The associations between metabolic profiles and sexual and physical abuse in depressed adolescent psychiatric outpatients: an exploratory pilot study.

Background: Sexual and physical abuse have been associated with long-term systemic alterations such as low-grade inflammation and changes in brain morphology that may be reflected in the metabolome. However, data on the metabolic consequences of sexual and physical abuse remain scarce.Objective: This pilot study sought to investigate changes in the metabolite profile related to sexual and physical abuse in depressed adolescent psychiatric outpatients.Method: The study included 76 patients aged 14-18 years, whose serum samples were analysed with a targeted metabolite profiling methodology. We estimated the associations between metabolite concentrations and the Trauma and Distress Scale (TADS) Sexual and Physical Abuse factor scores using three linear regression models (one unadjusted and two adjusted) per metabolite and trauma type pair. Additional variables in the two adjusted models were 1) the lifestyle indicators body mass index, tobacco use, and alcohol use, and 2) depression scores and the chronicity of depression.Results: TADS Sexual Abuse scores associated positively with homogentisic acid, as well as cystathionine, and negatively with choline in linear regression analysis, whereas TADS Physical Abuse scores associated negatively with AMP, choline, γ-glutamyl cysteine and succinate, and positively with D-glucuronic acid.Conclusions: This pilot study did not include a healthy control group for comparison and the cohort was relatively small. Nevertheless, we observed alterations in metabolites related to one-carbon metabolism, mitochondrial dysfunction, oxidative stress, and inflammation in depressed patients with a history of sexual or physical abuse.

Metabolomic profiles associate with sexual or physical abuse.Metabolites relate to mitochondria, one-carbon, oxidative stress, and inflammation.Metabolomics a possible tool for precision psychiatry in the future.

Long-term changes in sense of coherence and mortality among middle-aged men: A population -based follow-up study.

Sense of coherence (SOC) scale measures one's orientation to life. SOC is the core construct in Antonovsky's salutogenic model of health. It has been shown that weak SOC correlates with poor perceived health, low quality of life, and increased mortality. Some studies have indicated that SOC is not stable across life, but there are no previous studies on how a change of SOC is reflected in mortality. However, there is some evidence that a change in perceived quality of life is associated with mortality. The study explores the association between the change in SOC and mortality using longitudinal data from a cohort of middle-aged Finnish men recruited between 1986 and 1989. Approximately 11 years after the baseline examinations, between 1998 and 2001, 854 men returned the SOC questionnaire a second time. The baseline SOC was adjusted for the regression to the mean phenomenon between the two measurements. The hazard ratios of the SOC difference scores were adjusted for initial SOC age and 12 somatic risk factors of mortality (alcohol consumption, blood pressure, body mass index, cholesterol concentration, physical activity, education, smoking, marital status, employment status, history of cancer, history of cardiovascular disease and diabetes). SOC was not stable among middle-aged Finnish men and a decline in SOC was associated with an increased hazard of all-cause mortality. In the fully adjusted model, a decrease of one standard deviation (SD) of the SOC mean difference increased the mortality hazard by about 35 %, two SDs decrease about 70 %, and 2.5 SDs about 100 %. Strengthening SOC showed a limited association with decreasing mortality hazards in the age-adjusted model. Policies, strategies, or plans, supporting SOC in the middle-age may help to decrease mortality and increase quality of life in later years.

The effects of loneliness and social isolation on all-cause, injury, cancer, and CVD mortality in a cohort of middle-aged Finnish men. A prospective study.

OBJECTIVES: Loneliness and social isolation both increase mortality and are likely to affect health via several pathways. However, information on the potential pathways remains scarce. We investigated the associations between loneliness, social isolation, and mortality, and possible mechanisms underlying these connections. METHODS: The analyzed data comprised a prospective population-based cohort of Finnish men (42-61 years at baseline, n = 2588) who were followed up for an average of 23.2 years. Mortality data were obtained from the national population register in 2012. Cox proportional hazards analysis with adjustments for possible confounding factors was used to examine the associations between loneliness and social isolation at baseline and all-cause, injury, cancer, and cardiovascular disease (CVD) mortality. Mediation analysis was conducted to investigate the mechanisms underlying the associations of loneliness and social isolation with mortality. RESULTS: Loneliness predicted all-cause mortality, even after adjustments for all covariates. Loneliness predicted cancer mortality, except after adjustments for lifestyle variables or Human Population Laboratory (HPL) depression scores, and also predicted CVD mortality, except after adjustments for HPL depression scores. Social isolation predicted all-cause mortality and injury mortality. The effect of social isolation on all-cause mortality was mediated by loneliness and HPL depression scores. CONCLUSIONS: Our findings suggest that both loneliness and social isolation increase the risk of all-cause mortality, while they have differing effects on different causes of death. Loneliness and depressive symptoms may mediate the effect of social isolation on increased mortality.

Loneliness and social isolation increase cancer incidence in a cohort of Finnish middle-aged men. A longitudinal study.

Globally, cancer is the second leading cause of death. Loneliness has been suggested as a risk factor for cancer mortality. However, connections between loneliness, social isolation, and cancer are poorly understood. In our longitudinal study (mean follow-up: 20.44 years) of 2570 middle-aged men, loneliness, social isolation, and health-related factors were measured at baseline. Cox proportional hazards analysis was used to examine the association between cancer incidence, loneliness, and social isolation. The effect of relationship status on cancer mortality among cancer patients was tested with the Kaplan-Meier method. Loneliness was associated with total cancer incidence after adjustments for tested lifestyle and health-related covariates. Social Isolation was associated with total cancer incidence, except when adjusted for lifestyle, diet, or Human Population Laboratory (HPL) Depression Scale scores. Loneliness was associated with lung cancer incidence, except when adjusted for HPL Depression Scale scores. There was no significant association between social isolation and lung cancer. Neither loneliness nor social isolation were connected with prostate or colorectal cancer. Being single at baseline was associated with worse survival outcomes for cancer patients. Our findings suggest that regardless of the social network size, loneliness among middle-aged men is associated with an increased likelihood of cancer.

MRI-guided brachytherapy for locally advanced cervical cancer: Program initiation, learning curve and dose delivery results in Kuopio University Hospital.

BACKGROUND AND PURPOSE: Image guided adaptive brachytherapy, the standard treatment for locally advanced cervical cancer (LACC), is a complex medical procedure that requires an experienced multidisciplinary team. The aims of this analysis were to assess (1) the learning curve of brachytherapy team, (2) dose-volume parameters, (3) the use of an interstitial component, and (4) the overall treatment time (OTT). MATERIALS AND METHODS: Our study cohort comprised 117 LACC patients treated in Kuopio University Hospital with magnetic resonance imaging guided intracavitary (IC) or combined intracavitary/interstitial (IC/IS) high dose rate brachytherapy during 2009-2018. Target volumes and organs at risk (OAR) were contoured according to ICRU/GEC-ESTRO recommendations. Treatment plans were optimized individually without using standard loading patterns. RESULTS: Mean dose to 90% of the high-risk clinical target volume (HR-CTV D90) improved after the first 15 patients, however the team's learning curve to reliably fulfill the main planning aim (PA) of 85 Gy required a total 43 patients and more than 10 patients annually. Significant difference was detected between IC and IC/IS brachytherapy in achieving the PA of HR-CTV D90. Especially, HR-CTV volumes >30 cm3 benefitted from IS needles. Needle insertion did not cause serious complications. With the brachytherapy program, the OTT of patients from outside institutions was reduced to the same level as our own patients. CONCLUSION: Brachytherapy requires good experience of multidisciplinary team and the continuous development of the program to fulfill PA and to avoid OTT prolongation. The use of IS needles is safe and improves the fulfillment of PA to target volume.

Parental Alcohol Problems, Parental Divorce, and Type 2 Diabetes in Adulthood: A Longitudinal Prospective Cohort Study in Middle-Aged Men.

OBJECTIVE: Type 2 diabetes is a chronic disease and a serious global public health concern increasing both mortality and morbidity. Previous studies have found evidence for an association between early psychological stress and diabetes later in life. METHODS: This study examined the association between parental alcohol problems and parental divorce and the incidence of type 2 diabetes in Finnish men aged 42 to 61 years (n = 754) in a prospective setting. Information on parental alcohol problems and parental divorce was derived from school records and subjective experiences of the same events from self-rated questionnaires. The average follow-up time for the participants until the first type 2 diabetes diagnosis was 23.3 years (25th-75th percentile, 21.2-27.9 years). RESULTS: Cox regression analyses revealed that parental alcohol problems (hazard ratio = 3.09, 95% confidence interval = 1.38-6.88) were associated with an increased risk of type 2 diabetes during the follow-up, even after adjustment for age, marital status, education, Human Population Laboratory Depression Scale scores, smoking, alcohol consumption, body mass index, and serum high-sensitivity C-reactive protein. In a similar model, parental divorce (hazard ratio = 1.69, 95% confidence interval = 0.40-7.05) was not associated with an increased risk of type 2 diabetes during the follow-up. CONCLUSIONS: Our findings suggest that not all adverse childhood experiences contribute equally to the risk of type 2 diabetes. Parental alcohol problems, but not parental divorce, were associated with an increased risk of type 2 diabetes in men. These findings highlight the need for early interventions targeting parents with excessive alcohol consumption to reduce their offspring's risk of life-style-related disorders.

Repeated Transcranial Magnetic Stimulation-Induced Motor Evoked Potentials Correlate With the Subject-Specific Serum Metabolic Profile of Creatine.

PURPOSE: Transcranial magnetic stimulation-induced motor responses have been considered to mainly reflect the electrophysiological characteristics of the central motor system. However, certain motor phenomena, such as the magnitude of repetition suppression measured with motor evoked potentials (MEPs), could also in part be influenced by metabolic processes in the peripheral muscles and in both the peripheral and central nervous system. Repetition suppression is an inhibitory phenomenon in which the amplitude of MEP decreases in comparison to that of the first MEP in a train of transcranial magnetic stimulation pulses. This study aimed to identify possible metabolic processes influencing repetition suppression. METHODS: The metabolic profiles from serum samples and repetition suppression from the right abductor pollicis brevis muscle were measured in 73 subjects (37 female subjects). Repetition suppression was measured using trains of transcranial magnetic stimulation stimuli consisting of 4 identical single pulses at 1-second intervals. The trains were repeated every 20 seconds, and 30 trains were given with a stimulation intensity of 120% of the resting motor threshold of the abductor pollicis brevis. Thus, a total of 120 stimuli were administered. RESULTS: The main finding was a significant negative relationship between serum creatine levels and the magnitude of repetition suppression (standardized ß coefficient (ß) = -0.43; P < 0.001). In other words, higher creatine levels corresponded to a smaller decrement in the MEP amplitude in response to repetition. When MEPs were not repeated, no relationship was observed (ß = 0.09; P = 0.454). Creatine is used to form phosphocreatine, which in turn is needed to resynthesize adenosine triphosphate from adenosine diphosphate in situations requiring high amounts of energy in muscles and neural cells. CONCLUSIONS: For the first time, this study demonstrated a connection between repeated MEPs and peripheral serum metabolites linked to muscle function. These findings could explain some of the intersubject variability commonly observed in MEPs when the pulses are repeated.

Self-reported sleep disturbance and incidence of dementia in ageing men.

BACKGROUND: Sleep disturbance is suggested to contribute to the development of dementia. However, prospective longitudinal data from middle-aged populations are scarce. METHODS: We investigated a population-based sample of 2386 men aged 42-62 years at baseline during 1984-1989. Participants having a history of mental illnesses, psychiatric medication, Parkinson's disease or dementia within 2 years after baseline (n=296) were excluded. Difficulty falling asleep or maintaining sleep, sleep duration and daytime tiredness were enquired. Dementia diagnoses (n=287) between 1984 and 2014 were obtained through linkage with hospital discharge, national death and special reimbursement registers. Cox proportional hazards analyses were performed for all dementias, and separately for Alzheimer's disease (n=234) and other phenotypes (n=53). Additional analyses were performed on a subsample of an apolipoprotein E (APOE) genotype-tested population (n=1199). RESULTS: The risk ratio for dementia was 1.58 (95% CI 1.10 to 2.27) in men with frequent sleep disturbance after adjustments for age, examination year, elevated depressive symptoms, physical activity, alcohol consumption, cumulative smoking history, systolic blood pressure, body mass index, low-density lipoprotein and high-density lipoprotein cholesterol, high-sensitivity C reactive protein, cardiovascular disease history, education years and living alone. Daytime tiredness and sleep duration were not associated with dementia in adjusted analysis. In the APOE subsample, both APOE ε4 genotype and frequent sleep disturbance were associated with increased dementia risk, but in the interaction analysis they had no joint effect. CONCLUSIONS: Self-reported frequent sleep disturbance in middle-aged men may relate to the development of dementia in later life. Having an APOE ε4 genotype did not affect the relationship.

Purine metabolism is dysregulated in patients with major depressive disorder.

INTRODUCTION: The purine cycle and altered purinergic signaling have been suggested to play a role in major depressive disorder (MDD). Nevertheless, data on this topic are scarce. Based on previous studies, we hypothesized that compared with non-depressed controls, MDD patients have distinct purine metabolite profiles. METHODS: The samples comprised 99 MDD patients and 253 non-depressed controls, aged 20-71 years. Background data were collected with questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) to determine seven purine cycle metabolites belonging to the purine cycle. We investigated the levels of these metabolites in three settings: (1) MDD patients vs. non-depressed controls and (2) remitted vs. non-remitted MDD patients, and also (3) within-group changes in metabolite levels during the follow-up period. RESULTS: In logistic regression adjusted for age, gender, smoking, alcohol use, physical exercise, glycosylated hemoglobin, and high-density lipoprotein cholesterol, lower levels of inosine (OR 0.89, 95% CI 0.82-0.97) and guanosine (OR 0.32, 95% CI 0.17-0.59), and higher levels of xanthine (OR 2.21, 95% CI 1.30-3.75) were associated with MDD vs. the non-depressed group. Levels of several metabolites changed significantly during the follow-up period in the MDD group, but there were no differences between remitted and non-remitted groups. CONCLUSIONS: We observed altered purine metabolism in MDD patients compared with non-depressed controls. Furthermore, our observations suggest that circulating xanthine may accumulate in MDD patients.

Serum copper, zinc and high-sensitivity C-reactive protein in short and long sleep duration in ageing men.

BACKGROUND: Serum levels of zinc and copper have been proposed to associate with sleep duration. Mechanisms, such as inflammatory processes, have been suggested to relate this association. However, earlier studies have been conducted in small sample sizes. Human studies investigating the suggested associations while controlling for potential confounding factors are lacking. METHODS: Population-based data consisted of 2570 men (aged 42-60 years) from Eastern Finland. The participants reported an estimate of their sleep duration. The serum levels of zinc (S-Zn), copper (S-Cu) and high-sensitivity C-reactive protein (hs-CRP) were measured. Analysis of covariance was used for multivariate analyses. RESULTS: S-Zn levels and Zn/Cu ratio were lowest in ≤6h sleep. S-Cu levels were highest in ≥10h sleep. Elevated levels (>3.0mmol/l) of hs-CRP were observed in ≤6h and ≥10h sleep. After adjustments for age, cumulative smoking history (pack-years), alcohol consumption (g/week), Human Population Laboratory depression scale scores, physical activity (kcal/day), cardiometabolic syndrome, and cardiovascular disease history, sleep duration was significantly associated with levels of both S-Cu and hs-CRP. The association with S-Cu remained statistically significant following further adjustment for hs-CRP in the same model. CONCLUSIONS: Our data suggests an association between S-Cu and sleep duration in ageing men. Elevated inflammation (measured as serum hs-CRP) does not explain this relationship. Mechanisms underlying the relationship require further investigation, as S-Cu may contribute to sleep regulation through pro-oxidative processes and copper-dependent N-methyl-d-aspartate receptor activity.

Alcohol use among adolescents, aggressive behaviour, and internalizing problems.

Alcohol use is common among adolescents, but its association with behavioural and emotional problems is not well understood. This study aimed to investigate how self-reported psychosocial problems were associated with the use of alcohol in a community sample consisting of 4074 Finnish adolescents aged 13-18 years. Aggressive behaviour associated with alcohol use and a high level of alcohol consumption, while internalizing problems did not associate with alcohol use. Having problems in social relationships associated with abstinence and lower alcohol consumption. Tobacco smoking, early menarche and attention problems also associated with alcohol use.

Sleep duration and incidence of lung cancer in ageing men.

BACKGROUND: Previous studies have suggested an association between sleep duration and cancer. However, the information on sleep duration regard to risk of lung cancer is scanty. METHODS: Analysed data comprised prospective population-based cohort of 2586 men (aged 42-60 years) from Eastern Finland. Baseline survey and clinical examinations took place 1984-1989, and diagnosed lung cancers were obtained until the end of 2011 through linkage with the Finnish Cancer Registry. Self-reported sleep was categorized as ≤6.5 h, 7-7.5 h, and ≥8 h. Subjects with prior history of cancer or psychotropic medication (hypnotics or sedatives) were excluded from the analyses. Cox proportional hazards models with adjustments for possible confounders were used to examine the association. RESULTS: Significant association between sleep duration and increased lung cancer risk was observed after adjustments for age, examination years, cumulative smoking history, family cancer history and Human Population Laboratory Depression scale scores (HR 2.12, 95% CI 1.17-3.85 for ≤6.5 h sleep, and HR 1.88, 95% CI 1.09-3.22 for ≥8 h sleep). Associations were even stronger among current smokers (HR 2.23, 95% CI 1.14-4.34 for ≤6.5 h sleep, and HR 2.09, 95% CI 1.14-3.81 for ≥8 h sleep). After further adjustments for alcohol consumption, physical activity, body mass index, marital status, education years, night work, employment status, asthma and chronic bronchitis, the association remained significant both in the whole study population and among smokers. When cumulative smoking history was replaced by current smoking in the adjustments, the increased risk was limited to those who slept<6.5 h. CONCLUSIONS: Sleep duration of less than 7-7.5 hours or more than 7-7.5 hours associates with increased lung cancer risk. The physiological factors underlying the association are complex, and they may relate to melatonin excretion patterns, low-grade inflammation in cancer development process or disruptions in circadian rhythmicity.

Dietary patterns are associated with the prevalence of elevated depressive symptoms and the risk of getting a hospital discharge diagnosis of depression in middle-aged or older Finnish men.

BACKGROUND: Previous studies assessing the role of dietary factors in depression have mainly focused on nutrients, while the association between dietary patterns and depression is less studied. OBJECTIVE: The aim was to assess the role of dietary patterns in depression in both cross-sectional and prospective analyses. DESIGN: The study population consisted of 1003 Finnish middle-aged or older men from the Kuopio Ischemic Heart Disease Risk Factor Study. Food consumption was assessed by food frequency questionnaire in 1991-1993 and dietary patterns from 25 predefined food groups were extracted by factor analysis. Depressive symptoms were assessed with the self-administered Human Population Laboratory Depression Scale, cut-off point of five or more indicating elevated depressive symptoms. RESULTS: Altogether 72 (7.2%) subjects had elevated depressive symptoms. Three dietary patterns were identified: "prudent", "Western" and "mixed". In cross-sectional analysis, after adjustments for age, examination year, BMI, smoking, alcohol consumption, education, marital status, leisure-time physical activity, history of mental illness and cardiovascular disease the prudent dietary pattern was associated with a 25% lower prevalence of elevated depressive symptoms (OR: 0.75; 95% CI: 0.57, 0.99; P=0.036), whereas the Western dietary pattern was associated with increased prevalence of elevated depressive symptoms (OR: 1.41; 95% CI: 1.08, 1.84; P=0.011). In the prospective analysis (16.5 follow-up years), the prudent dietary pattern was inversely associated with the risk of getting a hospital discharge diagnosis of depression (HR: 0.66; 95% CI 0.47, 0.93; P=0.018). CONCLUSIONS: Adherence to healthy dietary pattern is associated with lower risk of getting a hospital discharge diagnosis of depression.

Trait anxiety and somatic concerns associate with increased mortality risk: a 23-year follow-up in aging men.

PURPOSE: We aimed to examine the impact of anxiety and somatic concerns on the mortality risk during a 23-year follow-up of a representative sample of men. METHODS: Finnish men aged 42-61 years (n = 2388) were followed up for a median of 23.4 years. Anxiety was assessed using baseline scores for the Minnesota Multiphasic Personality Inventory Psychasthenia subscale and somatic concerns were measured with the Hypochondriasis subscale. Mortality data were obtained from the National Population Register. RESULTS: All-cause, injury, disease, cardiovascular, and cancer mortalities were examined as endpoints. Adjustments were performed for age, smoking, alcohol consumption, physical activity, low- and high-density lipoprotein cholesterol, body mass index, systolic blood pressure, a history of cardiovascular disease, marital status, socioeconomic status, the Framingham Type A Behavior Pattern Scale, and life events during the 12 months before the baseline examination. Anxiety and somatic concerns predicted the all-cause mortality risk after full adjustments for sociodemographic background, lifestyle factors, and descriptors of somatic health. Regarding other forms of mortality, the risk ratios were significant after full adjustments in anxiety for injury and in somatic concerns for disease death. CONCLUSIONS: This study supported previous findings of anxiety predicting the all-cause mortality risk in men. Somatic concerns are a novel factor that needs to be taken into account while examining associations between personality and the risk of increased mortality.

Dietary zinc intake and the risk of depression in middle-aged men: a 20-year prospective follow-up study.

BACKGROUND: Zinc is an immunomodulatory trace element suggested to be beneficial in the augmentation of antidepressant therapy. Cross-sectional studies have also suggested an association between low dietary zinc and depression. This study examined the association between dietary zinc intake and depression in a prospective setting in initially depression-free men during a 20-year follow-up. METHODS: The study formed a part of the population-based Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, and comprised 2317 Finnish men aged 42-61 years. Zinc intake was assessed at baseline by a 4-d food record. Baseline depression severity was recorded with the Human Population Laboratory Depression Scale. In the prospective setting, depression was defined as having received a hospital discharge diagnosis of unipolar depressive disorder. Individuals who at baseline had elevated depressive symptoms were excluded (n=283). RESULTS: Altogether, 60 (2.7%) individuals received a hospital discharge diagnosis of depression during the 20-year follow-up. In Cox regression analysis adjusted for age, baseline depression severity, smoking, alcohol use, physical exercise and the use of dietary supplements, belonging to the lowest tertile of energy-adjusted zinc intake was not associated with an increased depression risk (RR 1.06, 95% CI 0.59-1.90). LIMITATIONS: These observations may not be generalizable to women, or to individuals with a depression level not warranting hospitalization. CONCLUSIONS: Our findings suggest that a low dietary zinc intake may not longitudinally precede depression in men. Dietary zinc intake may not have relevance for the prevention of depression in middle-aged men with a sufficient dietary zinc intake.

Low-grade inflammation and depressive symptoms as predictors of abdominal obesity.

AIM: Abundant evidence suggests that depression is a risk factor for cardiovascular disease and metabolic syndrome. Systemic low-grade inflammation and evolving abdominal obesity are hypothesised to be underlying mechanisms explaining the relationship. To test this hypothesis we examined the association of depressive symptoms and inflammation in developing abdominal obesity. METHODS: The subjects were 726 non-diabetic men, 42-60 of age at baseline, participating in the Kuopio Ischemic Heart Disease Risk Factor Study. The follow-up data was collected 11 years after the baseline. Low-grade inflammation was defined as serum C-reactive protein ≥2 mg/l and depressive symptoms were assessed by the Human Population Laboratory Depression Scale. Incident abdominal obesity was defined as waist girth >102 cm. RESULTS: Men with low-grade inflammation and depressive symptoms were more likely (OR 4.28, 95% CI 1.93-12.01) to develop abdominal obesity during the 11-year follow-up than in men not having either of these conditions, adjusting for age, smoking, alcohol consumption, prevalent cardiovascular disease, physical activity and socioeconomic status. These men were also more likely (OR 3.94, 95% CI 1.38-11.26) to develop metabolic syndrome. CONCLUSIONS: The presence of systemic low-grade inflammation together with depressive symptoms seems to detect men at a particularly high risk of developing abdominal obesity over a long period of time.

Serum adipokine levels in adults with a history of childhood maltreatment.

Individuals with a history of childhood maltreatment present increased rates of metabolic disturbances, but the underlying mechanisms for such phenomena are poorly understood. This study examined whether the secretion of adipokines, adipocyte-derived inflammation markers closely associated with metabolic disorders, is altered in individuals with a history of childhood maltreatment. The serum levels of inflammatory markers adiponectin and resistin were measured from 147 general population participants who had a history of adverse mental symptoms, and who also reported their experiences of childhood maltreatment. Participants with experiences of childhood maltreatment (n=30) had lowered levels of serum adiponectin (p=0.007) and resistin (p=0.028). The differences in adiponectin levels persisted in multivariate modeling with adjustments for age, gender, and body mass index (OR for each 1 standard deviation decrease in the serum adiponectin level 2.65, 95% CI 1.31-5.35, p=0.007). Additional adjustments for marital status or a diagnosis of major depressive disorder, or the exclusion of individuals using NSAIDs, oral corticosteroids, or antidepressants did not alter the results. The association between resistin levels and childhood maltreatment did not remain independent in the same models. Our findings suggest that in individuals with previously reported adverse mental symptoms, a history of childhood maltreatment is independently associated with lowered levels of the anti-inflammatory marker adiponectin. This may lead to a lowered anti-inflammatory buffer capacity, which can, in turn, increase the susceptibility to physical and psychological states characterized by pronounced pro-inflammation.

Serum polyunsaturated fatty acids are not associated with the risk of severe depression in middle-aged Finnish men: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study.

PURPOSE: The aim of this study is to investigate whether serum n - 3 polyunsaturated fatty acids (PUFAs) or n - 6 to n - 3 ratio is associated with risk of severe depression in middle-aged Finnish men. METHODS: The association between the serum concentrations of fatty acids and depression was investigated in 2077 men aged 42-60 years at baseline in a prospective follow-up setting. The population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study cohort was recruited between 1984 and 1989 and followed until the end of 2007. The baseline levels of serum total n - 3 PUFAs, n - 6 PUFAs and individual fatty acids were determined. Data on hospital treatments due to major depressive disorder were derived from the national hospital discharge register. RESULTS: During the average follow-up time of 18 years, 46 men received a discharge diagnosis of depression. When the Cox proportional hazards model was adjusted for age, examination year, baseline socioeconomic status, alcohol consumption, smoking, maximal oxygen uptake and body mass index, there was no association between serum total n - 3 PUFAs and the risk of depression [relative risk (RR) in the highest compared to the lowest tertile 0.71, 95% confidence interval (CI): 0.38; 1.43]. Serum concentrations of n - 6 PUFAs, n6/n3 PUFA ratio, or individual fatty acids were not associated with the risk of severe depression, either. CONCLUSIONS: We did not find evidence that serum n - 3 PUFA concentration or n - 6/n - 3 ratio would be associated with risk of severe depression in middle-aged Finnish men.

Stability of alexithymia in the general population: an 11-year follow-up.

OBJECTIVES: There is an ongoing debate concerning the temporal stability of alexithymia. Most previous studies have been conducted on clinical populations of psychiatric and somatic patients. However, psychiatric and somatic morbidity have been found to confound the findings so that in their presence, alexithymia appears to be less stable. Nevertheless, few general population studies have been published, and there have been no follow-ups longer than 5 years. METHOD: In a population-based sample of middle-aged Finnish men, 755 participants completed the Toronto Alexithymia Scale (TAS)-26 at baseline and on 11-year follow-up. Absolute or mean stability refers to the extent to which scores change over time, and it was measured with group comparisons of paired samples. Relative stability refers to the consistency of relative differences in alexithymia levels among the study subjects, and it was measured with test-retest correlations. RESULTS: Changes in the total scores and the subscales of the TAS-26 were all statistically significant but had low effect sizes (0.09-0.20) for the change-suggested absolute stability. The correlations between baseline and follow-up scores were high (ρ = 0.51-0.63), indicating relative stability. The exclusion of depressive symptoms, a history of mental illnesses, and cancer or cardiovascular diseases at baseline and at the 4- and 11-year follow-ups did not essentially alter these findings. Of the background variables, a higher age independently associated with the increase in the TAS-26 scores. Those with alexithymia at baseline were more likely to have elevated depressive symptoms at the 4- and 11-year follow-ups. CONCLUSIONS: Both the absolute and relative stabilities of alexithymia in the general population are high, even for a long follow-up period. These results may support the assumption that alexithymia represents a stable personality trait in general. Alexithymia may increase vulnerability to depressive symptoms.

Serum anti-inflammatory markers in general population subjects with elevated depressive symptoms.

Anti-inflammatory substances have previously been suggested to show compensatory elevations in depressed individuals with pronounced inflammatory changes. In order to further clarify these observations, we examined depression-related alterations in the serum levels of anti-inflammatory markers interleukin (IL)-1 receptor antagonist (RA) and IL-10 and the pro-inflammatory marker IL-6 in 416 general population participants. Depression was evaluated with the Beck Depression Inventory (BDI). Participants with elevated depressive symptoms (BDI>14, n=44) had increased levels of IL-1 RA and IL-6. No changes were observed in their IL-10 levels. In multivariate modeling with adjustments for age, gender, obesity, regular smoking, alcohol use, metabolic syndrome, physical exercise, sleep disturbance, and the use of non-steroidal anti-inflammatory drugs, a high level of IL-1 RA was associated with an increased likelihood of belonging to the group with elevated depressive symptoms (OR for each 1 SD increase in the serum level of IL-1 RA: 2.17, 95% CI 1.35-3.48, p=0.001). The significance of IL-6 alterations did not persist in the same model. The pronounced secretion of anti-inflammatory marker IL-1 RA may reflect the presence of compensatory mechanisms during a depression-related inflammatory state.