Studies suggest prenatal cannabis exposure is associated with mood/behavioral problems in children. However, it is unclear if targeting modifiable domains like sleep behaviors would improve outcomes ...in exposed youth. Using a causal inference framework, the effect of changing sleep‐hours on changing internalizing/externalizing problems in children was examined using the Adolescent Brain Cognitive Development™ study baseline (ages 9–10; collected during 2016–2018) and year‐1 follow‐up data (N = 9825; 4663 female; 5196 white). Average treatment effects (ATE) indicated that more sleep predicted less internalizing (ATE = −.34, SE = .08, p < .001) and externalizing (ATE = −.29, SE = .07, p < .001) problems over time. However, prenatal cannabis exposure moderated the ATE on internalizing (conditional‐ATE = .91, SE = .39, p = .019), whereby participants with exposure (n = 605) did not show any effect of changing sleep‐hours on mood (B = .09, SE = .24).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Background Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity ...and their relation to antisocial behavior and adversity are poorly understood. Methods Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (N=1830) of 14-15 year old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g. family conflict, serious accidents) and antisocial behaviors (e.g. precocious sexual activity, bullying, illicit substance use). Results Greater temporal discounting (more impulsivity) was associated with i) lower volume in frontomedial cortex and bilateral insula, and ii) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. Conclusions Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Impulsivity profiles of cannabis using anxious/depressed patients is understudied.•Patients were compared to matched very-low cannabis users and healthy controls.•Multiple facets of impulsivity were ...interrogated.•A propensity to act rashly when experiencing strong affect was found in patients.•Bayes factor analysis indicated substantial support for the null fMRI results.
Individuals with anxiety/depression may impulsively use cannabis to acutely induce positive affect and attenuate aversive mood states. However, few studies have attempted to parse impulsivity displayed by anxious/depressed cannabis users. This investigation examined what aspects of impulsivity characterize those individuals using self-report and functional MRI (fMRI) measures.
Individuals with any lifetime anxiety/depression diagnoses and problematic cannabis use (“Anx/Dep+CB”; n=42) were compared to a propensity score-matched group with very low cannabis use (“Anx/Dep-lowCB”; n=42), and a healthy control group (n=37). Impulsivity was measured using the UPPS-P Impulsivity Questionnaire and the Stop Signal Task (SST) during fMRI. For UPPS-P, regression models estimated group-by-impulsivity subscale interactions with post-hoc pairwise tests. For the SST, similar regression models were estimated with four a-priori regions of interest (ROIs; right opercularis, orbitalis, dorsal and ventral anterior insula) during stop-success and stop-failure processing. Null SST findings were followed up using Bayes factor analysis to quantify the evidence in support of the null hypothesis.
For the UPPS-P, a significant group-by-subscale interaction indicated that the Anx/Dep+CB group exhibited higher levels of impulsivity on the negative- and positive-urgency subscales relative to both comparison groups. Higher negative-urgency correlated with heavier lifetime cannabis use across groups. For the SST, there were no ROI task activation differences. Bayes factor analysis determined the null findings were at least three times more likely than the alternative hypothesis for all ROIs.
Impulsivity under periods of heightened affect, but not motor response inhibitions, characterized anxious/depressed individuals who use cannabis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Major depressive disorder (MDD) is associated with immunologic and metabolic alterations linked to central processing dysfunctions, including attenuated reward processing. This study investigated the ...associations between inflammation, metabolic hormones (leptin, insulin, adiponectin), and reward-related brain processing in MDD patients with high (MDD-High) and low (MDD-Low) C-reactive protein (CRP) levels compared to healthy comparison subjects (HC). Participants completed a blood draw and a monetary incentive delay task during functional magnetic resonance imaging. Although groups did not differ in insulin or adiponectin concentrations, both MDD-High (Wilcoxon p = 0.004, d = 0.65) and MDD-Low (Wilcoxon p = 0.046, d = 0.53) showed higher leptin concentrations than HC but did not differ from each other. Across MDD participants, higher leptin levels were associated with lower brain activation during reward anticipation in the left insula (r = - 0.30, p = 0.004) and left dorsolateral putamen (r = -- 0.24, p = 0.025). In contrast, within HC, higher leptin concentrations were associated with higher activation during reward anticipation in the same regions (insula: r = 0.40, p = 0.007; putamen: r = 0.37, p = 0.014). Depression may be characterized by elevated pro-inflammatory signaling via leptin concentrations through alternate inflammatory pathways distinct to CRP.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•MDD-High exhibited lower striatal reward anticipation than MDD-Low.•MDD-High had higher sICAM-1 and IL-6 concentrations than MDD-Low and HC.•Within MDD-High, higher sICAM-1 levels were associated ...with lower striatal reward anticipation.•MDD exhibited lower precuneus response to large wins than HC.•MDD had higher IL-1ra, MDC and MIP-1α concentrations than HC.
Major depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.
MDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.
MDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.
Within MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.
The ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Although chronic irritability in childhood is prevalent, impairing, and predictive of later maladjustment, its pathophysiology is largely unknown. Deficits in reward processing are hypothesized to ...play a role in irritability. The current study aimed to identify how the developmental timing of irritability during preschool- and school-age relates to reward-related brain function during school-age.
Children's irritability was assessed during the preschool period (wave 1; ages 3.0-5.9 years) and 3 years later (wave 2; ages 5.9-9.6 years) using a clinical interview. At wave 2, children (N = 46; 28 female and 18 male) performed a monetary incentive delay task in which they received rewards, if they successfully hit a target, or no reward regardless of performance, during functional magnetic resonance imaging.
Children with more versus less severe preschool irritability, controlling for concurrent irritability, exhibited altered reward-related connectivity: right amygdala with insula and inferior parietal lobe as well as left ventral striatum with lingual gyrus, postcentral gyrus, superior parietal lobe, and culmen. Children with more versus less severe concurrent irritability, controlling for preschool irritability, exhibited a similar pattern of altered connectivity between left and right amygdalae and superior frontal gyrus and between left ventral striatum and precuneus and culmen. Neural differences associated with irritability were most evident between reward and no-reward conditions when participants missed the target.
Preschool-age irritability and concurrent irritability were uniquely associated with aberrant patterns of reward-related connectivity, highlighting the importance of developmental timing of irritability for brain function.
•We characterize the association between age-related cerebral cortical change and conduct problems in a large longitudinal, community-based sample of adolescents (N = 1039).•Higher levels of conduct ...problems were associated with accelerated age-related cerebral cortical thinning.•Findings were not meaningfully altered when controlling for alcohol use, co-occurring psychopathology, and socioeconomic status.•This work represents the largest study to date of conduct problems and cerebral cortical thickness development.
Few studies have examined the association between conduct problems and cerebral cortical development. Herein, we characterize the association between age-related brain change and conduct problems in a large longitudinal, community-based sample of adolescents. 1,039 participants from the IMAGEN study possessed psychopathology and surface-based morphometric data at study baseline (M = 14.42 years, SD = 0.40; 559 females) and 5-year follow-up. Self-reports of conduct problems were obtained using the Strengths and Difficulties Questionnaire (SDQ). Vertex-level linear mixed effects models were implemented using the Matlab toolbox, SurfStat. To investigate the extent to which cortical thickness maturation was qualified by dimensional measures of conduct problems, we tested for an interaction between age and SDQ Conduct Problems (CP) score. There was no main effect of CP score on cortical thickness; however, a significant “Age by CP” interaction was revealed in bilateral insulae, left inferior frontal gyrus, left rostral anterior cingulate, left posterior cingulate, and bilateral inferior parietal cortices. Across regions, follow-up analysis revealed higher levels of CP were associated with accelerated age-related thinning. Findings were not meaningfully altered when controlling for alcohol use, co-occurring psychopathology, and socioeconomic status. Results may help to further elucidate neurodevelopmental patterns linking adolescent conduct problems with adverse adult outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Historically, neuroscientific research into addiction has emphasized affective and reinforcement mechanisms as the essential elements underlying the pursuit of drugs, their abuse, and difficulties ...associated with abstinence. However, research over the last decade or so has shown that cognitive control systems, associated largely but not exclusively with the frontal lobes, are also important contributors to drug use behaviors. Here, we focus on inhibitory control and its contribution to both current use and abstinence. A body of evidence points to impaired inhibitory abilities across a range of drugs of abuse. Typically, studies suggest that substance-abusing individuals are characterized by relative hypoactivity in brain systems underlying inhibitory control. In contrast, abstinent users tend to show either normal or supernormal levels of activity in the same systems attesting to the importance of inhibitory control in suppressing the drug use urges that plague attempts at abstinence. In this chapter, the brain and behavioral basis of response inhibition will be reviewed, with a focus on neuroimaging studies of response inhibition in current and abstinent drug abusers.
Research suggests that disproportionate exposure to risk factors places American Indian (AI) peoples at higher risk for substance use disorders (SUD). Although SUD is linked to striatal ...prioritization of drug rewards over other appetitive stimuli, there are gaps in the literature related to the investigation of aversive valuation processing, and inclusion of AI samples. To address these gaps, this study compared striatal anticipatory gain and loss processing between AI-identified with SUD (SUD+; n = 52) and without SUD (SUD-; n = 35) groups from the Tulsa 1000 study who completed a monetary incentive delay (MID) task during functional magnetic resonance imaging. Results indicated that striatal activations in the nucleus accumbens (NAcc), caudate, and putamen were greatest for anticipating gains (ps < 0.001) but showed no group differences. In contrast to gains, the SUD+ exhibited lower NAcc (p = .01, d =0.53) and putamen (p = .04, d =0.40) activation to anticipating large losses than the comparison group. Within SUD+ , lower striatal responses during loss anticipations were associated with slower MID reaction times (NAcc: r = −0.43; putamen: r = −0.35) during loss trials. This is among the first imaging studies to examine underlying neural mechanisms associated with SUD within AIs. Attenuated loss processing provides initial evidence of a potential mechanism wherein blunted prediction of aversive consequences may be a defining feature of SUD that can inform future prevention and intervention targets.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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