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Kelli Lehto

Publications and source records attributed to Kelli Lehto.

3 recordsLinked to original sources

Acute COVID-19 severity and impaired cognitive function up to 32 months after diagnosis: an observational study.

BACKGROUND: Cognitive dysfunction ("brain fog") is a commonly reported post-COVID-19 symptom. Leveraging data from five general population cohorts across four European countries (Estonia, Iceland, Norway, and Sweden), we assessed long-term prevalence of impaired subjective cognitive function among individuals diagnosed with COVID-19 by acute illness severity. METHODS: The included cohorts consisted of adult participants recruited from March 2020 and followed with self-report measures of cognitive function and past COVID-19 infection (except one cohort consisting of clinically confirmed COVID-19 cases) through February 2023. In a cross-sectional analysis we contrasted the prevalence of impaired cognitive function among individuals with and without a COVID-19 diagnosis, overall and by illness severity up to 32&#xa0;months post-diagnosis. We adjusted for age, gender, education, relationship status, binge drinking, body mass index, previous psychiatric diagnosis, number of chronic medical conditions, and response period. In a longitudinal analysis, we assessed potential changes in cognitive function scores before and after COVID-19 diagnosis. RESULTS: The study population consisted of 153,841 participants (71% women), with 31,359 (20.4%) reporting a positive COVID-19 test. Overall, a COVID-19 diagnosis was not statistically significantly associated with increased prevalence ratio (PR) of impaired cognitive function (PR 1.30 [95% CI: 0.98-1.71]). Individuals bedridden due to COVID-19 for 1-6&#xa0;days (PR 1.38 [95% CI 0.96-1.99]) or&#x2009;&#x2265;&#x2009;7&#xa0;days (2.59 [1.55-4.33]) had higher prevalence of impaired cognitive function compared to those never diagnosed, while individuals never bedridden had a lower prevalence to those never diagnosed with COVID-19 (0.89 [0.80-1.00]). These findings were corroborated in the longitudinal analysis where a pre- to post diagnosis decline in cognitive function was observed among individuals bedridden due to COVID-19 (p&#x2009;<&#x2009;0.0001). CONCLUSIONS: The data indicates that a severe COVID-19 acute illness course is associated with impaired cognitive function up to 18-32&#xa0;months after COVID-19 diagnosis.

Adult

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article

Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases.

IMPORTANCE: Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE: Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS: Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES: Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS: The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE: Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Journal Article