Abnormal neural sensitivity to rewards as a candidate process of high depression risk in the FMR1 premutation: A pilot study.

The etiological heterogeneity of depression poses a challenge for prevention and intervention efforts. One solution is to map unique etiological pathways for subgroups defined by a singular risk factor. A relevant population for this approach is women who carry the premutation of the fragile X messenger ribonucleoprotein 1 (FMR1) gene, who are at high risk for adult-onset depression. This study explores a candidate neurophysiological marker of depression risk: reduced reward sensitivity, indexed by the reward positivity (RewP). The RewP has been linked to depression risk in the general population, but is unexplored within FMR1 premutation carriers. 16 women with the FMR1 premutation and a matched control group completed a simple guessing task while the electroencephalogram was recorded. Among premutation carriers, RewP difference score (win versus loss) was reduced. These preliminary finding suggest that the FMR1 premutation may confer increased risk for depression in part through abnormal neural sensitivity to rewards.

Error-related brain activity shapes the association between trait neuroticism and internalizing symptomatology in two tasks.

The current study examined how individual differences in error-related brain activity might moderate the association between high trait neuroticism and internalizing symptoms. Data were collected from a sample of high-achieving young adults (N = 188) as part of a larger study on risk versus resiliency for psychopathology. Participants completed two behavioral tasks to elicit the error-related negativity (ERN): an arrow Flanker task and a Go/No-Go task. Analyses were constrained to two internalizing symptom dimensions of checking behavior and irritability. Contrary to expectations, ERN amplitude was not related to symptom severity at the bivariate level. However, ERN amplitude moderated the association between trait neuroticism and symptoms of ill temper, such that the neuroticism-irritability association was strongest among individuals with a blunted ERN. In addition, this finding was relatively consistent across tasks and across two complementary methods of scoring the ERN, suggesting an effect of ERN variance that is shared between tasks and that is relatively robust regarding processing differences. In all, the current study represents the first attempt to investigate how the ERN interacts with trait neuroticism to predict transdiagnostic symptom dimensions in adulthood.

When they just don't sleep: differential impacts of reduced child sleep on depression, anxiety, and stress among caregivers of children with and without neurogenetic syndromes.

Introduction: Children with neurogenetic syndromes commonly experience significant and pervasive sleep disturbances, however, associations with caregiver mental health remains unclear. Previous studies have linked sleep disturbances with increased caregiver depression in typically developing populations, and heightened caregiver stress among neurogenetic populations. The present study expands on findings by exploring the longitudinal association between child sleep duration and caregiver mental health (depression, anxiety, stress) throughout development (infancy to school-aged children) in dyads with and without a child affected by a neurogenetic syndrome. Methods: Participants were drawn from the Purdue Early Phenotype Study, including 193 caregivers (Age: M = 34.40 years, SD = 4.53) of children with neurogenetic syndromes (Age: M = 40.91 months, SD =20.72) and typically developing children (n = 55; Age: M = 36.71 months, SD = 20.68). Children in the neurogenetic group were diagnosed with Angelman (n = 49), Prader Willi (n = 30), Williams (n = 51), and Fragile X (n = 8) syndromes. Caregivers completed assessments every six months up to child age three, and annual assessments thereafter. Child sleep duration was measured using the Brief Infant Sleep Questionnaire, and caregiver internalizing symptoms were assessed using the Depression, Anxiety, Stress Scale. Multilevel models were conducted to examine caregiver depression, anxiety, and stress in relation to child sleep duration at both between- and within-person levels, with child age as a moderator. Results: Results indicated a between-person effect of child sleep duration on caregiver depression (i.e., differences between families) and a within-person effect on caregiver stress (i.e., change over time) in the full, combined sample. These effects were not maintained when examined separately in neurogenetic and typically developing groups, except for a between-person effect on caregiver stress in the typically developing cohort. Moderating effects of child age were significant for depression and stress only in the typically developing cohort. Discussion: In summary, persistent child sleep disruptions were linked to exacerbated caregiver depression across the sample, while acute child sleep disruptions exacerbate caregiver stress within dyads over time. These findings emphasize the importance of addressing child sleep to enhance caregiver wellbeing and has potential relevance for a wide range of neurogenetic syndromes.

Whole-brain mapping of increased manganese levels in welders and its association with exposure and motor function.

Although manganese (Mn) is a trace metal essential for humans, chronic exposure to Mn can cause accumulation of this metal ion in the brain leading to an increased risk of neurological and neurobehavioral health effects. This is a concern for welders exposed to Mn through welding fumes. While brain Mn accumulation in occupational settings has mostly been reported in the basal ganglia, several imaging studies also revealed elevated Mn in other brain areas. Since Mn functions as a magnetic resonance imaging (MRI) T1 contrast agent, we developed a whole-brain MRI approach to map in vivo Mn deposition differences in the brains of non-exposed factory controls and exposed welders. This is a cross-sectional analysis of 23 non-exposed factory controls and 36 exposed full-time welders from the same truck manufacturer. We collected high-resolution 3D MRIs of brain anatomy and R1 relaxation maps to identify regional differences using voxel-based quantification (VBQ) and statistical parametric mapping. Furthermore, we investigated the associations between excess Mn deposition and neuropsychological and motor test performance. Our results indicate that: (1) Using whole-brain MRI relaxometry methods we can generate excess Mn deposition maps in vivo, (2) excess Mn accumulation due to occupational exposure occurs beyond the basal ganglia in cortical areas associated with motor and cognitive functions, (3) Mn likely diffuses along white matter tracts in the brain, and (4) Mn deposition in specific brain regions is associated with exposure (cerebellum and frontal cortex) and motor metrics (cerebellum and hippocampus).

Resting-state EEG power differences in autism spectrum disorder: a systematic review and meta-analysis.

Narrative reviews have described various resting-state EEG power differences in autism across all five canonical frequency bands, with increased power for low and high frequencies and reduced power for middle frequencies. However, these differences have yet to be quantified using effect sizes and probed robustly for consistency, which are critical next steps for clinical translation. Following PRISMA guidelines, we conducted a systematic review of published and gray literature on resting-state EEG power in autism. We performed 10 meta-analyses to synthesize and quantify differences in absolute and relative resting-state delta, theta, alpha, beta, and gamma EEG power in autism. We also conducted moderator analyses to determine whether demographic characteristics, methodological details, and risk-of-bias indicators might account for heterogeneous study effect sizes. Our literature search and study selection processes yielded 41 studies involving 1,246 autistic and 1,455 neurotypical individuals. Meta-analytic models of 135 effect sizes demonstrated that autistic individuals exhibited reduced relative alpha (g = -0.35) and increased gamma (absolute: g = 0.37, relative: g = 1.06) power, but similar delta (absolute: g = 0.06, relative: g = 0.10), theta (absolute: g = -0.03, relative: g = -0.15), absolute alpha (g = -0.17), and beta (absolute: g = 0.01, relative: g = 0.08) power. Substantial heterogeneity in effect sizes was observed across all absolute (I2: 36.1-81.9%) and relative (I2: 64.6-84.4%) frequency bands. Moderator analyses revealed that age, biological sex, IQ, referencing scheme, epoch duration, and use of gold-standard autism diagnostic instruments did not moderate study effect sizes. In contrast, resting-state paradigm type (eyes-closed versus eyes-open) moderated absolute beta, relative delta, and relative alpha power effect sizes, and resting-state recording duration moderated relative alpha power effect sizes. These findings support further investigation of resting-state alpha and gamma power as potential biomarkers for autism.

Distinct profiles of anhedonia and reward processing and their prospective associations with quality of life among individuals with mood disorders.

Leading professional health bodies have called for the wider adoption of Patient Reported Outcome Measures, such as quality of life, in research and clinical practice as a means for understanding why the global burden of depression continues to climb despite increased rates of treatment use. Here, we examined whether anhedonia-an often recalcitrant and impairing symptom of depression-along with its neural correlates, was associated with longitudinal changes in patient-reported quality of life among individuals seeking treatment for mood disorders. We recruited 112 participants, including n = 80 individuals with mood disorders (58 unipolar, 22 bipolar) and n = 32 healthy controls (63.4% female). We assessed anhedonia severity along with two electroencephalographic markers of neural reward responsiveness (scalp-level 'Reward Positivity' amplitude and source-localized reward-related activation in the dorsal anterior cingulate cortex), and assessed quality of life at baseline, 3- and 6-month follow-up. Anhedonia emerged as a robust correlate of quality of life cross-sectionally and longitudinally among individuals with mood disorders. Furthermore, increased neural reward responsiveness at baseline was associated with greater improvements in quality of life over time, and this improvement was mediated by longitudinal improvements in anhedonia severity. Finally, differences in quality of life observed between individuals with unipolar and bipolar mood disorders were mediated by differences in anhedonia severity. Our findings indicate that anhedonia and its reward-related neural correlates are linked to variability in quality of life over time in individuals with mood disorders. Treatments capable of improving anhedonia and normalizing brain reward function may be necessary for improving broader health outcomes for individuals seeking treatment for depression.ClinicalTrials.gov identifier: NCT01976975.

Abnormal neurophysiological sensitivity to rewards in depression is moderated by sex and age in middle adulthood.

A candidate pathophysiological process in major depressive disorder is diminished neural reactivity to reward delivery, which is theorized to give rise to anhedonia. Reduced amplitude in the reward positivity (RewP), which captures initial reward evaluation, has been linked to current symptoms of depression among child, adolescent, and young adult samples. However, the developmental trajectory of this association is incomplete, with relatively few studies in middle and older adulthood. Further, emerging evidence in the literature also suggests that this association may be linked to female sex-specific processes, but no studies to date have directly contrasted the effect of sex on the depression-RewP association. The current study sought to address these gaps by testing how sex and age may moderate the depression-RewP association within a mature adult community sample. Symptoms of depression were evaluated using a survey and a clinical interview, and the RewP was elicited using a simple guessing task. There was a three-way interaction between depression symptom severity, age, and sex in predicting RewP amplitude. This was driven by younger (late 30's to early 40's) female-sexed people such that for this group, elevated symptoms of depression were associated with blunting of the RewP. This association tapered around age 50. This effect was specific to clinician-rated rather than self-reported depressive symptom severity. This pattern of effects suggests that among female-sexed people, developmental processes continue to shape the association between reward responsiveness and depression throughout middle adulthood.

Neural deficits in anticipatory and consummatory reward processing are uniquely associated with current depressive symptoms during adolescence.

Deficits within the consummatory phase of reward processing are associated with increased depression symptoms and risk; however, few studies have also examined other aspects of reward processing in relation to depression. In the current study, a community sample of 121 adolescents (Mage  = 13.1, Min = 11.14; Max = 15.12; 54% male) completed self-report questionnaires to assess depressive symptoms and the monetary incentive delay (MID) task while EEG was recorded. Results indicated that a reduced cue-P300 as well as a reduced reward positivity (RewP) and feedback negativity (FN) to gain and loss feedback, respectively, were associated with increased depressive symptoms; on the other hand, SPN and feedback P300 were unrelated to depressive symptoms. An exploratory multiple regression analysis revealed that a reduced money cue-P300, a reduced RewP, and a reduced (i.e., less negative) FN, all explained unique variance in depressive symptoms. The current study demonstrates that reduced cue-P300, RewP, and FN amplitudes may reflect distinct deficits in reward processing among adolescents with increased depressive symptoms. Notably, this study is one of the first to leverage the MID task in adolescents in relation to depressive symptoms, allowing for a more in-depth view of the individual differences in reward processing among adolescents with increased depressive symptomatology.

An Ethics and Social-Justice Approach to Collecting and Using Demographic Data for Psychological Researchers.

The collection and use of demographic data in psychological sciences has the potential to aid in transforming inequities brought about by unjust social conditions toward equity. However, many current methods surrounding demographic data do not achieve this goal. Some methods function to reduce, but not eliminate, inequities, whereas others may perpetuate harmful stereotypes, invalidate minoritized identities, and exclude key groups from research participation or access to disseminated findings. In this article, we aim to (a) review key ethical and social-justice dilemmas inherent to working with demographic data in psychological research and (b) introduce a framework positioned in ethics and social justice to help psychologists and researchers in social-science fields make thoughtful decisions about the collection and use of demographic data. Although demographic data methods vary across subdisciplines and research topics, we assert that these core issues-and solutions-are relevant to all research within the psychological sciences, including basic and applied research. Our overarching aim is to support key stakeholders in psychology (e.g., researchers, funding agencies, journal editors, peer reviewers) in making ethical and socially-just decisions about the collection, analysis, reporting, interpretation, and dissemination of demographic data.

Temporal dynamics of emotional processing: Parsing trial-wise variance of the late positive potential using Generalizability Theory.

The reliability of individual trial event-related potential (ERP) components extracted from electroencephalogram has been consistently questioned since ERP research began. This ambivalence is based on misunderstood assumptions stemming from Cronbach and Classical Test Theory. Contemporary methods allow for the reliability of individual ERP trials to be estimated and for analyses of these trial-level ERP components to be meaningfully parsed. We illustrate the use of Generalizability Theory procedures in estimating the reliability of trial-level ERPs using the late positive potential (LPP), a neural measure of motivated attention toward emotionally evocative stimuli. Individuals (N = 88) completed a passive viewing task while continuous EEG was recorded. Variability in trial-level LPP responses was decomposed into facets corresponding to individual differences, chronological trial within block, stimulus type, their two-way interactions, and specific stimuli. We estimated various reliability coefficients and found that both overall and category-specific person-level LPP estimates have good-to-excellent reliability, while the reliability of within-person differences (i.e., change) between arousal categories was fair for the early LPP. These results were generally consistent across time windows, but were highest early in the LPP time course. We argue that investigating reliability using trial-level data allows researchers to pursue hypotheses focused on neurophysiological dynamics that unfold over the course of an experiment and not risk false inferences (i.e., ecological fallacy) when using person-level aggregates to deduce such processes. Moreover, such analyses provide information that allows researchers to optimize their protocols by potentially reducing the number of individual trials, burden on participants, and cost, while retaining sufficient reliability.

Mismatch negativity and clinical trajectories in psychotic disorders: Five-year stability and predictive utility.

BACKGROUND: Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear. METHOD: We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning. RESULTS: MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (ß = 0.19), everyday functioning (ß = -0.13), and illness severity (ß = -0.12) at follow-up. Meanwhile, initial IQ (ß = -0.24), negative symptoms (ß = 0.23), and illness severity (ß = -0.16) were significant predictors of worsening MMN amplitude five years later. CONCLUSIONS: These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.

All the Pringle ladies: Neural and behavioral responses to high-calorie food rewards in young adult women.

Reward processing is vital for learning and survival, and can be indexed using the Reward Positivity (RewP), an event-related potential (ERP) component that is larger for rewards than losses. Prior work suggests that heightened motivation to obtain reward, as well as greater reward value, is associated with an enhanced RewP. However, the extent to which internal and external factors modulate neural responses to rewards, and whether such neural responses motivate reward-seeking behavior, remains unclear. The present study investigated whether the degree to which a reward is salient to an individual's current motivational state modulates the RewP, and whether the RewP predicts motivated behaviors, in a sample of 133 women. To elicit the RewP, participants completed a forced-choice food reward guessing task. Data were also collected on food-related behaviors (i.e., type of food chosen, consumption of the food reward) and motivational salience factors (i.e., self-reported hunger, time since last meal, and subjective "liking" of food reward). Results showed that hungrier participants displayed an enhanced RewP compared to less hungry individuals. Further, self-reported snack liking interacted with RewP magnitude to predict behavior, such that when participants reported low levels of snack liking, those with a smaller RewP were more likely to consume their snacks than those with a larger RewP. Our data suggest that food-related motivational state may increase neural sensitivity to food reward in young women, and that neural markers of reward sensitivity might interact with subjective reward liking to predict real-world eating behavior.

The novel frontal alpha asymmetry factor and its association with depression, anxiety, and personality traits.

Frontal alpha asymmetry (FAA) is widely examined in EEG research, yet a procedural consensus on its assessment is lacking. In this study, we tested a latent factorial approach to measure FAA. We assessed resting-state FAA at broad, low, and high alpha bands (8-13; 8-10.5; and 11-13 Hz) using mastoids as reference electrodes and Current Source Density (CSD) transformation (N = 139 non-clinical participants). From mastoid-referenced data, we extracted a frontal alpha asymmetry factor (FAAf) and a parietal factor (PAAf) subjecting all asymmetry indices to a varimax-rotated, principal component analysis. We explored split-half reliability and discriminant validity of the mastoid factors and the mastoid and CSD raw asymmetry indices (F3/4, F7/8, P3/4, and P7/8). Both factor and raw scores reached an excellent split-half reliability (>.99), but only the FAAf reached the maximum discriminant validity from parietal scores. Next, we explored the correlations of latent factor and raw FAA scores with symptoms of depression, anxiety, and personality traits to determine which associations were driven by FAA after variance from parietal activity was removed. After correcting for false discovery rate, only FAAf at the low alpha band was negatively associated with depression symptoms (a latent CES-D factor) and significantly diverged from PAAf's association with depression symptoms. With respect to personality traits, only CSD-transformed F7/8 was positively correlated with Conscientiousness and significantly diverged from the correlations between Conscientiousness and P3/4 and P7/8. Overall, the latent factor approach shows promise for isolating functionally distinct resting-state EEG signatures, although further research is needed to examine construct validity.

Electroencephalogram aperiodic power spectral slope can be reliably measured and predicts ADHD risk in early development.

The aperiodic exponent of the electroencephalogram (EEG) power spectrum has received growing attention as a physiological marker of neurodevelopmental psychopathology, including attention-deficit/hyperactivity disorder (ADHD). However, its use as a marker of ADHD risk across development, and particularly in very young children, is limited by unknown reliability, difficulty in aligning canonical band-based measures across development periods, and unclear effects of treatment in later development. Here, we investigate the internal consistency of the aperiodic EEG power spectrum slope and its association with ADHD risk in both infants (n = 69, 1-month-old) and adolescents (n = 262, ages 11-17 years). Results confirm good to excellent internal consistency in infancy and adolescence. In infancy, a larger aperiodic exponent was associated with greater family history of ADHD. In contrast, in adolescence, ADHD diagnosis was associated with a smaller aperiodic exponent, but only in children with ADHD who had not received stimulant medication treatment. Results suggest that disruptions in cortical development associated with ADHD risk may be detectable shortly after birth via this approach. Together, findings imply a dynamic developmental shift in which the developmentally normative flattening of the EEG power spectrum is exaggerated in ADHD, potentially reflecting imbalances in cortical excitation and inhibition that could contribute to long-lasting differences in brain connectivity.

A randomized trial of aerobic exercise for major depression: examining neural indicators of reward and cognitive control as predictors and treatment targets.

BACKGROUND: Aerobic exercise has demonstrated antidepressant efficacy among adults with major depression. There is a poor understanding of the neural mechanisms associated with these effects. Deficits in reward processing and cognitive control may be two candidate targets and predictors of treatment outcome to exercise in depression. METHODS: Sixty-six young adults aged 20.23 years (s.d. = 2.39) with major depression were randomized to 8 weeks of moderate-intensity aerobic exercise (n = 35) or light stretching (n = 31). Depressive symptoms were assessed across the intervention to track symptom reduction. Reward processing [reward positivity (RewP)] and cognitive control [error-related negativity (ERN)] were assessed before and after the intervention using event-related brain potentials. RESULTS: Compared to stretching, aerobic exercise resulted in greater symptom reduction (gs = 0.66). Aerobic exercise had no impact on the RewP (gav = 0.08) or ERN (gav = 0.21). In the aerobic exercise group, individuals with a larger pre-treatment RewP [odds ratio (OR) = 1.45] and increased baseline depressive symptom severity (OR = 1.18) were more likely to respond to an aerobic exercise program. Pre-treatment ERN did not predict response (OR = 0.74). CONCLUSIONS: Aerobic exercise is effective in alleviating depressive symptoms in adults with major depression, particularly for those with increased depressive symptom severity and a larger RewP at baseline. Although aerobic exercise did not modify the RewP or ERN, there is preliminary support for the utility of the RewP in predicting who is most likely to respond to exercise as a treatment for depression.

Mother-infant convergence of event-related potentials elicited by face and object processing.

Prior work has provided conceptual support for developmental changes in face and object processing, such that: face processing, as captured by the N290 event-related potential (ERP) component in infancy, may develop into the N170 in adulthood; and motivated attention, as captured by the negative central (Nc) in infancy, may develop into the late positive potential (LPP). The present study examined these neural correlates in 12-month-old infants and their mothers (N = 33 dyads). Dyads completed a viewing task consisting of familiar and novel face and toy stimuli while electroencephalography was recorded. Results suggest that for mothers, the N170 was larger for faces than toys, regardless of familiarity, and the LPP was largest for familiar faces. In infants, the N290 was somewhat larger for faces than toys (p < .10); the Nc did not vary by condition. Adult ERPs demonstrated fair to good reliability; reliability of infant ERPs was lower and was influenced by looking behaviors. Intergenerational associations were strongest between the LPP and Nc, particularly when electrode and time window were taken into account. Refinement of data handling and ERP scoring procedures for infant ERPs are crucial next steps for estimation of intergenerational associations and further examination of developmental changes in face and object processing.

Mismatch negativity amplitude in first-degree relatives of individuals with psychotic disorders: Links with cognition and schizotypy.

Mismatch negativity (MMN) amplitude is reliably reduced in psychotic disorders. While several studies have examined this effect in first-degree relatives of individuals with schizophrenia, few have sought to quantify deficits in relatives of individuals with other psychotic disorders. While some conclude that, compared to healthy subjects, first-degree relatives of schizophrenia show reduced MMN, others contradict this finding. Furthermore, though MMN is often shown to be associated with cognitive impairments and clinical symptoms in psychotic disorders, to our knowledge no studies have sought to fully examine these relationships in studies of first-degree relatives. The present study sought to clarify the extent of MMN amplitude reductions in a large sample of siblings of individuals with diverse psychotic disorders (n = 67), compared to probands with psychosis (n = 221) and never psychotic comparison subjects (n = 251). We further examined associations of MMN amplitude with cognition and schizotypal symptoms across these groups. We found that MMN amplitude was intact in siblings compared to probands. MMN amplitude was associated with cognition and schizotypal symptoms dimensionally across levels of familial risk. The present results imply that MMN reductions do not reflect genetic risk for psychotic disorders per se, and instead emerge as a result of, or in conjunction with, clinical features associated with psychosis. Such findings carry important implications for the utility of MMN amplitude as an indicator of inherited risk, and suggest that this component may be best conceptualized as an endophenotype for clinical symptoms and cognitive impairments, rather than risk for psychosis per se.

Predicting Long-Term Outcomes in First-Admission Psychosis: Does the Hierarchical Taxonomy of Psychopathology Aid DSM in Prognostication?

The Hierarchical Taxonomy of Psychopathology (HiTOP) is an empirical, dimensional model of psychological symptoms and functioning. Its goals are to augment the use and address the limitations of traditional diagnoses, such as arbitrary thresholds of severity, within-disorder heterogeneity, and low reliability. HiTOP has made inroads to addressing these problems, but its prognostic validity is uncertain. The present study sought to test the prediction of long-term outcomes in psychotic disorders was improved when the HiTOP dimensional approach was considered along with traditional (ie, DSM) diagnoses. We analyzed data from the Suffolk County Mental Health Project (N = 316), an epidemiologic study of a first-admission psychosis cohort followed for 20 years. We compared 5 diagnostic groups (schizophrenia/schizoaffective, bipolar disorder with psychosis, major depressive disorder with psychosis, substance-induced psychosis, and other psychoses) and 5 dimensions derived from the HiTOP thought disorder spectrum (reality distortion, disorganization, inexpressivity, avolition, and functional impairment). Both nosologies predicted a significant amount of variance in most outcomes. However, except for cognitive functioning, HiTOP showed consistently greater predictive power across outcomes-it explained 1.7-fold more variance than diagnoses in psychiatric and physical health outcomes, 2.1-fold more variance in community functioning, and 3.4-fold more variance in neural responses. Even when controlling for diagnosis, HiTOP dimensions incrementally predicted almost all outcomes. These findings support a shift away from the exclusive use of categorical diagnoses and toward the incorporation of HiTOP dimensions for better prognostication and linkage with neurobiology.

Authors' reply to the commentary on "Establishing norms for error-related brain activity during the arrow Flanker task among young adults".

In their commentary on our article, "Establishing norms for error-related brain activity during the arrow Flanker task among young adults" (Imburgio et al., 2020), Clayson and colleagues (2021) voiced their concerns about our development of norms for an event-related potential measure of error monitoring, the error-related negativity (ERN). The central flaw in their commentary is the idea that because we don't know all the factors that can affect the ERN, it should not be normed. We respond to this idea, while also reiterating points made in our original manuscript: a) at present, the reported norms are not intended to be used for individual clinical assessment and b) our norms should be considered specific to the procedures (i.e., recording and processing parameters) and task used (i.e., arrow Flanker). Contrary to Clayson and colleagues' claims, we believe that information about the distribution of the ERN (i.e., our norms) in a large sample representative of those used in much of the ERN literature (i.e., unselected young adults) will be useful to the field and that this information stands to increase, not decrease, understanding of the ERN.

Mapping Disease Course Across the Mood Disorder Spectrum Through a Research Domain Criteria Framework.

BACKGROUND: The National Institute of Mental Health Research Domain Criteria (RDoC) initiative aims to establish a neurobiologically valid framework for classifying mental illness. Here, we examined whether the RDoC construct of reward learning and three aspects of its underlying neurocircuitry predicted symptom trajectories in individuals with mood pathology. METHODS: Aligning with the RDoC approach, we recruited individuals (n = 80 with mood disorders [58 unipolar and 22 bipolar] and n = 32 control subjects; 63.4% female) based on their performance on a laboratory-based reward learning task rather than clinical diagnosis. We then assessed 1) anterior cingulate cortex prediction errors using electroencephalography, 2) striatal reward prediction errors using functional magnetic resonance imaging, and 3) medial prefrontal cortex glutamatergic function (mPFC Gln/Glu) using 1H magnetic resonance spectroscopy. Severity of anhedonia, (hypo)mania, and impulsivity were measured at baseline, 3 months, and 6 months. RESULTS: Greater homogeneity in aspects of brain function (mPFC Gln/Glu) was observed when individuals were classified according to reward learning ability rather than diagnosis. Furthermore, mPFC Gln/Glu levels predicted more severe (hypo)manic symptoms cross-sectionally, predicted worsening (hypo)manic symptoms longitudinally, and explained greater variance in future (hypo)manic symptoms than diagnostic information. However, rather than being transdiagnostic, this effect was specific to individuals with bipolar disorder. Prediction error indices were unrelated to symptom severity. CONCLUSIONS: Although findings are preliminary and require replication, they suggest that heightened mPFC Gln/Glu warrants further consideration as a predictor of future (hypo)mania. Importantly, this work highlights the value of an RDoC approach that works in tandem with, rather than independent of, traditional diagnostic frameworks.