Trajectory of depressive symptoms over adolescence in autistic and neurotypical youth.

BACKGROUND: Adolescence coincides with a dramatic rise in the onset of psychiatric conditions including depression. Depression symptoms may be particularly prevalent and impairing for youth with autism spectrum disorder (ASD). While prior research suggests adolescence is associated with worsening depression symptoms for typically developing (TD) and autistic youth, it is unclear if they follow a similar course. METHOD: The study examined the trajectory of depressive symptoms in autistic and neurotypical youth over a 4-year longitudinal study using linear and logistic mixed effects models. In youth with clinically relevant depressive scores (t-score > 65), moderating factors (i.e., diagnosis, age, puberty, sex) were explored. During Year 1, the sample included 244 youth 10-to-13 years: 140 in the ASD group (36 females) and 104 in the TD group (46 females). RESULTS: Autistic youth had elevated depression scores compared to TD peers (p < 0.001) and females were higher than males in both groups (p = 0.001). There was significant diagnosis by age (p < 0.001) and diagnosis by pubertal stage (p < 0.05) interactions. In the ASD group, elevated depressive scores presented in early adolescence and decreased during middle adolescence and puberty, whereas the TD group showed the opposite trend with an increase in depression symptoms with advancing development. LIMITATIONS: Limitations include an unequal sex distribution (fewer females), non-representative autistic sample (e.g., cognition and race/ethnicity), and potential confound of the COVID-19 pandemic. CONCLUSIONS: Autistic youth present with higher rates of depressive symptoms early in development; yet, approaching middle adolescence and puberty, the symptom trajectory in the autistic youth declines coinciding with an increase in the TD youth. While group trajectories are divergent, they lead to similar levels of depression in late adolescence with higher symptoms in females. Findings suggest a period of quiescence in depressive symptomology influenced by biopsychosocial factors impacting affective profiles.

Gender diversity in autistic and neurotypical youth over adolescence and puberty: A longitudinal study.

Recent research in autism spectrum disorder (ASD) has suggested a higher prevalence of gender diversity in individuals diagnosed with ASD. Adolescence is a critical period for the consolidation of gender identity, yet the extent to which the experience of gender diversity is stable over adolescence and puberty in autistic youth is poorly understood. The aim of the study was to examine the consistency of gender diversity using the gender diversity screening questionnaire for self- and parent-report of youth (GDSQ-S, GDSQ-P) over a four-year longitudinal study of pubertal development in youth with ASD (N = 140, 36 assigned-female-at birth (AFAB)) and typical development (TD, N = 104, 58 assigned-male-at-birth [AMAB]) and their parents. The extent to which diagnosis (ASD vs. TD), assigned sex (AFAB vs. AMAB) and developmental level (age, puberty) predict GDSQ trajectory over time was explored. There was a significant diagnosis by sex-assigned-at-birth by age interaction for GDSQ-S Gender Diversity, p = 0.002, showing higher scores in autistic AFAB youth over adolescence, and TD AFAB showing initially lower, then increasing levels over adolescence. For GDSQ-P, Gender Incongruence was significantly different between the groups, p = 0.032, showing higher incongruence for autistic AFAB around age 10, decreasing between age 12-14 before increasing again, while TD AFAB evidence the inverse trend. AMAB trends were stable. The significant diagnostic, developmental and sex-based differences indicate AFAB youth experience greater gender diversity that evolves over development. Findings suggest gender identity formation is nuanced and may be influenced by pubertal progression, hormonal patterns, and psychosocial factors. Results underscore the need for enhanced understanding of the unique, dynamic profiles of females-assigned-at-birth.

Predictive Dosimetry and Outcomes of Hepatocellular Carcinoma Treated by Yttrium-90 Resin Microsphere Radioembolization: A Retrospective Analysis Using Technetium-99m Macroaggregated Albumin SPECT/CT and Planning Software.

PURPOSE: To characterize estimated mean absorbed tumor dose (ADT), objective response (OR), and estimated target dose of hepatocellular carcinoma (HCC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between October 2015 and June 2022 was performed using a commercial software package and pretreatment technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT)/computed tomography (CT). In total, 101 patients with HCC underwent 102 treatments of 127 index tumors. Patients underwent imaging every 2-3 months after treatment to determine best response per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Best response was defined as the greatest response category per mRECIST and categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and progression-free survival using ADT. RESULTS: The median follow-up period was 148 days (interquartile range [IQR], 92-273 days). The median ADT of OR was 141.9 Gy (IQR, 89.4-215.8 Gy) compared with the median ADT of NR treatments of 70.8 Gy (IQR, 42.0-135.3 Gy; P < .001). Only ADT was predictive of response (hazard ratio = 2.79 [95% confidence interval {CI}: 1.44-5.40]; P = .003). At 6 months, an ADT of 157 Gy predicted 90.0% (95% CI: 41.3%-98.3%) probability of OR. At 1 year, an ADT of 157 Gy predicted 91.6% (95% CI: 78.3%-100%) probability of progression-free survival. Partition modeling and delivered activity were predictive of progression (P = .021 and P = .003, respectively). CONCLUSIONS: For HCC treated with resin microspheres, tumors receiving higher ADT exhibited higher rates of OR. An ADT of 157 Gy predicted 90.0% OR at 6 months.

Use of ECT for Children With and Without Catatonia: A Single-Site Retrospective Analysis.

OBJECTIVES: The objective study was to investigate the safety and efficacy of electroconvulsive therapy (ECT) in a retrospective cohort of pediatric patients. METHODS: A single-site retrospective analysis was conducted of patients aged younger than 18 years who received ECT in a private university hospital from January 28, 2012 to April 8, 2023. Treatment efficacy and adverse events were determined retrospectively through review of the medical record. RESULTS: A total of 36 pediatric patients met the inclusion criteria. Catatonia was the most common presenting indication for ECT, followed by psychosis and suicidal ideation. For all patients, Clinical Global Impressions-Improvement scale scores indicated that it was very likely for a subject to experience at least "much improvement" with the estimated probability of receiving a Clinical Global Impressions-Improvement scale score better than 3 of 0.852 (t.s. = 16.3; P < 0.001; 95% confidence interval, 0.711-0.931). All patients with catatonia demonstrated a positive clinical response and experienced a statistically significant reduction in total Bush-Francis Catatonia Rating Scale scores observed (t = 11.9; df = 20; SD = 6.3; P < 0.001; 95% confidence interval, 12.6-17.9). No significant adverse events were reported for any patient in the cohort. However, 14 (38.9%) patients experienced prolonged seizures, all of which were terminated with propofol (mean, 49.7 mg). CONCLUSIONS: This study provides further data supporting the safe and effective use of pediatric ECT in the treatment of various psychiatric conditions. However, more research is needed to determine the risk factors associated with prolonged seizures and the optimal seizure parameters in young people.

In-hospital catatonia, delirium, and coma and mortality: Results from the delirium and catatonia prospective cohort investigation.

BACKGROUND: Catatonia, a form of acute brain dysfunction typically linked with severe affective and psychotic disorders, occurs in critical illness with delirium and coma. Delirium and coma are associated with mortality, though catatonia's relationship with mortality is unclear. We aim to describe whether catatonia, delirium, and coma are associated with mortality. METHODS: We enrolled a convenience cohort of critically ill adults (N = 378) at an academic medical center. We assessed catatonia, delirium, and coma using the Bush-Francis Catatonia Rating Scale, the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. We tested the associations between previous day brain dysfunction state occurrence with in-hospital and one-year mortality using multivariable time-dependent risk models. Additionally, we tested the association between brain dysfunction duration and one-year mortality. RESULTS: Catatonia was not associated with death on the day after diagnosis during hospitalization, and neither previous catatonia occurrence nor duration was associated with one-year mortality. Delirium was not associated with death on any day following diagnosis during hospitalization, and neither previous delirium occurrence nor duration was associated with one-year mortality. The occurrence of coma was associated with death on any day after diagnosis during hospitalization (HR 2.30,CI 1.19-4.44,p = 0.014), as well as through one year following hospital discharge (HR 1.68,CI 1.09-2.59,p = 0.02). CONCLUSIONS: Coma, but neither catatonia nor delirium, was associated with future day in-hospital and one-year mortality. More research is needed to understand catatonia's clinical impact. Delirium results differ from existing literature likely due to cohort demographics and size. Coma results highlight the prognostic significance of suppressed arousal while critically ill.

Sex differences in COVID-19 symptom severity and trajectories among ambulatory adults.

Background: The ongoing COVID-19 pandemic has led to hundreds of millions of infections worldwide. Although differences in COVID-19 hospitalization rates between males and females have been described, many infections in the general population have been mild, and the severity of symptoms during the course of COVID-19 in non-hospitalized males and females is not well understood. Methods: We conducted a case-ascertained study to examine household transmission of SARS-CoV-2 infections in Nashville, Tennessee, between April 2020 and April 2021. Among enrolled ambulatory adult participants with laboratory-confirmed SARS-CoV-2 infections, we assessed the presence and severity of symptoms (total, systemic, and respiratory) daily using a symptoms severity questionnaire, from illness onset and throughout the 2-week follow-up period. We compared the mean daily symptom severity scores (0-3: none, mild, moderate, and severe) and change in symptoms between males and females using a multivariable linear mixed effects regression model. Results: The analysis included 223 enrolled adults with SARS-CoV-2 infection (58% females, mostly white, non-Hispanic) from 146 households with 2917 total daily symptom reports. The overall mean severity of total symptoms reported over the illness period was 1.04 and 0.90 for females and males, respectively. Mean systemic and respiratory scores were higher for females than for males (p < 0.001). In multivariable analyses, females reported more severe total and systemic symptoms during the illness period compared with males. However, no significant differences in reported respiratory symptoms were observed. Conclusions: Our findings indicate that among ambulatory adults with SARS-CoV-2 infections, females reported slightly higher symptom severity during their illness compared with males.

Partition Dosimetry and Outcomes of Metastatic Neuroendocrine Tumors after Yttrium-90 Resin Microsphere Radioembolization.

PURPOSE: To characterize estimated mean tumor-absorbed dose (ADT) and objective response of metastatic neuroendocrine tumor (NET) after resin microsphere yttrium-90 (90Y) hepatic radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors receiving 90Y radioembolization between 2013 and 2022 involved the use of Sureplan (MIM Software, Cleveland, Ohio) and technetium-99m macroaggregated albumin single photon emission computed tomography (SPECT) combined with computed tomography. Thirty-six patients with NET underwent treatment of 56 index tumors. Patients underwent imaging every 3-6 months after treatment to determine best response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria. Responses were categorized as objective response (OR) or nonresponse (NR). Wilcoxon rank sum test evaluated differences in continuous variables, and Pearson χ2 test evaluated differences in categorical variables. RESULTS: Median follow-up was 582 days (IQR, 187-1,227 days). Per RECIST 1.1, 27 patients (75%) experienced OR and 9 patients experienced (25%) NR. Of the 36 patients, 33 (92%) showed hypervascular, mRECIST-evaluable tumors. Among them, 28 patients (85%) showed mRECIST OR and 5 patients (15%) showed NR. The mRECIST OR group received a higher ADT than the NR group (median, 107 Gy; IQR, 95.1-154 Gy vs median, 70.4 Gy; IQR, 62.9-87.6 Gy; P = .048). All tumors receiving at least 120 Gy showed mRECIST OR. CONCLUSIONS: In hypervascular metastatic NET treated by 90Y resin microsphere radioembolization, higher tumor dose was associated with better tumor response per mRECIST. Doses of ≥120 Gy led to OR.

Predictive Partition Dosimetry and Outcomes after Yttrium-90 Resin Microsphere Radioembolization of Colorectal Cancer Metastatic to the Liver: A Retrospective Analysis.

PURPOSE: To characterize estimated absorbed tumor dose (ADT), objective response (OR), and estimated target dose of liver metastatic colorectal cancer (mCRC) after resin microsphere yttrium-90 (90Y) radioembolization using partition dosimetry. MATERIALS AND METHODS: In this retrospective, single-center study, multicompartment dosimetry of index tumors undergoing 90Y radioembolization from October 2013 to July 2022 was performed using MIM SurePlan and pretreatment technetium-99m macroaggregated albumin infusion data. Thirty-eight patients with mCRC underwent treatments for 59 index tumors. Patients were imaged every 2-3 months after treatment and then every 3-6 months after disease control to determine the best response per Response Evaluation Criteria in Solid Tumors 1.1. Responses were categorized as OR or nonresponse (NR). A Cox proportional hazards model evaluated the probability of tumor OR and local progression-free survival (LPFS) based on ADT. RESULTS: Patients had a median follow-up of 116 days (interquartile range [IQR], 69-231 days). The ADT was higher for OR patients than for NR patients (median, 130.8 [IQR, 85.6-239.0] vs 40.6 [IQR, 26.0-66.3] Gy; P < .001). A greater percentage of OR than NR patients were treated with activities calculated by partition modeling (54% vs 12%; P = .005). Only ADT predicted response (P = .032). At 6 months, an ADT of 120 Gy predicted a 55% (95% CI, 0.0%-89%) probability of OR. Only ADT (P = .010) and female sex (P = .014) predicted LPFS. At 1 year, an ADT of 120 Gy predicted a 70% (95% CI, 35%-100%) probability of LPFS. CONCLUSIONS: Tumor dose was the strongest predictor of OR for mCRC. Administration of an estimated 120 Gy to mCRC predicted 55% OR with 90Y resin microspheres at 6 months.

The developmental trajectory of diurnal cortisol in autistic and neurotypical youth.

Increasing age and puberty affect the hypothalamic pituitary adrenal (HPA) axis maturation, which is likely associated with an increase in environmental demands (e.g., social) and vulnerability for the onset of psychiatric conditions (e.g., depression). There is limited research as to whether such patterns are consonant in youth with autism spectrum disorder (ASD), a condition marked by social challenges, dysregulation of the HPA axis, and higher rates of depression setting the stage for enhanced vulnerability during this developmental period.The current study interrogated diurnal cortisol by examining (1) cortisol expression longitudinally over the pubertal transition between autistic and neurotypical youth, (2) the trajectory of diurnal cortisol and the unique contributions of age vs. puberty, and (3) potential sex differences. As hypothesized, results indicate autistic compared to typically developing youth demonstrate a shallower diurnal slope and elevated evening cortisol. These differences were in the context of higher cortisol and flatter rhythms based on age and pubertal development. Also, sex-based differences emerged such that females in both groups had higher cortisol, flatter slopes, and higher evening cortisol than males. The results show that despite the trait-like stability of diurnal cortisol, HPA maturation is impacted by age, puberty, sex, as well as an ASD diagnosis.

Alternative psychopharmacologic treatments for pediatric catatonia: a retrospective analysis.

Introduction: Pediatric catatonia is a highly co-morbid condition with treatment options often limited to electroconvulsive therapy (ECT) or lorazepam. However, lorazepam may not be readily available, and access to ECT is limited by restrictive legislation and stigma. This study aims to provide alternative treatment options for pediatric catatonia. Methods: The study involved a single-site retrospective analysis of a private university hospital in the southern United States. The study included patients under eighteen with catatonia who received psychopharmacologic treatment with an agent other than lorazepam. The patients were evaluated with the Bush-Francis Catatonia Rating Scale (BFCRS), Kanner Catatonia Severity Scale (KCS), and Kanner Catatonia Examination (KCE) at the time of initial evaluation and upon stabilization. A retrospective clinical global impressions-improvement (CGI-I) score was assigned by four authors. Results: 102 pediatric patients diagnosed with catatonia were identified, and 31 met criteria for the study. 20 (65%) were white, 6 (19%) were Black, 4 (13%) were Hispanic, and 1 (3%) were Indian. Most patients (N = 18; 58%) were insured by Medicaid. The mean age at the time of catatonia diagnosis was 13.5 years. All patients were stabilized on either clonazepam or diazepam, with 21 (68%) requiring treatment with an additional medication of either an anti-epileptic, N-methyl-D-aspartate (NMDA) receptor antagonist, and aripiprazole or clozapine. Statistically significant reductions in the BFCRS [t = 11.2, df = 30, std = 6.3, p < 0.001, 95% CI = (7.8, 15.1)], KCS [t = 4.6, df = 38, p < 0.001, 95% CI = (12.0, 31.0)], and KCE [t = 7.8, df = 30, std = 1.8, p < 0.001, 95% CI = (1.9, 3.2)] were observed. For CGI-I the results showed that the estimated probability of observing a score better than no change (>4) is 0.976 [t.s. = 43.2, p < 0.001, 95% CI = (0.931,0.992)], indicating the average subject is expected to experience some improvement. Discussion: In conclusion, all patients responded to these treatments with improvement in their catatonic symptoms. Alternative pharmacologic interventions for catatonia, including benzodiazepines other than lorazepam, valproic acid, NMDA receptor antagonists, and atypical antipsychotics were safe and effective in treating catatonia in this population.