European Archives of Psychiatry and Clinical Neuroscience最新文献

Background: Sleep traits have been linked to cognitive aging, but observational associations are susceptible to confounding and reverse causation. Using genetically informed polygenic risk scores (PRSs), this study examined associations between genetic liability to sleep traits and cognitive function in an East Asian population. We further assessed whether educational attainment, as a marker of cognitive reserve, modifies these associations.

Methods: Participants aged ≥ 60 years from the Taiwan Biobank underwent cognitive assessment using the Mini-Mental State Examination (MMSE) at baseline (n = 27,343) and follow-up (n = 6,273; mean follow-up = 3.9 years). PRSs for chronotype, sleep duration, long sleep, short sleep, insomnia, and daytime napping were constructed. Associations with baseline MMSE and longitudinal MMSE change were evaluated, and PRS × education interactions were tested.

Results: Higher PRSs for early chronotype, longer sleep duration, and long sleep (> 8 h) were associated with lower baseline MMSE scores (β range per SD increase: -0.05 to - 0.03), but were not associated with MMSE change over follow-up. A significant interaction was observed between long-sleep PRS and education for MMSE change (p for interaction = 0.0008), with greater decline among individuals with lower educational attainment. In contrast, no association was observed in higher-education groups.

Conclusions: Genetic liability to early chronotype and long sleep duration is associated with lower late-life cognitive performance, primarily reflecting differences in baseline cognitive status rather than short-term cognitive decline. Higher educational attainment may mitigate cognitive vulnerability associated with genetic predisposition to long sleep, consistent with a cognitive-reserve framework.

Purpose: Childhood-onset asthma is associated with an increased risk of severe mental illnesses later in life. However, the causal relationship between childhood-onset asthma and major mental disorders remains unclear.

Methods: A two-sample Mendelian randomization (MR) analysis was conducted to investigate the causal effects of childhood-onset asthma (n = 327,670) on six major mental illnesses, including major depressive disorder (n = 143,265), bipolar disorder (n = 353,899), schizophrenia (n = 130,644), anxiety (n = 10,240), autism (n = 46,350), and ADHD (n = 225,534), using summary statistics of genome-wide association studies (GWAS). The inverse variance weighted (IVW) method, along with the weighted median and the MR-Egger method, was employed to obtain causal estimates. Multiple sensitivity analyses were conducted to examine the robustness of the estimates. Additionally, the direct effects of childhood-onset asthma on mental disorders after accounting for the effects of adult-onset asthma were evaluated through the multivariable MR (MVMR) analysis. To eliminate potential reverse causality, a reverse MR analysis was conducted, treating mental disorders as the exposure and childhood-onset asthma as the outcome.

Results: Genetically determined, childhood-onset asthma was significantly associated with an increased risk of depression (IVW OR = 1.059, 95% CI: 1.025-1.095, p = 5.72e-04) and bipolar disorder (IVW OR = 1.065, 95% CI: 1.027- 0.105, p = 6.75e-04). However, it was not associated with other mental disorders. Further MVMR analysis indicated that the causal relationships remained significant after accounting for adult-onset asthma. Interestingly, childhood- and adult-onset asthma exerted distinct causal effects on depression and bipolar disorder. Reverse MR analysis revealed no causal relationships between the six assessed mental disorders and either childhood-onset asthma or the age of asthma onset.

Conclusions: The MR analysis revealed a significant causal relationship between genetically determined, childhood-onset asthma and an elevated risk of depression and bipolar disorder later in life. The causal effects of childhood-onset asthma were distinct from those of adult-onset asthma. Further studies are warranted to investigate the underlying mechanisms of these causal relationships.

Previous observational studies showed associations between obstructive sleep apnea (OSA) and depression and other negative moods. However, the causality has not been determined. Single nucleotide polymorphisms were identified as instrumental variables by screening from genome-wide association studies. Bidirectional two-sample mendelian randomization (MR) was applied to assess the potential causal relationship between OSA and depression, subjective well-being, negative moods. Inverse variance weighting (IVW) method and weight median were chosen as the main methods to estimate possible causal effects. MR-Egger, MR pleiotropy residual sum and outlier and leave-one-out analysis methods, were used as sensitivity analysis methods to ensure robust results. MR analyses indicated significantly causal association of OSA on depression (OR = 1.22, P = .010) and major depressive disorder (OR = 1.02, P = .006). Furthermore, genetically predicted OSA was negatively associated with subjective well-being (β_IVW = -0.06, P = .009), and was positively associated with negative moods including depressed affect (OR = 1.04, P = .012), irritable mood (P = .006), feeling lonely (P = .011), feeling fed-up (P = .005) and mood swings (P = .017). There is no reverse effect of the above psychiatric traits on OSA. Genetic predisposition to OSA causally increased depression and major depressive disorder. Consistently, OSA has causal impacts on both subjective well-being, representing positive emotions, and negative moods.

Data on the comparative usefulness of medications commonly prescribed to individuals with alcohol use disorder (AUD) are scarce. This study compared the association between antidepressants, relapse-preventive AUD medication, both, and neither on the risk of subsequent alcohol-related hospitalization in individuals with severe AUD. This retrospective analysis of Swedish nationwide register data used Cox (primary analysis) and logistic (sensitivity analysis) regression models to assess the associations between medication exposure (antidepressants, AUD medication, both, neither) and risk of subsequent alcohol-related hospitalization. The analysis included data on 14,026 individuals who were admitted to the hospital for severe AUD between 2009 and 2020. Antidepressants were not significantly associated with a lower risk of subsequent alcohol-related hospitalization (hazard ratio [HR] = 0.94, 95% confidence interval [CI] = 0.82-1.08), but AUD medication was (HR = 0.61, 95% CI = 0.54-0.69), as were antidepressants plus AUD medication (HR = 0.63, 95% CI = 0.45-0.87) (reference: exposure to neither). Pairwise comparisons showed that AUD medication was associated with a lower risk of hospitalization than antidepressants (HR = 0.65, 95% CI = 0.54-0.78). Antidepressants alone were associated with a higher risk than antidepressants plus AUD medication (HR = 1.50, 95% CI = 1.05-2.15). The sensitivity analysis confirmed the association between AUD medication and lower hospitalization risk. Antidepressant monotherapy was not associated with a lower risk of subsequent alcohol-related hospitalization, but relapse-preventive medication for AUD was, both alone and in combination with antidepressants. These findings support the use of relapse-preventive medication to reduce hospitalization risk in individuals with severe AUD and raise questions about the benefit of antidepressant monotherapy for this purpose.