Maternal psychopathology is differentially associated with adolescent offspring neural response to reward given offspring ADHD risk.

Reinforcement sensitivity is a hypothesized attention-deficit/hyperactivity disorder (ADHD) intermediate phenotype but its role in transgenerational transmission of ADHD-linked psychopathology risk is largely unknown. We examined, in a carefully phenotyped, N = 123 sample of adolescents (Mage = 15.27 years, SD = 0.984; 61.78% boys), whether (1) parental psychopathology is differentially associated with fMRI-indexed neural response to reward receipt and (2) both maternal and paternal psychopathology are associated with neural response to reward; across adolescents at-risk for and not at-risk for ADHD. Indices of parental psychopathology were differentially associated with adolescent offspring neural response to reward such that across measures, parental psychopathology was negatively or not associated with offspring superior frontal gyrus (SFG) response to reward receipt in adolescents at-risk for ADHD, but parental psychopathology was positively associated with offspring SFG response in adolescents not at-risk. Further, across measures, greater maternal psychopathology was associated with blunted adolescent SFG response to reward in adolescents at-risk for ADHD whereas greater maternal externalizing problems were linked to enhanced adolescent SFG response in adolescents not at-risk. Across measures, paternal psychopathology was not associated with adolescent response to reward, in either group. ADHD risk confers differential reward-related susceptibility to the effects of parental psychopathology. Results also show this association is nonspecific in terms of parental psychopathology type but is specific to maternal psychopathology.

Amygdala Volume is Associated with ADHD Risk and Severity Beyond Comorbidities in Adolescents: Clinical Testing of Brain Chart Reference Standards.

Understanding atypicalities in ADHD brain correlates is a step towards better understanding ADHD etiology. Efforts to map atypicalities at the level of brain structure have been hindered by the absence of normative reference standards. Recent publication of brain charts allows for assessment of individual variation relative to age- and sex-adjusted reference standards and thus estimation not only of case-control differences but also of intraindividual prediction. METHODS: Aim was to examine, whether brain charts can be applied in a sample of adolescents (N = 140, 38% female) to determine whether atypical brain subcortical and total volumes are associated with ADHD at-risk status and severity of parent-rated symptoms, accounting for self-rated anxiety and depression, and parent-rated oppositional defiant disorder (ODD) as well as motion. RESULTS: Smaller bilateral amygdala volume was associated with ADHD at-risk status, beyond effects of comorbidities and motion, and smaller bilateral amygdala volume was associated with inattention and hyperactivity/impulsivity, beyond effects of comorbidities except for ODD symptoms, and motion. CONCLUSIONS: Individual differences in amygdala volume meaningfully add to estimating ADHD risk and severity. Conceptually, amygdalar involvement is consistent with behavioral and functional imaging data on atypical reinforcement sensitivity as a marker of ADHD-related risk. Methodologically, results show that brain chart reference standards can be applied to address clinically informative, focused and specific questions.

Concurrent and Prospective Associations of Reward Response with Affective and Alcohol Problems: ADHD-Related Differential Vulnerability.

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous disorder. Data on the role of transdiagnostic, intermediate phenotypes in ADHD-relevant characteristics and outcomes are needed to advance conceptual understanding and approaches to precision psychiatry. Specifically, the extent to which the association between neural response to reward and ADHD-associated affective, externalizing, internalizing, and substance use problems differ depending on ADHD status is unknown. Aims were to examine, in 129 adolescents, whether concurrent and prospective associations of fMRI-measured initial response to reward attainment (relative to loss) with affectivity and externalizing, internalizing, and alcohol use problems differs between youth at-risk for (i.e., subclinical) (n = 50) and not at-risk for ADHD. Adolescents were, on average, 15.29 years old (SD = 1.00; 38% female), 50 were at-risk for (Mage = 15.18 years, SD = 1.04; 22% female) and 79 not at-risk for (Mage = 15.37 years, SD = 0.98; 48.1% female) ADHD. Both concurrent and prospective relations differed given ADHD risk: across analyses, in at-risk youth, greater superior frontal gyrus response was associated with lower concurrent depressive problems but in not at-risk youth, these characteristics were not related. Controlling for baseline use, in at-risk youth, greater putamen response was associated with greater 18-month hazardous alcohol use, whereas in not at-risk youth, greater putamen response was associated with lower use. Where in brain and for which outcomes modulate (direction of) observed relations: superior frontal gyrus response is relevant for depressive problems whereas putamen response is relevant for alcohol problems and greater neural responsivity is linked to less depressive but to more alcohol problems in adolescents at-risk for ADHD and less alcohol problems in adolescents not at-risk. Differences in neural response to reward differentially confer vulnerability for adolescent depressive and alcohol problems depending on ADHD risk.

Reliability of reward ERPs in middle-late adolescents using a custom and a standardized preprocessing pipeline.

Despite advantage of neuroimaging measures in translational research frameworks, less is known about the psychometric properties thereof, especially in middle-late adolescents. Earlier, we examined evidence of convergent and incremental validity of reward anticipation and response event-related potentials (ERPs) and here we examined, in the same sample of 43 adolescents (Mage  = 15.67 years; SD = 1.01; range: 14-18; 32.6% boys), data quality (signal-to-noise ratio [SNR]), stability (mean amplitude across trials), and internal consistency (Cronbach's α and split-half reliability) of the same ERPs. Further, because observed time course and peak amplitude of ERP grand averages and thus findings on SNR, stability, and internal consistency may depend on preprocessing method, we employed a custom and a standardized preprocessing pipeline and compared findings across those. Using our custom pipeline, reward anticipation components were stable by the 40th trial, achieved acceptable internal consistency by the 19th, and all (but the stimulus-preceding negativity [SPN]) achieved acceptable SNR by the 41st trial. Initial response to reward components were stable by the 20th trial and achieved acceptable internal consistency by the 11th and acceptable SNR by the 45th trial. Difference scores had worse psychometric properties than parent measures. Time course and peak amplitudes of ERPs and thus results on SNR, stability, and internal consistency were comparable across preprocessing pipelines. In case of reward anticipation ERPs examined here, 41 trials (+4 artifacted and removed) and, in case of reward response ERPs, 45 trials (+5 artifacted) yielded stable and internally consistent estimates with acceptable SNR. Results are robust across preprocessing methods.

Neural and self-reported reward responsiveness are associated with dispositional affectivity and emotion dysregulation in adolescents with evidence for convergent and incremental validity.

Adolescence is a developmental period characterized by heightened reward sensitivity which, in turn, confers risk for pertinent negative outcomes, underscoring the need to better understand biological bases and behavioral correlates of reward responsiveness during this developmental phase. Our goals in the current study were to examine, in a sample of 43 typically developing adolescents (Mage  = 15.67 years; SD = 1.01; 32.6% boys), (1) evidence of convergent validity between neural and self-report reward responsiveness, (2) associations between neural reward responsiveness and self-report dispositional affectivity and emotion dysregulation (ED) and (3) evidence of incremental validity of self-report beyond neural reward responsiveness in predicting affectivity and ED. During electroencephalography (EEG), adolescents completed two experimental paradigms probing event-related potential (ERP) indices of reward anticipation and initial responsiveness to reward attainment. Following EEG, they completed self-report measures of reward responsiveness, affectivity, and ED. Findings indicated some evidence of convergent validity between enhanced ERP indices of reward anticipation and initial response to reward and greater reinforcement sensitivity; that ERP indices of both reward responsiveness aspects predicted lower negative affectivity and less ED; and evidence of incremental validity of self-report beyond neural reward responsiveness in predicting outcomes. Results underscore the utility of a multi-method framework in assessing adolescent reward responsiveness and support the relevance of reward responsiveness in explaining individual differences in dispositional affectivity and ED.

The association between reinforcement sensitivity and substance use is mediated by individual differences in dispositional affectivity in adolescents.

BACKGROUND: Adolescence marks the onset of substance use experimentation and adolescents are particularly vulnerable to certain negative effects of substances. Some evidence indicates reinforcement sensitivity is associated with substance use, though little is known about mechanisms underlying such association. AIMS: in the current study were to examine, (1) associations between behavioral activation (BAS) and behavioral inhibition (BIS) system sensitivity, positive (PA) and negative affectivity (NA), and alcohol use and alcohol problems as well as tobacco, and marijuana use, and whether (2) associations are mediated by PA or NA. METHODS: Participants were a community sample of N = 125 adolescents (Mage = 15.67 years; SD = 0.93; 52% boys) who completed self-report measures. RESULTS: evinced associations, generally as expected, across variables (all ps < 0.05). In mediation analyses, an association emerged between BIS sensitivity and alcohol use, mediated by NA (95%CIs [0.034; 0.390]); greater BIS sensitivity was associated with greater NA and greater NA was associated with greater alcohol use. These findings were replicated with alcohol problems. An association also emerged between BAS sensitivity and marijuana use, mediated by PA (95%CIs [-0.296; -0.027]); greater BAS sensitivity was associated with greater PA and greater PA was associated with lower marijuana use. Finally, BIS sensitivity was associated with tobacco use through NA (95%CIs [0.023; 0.325]) and PA (95%CIs [0.004; 0.116]), with NA linked to greater, but PA linked to lower tobacco use. BAS sensitivity was also associated with tobacco use through PA (95%CIs [-0.395; -0.049]), with PA linked again to lower tobacco use. CONCLUSIONS: There are unique and shared effects of domains of reinforcement sensitivity on adolescent substance use and these vary with index of dispositional affectivity and type of substance considered.