Discounting future outcomes as a function of their deferred availability underlies much of human decision making. Discounting, or preference for immediate over delayed rewards of larger value, is ...often associated with impulsivity and is a risk factor for addictive disorders such as pathological gambling, cigarette smoking, and drug and alcohol abuse. The ventral striatum (VS) is involved in mediating behavioral responses and physiological states associated with reward, and dysregulation of the VS contributes to addiction, perhaps by affecting impulsive decision-making. Behavioral tests of delay discounting (DD), which index preference for smaller immediate over larger delayed rewards, covary with impulsive tendencies in humans. In the current study, we examined the relationship between individual differences in DD, measured in a behavioral assessment, and VS activity measured with blood oxygenation level-dependent functional magnetic resonance imaging, in 45 adult volunteers. VS activity was determined using a task involving positive and negative feedback with monetary reward. Analyses revealed that individual differences in DD correlate positively with magnitude of VS activation in response to both positive and negative feedback, compared with a no-feedback control condition. Variability in DD was also associated with differential VS activation in response to positive, compared with negative, feedback. Collectively, our results suggest that increased preference for smaller immediate over larger delayed rewards reflects both a relatively indiscriminate and hyper-reactive VS circuitry. They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction.
Objective
Previous research with civilian populations has found strong associations between fibromyalgia (FM) and posttraumatic stress disorder (PTSD). We undertook this study to investigate the ...prevalence of FM in military service members with and without PTSD.
Methods
Participants were active duty military personnel recruited into either an epidemiologic cohort study of service members before a military deployment or 1 of 3 PTSD treatment trials. Instruments used to document FM and PTSD included the PTSD Checklist–Stressor‐Specific Version, the PTSD Symptom Scale‐Interview, and the 2012 American College of Rheumatology FM questionnaire.
Results
Across the 4 studies, 4,376 subjects completed surveys. The prevalence of FM was 2.9% in the predeployment cohort, and the prevalence was significantly higher in individuals with PTSD (10.8%) compared with those without PTSD (0.8%). In the treatment trials, all of the participants met criteria for PTSD before starting treatment, and the prevalence of FM was 39.7%.
Conclusion
The prevalence of FM in active duty service members preparing to deploy is similar to that reported for the general population of the US but is higher than expected for a predominantly male cohort. Furthermore, the prevalence of FM was significantly higher in service members with comorbid PTSD and was highest among those seeking treatment for PTSD. Further investigation is needed to determine the factors linking PTSD and FM.
•Depression is characterized by reduced neural response to reward, particularly in the ventral striatum.•Few studies have examined if alterations in reward functioning are present before the onset of ...depression.•Youth at high- and low-familial risk for depression completed a reward task during a fMRI scan.•High-risk youth had significantly less ventral striatal reactivity than low-risk youth during reward anticipation.•Reward functioning is altered in individuals at high-familial risk for depression before the onset of the disorder.
Offspring of depressed parents are at risk for depression and recent evidence suggests that reduced positive affect (PA) may be a marker of risk. We investigated whether self-reports of PA and fMRI-measured striatal response to reward, a neural correlate of PA, are reduced in adolescent youth at high familial risk for depression (HR) relative to youth at low familial risk for depression (LR). Functional magnetic resonance imaging assessments were conducted with 14 HR and 12 LR youth. All youth completed an ecological momentary assessment protocol to measure PA in natural settings and a self-report measure of depression symptomatology. Analyses found that HR youth demonstrated lower striatal response than LR youth during both reward anticipation and outcome. However, after controlling for youth self-reports of depression, HR youth demonstrated lower striatal response than LR youth only during reward anticipation. No significant differences were found between HR and LR youth on subjective ratings of PA or depressive symptoms. Results are consistent with previous findings that reduced reward response is a marker of risk for depression, particularly during reward anticipation, even in the absence of (or accounting for) disrupted subjective mood. Further examinations of prospective associations between reward response and depression onset are needed.
ABSTRACTBackgroundAlcohol use has been reliably associated with smaller subcortical and cortical regional gray matter volumes (GMVs). Whether these associations reflect shared predisposing risk ...factors and/or causal consequences of alcohol use remains poorly understood. MethodsData came from 3 neuroimaging samples (total n=2,423), spanning childhood/adolescence to middle age, with prospective or family-based data. First, we identified replicable GMV correlates of alcohol use. Next, we used family-based and longitudinal data to test whether these associations may plausibly reflect a predispositional liability for alcohol use, and/or a causal consequence of alcohol use. Finally, we evaluated whether GWAS-defined genomic risk for alcohol consumption is enriched for genes preferentially expressed in regions identified in our neuroimaging analyses, using heritability and gene-set enrichment, and transcriptome-wide association study (TWAS) approaches. ResultsSmaller right dorsolateral prefrontal cortex (DLPFC; i.e., middle and superior frontal gyri) and insula GMVs were associated with increased alcohol use across samples. Family-based and prospective longitudinal data suggest these associations are genetically-conferred and that DLPFC GMV prospectively predicts future use and initiation. Genomic risk for alcohol use was enriched in gene-sets preferentially expressed in the DLPFC, and associated with replicable differential gene expression in the DLPFC. ConclusionsThese data suggest that smaller DLPFC and insula GMV plausibly represent genetically-conferred predispositional risk factors for, as opposed to consequences of, alcohol use. DLPFC and insula GMV represent promising biomarkers for alcohol consumption liability and related psychiatric and behavioral phenotypes.
Studies evaluating neuroimaging, genetically predicted gene expression, and pre-clinical genetic models of PTSD, have identified PTSD-related abnormalities in the prefrontal cortex (PFC) of the ...brain, particularly in dorsolateral and ventromedial PFC (dlPFC and vmPFC). In this study, RNA sequencing was used to examine gene expression in the dlPFC and vmPFC using tissue from the VA National PTSD Brain Bank in donors with histories of PTSD with or without depression (dlPFC n = 38, vmPFC n = 35), depression cases without PTSD (n = 32), and psychopathology-free controls (dlPFC n = 24, vmPFC n = 20). Analyses compared PTSD cases to controls. Follow-up analyses contrasted depression cases to controls. Twenty-one genes were differentially expressed in PTSD after strict multiple testing correction. PTSD-associated genes with roles in learning and memory (FOS, NR4A1), immune regulation (CFH, KPNA1) and myelination (MBP, MOBP, ERMN) were identified. PTSD-associated genes partially overlapped depression-associated genes. Co-expression network analyses identified PTSD-associated networks enriched for immune-related genes across the two brain regions. However, the immune-related genes and association patterns were distinct. The immune gene IL1B was significantly associated with PTSD in candidate-gene analysis and was an upstream regulator of PTSD-associated genes in both regions. There was evidence of replication of dlPFC associations in an independent cohort from a recent study, and a strong correlation between the dlPFC PTSD effect sizes for significant genes in the two studies (r = 0.66, p < 2.2 × 10−16). In conclusion, this study identified several novel PTSD-associated genes and brain region specific PTSD-associated immune-related networks.
Summary Objective Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical (HPA) axis have been shown in animal models and emerge over puberty. However, parallel work in ...humans is lacking despite implications for elucidating the emergence of sex differences in depression over puberty. We investigated sex differences in HPA response to corticotropin releasing hormone (CRH) challenge over puberty in a carefully screened normative sample. Methods Participants were 68 healthy children (41% girls), ages 6–16, with no personal or family history of psychiatric disorder. Pubertal maturation was determined by Tanner staging. Following 24 h of adaptation, 9–10 plasma cortisol samples were collected over 30–40 min pre-infusion baseline, 1 μg/kg CRH infusion, and 90–180 min post-infusion recovery. Thirty-seven participants completed 2+ CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses. The influence of gender and pubertal maturation on parameters of cortisol response to CRH challenge was investigated using nonlinear mixed model methodology. Results Girls showed increasing total cortisol output following CRH challenge over puberty, while boys showed little change in total cortisol output over puberty. Increased cortisol output in girls was explained by slower reactivity and recovery rates leading to prolonged time to reach peak cortisol and delayed return to baseline over puberty. Girls also showed increasing baseline cortisol over puberty, while boys showed declining baseline over puberty. Conclusion Results reveal subtle normative sex differences in the influence of pubertal maturation on HPA regulation at the pituitary level. This normative shift may tip the balance towards stress response dysregulation in girls at high risk for depression, and may represent one potential mechanism underlying elevated rates of depression among pubescent girls.
•Greater amygdala reactivity to angry faces predicted youth antisocial behavior.•Callous-unemotional traits were not related to amygdala reactivity.•Findings were similar across sex, ethnicity, and ...pubertal stage.
Recent neuroimaging studies have suggested divergent relationships between antisocial behavior (AB) and callous-unemotional (CU) traits and amygdala reactivity to fearful and angry facial expressions in adolescents. However, little work has examined if these findings extend to dimensional measures of behavior in ethnically diverse, non-clinical samples, or if participant sex, ethnicity, pubertal stage, and age moderate associations. We examined links between amygdala reactivity and dimensions of AB and CU traits in 220 Hispanic and non-Hispanic Caucasian adolescents (age 11–15; 49.5% female; 38.2% Hispanic), half of whom had a family history for depression and thus were at relatively elevated risk for late starting, emotionally dysregulated AB. We found that AB was significantly related to increased right amygdala reactivity to angry facial expressions independent of sex, ethnicity, pubertal stage, age, and familial risk status for depression. CU traits were not related to fear- or anger-related amygdala reactivity. The present study further demonstrates that AB is related to increased amygdala reactivity to interpersonal threat cues in adolescents, and that this relationship generalizes across sex, ethnicity, pubertal stage, age, and familial risk status for depression.
Purpose: A common way of eliciting speech from individuals is by using passages of written language that are intended to be read aloud. Read passages afford the opportunity for increased control over ...the phonetic properties of elicited speech, of which phonetic balance is an often-noted example. No comprehensive analysis of the phonetic balance of read passages has been reported in the literature. The present article provides a quantitative comparison of the phonetic balance of widely used passages in English. Method: Assessment of phonetic balance is carried out by comparing the distribution of phonemes in several passages to distributions consistent with typical spoken English. Data regarding the distribution of phonemes in spoken American English are aggregated from the published literature and large speech corpora. Phoneme distributions are compared using Spearman rank order correlation coefficient to quantify similarities of phoneme counts in those sources. Results: Correlations between phoneme distributions in read passages and aggregated material representative of spoken American English ranged from 0.70 to 0.89. Correlations between phoneme counts from all passages, literature sources, and corpus sources ranged from 0.55 to 0.99. All correlations were statistically significant at the Bonferroni-adjusted level. Conclusions: Passages considered in the present work provide high, but not ideal, phonetic balance. Space exists for the creation of new passages that more closely match the phoneme distributions observed in spoken American English. "The Caterpillar" provided the best phonetic balance, but phoneme distributions in all considered materials were highly similar to each other.
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