Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders.

Importance: Biomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent. Objective: To examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders. Design, Setting, and Participants: This population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023. Exposures: Lipid, apolipoprotein, and carbohydrate biomarkers measured in blood. Main Outcomes and Measures: The associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls. Results: A total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants. Conclusions and Relevance: In this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

Lifestyle and medical conditions in relation to ALS risk and progression-an introduction to the Swedish ALSrisc Study.

BACKGROUND: This study was an introduction to the Swedish ALSrisc Study and explored the association of lifestyle and medical conditions, with risk and progression of amyotrophic lateral sclerosis (ALS). METHODS: We included 265 newly diagnosed ALS patients during 2016-2022 in Stockholm and 207 ALS-free siblings and partners of the patients as controls. Information on body mass index (BMI), smoking, and history of head injuries, diabetes mellitus, hypercholesterolemia, and hypertension was obtained through the Euro-MOTOR questionnaire at recruitment. Patients were followed from diagnosis until death, invasive ventilation, or November 30, 2022. RESULTS: Higher BMI at recruitment was associated with lower risk for ALS (OR 0.89, 95%CI 0.83-0.95), especially among those diagnosed after 65 years. One unit increase in the average BMI during the 3 decades before diagnosis was associated with a lower risk for ALS (OR 0.94, 95%CI 0.89-0.99). Diabetes was associated with lower risk of ALS (OR 0.38, 95%CI 0.16-0.90), while hypercholesterolemia was associated with higher risk of ALS (OR 2.10, 95%CI 1.13-3.90). Higher BMI at diagnosis was associated with lower risk of death (HR 0.91, 95%CI 0.84-0.98), while the highest level of smoking exposure (in pack-years) (HR 1.90, 95%CI 1.20-3.00), hypercholesterolemia (HR 1.84, 95%CI 1.06-3.19), and hypertension (HR 1.76, 95%CI 1.03-3.01) were associated with higher risk of death, following ALS diagnosis. CONCLUSIONS: Higher BMI and diabetes were associated with lower risk of ALS. Higher BMI was associated with lower risk of death, whereas smoking (especially in high pack-years), hypercholesterolemia, and hypertension were associated with higher risk of death after ALS diagnosis.

Short-term improvement of mental health after a COVID-19 vaccination.

INTRODUCTION: The role of COVID-19 vaccination on the mental health of the general population remains poorly understood. This study aims to assess the short-term change in depressive and anxiety symptoms in relation to COVID-19 vaccination among Swedish adults. METHODS: A prospective study of 7,925 individuals recruited from ongoing cohort studies at the Karolinska Institutet, Stockholm, Sweden, or through social media campaigns, with monthly data collections on self-reported depressive and anxiety symptoms from December 2020 to October 2021 and COVID-19 vaccination from July to October 2021. Prevalence of depressive and anxiety symptoms (defined as a self-reported total score of ≥10 in PHQ-9 and GAD-7, respectively) was calculated one month before, one month after the first dose, and, if applicable, one month after the second dose. For individuals not vaccinated or choosing not to report vaccination status (unvaccinated individuals), we selected three monthly measures of PHQ-9 and GAD-7 with 2-month intervals in-between based on data availability. RESULTS: 5,079 (64.1%) individuals received two doses of COVID-19 vaccine, 1,977 (24.9%) received one dose, 305 (3.9%) were not vaccinated, and 564 (7.1%) chose not to report vaccination status. There was a lower prevalence of depressive and anxiety symptoms among vaccinated, compared to unvaccinated individuals, especially after the second dose. Among individuals receiving two doses of vaccine, the prevalence of depressive and anxiety symptoms was lower after both first (aRR = 0.82, 95%CI 0.76-0.88 for depression; aRR = 0.81, 95%CI 0.73-0.89 for anxiety) and second (aRR = 0.79, 95%CI 0.73-0.85 for depression; aRR = 0.73, 95%CI 0.66-0.81 for anxiety) dose, compared to before vaccination. Similar results were observed among individuals receiving only one dose (aRR = 0.76, 95%CI 0.68-0.84 for depression; aRR = 0.82, 95%CI 0.72-0.94 for anxiety), comparing after first dose to before vaccination. CONCLUSIONS: We observed a short-term improvement in depressive and anxiety symptoms among adults receiving COVID-19 vaccines in the current pandemic. Our findings provide new evidence to support outreach campaigns targeting hesitant groups.

Elevated symptoms of depression and anxiety among family members and friends of critically ill COVID-19 patients - an observational study of five cohorts across four countries.

Background: Little is known regarding the mental health impact of having a significant person (family member and/or close friend) with COVID-19 of different severity. Methods: The study included five prospective cohorts from four countries (Iceland, Norway, Sweden, and the UK) with self-reported data on COVID-19 and symptoms of depression and anxiety during March 2020-March 2022. We calculated prevalence ratios (PR) of depression and anxiety in relation to having a significant person with COVID-19 and performed a longitudinal analysis in the Swedish cohort to describe temporal patterns. Findings: 162,237 and 168,783 individuals were included in the analysis of depression and anxiety, respectively, of whom 24,718 and 27,003 reported a significant person with COVID-19. Overall, the PR was 1.07 (95% CI: 1.05-1.10) for depression and 1.08 (95% CI: 1.03-1.13) for anxiety in relation to having a significant person with COVID-19. The respective PRs for depression and anxiety were 1.15 (95% CI: 1.08-1.23) and 1.24 (95% CI: 1.14-1.34) if the patient was hospitalized, 1.42 (95% CI: 1.27-1.57) and 1.45 (95% CI: 1.31-1.60) if the patient was ICU-admitted, and 1.34 (95% CI: 1.22-1.46) and 1.36 (95% CI: 1.22-1.51) if the patient died. Individuals with a significant person with hospitalized, ICU-admitted, or fatal COVID-19 showed elevated prevalence of depression and anxiety during the entire year after the COVID-19 diagnosis. Interpretation: Family members and close friends of critically ill COVID-19 patients show persistently elevated prevalence of depressive and anxiety symptoms. Funding: This study was primarily supported by NordForsk (COVIDMENT, 105668) and Horizon 2020 (CoMorMent, 847776).

Large, Slowly Growing, Benign Thyroid Nodules Frequently Coexist With Synchronous Thyroid Cancers.

CONTEXT: Thyroid nodules' size should not be the sole criterion for thyroidectomy; however, many patients undergo surgery for large or slowly growing nodules. OBJECTIVE: We evaluated risk for clinically significant thyroid cancer in patients with large or slowly growing nodules. METHODS: We reviewed data from 2 prospectively collected databases of patients undergoing thyroidectomies in tertiary referral centers in the USA and Greece over 14 consecutive years. We collected data on the preoperative surgical indication, FNA cytology, and surgical pathology. We included subjects operated solely for large or growing thyroid nodules, without any known or presumed thyroid cancer or high risk for malignancy, family history of thyroid cancer, or prior radiation exposure. RESULTS: We reviewed 5523 consecutive cases (USA: 2711; Greece: 2812). After excluding 3059 subjects, we included 2464 subjects in the present analysis. Overall, 533 thyroid cancers were identified (21.3%): 372 (69.8%) microcarcinomas (<1 cm) and 161 (30.2%) macrocarcinomas (≥1 cm). The histology was consistent with papillary cancer (n = 503), follicular cancer (n = 12), Hürthle cell cancer (n = 9), medullary cancer (n = 5), and mixed histology cancers n = 4. Only 47 (1.9%) of our subjects had any form of thyroid cancer in the nodule that originally led to surgery. The cancers were multifocal in 165 subjects; had extrathyroidal extension in 61, capsular invasion in 80, lymph node involvement in 35, and bone metastasis in 2 subjects. CONCLUSION: The risk of synchronous, clinically important thyroid cancers is small, but not null in patients with large or slow growing thyroid nodules. Therefore, more precise preoperative evaluation is needed to separate the patients who would clearly benefit from thyroid surgery from the vast majority of those who do not need to be operated.

Incidentally Discovered Papillary Thyroid Microcarcinomas Are More Frequently Found in Patients with Chronic Lymphocytic Thyroiditis Than with Multinodular Goiter or Graves' Disease.

Background: Incidental finding of differentiated thyroid microcarcinomas (DTMc) in patients undergoing thyroid surgery for benign indications has become increasingly common. Even though carcinogenesis might relate to the background disease of the gland, the incidence of DTMc in the setting of various thyroid disorders remains unclear. We designed the present study to address this question. Materials and Methods: We reviewed data from two prospectively collected databases of consecutive patients undergoing thyroid surgery in two high-volume tertiary care referral centers, one in the United States (A) and the other one in Greece (B) over 18 years. We collected data on the preoperative surgical indication, fine-needle aspiration (FNA) cytology, and surgical pathology. We excluded subjects operated for thyroid cancer or with high risk for malignancy (FNA suspicious for thyroid cancer, follicular neoplasm, suspicious for follicular neoplasm, follicular lesion of undetermined significance/atypia of undetermined significance, or preoperative features of malignancy) and those with postsurgical pathology consistent with papillary thyroid cancer (PTC) ≥1 cm in largest diameter. We divided our subjects based on pathology data into those with chronic lymphocytic thyroiditis (CLT), Graves' disease (GD), or multinodular goiter (MNG). Results: We reviewed 6096 cases of thyroid surgery (A: 2711, B: 3385). We included 3909 subjects in the analysis. Overall, 569 (14.6%) PTC subjects were identified (A: 221/2003 [11%], B: 348/1906 [18.3%], odds ratios [OR] = 0.56, p < 0.0001). CLT was present in 617 subjects; PTC sonographic was present in 143 subjects (23.2%) (A: 79/404 [19.6%], B: 64/213 [30%], OR = 0.56, p = 0.003). GD was present in 359 subjects; PTC was present in 37 subjects (10.3%) (A: 12/197 [6.1%], B: 25/162 [15.4%], OR = 0.36, p = 0.004). MNG was present in 2933 subjects; PTC was present in 389 subjects (13.3%) (A: 130/1402 [9.3%], B: 259/1531 [16.9%], OR = 0.50, p < 0.0001). The incidence of PTC was significantly higher in CLT compared with MNG (OR = 1.75, p < 0.0001) or GD (OR = 2.25, p < 0.0001) but not in MNG compared with GD (OR = 1.29, p > 0.05). Conclusions: Incidentally discovered PTC are more commonly identified in surgical specimens from subjects with CLT compared with patients with MNG, while patients with GD present with a lower incidence compared with both groups. These data support previously published findings that euthyroid Hashimoto thyroiditis favors carcinogenesis, while GD may have a protective role.