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- Du Rietz, Ebba, et al.
(författare)
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Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden : a genetically informed register study
- 2021
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Ingår i: Lancet psychiatry. - : Elsevier. - 2215-0374 .- 2215-0366. ; 8:9, s. 774-783
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.METHODS: We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973-2013) and outpatient (recorded 2001-13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.FINDINGS: 4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18-81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50-4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42-3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60-69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.INTERPRETATION: This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.FUNDING: Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.
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| 2. |
- Leone, Marica, et al.
(författare)
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Association of Youth Depression With Subsequent Somatic Diseases and Premature Death
- 2021
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Ingår i: JAMA psychiatry. - : American Medical Association. - 2168-6238 .- 2168-622X. ; 78:3, s. 302-310
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Early-onset depression has been linked to poor health outcomes. However, it is unclear the extent to which this disorder is associated with specific diseases and premature death and whether these associations remain after controlling for psychiatric comorbidity.Objective: To quantify the association of youth depression with subsequent diagnoses of numerous somatic diseases and mortality.Design, Setting, and Participants: A population-based cohort study was conducted using Swedish national registers containing data on all individuals born in Sweden between 1982 and 1996. A total of 1 487 964 participants were followed up from age 5 years through 2013 if no censoring occurred. Data analysis was performed from January 15, 2019, to August 10, 2020.Exposures: Youth depression was defined as having received at least 1 diagnosis of depression from inpatient or outpatient care between ages 5 and 19 years.Main Outcomes and Measures: This study examined 69 somatic conditions diagnosed after youth depression, as well as all-cause and cause-specific mortalities. Overall and sex-specific hazard ratios (HRs), together with 95% CIs, were estimated using Cox proportional hazards regression with attained age as underlying timescale and time-varying exposure, and adjusted for birth year and sex. All analyses were repeated controlling for psychiatric comorbidities. Absolute risk differences were calculated using standardization with Cox proportional hazards regression.Results: Of 1 487 964 individuals included in the analysis, 51.2% were male. A total of 37 185 patients (2.5%; 67.4% female) had an inpatient or outpatient contact for depression between ages 5 and 19 years (mean [SD] age at first recorded diagnosis of depression, 16.7 [2.1] years for males and 16.7 [1.8] years for females). Age at the end of follow-up ranged between 17 and 31 years. Individuals with youth depression had higher relative risks for 66 of the 69 somatic diagnoses. Strong associations were observed for certain injuries, especially self-harm in females (HR, 14.4; 95% CI, 13.8-15.1), sleep disorders (HR, 8.1; 95% CI, 7.6-8.7), viral hepatitis (HR, 6.1; 95% CI, 5.4-6.8), all-cause mortality (HR, 5.9; 95% CI, 5.3-6.6), and cause-specific mortalities, especially death by intentional self-harm (HR, 14.6; 95% CI, 12.6-16.9). Most associations were attenuated but persisted after adjusting for psychiatric comorbidity. The absolute risk difference of a specific disease within 12 years from the first diagnosis of depression during youth ranged from -0.2% (95% CI, -1.0% to 0.6%) for arthropathies among males to 23.9% (95% CI, 22.7%-25.0%) for the broader category of injuries among females.Conclusions and Relevance: In this Swedish population cohort study, patients with depression diagnosed during their youth appeared to have increased risks for many somatic diseases as well as for mortality, even after controlling for other psychiatric disorders. These findings suggest that several medical conditions should be considered when investigating youth depression.
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| 3. |
- Leone, Marica, et al.
(författare)
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FAMILIAL LIABILITY FOR ENDOCRINE-METABOLIC DISORDERS AND DEPRESSION
- 2021
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 51, s. e112-e112
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Endocrine-metabolic disorders are common in individuals with depression. Better understanding of the underlying factors contributing to their concomitant occurrence is needed. This study investigates the familial co-aggregation of depression and endocrine-metabolic disorders and estimates the contribution of genetic and environmental risk factors to their co-occurrence.Methods: We conducted a population-based cohort study using Swedish national data. A total of 2,263,311 individuals born between 1973 and 1996 were included and followed up until death, emigration, or December 31, 2013, whichever occurred first. Each participant was linked to their biological parents, allowing identification of full-, maternal half-, and paternal half-siblings. We investigated clinical diagnoses of depression and endocrine-metabolic disorders diagnosed at any point during the follow-up period, grouping the latter into autoimmune disorders (i.e., hypothyroidism, Graves’ disease, and type 1 diabetes) and non-autoimmune disorders (i.e., type 2 diabetes, obesity, and polycystic ovarian syndrome). Logistic regression and Cox proportional hazards regression were used to estimate the association between endocrine-metabolic disorders and depression within the same individual and across siblings. Quantitative genetic modeling was performed to investigate the relative contribution of genetic and environmental influences.Results: Individuals diagnosed with endocrine-metabolic disorders had significantly higher risk of depression, with odds ratios ranging from 1.43 [95% CI, 1.30-1.57] for Graves’ disease to 2.44 [2.37-2.50] for obesity. Overall, increased risks extended to full- and half-siblings. Quantitative genetic modeling showed that shared genetic factors explained the phenotypic correlations between endocrine-metabolic disorders and depression to different extents (ranging from 36% for autoimmune hypothyroidism, to 74% for obesity), except for type 1 diabetes, for which the association was mainly explained by non-shared environmental factors (84%).Discussion: Endocrine-metabolic disorders and depression co-occur in individuals and display familial co-aggregation. Shared genetic risk factors explained much of this relationship, but unique environmental influences also contributed significantly. These findings expand the current knowledge of the etiological sources of comorbidity between somatic and psychiatric disorders, which could guide future research aiming at identifying the pathophysiological mechanisms and potentially intervention targets.
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