Prevalence and characteristics of genetic disease in adult kidney stone formers.

BACKGROUND: Molecular mechanisms of kidney stone formation remain unknown in most patients. Previous studies have shown a high heritability of nephrolithiasis, but data on the prevalence and characteristics of genetic disease in unselected adults with nephrolithiasis are lacking. This study was conducted to fill this important knowledge gap. METHODS: We performed whole exome sequencing in 787 participants in the Bern Kidney Stone Registry, an unselected cohort of adults with one or more past kidney stone episodes [kidney stone formers (KSFs)] and 114 non-kidney stone formers (NKSFs). An exome-based panel of 34 established nephrolithiasis genes was analysed and variants assessed according to American College of Medical Genetics and Genomics criteria. Pathogenic (P) or likely pathogenic (LP) variants were considered diagnostic. RESULTS: The mean age of KSFs was 47 ± 15 years and 18% were first-time KSFs. A Mendelian kidney stone disease was present in 2.9% (23/787) of KSFs. The most common genetic diagnoses were cystinuria (SLC3A1, SLC7A9; n = 13), vitamin D-24 hydroxylase deficiency (CYP24A1; n = 5) and primary hyperoxaluria (AGXT, GRHPR, HOGA1; n = 3). Of the KSFs, 8.1% (64/787) were monoallelic for LP/P variants predisposing to nephrolithiasis, most frequently in SLC34A1/A3 or SLC9A3R1 (n = 37), CLDN16 (n = 8) and CYP24A1 (n = 8). KSFs with Mendelian disease had a lower age at the first stone event (30 ± 14 versus 36 ± 14 years; P = .003), were more likely to have cystine stones (23.4% versus 1.4%) and less likely to have calcium oxalate monohydrates stones (31.9% versus 52.5%) compared with KSFs without a genetic diagnosis. The phenotype of KSFs with variants predisposing to nephrolithiasis was subtle and showed significant overlap with KSFs without diagnostic variants. In NKSFs, no Mendelian disease was detected and LP/P variants were significantly less prevalent compared with KSFs (1.8% versus 8.1%). CONCLUSION: Mendelian disease is uncommon in unselected adult KSFs, yet variants predisposing to nephrolithiasis are significantly enriched in adult KSFs.

Adult-Onset ADHD: A Critical Analysis and Alternative Explanations.

Attention deficit/hyperactivity disorder (ADHD) is characterized as a neurodevelopmental disorder. However, data from several recent studies suggest that there may be adults who meet current criteria for ADHD, yet did not experience symptoms until adulthood (i.e., "adult-onset ADHD"). This systematic review evaluated and synthesized the empirical evidence on adult-onset ADHD to answer the question: Is the extant literature strong enough to evaluate adult-onset ADHD? Nine studies met strict inclusion/exclusion criteria. Results suggest that the methodologies of the extant studies were not strong enough to evaluate adult-onset ADHD. Insufficient methodologies provide presently unclear information about the nature of late-onset symptoms. These symptoms seem to exist but their source could be (1) adult-emergent symptoms that were previously surpassed due to lower environmental demands/supportive facilitators, (2) mimics that were not properly assessed, or (3) childhood-onset symptoms that were not detected earlier due to failure to come to clinical attention. Future directions, clinical recommendations, and limitations of the literature and the current review are discussed.

Prescription Stimulant Misuse and Risk Correlates among Racially-Diverse Urban Adolescents.

BACKGROUND: Most research on prescription stimulant misuse has focused on college students, and research on high school-aged adolescents is limited. OBJECTIVES: This study aimed to characterize risk correlates of prescription stimulant misuse among a racially-diverse and socioeconomically-disadvantaged sample of urban adolescents. METHOD: Cross-sectional data were drawn from an ongoing study of adolescent health behaviors, Project Teen. Participants were 414 9th to 11th graders (Mage=16.00 [SD = 1.08]; 57% female; 41% Black or African American, 22% White, 18% Asian, 17% Multiracial, 2% Pacific Islander, and 1% Native American; 12% Hispanic/Latinx). Participants completed a web-based survey assessing prescription stimulant misuse, demographics, mental health and personality, social environment, and substance use. RESULTS: Eight percent of participants endorsed past-year prescription stimulant misuse. Compared to non-misusing peers, participants endorsing past-year prescription stimulant misuse reported greater depression/anxiety symptoms, sensation seeking, perceived peer risk behavior, and alcohol and cigarette use, as well as a lower level of parental monitoring; null group differences were observed for academic goal orientation, perceived peer approval of risk behavior, and cannabis use. Binary logistic regression demonstrated that binge drinking and cigarette use were significantly associated with prescription stimulant misuse over and above all other identified risk variables. CONCLUSIONS: Adolescent prescription stimulant misuse appears to overlap with general adolescent substance use, sharing several known risk correlates. Results highlight potential targets for identification of emerging prescription stimulant misuse risk profiles at earlier stages of development. Longitudinal replication is needed to examine directional associations and risk mechanisms underlying adolescent prescription stimulant misuse.

Young Adult Outcomes for Children With 22q11 Deletion Syndrome and Comorbid ADHD.

Background: 22q11.2 deletion syndrome (22q11DS) is a common microdeletion syndrome associated with a variety of negative health, cognitive, emotional, and behavioral outcomes. 22q11DS is comorbid with many psychiatric disorders including attention-deficit/hyperactivity disorder (ADHD). The current study aimed to investigate the cognitive, behavioral, and functional outcomes that a childhood ADHD diagnosis predicts to in adulthood. Methods: This longitudinal study followed 52 individuals with 22q11DS over 9 years. Childhood ADHD was operationalized both categorically (Diagnostic and statistical manual - 4th edition (DSM-IV) ADHD diagnoses) and dimensionally (inattentive and hyperactive-impulsive symptoms) and was tested as predictors of young adult outcomes. Results: As young adults, children with 22q11DS + baseline ADHD had more parent-reported executive dysfunction and lower levels of clinician-rated overall functioning than those with 22q11DS yet without ADHD. Dimensional symptoms of ADHD in childhood did not predict young adult outcomes. No self-report differences emerged between those with and without baseline ADHD. The majority (82.4%) of individuals with 22q11DS + baseline ADHD were never treated with an ADHD medication. Conclusions: A categorical diagnosis of ADHD in childhood predicted a greater variety of worse outcomes than dimensional levels of ADHD symptoms. Despite the significant impact of comorbid ADHD in 22q11DS, evidence-based treatment rates were low.

The regeneration-responsive element careg monitors activation of Müller glia after MNU-induced damage of photoreceptors in the zebrafish retina.

In contrast to mammals, zebrafish can regenerate their damaged photoreceptors. This capacity depends on the intrinsic plasticity of Müller glia (MG). Here, we identified that the transgenic reporter careg, a marker of regenerating fin and heart, also participates in retina restoration in zebrafish. After methylnitrosourea (MNU) treatment, the retina became deteriorated and contained damaged cell types including rods, UV-sensitive cones and the outer plexiform layer. This phenotype was associated with the induction of careg expression in a subset of MG until the reconstruction of the photoreceptor synaptic layer. Single-cell RNA sequencing (scRNAseq) analysis of regenerating retinas revealed a population of immature rods, defined by high expression of rhodopsin and the ciliogenesis gene meig1, but low expression of phototransduction genes. Furthermore, cones displayed deregulation of metabolic and visual perception genes in response to retina injury. Comparison between careg:EGFP expressing and non-expressing MG demonstrated that these two subpopulations are characterized by distinct molecular signatures, suggesting their heterogenous responsiveness to the regenerative program. Dynamics of ribosomal protein S6 phosphorylation showed that TOR signaling became progressively switched from MG to progenitors. Inhibition of TOR with rapamycin reduced the cell cycle activity, but neither affected careg:EGFP expression in MG, nor prevented restoration of the retina structure. This indicates that MG reprogramming, and progenitor cell proliferation might be regulated by distinct mechanisms. In conclusion, the careg reporter detects activated MG, and provides a common marker of regeneration-competent cells in diverse zebrafish organs, including the retina.

Factors Associated with Parental Treatment Attitudes and Information-Seeking Behaviors for Childhood ADHD.

Objective: Despite the association between childhood ADHD and long-term negative outcomes, there is a significant delay to treatment and a low rate of lifetime treatment contact for individuals with ADHD. Method: The current study examined (a) variables associated with parental treatment-seeking attitudes and information-seeking behaviors and (b) the relationship between these attitudes and behaviors in 87 non-treatment-seeking parents whose children had elevated ADHD symptoms. Results: Regressions indicated that attitudes toward ADHD treatment were associated with ADHD knowledge and misconceptions (ps < .01), susceptibility to ADHD stigma (p < .001), and satisfaction with past providers (ps < .01). Experience with past providers was significantly associated with information-seeking behavior (ps < .01). Conclusion: Parental knowledge of ADHD, low levels of stigma, and positive experiences with past providers were the strongest predictors of positive attitudes about ADHD treatment. Experience with past providers was the only factor related to treatment-seeking behavior. These results offer avenues to decreasing barriers to treatment in pediatric ADHD.

Achievement goal orientation and stimulant misuse in college students.

Objective: The prevalence of stimulant medication misuse is rising in college students. Motivations to use stimulant medications differ from motivation to use other substances such as alcohol or cannabis. However, no previous research has examined the impact of achievement goal orientation on stimulant misuse in college students. Participants: 309 college students (mean age = 18.9; 117 males) without an ADHD diagnosis were invited to participate. Methods: Participants completed an online research questionnaire that assessed factors associated with stimulant medication misuse as well as achievement goal orientations (Learning and Performance Orientations). Results: Approximately 12% endorsed a history of stimulant misuse within the past year. More males (17.1%) than females (9.4%) reported stimulant misuse. Those with and without a history of stimulant misuse differed on Performance Orientation (misuse > no misuse) yet were comparable on Learning Orientation. Conclusions: Having a higher Performance Orientation independently predicted stimulant misuse.

Skidmore Clips of Neutral and Expressive Scenarios (SCENES): Novel dynamic stimuli for social cognition research.

Social cognition research has relied primarily on photographic emotional stimuli. Such stimuli likely have limited ecological validity in terms of representing real world social interactions. The current study presents evidence for the validity of a new stimuli set of dynamic social SCENES (Skidmore Clips of Emotional and Neutral Expressive Scenarios). To develop these stimuli, ten undergraduate theater students were recruited to portray members of an audience. This audience was configured to display (seven) varying configurations of social feedback, ranging from unequivocally approving to unequivocally disapproving (including three different versions of balanced/neutral scenes). Validity data were obtained from 383 adult participants recruited from Amazon's Mechanical Turk. Each participant viewed three randomly assigned scenes and provided a rating of the perceived criticalness of each scene. Results indicate that the SCENES reflect the intended range of emotionality, and pairwise comparisons suggest that the SCENES capture distinct levels of critical feedback. Overall, the SCENES stimuli set represents a publicly available (www.scenesstimuli.com) resource for researchers interested in measuring social cognition in the presence of dynamic and naturalistic social stimuli.