Markku Timonen

Co-occurrence of Metabolic Syndrome With Depression and Anxiety in Young Adults: The Northern Finland 1966 Birth Cohort Study

Objective: Only a few studies have dealt with the association of metabolic syndrome with depression and anxiety. We studied whether metabolic syndrome and its components are associated with depressive and anxiety symptoms in a young adult population cohort. Methods: This study forms part of the Northern Finland 1966 Birth Cohort Study. The study sample consists of 5,698 members of the cohort who participated in the field study in 1997 to 1998. Metabolic syndrome was defined according to the five criteria of the National Cholesterol Education Program. Depressive and anxiety symptoms were defined by the Hopkins Symptom Checklist-25 questionnaire. Results: Metabolic syndrome was not associated with depression or anxiety. The correlations between the components of the metabolic syndrome and psychological distress as continuous measures were low. High waist circumference (>102 cm in males and >88 cm in females) associated with depression (odds ratio, 1.30; 95% confidence interval, 1.05–1.61), but this association vanished when adjusted for gender, smoking, alcohol consumption, marital status, level of education, and physical activity. Conclusion: No clear association was found between the metabolic syndrome and psychological distress. ATP III = Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III); CI = confidence interval; HSCL-25 = Hopkins Symptom Checklist-25, OR = odds ratio; HDL = high-density lipoprotein.

Insulin resistance and depression: cross sectional study

A recent study found that depression is inversely associated with insulin resistance, but positively associated with diabetes.1 Association between insulin resistance and depression is a poorly studied area and the few earlier findings do not necessarily support this finding,1 indicating that patients with serious depression have insulin resistance assessed by insulin tolerance, intravenous, or oral glucose tolerance tests.2 Recently, depression was found to be associated with greater insulin resistance in women with polycystic ovary syndrome.3 Also, more than the normal rates of depression had already been noted in patients with clinically manifest diabetes.2 Since insulin resistance is positively associated with the development of diabetes,1 we hypothesised—given that disturbed glucoregulatory functions behind the development of diabetes might be associated with pathophysiological changes in depression2—that insulin resistance should be positively correlated with depressive symptoms. We also investigated whether depressive symptoms varied with different levels of a disturbed glucose metabolism. We invited all 1008 people born …

The Association Between C-Reactive Protein Levels and Depression: Results from the Northern Finland 1966 Birth Cohort Study

BACKGROUND To investigate whether depressive episodes (previous, current single, and recurrent) are associated in both genders with highly sensitive C-reactive protein (hs-CRP) levels, earlier recommended for risk assessment of cardiovascular disease. The impact of the severity of current single and recurrent depressive episodes on this putative association was also investigated. METHODS The genetically homogeneous Northern Finland 1966 Birth Cohort was followed until age 31, when, in a cross-sectional setting (n = 5269), the highly sensitive enzyme immunoassay (hs-EIA) method was used to measure CRP concentration. Depressive episodes were defined through mailed questionnaires, including Hopkins Symptom Checklist-25 (HSCL-25) and information on self-reported, doctor-diagnosed depression. RESULTS After adjusting for confounders, logistic regression analyses showed that in male subjects, elevated hs-CRP levels (> or =1.0 mg/L) increased the probability for severe current and recurrent depressive episodes 1.7-fold and 3.1-fold, respectively. Correspondingly, an hs-CRP level of >3.0 mg/L increased the probability for recurrent depression up to 4.1-fold. In female subjects, no statistically significant associations were found. CONCLUSIONS Our results support the hypothesis that an activation of systemic inflammatory processes may contribute to the pathophysiology of severe depression in men. Further investigations are needed regarding the impact of our findings on diagnostic/treatment strategies concerning severe and, especially recurrent, depression in men.

The association of preceding traumatic brain injury with mental disorders, alcoholism and criminality: the Northern Finland 1966 Birth Cohort Study

The purpose of this study was to test the hypothesis that traumatic brain injury (TBI) during childhood and adolescence is associated with psychiatric disorders, heavy alcohol use and criminal offenses in adulthood. We made use of an unselected, general population birth cohort (n=12058) in Northern Finland, which was followed up prospectively up to the age of 31. The data on TBIs of the cohort members were collected from the hospital case notes of the outpatient clinics of the hospitals in the region and from the Finnish Hospital Discharge Registers (FHDR). The data on mental disorders including alcohol diagnoses were also collected from the FHDR after a careful validation process. The Ministry of Justice provided information on criminal offenses for all subjects. The final number of subjects in our study was 5589 males and 5345 females. We found that after controlling for confounders, TBI during childhood or adolescence increased the risk of developing mental disorders two-fold (OR 2.1, 95% CI 1.1-3.6) and TBI was significantly related to later mental disorder with coexisting criminality in male cohort members (OR 4.1, 95% CI 1.2-13.6). The results support the TBIs association with psychiatric morbidity, which should not be overlooked when treating psychiatric patients, especially those with comorbid criminality.

Postchallenge Glucose, A1C, and Fasting Glucose as Predictors of Type 2 Diabetes and Cardiovascular Disease A 10-year prospective cohort study

OBJECTIVE A1C has been proposed as a new indicator for high risk of type 2 diabetes. The long-term predictive power and comparability of elevated A1C with the currently used high-risk indicators remain unclear. We assessed A1C, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) as predictors of type 2 diabetes and cardiovascular disease (CVD) at 10 years. RESEARCH DESIGN AND METHODS This prospective population-based study of 593 inhabitants from northern Finland, born in 1935, was conducted between 1996 and 2008. An oral glucose tolerance test (OGTT) was conducted at baseline and follow-up, and A1C was determined at baseline. Those with a history of diabetes were excluded from the study. Elevated A1C was defined as 5.7–6.4%. Incident type 2 diabetes was confirmed by two OGTTs. Cardiovascular outcome was measured as incident CVD or CVD mortality. Multivariate log-binomial regression models were used to predict diabetes, CVD, and CVD mortality at 10 years. Receiver operating characteristic curves compared predictive values of A1C, IGT, and IFG. RESULTS Incidence of diabetes during the follow-up was 17.1%. Two of three of the cases of newly diagnosed diabetes were predicted by a raise in ≥1 of the markers. Elevated A1C, IGT, or IFG preceded diabetes in 32.8, 40.6, and 21.9%, respectively. CVD was predicted by an intermediate and diabetic range of 2-h glucose but only by diabetic A1C levels in women. CONCLUSIONS A1C predicted 10-year risk of type 2 diabetes at a range of A1C 5.7–6.4% but CVD only in women at A1C ≥6.5%.

Depression in relation to survival among neurosurgical patients with a primary brain tumor: a 5-year follow-up study.

OBJECTIVE: The adverse impact of depression in relation to survival among cancer patients is currently a subject of great interest in research. In a 5-year follow-up study, we investigated the association of depression with survival of patients with a primary brain tumor. METHODS: The study population consisted of 75 patients with a solitary primary brain tumor treated surgically at the Oulu Clinic for Neurosurgery, Oulu University Hospital, in Northern Finland. The patients were interviewed during admission to the hospital for the tumor surgery. Assessment of depression was made using the Beck Depression Inventory and the Crown-Crisp Experiential Index. Information on all deaths within 60 months after tumor operation was collected from the Cause of Death Register, provided by Statistics Finland. RESULTS: The patients with a high-grade glioma had a survival time of 22.5 months (standard deviation, 21.4 mo), whereas the corresponding time was 50.2 months (standard deviation, 19.9 mo) for patients with a low-grade glioma and 58.2 months (standard deviation, 9.4 mo) for the patients with a histologically benign tumor (P < 0.001, difference between groups, Kruskal-Wallis test). In the subgroup of patients with low-grade gliomas, depressive patients had a significantly shorter survival time compared with nondepressive subjects (P = 0.031, Kaplan-Meier survival analysis). A corresponding difference was not found in patients with high-grade gliomas or benign tumors. Tumor location in one hemisphere compared with bilateral location and wider extent of tumor surgery was associated with better survival in patients with low-grade gliomas and benign tumors but not in patients with high-grade gliomas. CONCLUSION: Preoperative depression seemed to be a significant prognostic factor for worse survival in low-grade glioma patients. In clinical practice, an evaluation of depression among brain tumor patients by structured and standardized diagnostic methods is needed to distinguish the patients whose depression actually needs treatment. The effective treatment of clinical depression among brain tumor patients and the impact of treatment on the patients’ chances of survival should be a focus of future research.

Group-ICA Model Order Highlights Patterns of Functional Brain Connectivity

Resting-state networks (RSNs) can be reliably and reproducibly detected using independent component analysis (ICA) at both individual subject and group levels. Altering ICA dimensionality (model order) estimation can have a significant impact on the spatial characteristics of the RSNs as well as their parcellation into sub-networks. Recent evidence from several neuroimaging studies suggests that the human brain has a modular hierarchical organization which resembles the hierarchy depicted by different ICA model orders. We hypothesized that functional connectivity between-group differences measured with ICA might be affected by model order selection. We investigated differences in functional connectivity using so-called dual regression as a function of ICA model order in a group of unmedicated seasonal affective disorder (SAD) patients compared to normal healthy controls. The results showed that the detected disease-related differences in functional connectivity alter as a function of ICA model order. The volume of between-group differences altered significantly as a function of ICA model order reaching maximum at model order 70 (which seems to be an optimal point that conveys the largest between-group difference) then stabilized afterwards. Our results show that fine-grained RSNs enable better detection of detailed disease-related functional connectivity changes. However, high model orders show an increased risk of false positives that needs to be overcome. Our findings suggest that multilevel ICA exploration of functional connectivity enables optimization of sensitivity to brain disorders.

The association between anxiety and C-reactive protein (CRP) levels: Results from the Northern Finland 1966 Birth Cohort Study

BACKGROUND Anxiety frequently accompanies low-grade inflammation-associated conditions like depression, insulin resistance, coronary heart disease and metabolic syndrome. The association between anxiety and low-grade inflammation is, unlike between depression and low-grade inflammation, a very sparsely studied area in general populations. The aim of the present study was to investigate whether anxiety symptoms as well as comorbid anxiety and depressive symptoms are associated with low-grade inflammation at population level. METHODS The general population-based Northern Finland 1966 Birth Cohort was followed until age 31 (n=2688 males and 2837 females), when the highly sensitive CRP concentrations were measured. Anxiety and depressive symptoms were defined by Hopkins Symptom Checklist-25 (HSCL-25). RESULTS After adjusting for confounders, logistic regression analyses showed that anxiety symptoms alone increased the probability for elevated hs-CRP levels (>3.0mg/L) in males over two-fold (2.19 CI 95% 1.08-4.46), while comorbid anxiety and depressive symptoms caused a 1.7-fold (1.76 CI 95% 1.13-2.74) increase in the probability for elevated hs-CRP levels (1.0-3.0mg/L). CONCLUSIONS Our results support the hypothesis that anxiety as well as comorbid anxiety and depression can be associated with an increased risk for low-grade inflammation in males at population level.

C-reactive protein levels and sleep disturbances : Observations based on the northern Finland 1966 birth cohort study

Objective: To investigate whether sleep disturbances are associated with C-reactive protein (CRP) levels at the population level. Elevated CRP levels have been found to accompany sleep disturbances, but evidence so far comes only from limited clinical and experimental studies; epidemiological studies are lacking. Methods: We utilized the Northern Finland 1966 Birth Cohort, whose participants have been followed up to the age of 31 years. The hs-enzyme immunoassay method was used to measure highly sensitive-CRP (hs-CRP) concentrations (4011 participants). Self-reported sleep disturbances were ranked from 1 (no problem) to 5 (severe disturbances). Results: Multivariate analyses, after adjusting for confounders, revealed that hs-CRP levels in men in the sleep disturbance category “moderate, considerable and severe” (i.e., self-reported sleep disturbances rated 3, 4, or 5), were >18% (18.2%, 95% Confidence Interval 3.0% to 36.3%) higher than those in men with “no” sleep disturbance. In women, hs-CRP levels did not significantly differ between different sleep disturbance categories. Conclusions: Our results support the hypothesis that moderate-to-severe sleep disturbances in men are associated with slightly increased CRP levels at the epidemiological level. Further investigations are called for to see whether our results can be replicated in other databases. CRP = C-reactive protein; IL-6 = interleukin-6; EIA = enzyme immunoassay; Hs-CRP = highly sensitive C-reactive protein; HSCL-25 = Hopkins Symptom Checklist-25.

Depressive symptoms and insulin resistance in young adult males: results from the Northern Finland 1966 birth cohort

The association between insulin resistance (IR) and depression is a subject of growing research interest, especially as previous population-based studies have presented conflicting findings. The present study extends our understanding about the putative impact of the severity of depressive symptoms on this association and it provides further epidemiological evidence in support of earlier findings, suggesting that the association between IR and depression is present already in young adult males. To determine the impact of the severity of depressive symptoms on the putative association between IR and depression in young adult males, we were given access to the Northern Finland 1966 Birth Cohort database. During the 31-year follow-up survey of this genetically homogeneous birth cohort, IR was assessed by ‘Qualitative Insulin Sensitivity Check Index’ (QUICKI), and severity of depressive symptoms by ‘Hopkins’ Symptom Checklist-25’ (HSCL-25). This study involved 2609 male cohort members with complete variable information. In men, the means of the QUICKI-values decreased (i.e., IR increased) in line with the increased severity of depressive symptoms as assessed by HSCL-25 subgroups (analysis of covariance P-value for trend, P=0.003). In multivariate generalized logistic regression analyses, after adjusting for confounders, IR was positively associated with current severe depressive symptoms, the odds ratio (OR) being over threefold (adjusted OR 3.15, 95% confidence interval 1.48–6.68) and the value of OR increased in parallel with a tighter definition of IR (P-value for trend=0.007). The results indicate that in young males, a positive association exists specifically with severe depressive symptoms.