Metabolites and depressive symptoms: Network- and longitudinal analyses from the Finnish Depression and Metabolic Syndrome in Adults (FDMSA) Study.

BACKGROUND: Depression is associated with metabolic abnormalities linked to metabolic syndrome and tissue inflammation, but the interplay between metabolic markers and their association with subsequent depression is unknown. Therefore, we aimed to describe the network of metabolites and their prospective association with depressive symptoms. METHODS: The Finnish Depression and Metabolic Syndrome in Adults (FDMSA) cohort, originally a prospective case-control study, comprised a group with Beck Depression Inventory (BDI)-I scores ≥10 at baseline, and controls (n = 319, BDI-I < 10); mean (sd) follow-up time: 7.4 (0.7) years. Serum metabolic biomarkers were determined by proton nuclear magnetic resonance (NMR), and depressive symptoms sum-score by using the BDI-I. We examined the prospective associations between metabolites at baseline and BDI score at follow-up utilizing multivariate linear regression, parsimonious predictions models and network analysis. RESULTS: Some metabolites tended to be either negatively (e.g. histidine) or positively associated (e.g. glycoprotein acetylation, creatinine and triglycerides in very large high density lipoproteins [XL-HDL-TG]) with depressive symptoms. None of the associations were significant after correction for multiple testing. The network analysis suggested high correlation among the metabolites, but that none of the metabolites directly influenced subsequent depressive symptoms. LIMITATIONS: Although the sample size may be considered satisfactory in a prospective context, we cannot exclude the possibility that our study was underpowered. CONCLUSIONS: Our results suggest that the investigated metabolic biomarkers are not a driving force in the development of depressive symptoms. These findings should be confirmed in studies with larger samples and studies that account for the heterogeneity of depressive disorders.

A longitudinal study of restless legs symptoms among patients with depression.

BACKGROUND: The aim of this study was to analyse the relationship between depressive symptoms and clinical depression and restless legs symptoms in a longitudinal primary care setting. METHODS: The prevalence of restless legs symptoms at baseline and after a six-year follow-up was studied in 474 patients with depressive symptoms and 333 population-based control subjects without depressive symptoms. Depressive symptoms at the baseline and after the six-year follow-up were evaluated with the Beck Depression Inventory (BDI) Second Edition. A psychiatric diagnosis was confirmed with a diagnostic interview (M.I.N.I.). Statistical comparisons between groups were made using analysis of variance (ANOVA) for continuous variables and a chi-square test or logistic models for categorical variables. Repeated measures were analysed using generalizing estimating equations (GEE) models. RESULTS: At baseline the prevalence of restless legs symptoms was 24.3% in control subjects, 43.8% in the patients with depressive symptoms without a depression diagnosis, and 49.3% in clinically depressed patients. During the follow-up up the prevalence of restless legs symptoms declined significantly (p = 0.003). In addition to baseline restless legs symptoms, the prognostic factors for restless legs symptoms among patients with clinical depression were age and BDI score. In the control subjects, moderate and high leisure time physical activity was inversely associated with restless legs symptoms at the follow-up. CONCLUSIONS: A higher level of baseline depressive symptoms was a risk factor for restless legs symptoms in patients with clinical depression. In the prevention and treatment of restless legs symptoms among the patients with depression, the priority is the effective treatment of depression.

Does baseline leisure-time physical activity level predict future depressive symptoms or physical activity among depressive patients? Findings from a Finnish five-year cohort study.

OBJECTIVES: The aims of this study were to investigate whether baseline leisure-time physical activity (LTPA) is associated with future recovery from depression among patients with a depression diagnosis and whether baseline LTPA is associated with total physical activity after five years of follow-up. METHODS: A total of 258 patients aged ≥35 years with clinically confirmed depression at baseline participated. The study was conducted between 2008 and 2016 in municipalities within the Central Finland Hospital District. Depressive symptoms (DS) were determined with the Beck Depression Inventory (BDI) with a cutoff score ≥10, and depression diagnoses were confirmed by the Mini-International Neuropsychiatric Interview (MINI). Blood pressure and anthropometric parameters were measured and blood samples for glucose and lipid determinations were drawn at baseline. LTPA, physical activity, and other social and clinical factors were captured by standard self-administered questionnaires at baseline and the five-year follow-up point. RESULTS: Of the 258 patients, 76 (29%) had DS at follow-up. Adjusted odds ratio (OR) for future DS was 1.43 (confidence interval [CI] 0.69-2.95) for participants with moderate LTPA and 0.92 (CI 0.42-2.00) for participants with high LTPA, compared with low LTPA at baseline. Higher baseline LTPA levels were associated with higher total physical activity in the future (ß=0.14 [95% CI: 0.02-0.26] for linearity = 0.024). CONCLUSION: Baseline LTPA did not affect the five-year prognosis of depression among depressed patients in a Finnish adult population. Because the baseline LTPA level predicted the future total physical activity, it could be included as a part of the overall health management and treatment of depression in clinical practices.

The influence of restless legs symptoms on musculoskeletal pain in depression.

Background and aims Restless legs syndrome is a sensorimotor disorder associated with mental health conditions notably depression. Restless legs symptoms and depression are commonly associated with pain. The study investigated the influence of restless legs symptoms on musculoskeletal pain in patients with depression or with increased depressive symptoms. Methods A cross-sectional study of primary care patients in the Central Finland Hospital District. The prevalence of restless legs symptoms was studied in patients with depressive symptoms (n = 695) and controls without a psychiatric diagnosis (n = 410) by using a structured questionnaire. The depressive symptoms were evaluated with the Beck Depression Inventory and the psychiatric diagnosis was confirmed by means of a diagnostic interview (MINI). The prevalence and intensity of musculoskeletal pain was captured with form-based questions. A single-question screen for restless legs symptoms was applied. Results There was a significant difference in the prevalence of continuous widespread musculoskeletal pain between the three study groups: the controls 4.6% (95% CI: 2.8-7.1), the patients with symptoms of depression without a diagnosis 16.0% (11.7-21.1), and the patients with diagnosed depression 22.1% (18.3-23.3) (p = 0.006 after being adjusted for age, sex, smoking, use of alcohol, education years, body mass index, use of antidepressants, and physical activity, after multiple corrections, all groups were significantly different from each other). Compared with those not having restless legs symptoms, subjects with restless legs symptoms had more often continuous widespread musculoskeletal pain in the control subjects (p = 0.001; 2.3% vs. 10.5%) and in the patients with depressive symptoms without a depression diagnosis (p = 0.024; 9.1 vs. 18.7%) but not in those with diagnosed depression (p = 0.98; 19.5 vs. 19.4%). The restless legs symptoms were associated with the intensity of pain in all groups (p < 0.001). Conclusions Restless legs symptoms were related to continuous widespread musculoskeletal pain in subjects without depressive symptoms and in patients with depressive symptoms without a depression diagnosis. Pain intensity was higher in the subjects with restless legs symptoms regardless of depressive symtoms or depression. Implications Clinical management of pain in patients with restless legs symptoms should include an increased focus on the prevention and treatment of either conditions.

Leisure time physical activity and its relation to psychiatric comorbidities in depression. Findings from Finnish Depression and Metabolic Syndrome in Adults (FDMSA) study.

PURPOSE: The study aim was to examine association between leisure time physical activity (LTPA) and psychiatric comorbidities among people with depression. METHODS: Total 447 patients aged 35 years and older suffering from depressive symptoms (DS) and who were confirmed depression positive participated this study. The study was conducted between 2008 and 2011 in municipalities within Central Finland Hospital District. DS were determined with Beck Depression Inventory (BDI-21) with cutoff score ≥10 and psychiatric diagnoses were confirmed by Mini-International Neuropsychiatric Interview (M.I.N.I.). LTPA, other diseases as well as use of antidepressant were captured by self-reported questionnaire. Participants also took part in physical examination. The associations between LTPA and psychiatric comorbidities were analyzed using generalized linear models. RESULTS: LTPA level was not related to number of psychiatric comorbidities (after adjustment for age, gender, BMI, BDI and use of antidepressant p = 0.24) among depressed patients. The higher levels of LTPA were linearly associated with lower cardiovascular diseases (p = 0.036) and obesity (p = 0.006) as well as fewer DS (p < 0.001) among depressed patients. LIMITATIONS: Possibility of LTPA level overestimation and study results generalizability to younger persons. CONCLUSIONS: According to this study, LTPA level is not associated with psychiatric comorbidities among depressed patients in Finnish adult population. However, our results showed that the higher the LTPA level was, the less the participants suffered from depressive symptoms. In addition, higher levels of physical activity were associated with fewer heart diseases and obesity outlining the importance of overall health-care and health promotion although other forms of treatment are also needed.

The profiles of health care utilization among a non-depressed population and patients with depressive symptoms with and without clinical depression.

Objective: To examine health service (HS) utilization profiles among a non-depressive population and patients with depressive symptoms (DS) with and without clinical depression. Design, subjects and setting: The study population was based on primary care patients with DS scoring ≥10 in the 21-item Beck Depression Inventory (BDI) and who were at least 35 years old and had been referred to depression nurse case managers (n = 705). Their psychiatric diagnosis was confirmed with the Mini-International Neuropsychiatric Interview (M.I.N.I.). Of these patients, 447 had clinical depression. The number of patients with DS without clinical depression was 258. The control group consisted of a random sample of 414 residents with a BDI score < 10. Use of HS (visits and phone calls to a doctor and a nurse) was based on patient records. Main outcome measures: Number of visits and calls to physicians and nurses. Results: Patients with DS regardless of their depression diagnosis used primary health care (PHC) services three times more than the controls (p < 0.001). In the secondary care, the differences were smaller but significant. Of the controls, 70% had 0-4 HS contacts per year whereas a majority of the patients having DS had more than 5 contacts per year. The number of contacts correlated with the BDI from a score of 0 to 10 but not as clearly in the higher scores. Conclusion: Depressive symptoms, both with or without clinical depression, are associated with increased HS use, especially in PHC. This study suggests that even mild depressive symptoms are associated with an increased use of HS. KEY POINTS We analyzed the health service (HS) use among primary health care patients screened for depression and non-depressive population. Screen positive patients without clinical depression used as much HS as those having clinical depression. Regardless of depression diagnosis, screen positive patients visited a GP and nurse three times more often than the control population. In the screen negative control population, milder depressive symptoms were correlated with the use of HS. Primary health care was responsible for most of the HS use among patients having depressive symptoms.

Psychiatric diagnosis in primary care patients with increased depressive symptoms.

BACKGROUND: Screening of depression has been recommended in primary care and Beck's 21-item Depression Inventory (BDI-21) is a commonly used tool for screening. Depression has been shown to be frequently accompanied by comorbidities. AIMS: This study aimed to analyze the characteristics, psychiatric diagnoses, and psychiatric comorbidity of primary care patients who have been screened for depression and referred to a depression nurse. METHODS: The study subjects were primary care patients aged ≥ 35 years with depressive symptoms (BDI-21 > 9). Their psychiatric diagnosis were based on a diagnostic interview (Mini-International Neuropsychiatric Interview; M.I.N.I.) conducted by a trained study nurse. RESULTS: Of the 705 study subjects, 617 (87.5%) had at least one and 66.1% had at least two psychiatric diagnoses. The most common diagnosis was depression (63.4%). The next most common diagnoses were generalized anxiety disorder (GAD) (48.1%) and panic disorder (22.8%). Only 8.8% of the study subjects had depression without other psychiatric disorders. Ten percent of the subjects had both depression and a generalized anxiety disorder (GAD). Also other psychiatric comorbidities were common. Age was inversely associated with the psychiatric diagnosis in the M.I.N.I. CONCLUSIONS: This study suggests that most of the primary care patients with increased depressive symptoms have a psychiatric disorder. Although depression is the most common diagnosis, there are several other concurrent psychiatric comorbidities. Therefore, diagnostic assessment of primary care patients with a screening score over 9 in the BDI-21 should be reconsidered.

Elevation of tumor necrosis factor alpha levels is associated with restless legs symptoms in clinically depressed patients.

BACKGROUND: Restless legs syndrome is a sensorimotor disorder associated with several mental illnesses particularly depression. METHODS: A cross-sectional study of primary care patients. The prevalence of restless legs symptoms was studied in 706 patients with depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the BDI and the psychiatric diagnosis was confirmed by means of a diagnostic interview (M.I.N.I.). The subjects with elevated depressive symptoms were divided into two groups subjects with depressive symptoms with and without clinical depression. RESULTS: The prevalence of restless legs symptoms was 24.8% in the controls, 50.0% in the patients with clinical depression and 42.4% in the patients with depressive symptoms. CRP value was significantly higher (p = .003) in the clinically depressed patients than in the other groups. There was a higher concentration of TNF-α in the subjects with restless legs symptoms (7.4 ng/l ±â€¯3.2) compared with the subjects without symptoms (6.7 ng/l ±â€¯2.3)(p < .001). There was a significant difference in the TNF-α levels between the subjects with and without restless legs symptoms in the depression group (p < .001) and among the patients with depressive symptoms but no a depression diagnosis (p = .022). In these groups, restless legs symptoms were associated with elevated levels of TNF-α. CONCLUSIONS: TNF-α level was associated with restless legs symptoms only among subjects with depressive symptoms whether they had clinical depression or not. We suggest that TNF-α could be an underlying factor between restless legs symptoms and comorbidities.

Hemoglobin level and lipoprotein particle size.

BACKGROUND: Alterations in lipoprotein size are associated with increased cardiovascular disease risk. Higher hemoglobin levels may indicate a higher risk of atherosclerosis and was previously associated with obesity, metabolic syndrome, and insulin resistance. No previous studies have investigated an association between hemoglobin concentration and lipoprotein particle size. METHODS: We conducted a population-based, cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) born in Pieksämäki, Finland, who were categorized into five age groups. The concentrations and sizes of lipoprotein subclass particles were analyzed by high-throughput nuclear magnetic resonance (NMR) spectroscopy. RESULTS: Larger very low density lipoprotein (VLDL) particle diameter was associated with higher hemoglobin concentrations in men (p = 0.003). There was a strong relationship between smaller high density lipoprotein (HDL) particle size and higher hemoglobin concentration in both men and women as well as with smaller low density lipoprotein (LDL) particle size and higher hemoglobin concentration in men and women (p < 0.001; p = 0.009, p = 0.008). VLDL particle concentration had a moderate positive correlation with hemoglobin concentration (r = 0.15; p < 0.001). LDL particle concentration showed a statistical trend suggesting increasing particle concentration with increasing hemoglobin levels (r = 0.08; p = 0.05). CONCLUSION: Higher hemoglobin levels are associated with larger VLDL, smaller LDL, and smaller HDL particle sizes and increasing amounts of larger VLDL and smaller LDL particles. This suggests that a higher hemoglobin concentration is associated with an unfavorable lipoprotein particle profile that is part of states that increase cardiovascular disease risk like diabetes and metabolic syndrome.

Prevalence of restless legs symptoms according to depressive symptoms and depression type: a cross-sectional study.

BACKGROUND: Restless legs syndrome is a sensorimotor disorder and it is associated with several other diseases especially mental illnesses. AIMS: To analyze the relationship between the symptoms of restless legs syndrome and the severity of depressive symptoms and the prevalence of restless legs symptoms in depression subtypes. METHODS: A cross-sectional study of primary care patients in the Central Finland Hospital District. The prevalence of restless legs symptoms was studied in 706 patients with increased depressive symptoms and 426 controls without a psychiatric diagnosis by using a structured questionnaire. The depressive symptoms were evaluated with the Beck Depression Inventory (BDI) and the psychiatric diagnosis was confirmed by means of a diagnostic interview (Mini-International Neuropsychiatric Interview). The subjects with increased depressive symptoms were divided into three groups (subjects with depressive symptoms without a depression diagnosis, melancholic depression and non-melancholic depression). RESULTS: In the whole study population, the prevalence of restless legs symptoms increased with the severity of depressive symptoms. The prevalence of restless legs symptoms was highest in the melancholic and non-melancholic depressive patients (52 and 46%, respectively) and then in subjects with depressive symptoms without a depression diagnosis (43.4%), but the prevalence was also substantial (24.6%) in subjects without a psychiatric diagnosis. CONCLUSIONS: Restless legs symptoms are very common in primary care among subjects with depression, regardless of the depression type. The prevalence of restless legs symptoms increased with increasing severity of depressive symptoms, regardless of the diagnosis. These findings should be considered in clinical evaluation and treatment of patients visiting their physician due to restless legs or depressive symptoms.

An mHealth App for Supporting Quitters to Manage Cigarette Cravings With Short Bouts of Physical Activity: A Randomized Pilot Feasibility and Acceptability Study.

BACKGROUND: While gains in reducing smoking rates in Finland have been made, prevalence rates are still substantial. Relapse rates among smokers engaged in quit-smoking programs are high. Physical activity has been proposed as one means to help smokers manage cravings. Software and apps on mobile phone and handheld devices offer an opportunity to communicate messages on how to use physical activity to manage cravings as part of quit-smoking programs. OBJECTIVE: We aimed to test the feasibility, acceptability, usability, and preliminary efficacy of an mHealth mobile phone app, Physical activity over Smoking (PhoS), to assist smokers in quitting smoking in a randomized controlled trial. The app was designed to prompt smokers to engage in physical activities to manage their smoking cravings. METHODS: Regular smokers (n=44) attended a group-based behavioral counselling program aimed at promoting physical activity as an additional aid to quit. After quit day, participants were randomly allocated to an intervention (n=25) or to a comparison (n=19) group. Participants in the intervention group were provided with the PhoS app and training on how to use it to assist with relapse prevention. Participants in the comparison condition were provided with generalized relapse prevention training. RESULTS: Some participants reported that the PhoS app was useful in assisting them to successfully manage their cigarette cravings, although compliance across the sample was modest and participants reported low levels of usability. Participants receiving the PhoS app did not report greater abstinence than those who did not receive the app. However, participants receiving the app were more likely to report greater abstinence if they did not use pharmacological support, while those who did not receive the app reported greater abstinence when using pharmacological support. Participants receiving the app reported greater levels of physical activity than those who did not. Results revealed that the app resulted in better retention. CONCLUSIONS: The PhoS app showed some potential to reduce abstinence among participants not using pharmacological therapy and to increase physical activity. However, problems with usability and lack of effects on abstinence raise questions over the app's long-term effectiveness. Future research should prioritize further development of the app to maximize usability and test effects of the intervention independent of quit-smoking programs. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 55259451; http://www.controlled-trials.com/ISRCTN55259451 (Archived by WebCite at http://www.webcitation.org/6cKF2mzEI).

Musculoskeletal Pain in Melancholic and Atypical Depression.

Objective: Pain and depressive disorders often present together, but little is known about the prevalence of pain in depression subgroups. The objective of this study was to examine the possible differences in the prevalence of musculoskeletal pain between participants in melancholic and atypical depression subgroups. Design: Cross-sectional study. Setting: Depression nurse case managers where depression patients receive treatment in primary health care. Subjects: Participants included 413 depression patients and 401 controls. Methods: Depressive symptoms were determined with the Beck Depression Inventory (BDI-21), and diagnosis of depression was confirmed with the Mini-International Neuropsychiatric Interview (MINI). The participants were dichotomized into subgroups with melancholic depression (n = 269), atypical depression (n = 144), and controls (n = 401). Musculoskeletal pain was identified during last four weeks. Participants were enrolled in the study between 2008 and 2009. Results: The prevalence of pain was 37% in controls, 57% in atypical depression, and 71% in melancholic depression (P < 0.001, after adjusting for sex and age). A logistic regression model showed that the odds ratio of pain after adjusting for confounding factors was 2.35 (1.56 to 3.56) with atypical depression compared with controls (P < 0.001) and 4.38 (3.03 to 6.33) with melancholic depression compared with atypical depression (P = 0.006). BDI scores were higher for those with melancholic depression than for those with atypical depression (P < 0.001). Conclusions: Melancholic depression showed to be associated with a higher prevalence of musculoskeletal pain in comparison with atypical depression. This finding highlights the need for further studies about the mechanisms behind the association, particularly in melancholic depression.

Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase.

BACKGROUND: Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. OBJECTIVES: This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. METHODS: Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. RESULTS: Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R(2) = 0.94, slope 1.00 ± 0.03). CONCLUSIONS: Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects, and pharmacological mechanisms.

Effectiveness of a Mobile Phone App for Adults That Uses Physical Activity as a Tool to Manage Cigarette Craving After Smoking Cessation: A Study Protocol for a Randomized Controlled Trial.

BACKGROUND: Results from studies on the effects of exercise on smoking-related variables have provided strong evidence that physical activity acutely reduces cigarette cravings. Mobile technology may provide some valuable tools to move from explanatory randomized controlled trials to pragmatic randomized controlled trials by testing the acute effectiveness of exercise on quitters under real-life conditions. An mHealth app was developed to be used as a support tool for quitters to manage their cigarette cravings. OBJECTIVE: The primary aim of this paper is to present the protocol of a study examining the effectiveness of the Physical over smoking app (Ph.o.S) by comparing the point prevalence abstinence rate of a group of users to a comparator group during a 6-month follow-up period. METHODS: After initial Web-based screening, eligible participants are recruited to attend a smoking cessation program for 3 weeks to set a quit smoking date. Fifty participants who succeed in quitting will be randomly allocated to the comparator and experimental groups. Both groups will separately have 1 more counseling session on how to manage cravings. In this fourth session, the only difference in treatment between the groups is that the experimental group will have an extra 10-15 minutes of guidance on how to use the fully automated Ph.o.S app to manage cravings during the follow-up period. Data will be collected at baseline, as well as before and after the quit day, and follow-up Web-based measures will be collected for a period of 6 months. The primary efficacy outcome is the 7-day point prevalence abstinence rate, and secondary efficacy outcomes are number of relapses and cravings, self-efficacy of being aware of craving experience, self-efficacy in managing cravings, and power of control in managing cravings. RESULTS: Recruitment for this project commenced in December 2014, and proceeded until May 2015. Follow-up data collection has commenced and will be completed by the end of December 2015. CONCLUSIONS: If the Ph.o.S app is shown to be effective, the study will provide evidence for the use of the app as a support tool for people who are trying to manage cravings during smoking cessation programs. It is anticipated that the results of the study will provide knowledge of how physical activity affects cigarette craving in real-life situations and inform the development and delivery of relapse prevention in smoking cessation treatment. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): ISRCTN55259451; http://www.controlled-trials.com/ISRCTN55259451 (Archived by WebCite at http://www.webcitation.org/6cKF2mzEI).

Association between suicidal behaviour and impaired glucose metabolism in depressive disorders.

BACKGROUND: Disturbances in lipid metabolism have been linked to suicidal behaviour, but little is known about the association between suicide risk and abnormal glucose metabolism in depression. Hyperglycaemia and hyperinsulinaemia may increase the risk of depression and also the risk for suicide, we therefore studied associations between suicidal behaviour and disturbances in glucose metabolism in depressive patients who had been referred to depression nurse case managers. METHODS: Patients aged 35 years and older (N = 448, mean age 51 years) who were experiencing a new depressive episode, who were referred to depression nurse case managers in 2008-2009 and who scored ≥10 on the Beck Depression Inventory were enrolled in this study. The study was conducted in municipalities within the Central Finland Hospital District (catchment area of 274 000 inhabitants) as part of the Finnish Depression and Metabolic Syndrome in Adults study. The patients' psychiatric diagnoses and suicidal behaviour were confirmed by the Mini-International Neuropsychiatric Interview. Blood samples, for glucose and lipid determinations, were drawn from participants after 12 h of fasting, which was followed by a 2-hour oral glucose tolerance test (OGTT) when blood was drawn at 0 and 2 h. Insulin resistance was measured by the Quantitative Insulin Sensitivity Check Index (QUICKI) method. RESULTS: Suicidal ideation (49 %) and previous suicide attempts (16 %) were common in patients with major depressive disorder or dysthymia. Patients with depression and suicidal behaviour had higher blood glucose concentrations at baseline and at 2 hours in the OGTT. Glucose levels associated positively with the prevalence of suicidal behaviour, and the linearity was significant at baseline (p for linearity: 0.012, adjusted for age and sex) and for 2-hour OGTT glucose (p for linearity: 0.004, adjusted for age and sex). QUICKI levels associated with suicidal behavior (p for linearity across tertiles of QUICKI: 0.026). Total and LDL cholesterol and triglyceride levels were also higher in those patients with suicidal behaviour. Multivariate analysis revealed that blood glucose levels, BDI scores and antidepressive medications associated with suicidal behaviour. CONCLUSION: Insulin resistance and disturbances in glucose and lipid metabolism may be more common in middle-aged depressive patients with suicidal behaviour.

The Relationship between Thyroid Function and Depressive Symptoms-the FIN-D2D Population-Based Study.

The association between thyroid function and depression is controversial. Both conditions express many similar symptoms, but the studies done give conflicting results. This study draws on a random, population-based sample of 4500 subjects aged 45-75 years old from Finland. The basic clinical study was done in 2007 for 1396 men and 1500 women (64% participation rate). Thyroid stimulating hormone (TSH), free thyroxine (F-T4), and free triiodothyronine (F-T3) were measured in 2013 from frozen samples. The 21-item Beck Depression Inventory (BDI-21) was applied to assess depressive symptoms (score ≥10 points). The prevalence of depressive symptoms was 17.5% in women and 12.5% in men. In women, the mean levels of TSH, F-T4, and F-T3 without depressive symptoms vs. with the presence of depressive symptoms were 1.92/1.97 mU/L, 13.1/13.1 pmol/L, and 3.91/3.87 pmol/L (NS), respectively. In men, the levels were 1.87/1.94 mU/L, 13.5/13.7 pmol/L, and 4.18/4.12 pmol/L (NS), respectively. In multiple regression analysis, TSH had no relationship to BDI-21 total score. We found no association between depressive symptoms and thyroid values.

Cardiometabolic risk factors in patients referred to depression nurse case managers.

BACKGROUND: Disturbances in lipid and glucose metabolism are associated with depressive symptoms, and may increase suicidal behavior. AIMS: To investigate the prevalence of cardiometabolic risk factors, severity of depressive symptoms, and suicidal thoughts and previous attempts in patients referred to depression nurse case managers. METHODS: Blood cholesterol, triglyceride and glucose levels, depressive symptoms and suicidality were studied in 706 depressed participants and 426 controls. In addition, we compared the Beck Depression Inventory (BDI) with a diagnostic interview. RESULTS: 448 (63%) of the patients scoring ≥ 10 on BDI had major depression or dysthymic disorder, 258 had an anxiety or alcohol use disorder, 137 (19%) had two or more diagnoses in the Mini-International Neuropsychiatric Interview. Suicidal thoughts (49%) and previous suicide attempts (16%) were more common in patients with depressive disorders. Patients diagnosed with depression had highest BDI scores and higher blood glucose levels measured at baseline and at 2 h in the oral glucose tolerance test (OGTT). Both patient groups also had higher triglyceride levels compared with the controls. In addition, metabolic syndrome and type 2 diabetes were most common among the depressed participants. In the whole study population, levels of low-density lipoprotein-cholesterol as well as baseline and 2-h blood glucose in OGTT were higher among patients with suicidal behavior. CONCLUSIONS: Cardiometabolic risk factors and metabolic syndrome are common in patients with depression, and in patients with anxiety and alcohol use disorders. The results imply that disturbance in glucose metabolism may be associated with suicidal thoughts and previous attempts.

Changes in lifestyle modestly reduce the estimated cardiovascular disease risk in one-year follow-up of the Finnish diabetes prevention program (FIN-D2D).

AIMS: The purpose of this study was to assess whether changes in self-rated physical activity and diet during a type 2 diabetes (T2D) prevention program were associated with changes in estimated 10-year risk for cardiovascular disease (CVD) events and mortality in people at high risk for T2D. METHODS: Individuals were identified and offered lifestyle counseling as part of the Finnish diabetes prevention program. Ten-year risk for estimated CVD events and mortality were calculated with Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE) formula. FRS was available for 774 men and 1474 women and SCORE for 961 men and 1766 women. RESULTS: During the one-year follow-up, 9.6% of the men reported both an increase in physical activity and improved dietary pattern, 4.1% an increase in physical activity, 39.3% an increase in improved dietary pattern, while 47.0% reported no lifestyle changes. Corresponding numbers for women were 14.2%, 3.8%, 39.2% and 42.7%. Estimated 10-year risk for CVD events decreased 3.5% in men and 1.5% in women reporting an increase in physical activity and improvement in diet, compared to an increase of 0.15% in men (p<0.001, between groups) and decrease of 0.43% (p=0.027, between groups) in women with no lifestyle changes after adjustment for age and baseline FRS. Numbers needed to treat to prevent one CVD event by lifestyle changes were 25 for men and 59 for women. Lifestyle changes had no effect on estimated CVD mortality risk. CONCLUSIONS: Lifestyle counseling offered in primary health care for one year results in favorable changes in lifestyle, and lowered the estimated 10-year risk for CVD events.

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

BACKGROUND: Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. METHODS AND FINDINGS: We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% ± 3%; R(2)= 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; R(2) = 0.92). CONCLUSIONS: Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.

Serum ferritin levels and the development of metabolic syndrome and its components: a 6.5-year follow-up study.

BACKGROUND: The aim of this study was to investigate the relationship between changes in serum ferritin concentrations and the development of metabolic syndrome (MetS) and its components over a 6.5 year follow-up period in Finnish adults. METHODS: Adults born in Pieksämäki, Finland, in 1942, 1947, 1952, 1957, and 1962 (n = 1294) were invited to health checkups between 1997 and 1998 and 2003 and 2004. All of the required variables for both checkups were available from 691 (53%) subjects (289 men and 402 women). MetS was defined by the National Cholesterol Education Program criteria. RESULTS: During the 6.5-year follow-up period, 122 (18%) subjects developed incident cases of MetS. Increases in serum ferritin levels were significantly higher in both women and men with incident MetS compared with women and men without MetS (p = 0.04, p = 0.03). Also, serum ferritin levels increased significantly less in women in whom the criteria for MetS resolved during the follow-up period (p = 0.01). Increases in serum ferritin levels were significantly lower in women in whom the glucose criterion for MetS resolved, and higher in women for whom the waist criterion developed (p = 0.01 and p <0.001, respectively). Serum ferritin levels decreased significantly more in men in whom the triglyceride criterion for MetS resolved during the follow-up period (p = 0.01). There was a clear and significant correlation between change in serum ferritin level and change in waist circumference both in men and women (p <0.001, p <0.01). In addition, correlations between change in serum ferritin level and change in plasma triglyceride as well as glucose levels were strongly positive in men (p <0.001). There was negative correlation between change in serum ferritin and plasma high density cholesterol level both in men and women. CONCLUSIONS: Increases in serum ferritin over a 6,5 year period are associated with development of MetS in both men and women. Whereas, lower increases in serum ferritin over the same timeframe are associated with resolution of hypertriglyceridemia in men and hyperglycemia in women. Increases in waist circumference was positively correlated with increases in serum ferritin in both men and women.