| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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