Plasma neurofilament light chain is not elevated in people with first-episode psychosis or those at ultra-high risk for psychosis.

INTRODUCTION: Neurofilament light chain (NfL), a blood biomarker of neuronal injury, shows promise in distinguishing neurodegenerative disorders from psychiatric conditions. This is especially relevant in psychosis, given neurological conditions such as autoimmune encephalitis and Niemann Pick Type C disease (NPC) may initially present with psychotic symptoms. Whilst NfL levels have been studied in established schizophrenia cases, their levels in first-episode psychosis (FEP) and ultra-high risk (UHR) for psychosis individuals remain largely unexplored. This study aimed to compare plasma NfL in people with FEP or UHR with healthy controls, as well as explore its associations with clinical data. METHOD: We retrospectively analysed plasma NfL in 63 participants, consisting of 29 individuals with FEP, 10 individuals with UHR, and 24 healthy controls. We used general linear models (GLM), which were bootstrapped, to compute bias-corrected and accelerated (BCa) 95 % confidence intervals (CIs). RESULTS: Mean NfL levels were 5.2 pg/mL in FEP, 4.9 pg/mL in UHR, and 5.9 pg/mL in healthy controls. Compared to healthy controls, there were no significant differences in NfL levels in the FEP group (ß = -0.22, 95 % CI [-0.86, 0.39], p = 0.516) nor UHR group (ß = -0.37, 95 % CI [-0.90, 0.19], p = 0.182). There were no significant associations between NfL levels and clinical variables in the FEP group. DISCUSSION: Our study is the first to demonstrate that plasma NfL levels are not significantly elevated in individuals at UHR for psychosis compared to healthy controls, a finding also observed in the FEP cohort. These findings bolster the potential diagnostic utility of NfL in differentiating between psychiatric and neurodegenerative disorders.

Cerebrospinal fluid neurofilament light predicts longitudinal diagnostic change in patients with psychiatric and neurodegenerative disorders.

OBJECTIVE: People with neuropsychiatric symptoms often experience delay in accurate diagnosis. Although cerebrospinal fluid neurofilament light (CSF NfL) shows promise in distinguishing neurodegenerative disorders (ND) from psychiatric disorders (PSY), its accuracy in a diagnostically challenging cohort longitudinally is unknown. METHODS: We collected longitudinal diagnostic information (mean = 36 months) from patients assessed at a neuropsychiatry service, categorising diagnoses as ND/mild cognitive impairment/other neurological disorders (ND/MCI/other) and PSY. We pre-specified NfL > 582 pg/mL as indicative of ND/MCI/other. RESULTS: Diagnostic category changed from initial to final diagnosis for 23% (49/212) of patients. NfL predicted the final diagnostic category for 92% (22/24) of these and predicted final diagnostic category overall (ND/MCI/other vs. PSY) in 88% (187/212), compared to 77% (163/212) with clinical assessment alone. CONCLUSIONS: CSF NfL improved diagnostic accuracy, with potential to have led to earlier, accurate diagnosis in a real-world setting using a pre-specified cut-off, adding weight to translation of NfL into clinical practice.

Carer burden and behavioral disturbance is similar between younger-onset Alzheimer's disease and behavioral variant frontotemporal dementia.

OBJECTIVES: Carer burden is common in younger-onset dementia (YOD), often due to the difficulty of navigating services often designed for older people with dementia. Compared to Alzheimer's disease (AD), the burden is reported to be higher in behavioral variant frontotemporal dementia (bvFTD). However, there is little literature comparing carer burden specifically in YOD. This study hypothesized that carer burden in bvFTD would be higher than in AD. DESIGN: Retrospective cross-sectional study. SETTING: Tertiary neuropsychiatry service in Victoria, Australia. PARTICIPANTS: Patient-carer dyads with YOD. MEASUREMENTS: We collected patient data, including behaviors using the Cambridge Behavioral Inventory-Revised (CBI-R). Carer burden was rated using the Zarit Burden Inventory-short version (ZBI-12). Descriptive statistics and Mann-Whitney U tests were used to analyze the data. RESULTS: Carers reported high burden (ZBI-12 mean score = 17.2, SD = 10.5), with no significant difference in burden between younger-onset AD and bvFTD. CBI-R stereotypic and motor behaviors, CBI-R everyday skills, and total NUCOG scores differed between the two groups. There was no significant difference in the rest of the CBI-R subcategories, including the behavior-related domains. CONCLUSION: Carers of YOD face high burden and are managing significant challenging behaviors. We found no difference in carer burden between younger-onset AD and bvFTD. This could be due to similarities in the two subtypes in terms of abnormal behavior, motivation, and self-care as measured on CBI-R, contrary to previous literature. Clinicians should screen for carer burden and associated factors including behavioral symptoms in YOD syndromes, as they may contribute to carer burden regardless of the type.

Clinical, psychological and demographic factors in a contemporary adult cohort with diabetic ketoacidosis and type 1 diabetes.

BACKGROUND: Diabetic ketoacidosis (DKA) is a potentially life-threatening but often preventable acute complication of type 1 diabetes (T1D). Understanding clinical and psychosocial characteristics of people with DKA, particularly those with multiple presentations, may aid the development of prevention strategies. AIMS: To describe clinical, psychological and demographic factors in adults with DKA and particularly those factors associated with recurrent admissions. METHODS: A retrospective analysis was performed of all admissions with DKA in people with T1D over a 4-year period from 1 November 2013 to 31 October 2017 at a metropolitan tertiary hospital in Australia. Potential cases were identified by International Classification of Diseases-10th Revision coding data. Data were then manually extracted by clinicians from the electronic medical record. RESULTS: There were 154 clinician-adjudicated admissions for DKA among 128 people with T1D. Of these, 16 (13%) had multiple DKA admissions. Forty-one (32%) had a history of depression. The most common factors contributing to presentation included insulin omission (54%), infection (31%), alcohol excess (26%) and new diabetes diagnosis (16%). Compared to people with single admissions, those with recurrent DKA were more likely to smoke (69% vs 27%, P = 0.003), be unemployed (31% vs 11%, P = 0.04) and use illicit substances (44% vs 17%, P = 0.02). CONCLUSIONS: There is a high prevalence of psychiatric illness, illicit substance use and social disadvantage among people admitted with DKA, particularly those with recurrent presentations. Insulin omission, often due to inappropriate sick day management, was the most common reason for DKA occurrence. Innovative multidisciplinary models of care are required to address these challenges.