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Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.
Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.
In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.
This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.
Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifespan, we aimed to identify the SDoH that was most strongly related to newly diagnosed MDD in a cohort of older adults.
We used self-reported health-related survey data from 41 174 older adults (50–89 years, median age = 67 years) who participated in the Mayo Clinic Biobank, and linked ICD codes for MDD in the participants' electronic health records. Participants with a history of clinically documented or self-reported MDD prior to survey completion were excluded from analysis (N = 10 938, 27%). We used Cox proportional hazards models with a gradient boosting machine approach to quantify the RI of 30 pre-selected SDoH variables on the risk of future MDD diagnosis.
Following biobank enrollment, 2073 older participants were diagnosed with MDD during the follow-up period (median duration = 6.7 years). The most influential SDoH was perceived level of social activity (RI = 0.17). Lower level of social activity was associated with a higher risk of MDD [hazard ratio = 2.27 (95% CI 2.00–2.50) for highest v. lowest level].
Across a range of SDoH variables, perceived level of social activity is most strongly related to MDD in older adults. Monitoring changes in the level of social activity may help identify older adults at an increased risk of MDD.
Anxiety is a common human emotion and is experienced by all people at some point in life. It is characterized by a state of apprehension about a perceived threat or potentially dangerous situation. In addition, fear is a negative emotion caused by the belief that someone or something is dangerous, likely to cause pain, or a threat. At mild to moderate levels, anxiety can be adaptive, motivating, and can help improve performance and attention. For example, prior to a significant life event such as an important test or presentation, some individuals may experience anxiety, which could serve as a motivator to work harder and perform better. Similarly, fear can be an adaptive response when one is confronted with a life-threatening situation, and a fight or flight response to danger is present and adaptive across many animal species. However, for some, anxiety or fear may be overwhelming, distressing, and interfere with functioning. This may require a person to seek treatment depending on the level of interference and could also result in the development of a psychiatric condition.
Adding to the resilience model of Kalisch and colleagues, we suggest that resilience is associated with accurate rather than excessively positive or negative appraisal or reappraisal styles; that complex systems do not always change in linear fashion; that linkages of individuals, families, and communities markedly affect individual resilience; and that resilience research focus on specific factors or mechanisms as well as more global ones.
The aim of this meeting was to obtain a consensus on what constitutes good research practice in posttraumatic stress disorder (PTSD). Objectives were to review relevant parameters of trials, such as the patients recruited, the means of assessing PTSD at baseline, and the change in symptomatology in response to treatment, and to reach a consensus on the most appropriate parameters to use in future research. The bases for the discussion were the 1995 National Institute of Mental Health (NIMH) and the National Center for PTSD consensus on the assessment of PTSD, results of drug treatment trials, and information on the assessment scales used in PTSD research.