Loneliness associates strongly with anxiety and depression during the COVID pandemic, especially in men and younger adults.

Loneliness is associated with major depressive disorder (MDD), and likely also with generalized anxiety disorder (GAD). It is unclear if these associations are moderated by age, sex, or genetic susceptibility for MDD. We included 75,279 individuals from the Lifelines COVID-19 study, a longitudinal study of a Dutch population-based cohort. Participants completed up to sixteen digital questionnaires between March 2020 and January 2021, yielding a total of 616,129 observations. Loneliness was assessed with the Three-Item Loneliness Scale, and MDD and GAD with the Mini-International Neuropsychiatric Interview. We used generalized estimating equations to investigate the association between loneliness and MDD and GAD, and whether this association varied across time, age, sex and MDD polygenic risk. Loneliness was strongly associated with all MDD and GAD outcomes. Individuals with the highest loneliness scores were around 14 times more likely to have MDD, and 11 times more likely to have GAD, compared to individuals who reported the least loneliness. The association between loneliness and MDD symptoms was stronger in men, younger individuals, and increased across time. While MDD polygenic risk predicted MDD and GAD outcomes, we did not find an interaction effect with loneliness. Our study, which is the largest to date, confirms that loneliness is an important risk factor for MDD, GAD, depressive and anxiety symptoms, especially in men and younger individuals. Future studies should investigate the mechanisms of these associations and explore loneliness-based interventions to prevent and treat MDD and GAD.

Symptom networks in major depression do not diverge across sex, familial risk, and environmental risk.

BACKGROUND: Major depression (MD) is a heterogeneous disorder in terms of its symptoms. Symptoms vary by presence of risk factors such as female sex, familial risk, and environmental adversity. However, it is unclear if these factors also influence interactions between symptoms. This study investigates if symptom networks diverge across sex, familial risk, and adversity. METHODS: We included 9713 subjects from the general population who reported a lifetime episode of MD based on DSM-IV criteria. The survey assessed a wide set of symptoms, both from within the DSM criteria as well as other symptoms commonly experienced in MD. We compared symptom endorsement rates across sex, age at onset, family history and environmental adversity. We used the Network Comparison Test to test for symptom network differences across risk factors. RESULTS: We found differences in symptom endorsement between groups. For instance, participants with an early onset of MD reported suicidal ideation nearly twice as often compared to participants with a later onset. We did not find any robust differences in symptom networks, which suggests that symptom networks do not diverge across sex, familial risk, and adversity. LIMITATIONS: We estimated symptom networks of individuals during their worst lifetime episode of MD. Network differences might exist in a prodromal stage, while disappearing in full-blown MD (equifinality). Furthermore, as we used retrospective reports, results could be prone to recall bias. CONCLUSIONS: Despite MD's heterogeneous symptomatology, interactions between symptoms are stable across risk factors and sex.