerged on the predictive value of brain morphology for substance use initiation and related problems during adolescence. This systematic review provides an overview of longitudinal studies on pre-existing brain variations and later initiation of alcohol, tobacco, and cannabis use (N = 18). Adolescent structural neuroimaging studies that started before substance use initiation suggest that a smaller anterior cingulate cortex (ACC) volume, thicker or smaller superior frontal gyrus, and larger nucleus accumbens (NAcc) volume are associated with future alcohol use. Also, both smaller and larger orbitofrontal cortex (OFC) volumes were associated with future cannabis and combined alcohol/cannabis use. Smaller amygdala volumes were related to future daily tobacco smoking. These findings could point to specific vulnerabilities for adolescent substance use, as these brain areas are involved in cognitive control (ACC), reward (NAcc), motivation (OFC), and emotional memory (amygdala). However, the reported findings were inconsistent in directionality and laterality, and the largest study on alcohol use predictors reported null findings. Therefore, large population-based longitudinal studies should investigate the robustness and mechanisms of these associations. We suggested future research directions regarding sample selection, timing of baseline and follow-up measurements, and a harmonization approach of study methods.

Sensation seeking and its relationship with psychopathic traits, impulsivity and aggression: a validation of the Dutch Brief Sensation Seeking Scale (BSSS).

Sensation seeking is a personality trait that manifests as a preference for change, variety and novelty. Sensation seeking has been positively associated with different externalising behaviours. However, its associations with psychopathic traits, impulsivity and aggression are unclear. These associations were examined via the psychometric properties of the Dutch version of the Brief Sensation Seeking Scale (BSSS) using individuals from the general population and forensic patients. The results show that the BSSS has good psychometric properties, including test-retest reliability and a four-factor structure. Additionally, the results support associations between sensation seeking and psychopathic traits, impulsivity and total scores of aggression but revealed no specific associations with different types of aggression (e.g. proactive and reactive). The Dutch BSSS is a valuable tool for assessing sensation seeking in both the general population and forensic patients. Future research should further examine its utility and explore the role of sensation seeking in antisocial conduct.

Early life stress and behavior problems in early childhood: Investigating the contributions of child temperament and executive functions to resilience.

This preregistered study examined whether child temperament and executive functions moderated the longitudinal association between early life stress (ELS) and behavior problems. In a Dutch population-based cohort (n = 2803), parents reported on multiple stressors (age 0-6 years), child temperament (age 5), and executive functions (age 4), and teachers rated child internalizing and externalizing problems (age 7). Results showed that greater ELS was related to higher levels of internalizing and externalizing problems, with betas reflecting small effects. Lower surgency buffered the positive association of ELS with externalizing problems, while better shifting capacities weakened the positive association between ELS and internalizing problems. Other child characteristics did not act as moderators. Findings underscore the importance of examining multiple protective factors simultaneously.

Is irregular time estimation a common factor in smoking behavior and delay discounting?

INTRODUCTION: Smoking is known to be associated with steeper delay discounting which is a widely used measure of externalizing behavior. This study investigates individual aspects of time estimation and the extent to which these are associated with differences in delay discounting and smoking behavior. METHODS: The study was conducted as an online experiment in a sample of undergraduate students (N = 495), including 51 smokers. Participants completed a serial time estimation, delay discounting task (MCQ), BIS/BAS questionnaire, Fagerstrom test for nicotine dependence and an alcohol use assessment (QFV). RESULTS: Smoking, heavy drinking and delay discounting were associated with faster estimation of time. Furthermore, smoking and delay discounting were associated with differences in autocorrelation. Fun seeking was associated with smoking and alcohol use, but not with time estimation or delay discounting. CONCLUSIONS: This study provides evidence for the hypothesis that an acceleration of the internal clock might lead to time over-estimation which could lead towards delayed consequence sensitivity and addiction. The study also found further evidence for the hypothesis that distortions in time estimation (i.e., autocorrelation) may be related to delay discounting and smoking. Smoking and delay discounting were associated with faster estimations of time and differences in autocorrelation.

Borderline Personality Disorder With Versus Without Alcohol Use Disorder: Comparing Impulsivity and Schema Modes.

Substance use disorders (SUDs) and borderline personality disorder (BPD) are highly comorbid. In the present study, an attempt was made to understand the differences between BPD and BPD with comorbid SUD (BPD + alcohol use disorder [AUD]), by studying impulsivity and schema modes (i.e., maladaptive moment-to-moment emotional states and coping responses). BPD patients, BPD+AUD patients, and nonpatients (NP) were compared regarding behavioral impulsivity (motor impulsivity, risk taking, delay discounting), and schema modes. The two patient groups displayed greater delay discounting than the NP group. Further, BPD and BPD+AUD groups were different from the NP group regarding all schema modes investigated. However, no differences were found on any of the dependent variables between the two patient groups. It is suggested that although BPD patients are in general more impulsive and have more maladaptive moment-to-moment emotional states and coping responses, BPD patients with and without AUD seem not to be different in this respect.

Transcranial Direct Current Stimulation Targeting the Ventromedial Prefrontal Cortex Reduces Reactive Aggression and Modulates Electrophysiological Responses in a Forensic Population.

BACKGROUND: Studies have shown that impairments in the ventromedial prefrontal cortex play a crucial role in violent behavior in forensic patients who also abuse cocaine and alcohol. Moreover, interventions that aimed to reduce violence risk in those patients are found not to be optimal. A promising intervention might be to modulate the ventromedial prefrontal cortex by high-definition (HD) transcranial direct current stimulation (tDCS). The current study aimed to examine HD-tDCS as an intervention to increase empathic abilities and reduce violent behavior in forensic substance dependent offenders. In addition, using electroencephalography, we examined the effects on the P3 and the late positive potential of the event-related potentials in reaction to situations that depict victims of aggression. METHODS: Fifty male forensic patients with a substance dependence were tested in a double-blind, placebo-controlled randomized study. The patients received HD-tDCS 2 times a day for 20 minutes for 5 consecutive days. Before and after the intervention, the patients completed self-reports and performed the Point Subtraction Aggression Paradigm, and electroencephalography was recorded while patients performed an empathy task. RESULTS: Results showed a decrease in aggressive responses on the Point Subtraction Aggression Paradigm and in self-reported reactive aggression in the active tDCS group. Additionally, we found a general increase in late positive potential amplitude after active tDCS. No effects on trait empathy and the P3 were found. CONCLUSIONS: Current findings are the first to find positive effects of HD-tDCS in reducing aggression and modulating electrophysiological responses in forensic patients, showing the potential of using tDCS as an intervention to reduce aggression in forensic mental health care.

Characteristics and stability of hallucinations and delusions in patients with borderline personality disorder.

BACKGROUND: Psychotic features have been part of the description of the borderline personality disorder (BPD) ever since the concept "borderline" was introduced. However, there is still much to learn about the presence and characteristics of delusions and about the stability of both hallucinations and delusions in patients with BPD. METHODS: A follow-up study was conducted in 326 BPD outpatients (median time between baseline and follow-up = 3.16 years). Data were collected via telephone (n = 267) and face-to-face interviews (n = 60) including the Comprehensive Assessment of Symptoms and History interview, Positive And Negative Syndrome Scale and the Psychotic Symptom Rating Scale. RESULTS: The point prevalence of delusions was 26%, with a median strong delusion conviction. For the group as a whole, the presence and severity of both hallucinations and delusions was found to be stable at follow-up. Participants with persistent hallucinations experienced more comorbid psychiatric disorders, and they differed from those with intermittent or sporadic hallucinations with their hallucinations being characterized by a higher frequency, causing a higher intensity of distress and more disruption in daytime or social activities. CONCLUSIONS: Delusions in patients with BPD occur frequently and cause distress. Contrary to tenacious beliefs, hallucinations and delusions in participants with BPD are often present in an intermittent or persistent pattern. Persistent hallucinations can be severe, causing disruption of life. Overall, we advise to refrain from terms such as "pseudo", or assume transience when encountering psychotic phenomena in patients with BPD, but rather to carefully assess these experiences and initiate a tailor-made treatment plan.

Diminished error-related negativity and error positivity in children and adults with externalizing problems and disorders: a meta-analysis on error processing.

BACKGROUND: Deficits in error processing are reflected in an inability of people with externalizing problems to adjust their problem behaviour. The present study contains 2 meta-analyses, testing whether error processing - indexed by the event-related potentials error-related negativity (ERN) and error positivity (Pe) - is reduced in children and adults with externalizing problems and disorders compared to healthy controls. METHODS: We conducted a systematic search in PubMed (1980 to December 2018), PsycInfo (1980 to December 2018) and Scopus (1970 to December 2018), identifying 328 studies. We included studies that measured error processing using the Eriksen flanker task, the go/no-go task or the stop-signal task in healthy controls and in adults or children with clearly described externalizing behavioural problems (e.g., aggression) or a clinical diagnosis on the externalizing spectrum (e.g., addiction). RESULTS: Random-effect models (ERN: 23 studies, 1739 participants; Pe: 27 studies, 1456 participants) revealed a reduced ERN amplitude (Hedges' g = 0.44, 95% confidence interval [CI] 0.29 to 0.58) and a reduced Pe amplitude (Hedges' g = -0.27, 95% CI -0.44 to -0.09) during error processing in people with externalizing problems or disorders compared to healthy controls. Type of diagnosis, age and the presence of performance feedback or comorbidity did not moderate the results. The employed cognitive task was a moderator for Pe but not for ERN. The go/no-go task generated a greater amplitude difference in Pe than the Eriksen flanker task. Small-sample assessment revealed evidence of publication bias for both event-related potentials. However, a p curve analysis for ERN showed that evidential value was present; for Pe, the p curve analysis was inconclusive. LIMITATIONS: The moderators did not explain the potential heterogeneity in most of the analysis, suggesting that other disorder- and patient-related factors affect error processing. CONCLUSION: Our findings indicate the presence of compromised error processing in externalizing psychopathology, suggesting diminished activation of the prefrontal cortex during performance monitoring.

Alcohol use and brain morphology in adolescence: A longitudinal study in three different cohorts.

Alcohol consumption is commonly initiated during adolescence, but the effects on human brain development remain unknown. In this multisite study, we investigated the longitudinal associations of adolescent alcohol use and brain morphology. Three longitudinal cohorts in the Netherlands (BrainScale n = 200, BrainTime n = 239 and a subsample of the Generation R study n = 318) of typically developing participants aged between 8 and 29 years were included. Adolescent alcohol use was self-reported. Longitudinal neuroimaging data were collected for at least two time points. Processing pipelines and statistical analyses were harmonized across cohorts. Main outcomes were global and regional brain volumes, which were a priori selected. Linear mixed effect models were used to test main effects of alcohol use and interaction effects of alcohol use with age in each cohort separately. Alcohol use was associated with adolescent's brain morphology showing accelerated decrease in grey matter volumes, in particular in the frontal and cingulate cortex volumes, and decelerated increase in white matter volumes. No dose-response association was observed. The findings were most prominent and consistent in the older cohorts (BrainScale and BrainTime). In summary, this longitudinal study demonstrated differences in neurodevelopmental trajectories of grey and white matter volume in adolescents who consume alcohol compared with non-users. These findings highlight the importance to further understand underlying neurobiological mechanisms when adolescents initiate alcohol consumption. Therefore, further studies need to determine to what extent this reflects the causal nature of this association, as this longitudinal observational study does not allow for causal inference.