Faculty Bibliography

BACKGROUND:Despite evidence of the importance of interpersonal connectedness to our understanding of suicide risk, relatively little research has examined the protective and buffering effects of connectedness among adolescents. The aims of this study were to determine: (a) whether overall connectedness (composite of family, peer, and school) and specific domains of connectedness were related to a lower likelihood of suicide attempts, and (b) whether these factors buffer the prospective risk of suicide attempt for high-risk subgroups (i.e., recent suicidal ideation and/or lifetime history of suicide attempt, peer victimization, or sexual and gender minority status). METHODS:Participants were 2,897 adolescents (64.7% biological female), ages 12 to 17 (M = 14.6, SD = 1.6), recruited in collaboration with the Pediatric Emergency Care Applied Research Network (PECARN) from 14 emergency departments for the Emergency Department Screen for Teens at Risk for Suicide Study (ED-STARS). Suicide risk and protective factors were assessed at baseline; 3- and 6-month follow-ups were completed (79.5% retention). Multivariable logistic regressions were conducted, adjusting for established suicide risk factors. RESULTS:Higher overall connectedness and, specifically, school connectedness were associated with decreased likelihood of a suicide attempt across 6 months. Overall connectedness and connectedness domains did not function as buffers for future suicide attempts among certain high-risk subgroups. The protective effect of overall connectedness was lower for youth with recent suicidal ideation or a suicide attempt history than for those without this history. Similarly, overall connectedness was protective for youth without peer victimization but not those with this history. Regarding specific domains, family connectedness was protective for youth without recent suicidal ideation or a suicide attempt history and peer connectedness was protective for youth without peer victimization but not youth with these histories. CONCLUSIONS:In this large and geographically diverse sample, overall and school connectedness were related prospectively to lower likelihood of suicide attempts, and connectedness was more protective for youth not in certain high-risk subgroups. Results inform preventive efforts aimed at improving youth connectedness and reducing suicide risk.

Septo-optic dysplasia (SOD) syndrome is a rare congenital disorder characterized by a classic triad of optic nerve/chiasm hypoplasia, agenesis of septum pellucidum and corpus callosum, and hypoplasia of the hypothalamic-pituitary axis.Herein, we report the clinical case of 2-year-old boy presenting with psychomotor delay, nystagmus, congenital hypothyroidism, and a clinically relevant growth delay. The neuroradiological examination showed partial segmental agenesis of the corpus callosum, agenesis of the septum pellucidum, optic nerve hypoplasia, and a small pituitary gland with a small median pituitary stalk. A whole-exome sequencing analysis detected a novel heterozygous de novo variant c.1069_1070delAG in SON, predicted as likely pathogenic.To date, SON pathogenic variants have been described as responsible for Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome, a multisystemic neurodevelopmental disorder mainly characterized by intellectual disability, facial dysmorphisms, visual abnormalities, brain malformations, feeding difficulties, and growth delay. The herein described case is the first recognized clinic-radiological occurrence of SOD syndrome with hypothalamic-pituitary dysfunction in a patient carrying a SON gene variant, considered responsible of ZTTK syndrome, suggesting a possible relationship between SOD and SON gene alterations, never described so far, making the search for SON gene mutations advisable in patients with SOD.

Recent advances in open neuroimaging data are enhancing our comprehension of neuropsychiatric disorders. By pooling images from various cohorts, statistical power has increased, enabling the detection of subtle abnormalities and robust associations, and fostering new research methods. Global collaborations in imaging have furthered our knowledge of the neurobiological foundations of brain disorders and aided in imaging-based prediction for more targeted treatment. Large-scale magnetic resonance imaging initiatives are driving innovation in analytics and supporting generalizable psychiatric studies. We also emphasize the significant role of big data in understanding neural mechanisms and in the early identification and precise treatment of neuropsychiatric disorders. However, challenges such as data harmonization across different sites, privacy protection, and effective data sharing must be addressed. With proper governance and open science practices, we conclude with a projection of how large-scale imaging resources and collaborations could revolutionize diagnosis, treatment selection, and outcome prediction, contributing to optimal brain health.

BACKGROUND:Major depressive disorder (MDD) is one of the most prevalent and disabling illnesses worldwide. Treatment of MDD typically relies on trial-and-error to find an effective approach. Identifying early response-related biomarkers that predict response to antidepressants would help clinicians to decide, as early as possible, whether a particular treatment might be suitable for a given patient. METHODS:Data were from the two-stage Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC) trial. A whole-brain, voxel-wise, mixed-effects model was applied to identify early-treatment cerebral blood flow (CBF) changes as biomarkers of treatment response. We examined changes in CBF measured with arterial spin labeling 1-week after initiating double-masked sertraline/placebo. We tested whether these early 1-week scans could be used to predict response observed after 8-weeks of treatment. RESULTS:Response to 8-week placebo treatment was associated with increased cerebral perfusion in temporal cortex and reduced cerebral perfusion in postcentral region captured at 1-week of treatment. Additionally, CBF response in these brain regions was significantly correlated with improvement in Hamilton Depression Rating Scale score in the placebo group. No significant associations were found for selective serotonin reuptake inhibitor treatment. CONCLUSIONS:We conclude that early CBF responses to placebo administration in multiple brain regions represent candidate neural biomarkers of longer-term antidepressant effects.

IMPORTANCE/UNASSIGNED:Noninvasive brain stimulation (NIBS) interventions have been shown to be efficacious in several mental disorders, but the optimal dose stimulation parameters for each disorder are unknown. OBJECTIVE/UNASSIGNED:To define NIBS dose stimulation parameters associated with the greatest efficacy in symptom improvement across mental disorders. DATA SOURCES/UNASSIGNED:Studies were drawn from an updated (to April 30, 2023) previous systematic review based on a search of PubMed, OVID, and Web of Knowledge. STUDY SELECTION/UNASSIGNED:Randomized clinical trials were selected that tested transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) for any mental disorder in adults aged 18 years or older. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:Two authors independently extracted the data. A 1-stage dose-response meta-analysis using a random-effects model was performed. Sensitivity analyses were conducted to test robustness of the findings. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The main outcome was the near-maximal effective doses of total pulses received for TMS and total current dose in coulombs for tDCS. RESULTS/UNASSIGNED:A total of 110 studies with 4820 participants (2659 men [61.4%]; mean [SD] age, 42.3 [8.8] years) were included. The following significant dose-response associations emerged with bell-shaped curves: (1) in schizophrenia, high-frequency (HF) TMS on the left dorsolateral prefrontal cortex (LDLPFC) for negative symptoms (χ2 = 9.35; df = 2; P = .009) and TMS on the left temporoparietal junction for resistant hallucinations (χ2 = 36.52; df = 2; P < .001); (2) in depression, HF-DLPFC TMS (χ2 = 14.49; df = 2; P < .001); (3) in treatment-resistant depression, LDLPFC tDCS (χ2 = 14.56; df = 2; P < .001); and (4) in substance use disorder, LDLPFC tDCS (χ2 = 33.63; df = 2; P < .001). The following significant dose-response associations emerged with plateaued or ascending curves: (1) in depression, low-frequency (LF) TMS on the right DLPFC (RDLPFC) with ascending curve (χ2 = 25.67; df = 2; P = .001); (2) for treatment-resistant depression, LF TMS on the bilateral DLPFC with ascending curve (χ2 = 5.86; df = 2; P = .004); (3) in obsessive-compulsive disorder, LF-RDLPFC TMS with ascending curve (χ2 = 20.65; df = 2; P < .001) and LF TMS on the orbitofrontal cortex with a plateaued curve (χ2 = 15.19; df = 2; P < .001); and (4) in posttraumatic stress disorder, LF-RDLPFC TMS with ascending curve (χ2 = 54.15; df = 2; P < .001). Sensitivity analyses confirmed the main findings. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The study findings suggest that NIBS yields specific outcomes based on dose parameters across various mental disorders and brain regions. Clinicians should consider these dose parameters when prescribing NIBS. Additional research is needed to prospectively validate the findings in randomized, sham-controlled trials and explore how other parameters contribute to the observed dose-response association.

BACKGROUND:Pediatric cancer patients' oncology teams regularly take on a primary care role, but due to the urgent nature of cancer treatment, developmental screenings may be deprioritized. This leaves patients at risk of developmental diagnoses and referrals being delayed. AIMS/OBJECTIVE:Clarify the current developmental surveillance and screening practices of one pediatric oncology team. MATERIALS AND METHODS/METHODS:Researchers reviewed charts for patients (n = 66) seen at a pediatric oncology clinic in a suburban academic medical center to determine engagement in developmental screening (including functioning around related areas such as speech, neurocognition, etc.) and referrals for care in these areas. RESULTS:Developmental histories were collected from all patients through admission history and physical examination (H&P), but there was no routinized follow-up. Physicians did not conduct regular developmental screening per American Academy of Pediatrics guidelines for any patients but identified n = 3 patients with needs while the psychology team routinely surveilled all patients seen during this time (n = 41) and identified n = 18 patients as having delays. DISCUSSION/CONCLUSIONS:Physicians did not routinely screen for development needs beyond H&P and were inconsistent in developmental follow-up/referrals. Integrated psychologists were key in generating referrals for developmental-based care. However, many oncology patients were not seen by psychologists quickly or at all, creating a significant gap in care during a crucial developmental period. CONCLUSION/CONCLUSIONS:The case is made for further routinization of ongoing developmental screening in pediatric oncology care.