A methylation study implicates the rewiring of brain neural circuits during puberty in the emergence of sex differences in depression symptoms.

BACKGROUND: Women are 1.5-3 times more likely to suffer from depression than men. This sex bias first emerges during puberty and then persists across the reproductive years. As the cause remains largely elusive, we performed a methylation-wide association study (MWAS) to generate novel hypotheses. METHODS: We assayed nearly all 28 million possible methylation sites in blood in 595 blood samples from 487 participants aged 9-17. MWASs were performed to identify methylation sites associated with increasing sex differences in depression symptoms as a function of pubertal stage. Epigenetic deconvolution was applied to perform analyses on a cell-type specific level. RESULTS: In monocytes, a substantial number of significant associations were detected after controlling the FDR at 0.05. These results could not be explained by plasma testosterone/estradiol or current/lifetime trauma. Our top results in monocytes were significantly enriched (ratio of 2.48) for genes in the top of a large genome-wide association study (GWAS) meta-analysis of depression and neurodevelopment-related Gene Ontology (GO) terms that remained significant after correcting for multiple testing. Focusing on our most robust findings (70 genes overlapping with the GWAS meta-analysis and the significant GO terms), we find genes coding for members of each of the major classes of axon guidance molecules (netrins, slits, semaphorins, ephrins, and cell adhesion molecules). Many of these genes were previously implicated in rodent studies of brain development and depression-like phenotypes, as well as human methylation, gene expression and GWAS studies. CONCLUSIONS: Our study suggests that the emergence of sex differences in depression may be related to the differential rewiring of brain circuits between boys and girls during puberty.

HIV treatment-as-prevention and its effect on incidence of HIV among cisgender gay, bisexual, and other men who have sex with men in Australia: a 10-year longitudinal cohort study.

BACKGROUND: Although HIV treatment-as-prevention reduces individual-level HIV transmission, population-level effects are unclear. We aimed to investigate whether treatment-as-prevention could achieve population-level reductions in HIV incidence among gay, bisexual, and other men who have sex with men (GBM) in Australia's most populous states, New South Wales and Victoria. METHODS: TAIPAN was a longitudinal cohort study using routine health record data extracted from 69 health services that provide HIV diagnosis and care to GBM in New South Wales and Victoria, Australia. Data from Jan 1, 2010, to Dec 31, 2019, were linked within and between services and over time. TAIPAN collected data from all cisgender GBM who attended participating services, resided in New South Wales or Victoria, and were 16 years or older. Two cohorts were established: one included HIV-positive patients, and the other included HIV-negative patients. Population prevalence of viral suppression (plasma HIV viral load <200 RNA copies per µL) was calculated by combining direct measures of viral load among the HIV-positive cohort with estimates for undiagnosed GBM. The primary outcome of HIV incidence was measured directly via repeat testing in the HIV-negative cohort. Poisson regression analyses with generalised estimating equations assessed temporal associations between population prevalence of viral suppression and HIV incidence among the subsample of HIV-negative GBM with multiple instances of HIV testing. FINDINGS: At baseline, the final sample (n=101 772) included 90 304 HIV-negative and 11 468 HIV-positive GBM. 59 234 patients in the HIV-negative cohort had two or more instances of HIV testing and were included in the primary analysis. Over the study period, population prevalence of viral suppression increased from 69·27% (95% CI 66·41-71·96) to 88·31% (86·37-90·35), while HIV incidence decreased from 0·64 per 100 person-years (95% CI 0·55-0·76) to 0·22 per 100 person-years (0·17-0·28). Adjusting for sociodemographic characteristics and HIV pre-exposure prophylaxis (PrEP) use, treatment-as-prevention achieved significant population-level reductions in HIV incidence among GBM: a 1% increase in population prevalence of viral suppression corresponded with a 6% decrease in HIV incidence (incidence rate ratio [IRR] 0·94, 95% CI 0·93-0·96; p<0·0001). PrEP was introduced in 2016 with 17·60% uptake among GBM that year, which increased to 36·38% in 2019. The relationship between population prevalence of viral suppression and HIV incidence was observed before the availability of PrEP (IRR 0·98, 95% CI 0·96-0·99; p<0·0001) and was even stronger after the introduction of PrEP (0·80, 0·70-0·93; p=0·0030). INTERPRETATION: Our results suggest that further investment in HIV treatment, especially alongside PrEP, can improve public health by reducing HIV incidence among GBM. FUNDING: National Health and Medical Research Council of Australia.

Adjustment to college in students with ADHD.

OBJECTIVE: To examine college adjustment in students reporting an ADHD diagnosis and the effect of medication treatment on students' adjustment. METHOD: 1,648 first-semester freshmen attending a public and a private university completed a Web-based survey to examine their adjustment to college. RESULTS: Compared with 200 randomly selected control students, 68 students with ADHD reported more academic concerns and depressive symptoms. This was explained by higher rates of inattentive symptoms among students with ADHD and was unrelated to hyperactive-impulsive symptoms. Among students with ADHD, medication treatment was not related to better adjustment or diminished ADHD symptoms. The contribution of inattention to academic concerns and depressive symptoms remained significant when controlling for personality traits. CONCLUSION: Students with ADHD experience greater academic performance concerns and depressive symptoms during the transition to college. Medication treatment did not appear to diminish ADHD symptoms nor enhance students' adjustment.

Trauma, proximity, and developmental psychopathology: the effects of war and terrorism on children.

This report summarizes recent literature relevant to the effects of terrorism on children's mental health. The paper addresses three aspects of this topic. In the first section of the paper, data are reviewed concerning the relationships among stress, trauma, and developmental psychopathology. A particular emphasis is placed on associations with indirect forms of trauma, given that terrorism involves high levels of indirect trauma. Second, the paper delineates a set of key principles to be considered when considering ways in which the effects of terrorism on children's mental health can be minimized. Third, data are reviewed from studies in developmental psychobiology. These data are designed to illustrate the mechanisms through which children exhibit unique effects in the wake of traumatic circumstances.

Relations between Continuous Performance Test performance measures and ADHD behaviors.

The Conners' Continuous Performance Test (CPT) is a neuropsychological task that has repeatedly been shown to differentiate ADHD from normal groups. Several variables may be derived from the Conners' CPT including errors of omission and commission, mean hit reaction time(RT), mean hit RT standard error, d', and beta. What each CPT parameter actually assesses has largely been based upon clinical assumptions and the face validity of each measure (e.g., omission errors measure inattention, commission errors measure impulsivity). This study attempts to examine relations between various CPT variables and phenotypic behaviors so as to better understand the various CPT variables. An epidemiological sample of 817 children was administered the Conners' CPT. Diagnostic interviews were conducted with parents to determine ADHD symptom profiles for all children. Children diagnosed with ADHD had more variable RTs, made more errors of commission and omission, and demonstrated poorer perceptual sensitivity than nondiagnosed children. Regarding specific symptoms, generalized estimating equations (GEE) and ANCOVAs were conducted to determine specific relationships between the 18 DSM-IV ADHD symptoms and 6 CPT parameters. CPT performance measures demonstrated significant relationships to ADHD symptoms but did not demonstrate symptom domain specificity according to a priori assumptions. Overall performance on the two signal detection measures, d' and beta, was highly related to all ADHD symptoms across symptom domains. Further, increased variability in RTs over time was related to most ADHD symptoms. Finally, it appears that at least 1 CPT variable, mean hit RT, is minimally related to ADHD symptoms as a whole, but does demonstrate some specificity in its link with symptoms of hyperactivity.

Severity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication Adolescent Supplement.

CONTEXT: Estimates of DSM-IV disorder prevalence are high; stringent criteria to define need for services are desired. OBJECTIVE: To present US national data on the prevalence and sociodemographic correlates of 12-month serious emotional disturbance (SED), defined by the US Substance Abuse and Mental Health Services Administration, from the National Comorbidity Survey Replication Adolescent Supplement. DESIGN: The National Comorbidity Survey Replication Adolescent Supplement is a national survey of DSM-IV anxiety, mood, behavior, and substance disorders among US adolescents. SETTING: Dual-frame household and school samples of US adolescents. PARTICIPANTS: Total of 6483 pairs of adolescents aged 13 to 17 (interviews) and parents (questionnaires). MAIN OUTCOME MEASURES: The DSM-IV disorders were assessed with the World Health Organization Composite International Diagnostic Interview and validated with blinded clinical interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Serious emotional disturbance was operationalized as a DSM-IV/Composite International Diagnostic Interview disorder with a score of 50 or less on the Children's Global Assessment Scale (ie, moderate impairment in most areas of functioning or severe impairment in at least 1 area). Concordance of Composite International Diagnostic Interview SED diagnoses with blinded Schedule for Affective Disorders and Schizophrenia for School-Age Children diagnoses was good. RESULTS: The estimated prevalence of SED was 8.0%. Most SEDs were due to behavior (54.5%) or mood (31.4%) disorders. Although respondents with 3 or more disorders made up only 29.0% of those with 12-month DSM-IV/Composite International Diagnostic Interview disorders, they constituted 63.5% of SEDs. Predictive effects of high comorbidity were significantly greater than the product of their disorder-specific odds ratios and consistent across disorder types. Associations of sociodemographic variables with SED were generally nonsignificant after controlling for disorder type and number. CONCLUSIONS: The high estimated 12-month prevalence of DSM-IV disorders among US adolescents is largely due to mild cases. The significant between-disorder differences in risk of SED and the significant effect of high comorbidity have important public health implications for targeting interventions.

Needs assessment of rural communities: a focus on older adults.

High-quality community needs assessments can help focus limited resources on the needs of a rapidly expanding population-older Americans. Based on such assessments, organizations and communities can effectively plan and deliver cost-effective, appropriate health promotion/wellness programs and health/social services to targeted populations. This article, which describes the Arkansas Aging Initiative's (AAI) use of a community needs assessment to identify its constituents' top health needs, provides specific background information for communities with demographics similar to those in Arkansas and offers assessment strategies for communities throughout the US. The AAI used two complementary methodologies to obtain critical input from Arkansas providers and their communities: focus groups of healthcare providers and community members and surveys administered to older adults. The assessment confirmed that health problems in the communities were consistent with leading causes of morbidity and mortality at state and national levels. It indicated that respondents' top three health needs related to affordability, including affordability of prescription medications, medical care, and health insurance, and that needs varied inversely with age. In other findings, married individuals rated their own health as better than their single counterparts; whites rated their health better than non-whites; and more than half of respondents reported leaving their counties to receive healthcare. This community needs assessment has enabled the AAI to address respondents' needs by developing specific educational and interdisciplinary healthcare initiatives, such as increasing access to a prescription drug assistance program.