Depressive and attentional symptoms in narcolepsy: findings from patients, first-degree relatives, and controls

Brief introduction : Narcolepsy is increasingly recognized as a condition associated with substantial neuropsychiatric burden. Depression and attentional difficulties are common in narcolepsy. In family members of individuals with narcolepsy, distinguishing symptoms reflecting underlying vulnerability from those secondary to sleep-related factors is particularly important, as frequent sleep disturbance and daytime sleepiness may confound self-reported depressive and attentional symptoms. Accordingly, Family-based comparisons provide a useful background for evaluating whether psychological symptoms persist beyond the effects of sleep disturbance. If depressive symptoms reflect shared vulnerability, they would be expected to remain elevated in first-degree relatives even after adjustment for sleep-related factors. Conversely, symptoms that are primarily secondary to sleep disruption would be expected to attenuate after such adjustment.

Aim of the study: This study examined depressive symptoms and ADHD-related traits in patients with narcolepsy and their first-degree relatives, assessed persistence of group differences after adjustment for sleep-related factors, and compared findings between narcolepsy type 1 and type 2

Methods: Participants were recruited from the sleep clinic at St. Vincent’s Hospital and its affiliated medical centers. Diagnostic evaluation of narcolepsy included clinical assessment, overnight polysomnography (PSG), and a Multiple Sleep Latency Test (MSLT). Healthy controls were recruited from the community through advertisements. A cross-sectional study was conducted with 613 participants: narcolepsy patients (N=253), first-degree relatives (N=156), and healthy controls (N=204). We assessed symptoms using the Beck Depression Inventory-II (BDI-II), Adult ADHD Self-Report Scale (ASRS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). Group differences in demographic and clinical characteristics were examined using one-way ANOVA or Chi-square tests. To evaluate the independent effects of group status on depressive and attentional symptoms, analysis of covariance (ANCOVA) was conducted adjusting for age, sex, body mass index, sleep quality (PSQI), and excessive daytime sleepiness (ESS).

Summary of results: Patients were younger on average and exhibited significantly higher BMI, poorer sleep quality, and greater daytime sleepiness than controls. First-degree relatives demonstrated intermediate levels of sleep disturbance. Patients exhibited high unadjusted depression (mean 27.51) and attentional symptoms (mean 11.47). Although narcolepsy type 1 (NT1) is characterized by orexin deficiency, there were no significant differences between narcolepsy type 1 (NT1) and narcolepsy type 2 (NT2) in terms of depressive symptoms (BDI-II: 27.17±16.47vs. 27.94±16.86, p=0.704), sleep quality (PSQI, p=0.342), or inattention (ASRS, p=0.240). After covariate adjustment, group status remained strongly associated with BDI-II total score (F=25.03, p<.001); both patients and relatives showed higher depression than controls. Specifically, affective–cognitive BDI-II items remained elevated. In contrast, the group effect on ASRS after adjustment was no longer significant (F=1.45, p=.236).

Conclusions: Depressive symptoms remained elevated in patients and first-degree relatives after adjusting for sleep quality and sleepiness, suggesting a shared familial vulnerability. Conversely, ADHD-like complaints were largely explained by sleep quality and excessive daytime sleepiness, suggesting they are state-dependent.

References

1. Rauf R, Asif S, AlSaafeen A, Dhantapaani KG, Nadeem MM, Rao ZK, et al. Orexin Deficiency in Narcolepsy: Molecular Mechanisms, Clinical Phenotypes, and Emerging Therapeutic Frontiers. Brain Behav. 2025;15(10):e70984.