👤 Cristina L Ronchi

Suicidal ideation is prevalent among university students and is associated with a complex interplay of psychological, interpersonal, and behavioral factors. While prior research has examined individual predictors such as sleep disturbances, depressive symptoms, and impulsivity, less is known about how these factors co-occur in clinically distinct profiles. This study aimed to identify latent profiles of suicide risk using a multidimensional model.We conducted a secondary data analysis using the Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide (ANSWERS) dataset, which includes self-reported data from 971 U.S. university students aged 18 to 52 years (M = 20.10, SD = 2.41). Seven continuous variables were included as indicators: sleep quality (PSQI), insomnia severity (ISI), depressive symptoms (CES-D), suicidal ideation severity (C-SSRS), thwarted belongingness and perceived burdensomeness (INQ), and total impulsivity (UPPS-P). Latent Profile Analysis (LPA) was employed to identify subgroups, and model fit was assessed using the AIC, BIC, and entropy.Latent Profile Analysis identified five distinct profiles based on indicators of sleep, affect, interpersonal behavior, and impulsivity. These included a severely distressed profile characterized by elevated depressive symptoms, suicidal ideation, sleep disturbances, and interpersonal burden; an interpersonally burdened profile with mild affective symptoms; a moderately symptomatic profile; a psychologically resilient profile with minimal symptoms across domains; and a high impulsivity profile accompanied by emotional dysregulation.This study identified five clinically distinct profiles of suicide risk in a large sample of university students. These results may inform the development of tailored screening and intervention strategies in campus-based mental health settings. Show less

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing's syndrome. Individuals with PBMAH and glucose-dependent insulinotropic polypeptide (GIP)-dependent Cushing's syndrome due to ectopic expression of the GIP receptor (GIPR) typically harbor inactivating KDM1A sequence variants. Primary unilateral macronodular adrenal hyperplasia (PUMAH) with concomitant glucocorticoid and androgen excess has never been encountered or studied. We investigated a woman with a large, heterogeneous adrenal mass and severe adrenocorticotropic hormone-independent glucocorticoid and androgen excess, a biochemical presentation typically suggestive of adrenocortical carcinoma. The patient presented during pregnancy (22nd week of gestation) and reported an 18-month history of oligomenorrhea, hirsutism, and weight gain. We undertook an exploratory study with detailed histopathological and genetic analysis of the resected adrenal mass and leukocyte DNA collected from the patient and her parents. Histopathology revealed benign macronodular adrenal hyperplasia. Imaging showed a persistently normal contralateral adrenal gland. Whole-exome sequencing of 4 representative nodules detected KDM1A germline variants, benign NM₀₀₁₀₀₉₉₉₉.3:c.136G > A:p.G46S, and likely pathogenic NM₀₀₁₀₀₉₉₉₉.3:exon6:c.865₈₆₆del:p.R289Dfs*7. Copy number variation analysis demonstrated an additional somatic loss of the KDM1A wild-type allele on chromosome 1p36.12 in all nodules. RNA sequencing of a representative nodule showed low/absent KDM1A expression and increased GIPR expression compared with 52 unilateral sporadic adenomas and 4 normal adrenal glands. Luteinizing hormone/chorionic gonadotropin receptor expression was normal. Sanger sequencing confirmed heterozygous KDM1A variants in both parents (father: p.R289Dfs*7 and mother: p.G46S) who showed no clinical features suggestive of glucocorticoid or androgen excess. We investigated the first PUMAH associated with severe Cushing's syndrome and concomitant androgen excess, suggesting pathogenic mechanisms involving KDM1A. Show less

Previous SNP array analyses have revealed genomic alterations of the Notch pathway as being the most frequent abnormality in adrenocortical tumors (ACTs). The aim of the present study was to evaluate the expression of components of Notch signaling in ACTs and to correlate them with clinical outcome. The mRNA expression of JAG1, NOTCH1, and selected target genes of NOTCH1 (HES1, HES5, and HEY2) was evaluated in 80 fresh frozen samples (28 normal adrenal glands (NAGs), 24 adenomas (ACAs), and 28 carcinomas (ACCs)) by quantitative RT-PCR. Immunohistochemistry was performed in 221 tissues on paraffin slides (16 NAGs, 27 ACAs, and 178 ACCs) for JAG1, activated NOTCH1 (aNOTCH1), and HEY2. An independent ACC validation cohort (n=77) was then also investigated. HEY2 mRNA expression was higher in ACCs than it was in ACAs (P<0.05). The protein expression of all of the factors was high (H-score 2-3) in a larger proportion of ACCs as compared to ACAs and NAGs (JAG1 in 27, 15, and 10%; aNOTCH1 in 13, 8, and 0%; HEY2 in 66, 61, and 33% respectively, all P<0.001). High JAG1 expression was associated with earlier tumor stages and lower numbers of metastases in ACCs (both P=0.08) and favorably impacted overall and progression-free survival (PFS) (131 vs 30 months, hazard ratio (HR) 0.45, and 37 vs 9 months, HR 0.51, both P<0.005). This impact on overall survival (OS) was confirmed in the validation cohort. No such association was observed for aNOTCH1 or HEY2. In conclusion, different components of the Notch1 signaling pathway are overexpressed in ACCs, which suggests a role for the pathway in malignant transformation. However, JAG1 is overexpressed in a subgroup of ACCs with a better clinical outcome. Show less