| 1. |
- 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 severe childhood infections with depression and intentional self-harm in adolescents and young adults
- 2022
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Ingår i: Brain, behavior, and immunity. - : Elsevier. - 0889-1591 .- 1090-2139. ; 99, s. 247-255
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Tidskriftsartikel (refereegranskat)abstract
- Early-life infections have been linked with subsequent depression and self-harm. Examination of specific groups of infections and the role of familial factors may elucidate this observed relationship. We addressed these considerations in our investigations of the association of severe childhood infections with the risks of depression and self-harm in adolescence and early-adulthood. This population-based cohort study included all individuals born in Sweden between 1982 and 1996, with follow-up through 2013 (N = 1,506,070). Severe childhood infections were identified using inpatient and outpatient diagnoses from birth through age 12. Any infection as well as specific groups of infections were investigated. We examined diagnoses of depression and self-harm within inpatient and outpatient care and death by self-harm between ages 13 and 31. Cox proportional hazards regression models were used to estimate absolute risks, hazard ratios (HRs), and 95% CIs. When adjusting for sex and birth year, individuals exposed to any childhood infection demonstrated increased absolute risk differences for both outcomes (2.42% [95% CI, 0.41%-4.43%] of being diagnosed with depression up until age 31, and 0.73% [-2.05%-3.51%] of self-harm up until age 31) and increased relative risks (HR, 1.22 [1.20-1.24] for depression and HR, 1.29 [1.25-1.32] for self-harm). When controlling for unmeasured factors shared between family members by comparing discordant siblings, no strong association persisted. Our findings show that childhood infections may not be involved in the etiology of later depression and self-harm, and highlight the importance of identifying these genetic and environmental familial risk factors, which may serve as targets for interventions.
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| 3. |
- 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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| 4. |
- Leone, Marica
(författare)
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Depression in youth and adults : etiology, outcomes, and comorbidities
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Depression is a common and debilitating mental disorder characterized by low mood, loss of interest in activities, and long-lasting functional impairment. It is a worldwide psychiatric illness with a wide range of ages of onset, and it occurs about twice as often in women than men. However, most large observational studies have focused on adult populations, leaving pediatric depression largely unexplored. Depressive disorder is linked to poorer physical health and increased comorbidity and mortality, particularly by suicide. This mental condition is the result of a complex interaction between environmental, social, genetic, physiological, and psychological influences, with many risk factors and underlying mechanisms still unknown. This thesis leverages epidemiological statistics and the availability of nationwide registers in Sweden to enhance the understanding of depression in children, adolescents, and adults, exploring adverse health outcomes, psychiatric and somatic comorbidities, potential risk factors, and melatonin treatment for sleep disturbances. In Study I, we described the association of pediatric depression with a wide range of subsequent somatic conditions and premature death, while also exploring the potential role of psychiatric comorbidities. Compared to the general population, individuals diagnosed with depression during youth displayed higher risks for 66 of the 69 somatic diagnoses under investigation (including self-harm, endocrine and metabolic disorders, and sleep disturbances), as well as elevated risks for mortality, particularly for death by intentional self-harm. When adjusted for psychiatric comorbidity, associations were attenuated but persisted. This study provides new insights into the relationships between psychiatric and somatic disorders among a young population, increasing awareness about the burden of pediatric depression and providing a foundation for future research. In Study II, we investigated the link between early-life infections and the risks of depression and self-harm during adolescence and early adulthood. Increased risks of the outcomes were observed among individuals exposed to childhood infections, compared to the rest of the population. When adjusting for familial influences, risks were considerably attenuated and no strong association persisted. Our findings show that childhood infections may not be involved in the etiology of later depression and self-harm, and highlight the importance of identifying these genetic and environmental risk factors shared between family members, which represent potential targets for interventions. Study III explored the underlying factors contributing to the comorbidity of depression and endocrine-metabolic disorders. A family design was applied to investigate the familial co-aggregation of these medical conditions, while quantitative genetic modeling was used to quantify the relative contribution of genetic and environmental influences to the familial liability. We found evidence of shared etiology to the co-occurrence of depression and endocrine-metabolic conditions, which was primarily due to genetics for non-autoimmune conditions, and to unique environmental factors for autoimmune disorders, especially for type 1 diabetes. These findings expand current knowledge on the etiological sources of these comorbidities, which could guide future research aiming at identifying underlying pathophysiological mechanisms. In Study IV, we examined whether melatonin use in children and adolescents with sleep disturbances was associated with a reduced risk of self-harm and unintentional injuries. Risks of the outcomes were assessed in periods before and after melatonin-treatment initiation, among youth with and without psychiatric disorders, and across sexes, injury types, psychiatric disorder diagnoses, and age groups. Melatonin-use initiation was associated with reduced risks of self-harm among adolescent females with depression and anxiety disorders, suggesting that sleep interventions may be an important component to reduce risk of self-injurious behavior in this pediatric population. In conclusion, this thesis contributes to the understanding of depression in youth and adults, highlighting its extensive comorbidity and burden of disease, and posing quality-of-life and public health challenges. Our findings underscore an urgent need for screening, prevention, and early intervention of depression, particularly in young patients, as well as for adequate health care resources to treat this mental illness and its psychiatric and somatic comorbidities.
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| 5. |
- 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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| 6. |
- Leone, Marica, et al.
(författare)
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Genetic and Environmental Contribution to the Co-Occurrence of Endocrine-Metabolic Disorders and Depression : A Nationwide Swedish Study of Siblings
- 2022
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Ingår i: American Journal of Psychiatry. - : HighWire Press. - 0002-953X .- 1535-7228. ; 179:11, s. 824-832
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Depression is common in individuals with endocrine-metabolic disorders and vice versa, and a better understanding of the underlying factors contributing to the comorbidity of these disorders is needed. This study investigated the familial coaggregation of depression and endocrine-metabolic disorders and estimated the contribution of genetic and environmental factors to their co-occurrence.METHODS: This population-based cohort study included 2.2 million individuals born in Sweden between 1973 and 1996, with follow-up through 2013. Participants were linked to their biological parents, allowing identification of full siblings, maternal half siblings, and paternal half siblings. Diagnoses of depression and endocrine-metabolic conditions were investigated, with the latter grouped into autoimmune disorders (autoimmune hypothyroidism, Graves' disease, and type 1 diabetes) and non-autoimmune disorders (type 2 diabetes, obesity, and polycystic ovary syndrome). Logistic regression and Cox regression were used to estimate the associations 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 with endocrine-metabolic disorders had a significantly higher risk of depression, with odds ratios ranging from 1.43 (95% CI=1.30, 1.57) for Graves' disease to 3.48 (95% CI=3.25, 3.72) for type 2 diabetes. Increased risks extended to full and half siblings. These correlations were mainly explained by shared genetic influences for non-autoimmune conditions, and by nonshared environmental factors for autoimmune disorders, especially for type 1 diabetes.CONCLUSIONS: These findings provide phenotypic and etiological insights into the co-occurrence of depression and various endocrine-metabolic conditions, which could guide future research aiming at identifying pathophysiological mechanisms and intervention targets.
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| 7. |
- Leone, Marica, et al.
(författare)
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MELATONIN USE AND THE RISK OF SELF-HARM AND UNINTENTIONAL INJURIES IN YOUTHS
- 2022
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Ingår i: European Neuropsychopharmacology. - : Elsevier. - 0924-977X .- 1873-7862. ; 63, s. E113-E113
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is themost common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.Methods: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin-treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, in-jury type, psychiatric comorbidities, and age at melatonin-treatment initiation.Results: While body injuries, falls, and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-injurious behavior was highest in the months immediately prior medication and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.Discussion: Decreased risk of intentional injury was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-injurious behavior in this population.
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| 8. |
- Leone, Marica, et al.
(författare)
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Melatonin use and the risk of self-harm and unintentional injuries in youths with and without psychiatric disorders
- 2023
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Ingår i: Journal of Child Psychology and Psychiatry. - : John Wiley & Sons. - 0021-9630 .- 1469-7610. ; 64:7, s. 1027-1036
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Sleep disorders in youth have been associated with increased risks of injury, including suicidal behavior. This study investigated whether melatonin, which is the most common medication for sleep disturbances in youth in Sweden, is associated with a decreased risk of injury.METHODS: This population-based cohort study included 25,575 youths who initiated melatonin treatment between ages 6 and 18. Poisson regression was used to estimate rate of injuries in the year prior to and following melatonin treatment initiation. A within-individual design was used to estimate relative risks by comparing injury risk in the last unmedicated month with injury risks in the 12 months after medication initiation. Analyses were stratified by sex, injury type, psychiatric comorbidities and age at melatonin-treatment initiation.RESULTS: While body injuries, falls and transport accident rates were comparable in the year before and after melatonin-treatment initiation, the risk of self-harm was highest in the months immediately prior to medication, and decreased thereafter. This was particularly prominent among adolescents with depression and/or anxiety, with females displaying greater absolute risks than males. Compared to the last unmedicated month, the 12 months post medication initiation had decreased relative risks for self-harm, with an IRR [95% CI] in the month following melatonin-treatment initiation of 0.46 [0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.CONCLUSIONS: Decreased risk of intentional self-harm was observed following melatonin-treatment initiation among females with depression and anxiety, suggesting that sleep interventions could be considered in an effort to reduce risk of self-harm in this population.
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| 9. |
- Liu, Shengxin, et al.
(författare)
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Early-Onset Type 2 Diabetes and Mood, Anxiety, and Stress-Related Disorders: A Genetically Informative Register-Based Cohort Study.
- 2022
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:12, s. 2950-2956
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Tidskriftsartikel (refereegranskat)abstract
- To assess the association and familial coaggregation between early-onset type 2 diabetes (diagnosed before age 45 years) and mood, anxiety, and stress-related disorders and estimate the contribution of genetic and environmental factors to their co-occurrence.This population-based cohort study included individuals born in Sweden during 1968-1998, from whom pairs of full siblings, half-siblings, and cousins were identified. Information on diagnoses of early-onset type 2 diabetes and mood (including unipolar depression and bipolar disorder), anxiety, and stress-related disorders was obtained from the National Patient Register. Logistic and Cox regression models were used to assess the phenotypic association and familial coaggregation between type 2 diabetes and psychiatric disorders. Quantitative genetic modeling was conducted in full and maternal half-sibling pairs to estimate the relative contributions of genetic and environmental factors to the association.Among a total of 3,061,192 individuals, 7,896 (0.3%) were diagnosed with early-onset type 2 diabetes. These individuals had higher risks of any diagnosis (odds ratio [OR] 3.62 [95% CI 3.44, 3.80]) and specific diagnosis of unipolar depression (3.97 [3.75, 4.22]), bipolar disorder (4.17 [3.68, 4.73]), anxiety (3.76 [3.54, 3.99]), and stress-related disorders (3.35 [3.11, 3.61]). Relatives of individuals with early-onset type 2 diabetes also had higher overall risks of the examined psychiatric disorders (ORs 1.03-1.57). These associations are largely explained by genetic factors (51-78%), with the rest explained by nonshared environmental factors.Our findings highlight the burden of mood, anxiety, and stress-related disorders in early-onset type 2 diabetes and demonstrate that shared familial liability may contribute to their co-occurrence, suggesting that in the future research investigators should aim to identify shared risk factors and ultimately refine preventive and intervention strategies.
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