Associations of allostatic load with sociodemographic factors, depressive symptoms, lifestyle, and health characteristics in a large general population-based sample.

OBJECTIVE: We examined the associations between allostatic load (AL) and sociodemographic factors, depressive symptoms, lifestyle and health characteristics in a population-based sample of 4993 adults in Finland. METHODS: Thirteen biomarkers were used to construct AL. High AL was defined as scoring highly in ≥4 items. RESULTS: AL scores of 4 and above were exceeded in the age group of 45-54 years in men and 65-74 years in women. Age was the strongest predictor for belonging to the high AL score group. In addition, elevated depressive symptoms (BDI-6 ≥ 4), male sex, not engaging in physical exercise, high alcohol use and a low level of education were associated with an increased likelihood of belonging to the high AL group. CONCLUSION: The older the participants were, the greater their AL burden was. However, AL burden increased more steeply as a function of age in men. In addition to lifestyle interventions, effective prevention strategies for depression at the population level could have a major public health impact in reducing the accumulation of AL burden.

Alcohol use associated alterations in the circulating metabolite profile in the general population and in individuals with major depressive disorder.

Our aim was to evaluate whether alcohol use is associated with changes in the circulating metabolite profile similar to those present in persons with depression. If so, these findings could partially explain the link between alcohol use and depression. We applied a targeted liquid chromatography mass spectrometry method to evaluate correlates between concentrations of 86 circulating metabolites and self-reported alcohol use in a cohort of the non-depressed general population (GP) (n = 247) and a cohort of individuals with major depressive disorder (MDD) (n = 99). Alcohol use was associated with alterations in circulating concentrations of metabolites in both cohorts. Our main finding was that self-reported alcohol use was negatively correlated with serum concentrations of hippuric acid in the GP cohort. In the GP cohort, consumption of six or more doses per week was associated with low hippuric acid concentrations, similar to those observed in the MDD cohort, but in these individuals it was regardless of their level of alcohol use. Reduced serum concentrations of hippuric acid suggest that already moderate alcohol use is associated with depression-like changes in the serum levels of metabolites associated with gut microbiota and liver function; this may be one possible molecular level link between alcohol use and depression.

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.

The effects of motivational self-care promotion on depressive symptoms among adults with type 2 diabetes: A systematic review and meta-analysis.

In individuals with type 2 diabetes (T2D), comorbid depression leads to increased health care costs and unsatisfactory treatment outcomes. Supporting healthy behaviors and self-efficacy might provide means to prevent depressive symptoms. We assessed the effects of motivational interviewing (MI) - based self-care promotion that specifically targets health behaviors, on depressive symptoms in adults with T2D. We followed PRISMA guidelines and searched Pubmed, Scopus, PsycINFO, Cinahl, and Cochrane Library to find randomized controlled trials (RCTs) published up to February 2023. Eligible RCTs had to target the T2D adult population, examine MI-based interventions that focus on multiple health behaviors, and measure depressive symptoms on a validated scale. Standardized mean differences (SMD) with 95% confidence intervals were calculated using a random-effects model. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess the certainty of the evidence. After the screening, eleven studies with 2,682 individuals were eligible for the narrative synthesis. A meta-analysis of nine studies favored interventions with a pooled SMD of -0.19 (95% Cl = -0.34 to -0.05, p = 0.008, I2 = 52%). Due to the indirectness and imprecision of the evidence, we assessed the certainty of evidence based on GRADE as low. MI-based self-care promotion with a focus on health behaviors and implemented by a well MI-trained person had a preventive effect on depressive symptoms among adults with T2D. However, the certainty of evidence remained low. In future trials, the effect of MI-based self-care promotion on depression should be studied in clinically depressed populations.

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.

Serum levels of carnosine may be associated with the duration of MDD episodes.

BACKGROUND: Major depressive disorder (MDD) is a recurrent disorder that incurs a high societal burden. However, the etiology of MDD remains unclear. The functioning of several systems associated with the etiopathogenesis of MDD, such as inflammatory and stress systems, is partially modulated by the dipeptide carnosine. METHODS: The study comprised 99 MDD patients and 253 non-depressed controls aged 20-71 years. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of carnosine and its constituent, histidine. We compared these metabolites in three different settings: 1) MDD patients vs. non-depressed controls and 2) remitted vs. non-remitted MDD patients, as well as 3) changes in the metabolite levels during the follow-up period within a) the remitted group and b) the non-remitted group. In addition, we assessed the possible effect of medications on the measured metabolites. RESULTS: We observed higher serum levels of carnosine in the MDD group compared to the control group at baseline (OR = 1.895, 95%CI = 1.223-2.937, p = 0.004). Elevated serum levels of carnosine were also associated with a longer duration of the depressive episode (Z = 0.406, p = 0.001). However, the use of any antipsychotic medication (n = 36) was associated with lowered carnosine levels (p = 0.010 for use vs. non-use). At the follow-up, remitted and non-remitted participants displayed no significant differences in their carnosine levels (Z = -0.14, p = 0.891) or histidine (Z = -1.39 p = 0.164). CONCLUSIONS: An increase in circulating carnosine may characterize depressive episodes and may represent a protective homeostatic reaction against MDD-related oxidative stress and inflammation.

The effect of vitamin D supplementation on depressive symptoms in adults: A systematic review and meta-analysis of randomized controlled trials.

Neurosteroid and immunological actions of vitamin D may regulate depression-linked physiology. Meta-analyses investigating the effect of vitamin D on depression have been inconsistent. This meta-analysis investigated the efficacy of vitamin D in reducing depressive symptoms among adults in randomized placebo-controlled trials (RCT). General and clinical populations, and studies of ill individuals with systemic diseases were included. Light therapy, co-supplementation (except calcium) and bipolar disorder were exclusionary. Databases Medline, PsycINFO, CINAHL and The Cochrane Library were searched to identify relevant articles in English published before April 2022. Cochrane risk-of-bias tool (RoB 2) and GRADE were used to appraise studies. Forty-one RCTs (n = 53,235) were included. Analyses based on random-effects models were performed with the Comprehensive Meta-analysis Software. Results for main outcome (n = 53,235) revealed a positive effect of vitamin D on depressive symptoms (Hedges' g = -0.317, 95% CI [-0.405, -0.230], p < 0.001, I2 = 88.16%; GRADE: very low certainty). RoB assessment was concerning in most studies. Notwithstanding high heterogeneity, vitamin D supplementation ≥ 2,000 IU/day appears to reduce depressive symptoms. Future research should investigate possible benefits of augmenting standard treatments with vitamin D in clinical depression. PROSPERO registration number: CRD42020149760. Funding: Finnish Medical Foundation, grant 4120 and Juho Vainio Foundation, grant 202100353.

Association between alexithymia and substance use: A systematic review and meta-analysis.

Alexithymia has been associated with substance use, but the magnitude of the association has not been evaluated and sub-group differences, if any, are unknown. The aim of this meta-analysis is to systematically review the association between alexithymia and substance use (alcohol or illicit drugs). We identified studies through a systematic review of PubMed and Web of Science and obtained a total of 52 publications using the Toronto Alexithymia Scale-20 scale. Random effects meta-analysis was used to evaluate the overall and sub-group associations. Of the studies, 50 were cross-sectional and two longitudinal. Alexithymia was associated with any substance use (Cohen's d = 0.62, 95% confidence interval [CI] 0.49-0.76), with little difference between estimates for use of alcohol or illicit drugs. A stronger association was observed for the alexithymia dimension "Difficulty in Identifying Feelings" (d = 0.64, 95% CI = 0.47-0.81) and "Difficulty in Describing Feelings" (d = 0.44, 95% CI = 0.32-0.55) than for "Externally Oriented Thinking" (d = 0.19, 95% CI = 0.09-0.28). The association was stronger in studies with clinical patient populations (d = 0.83, 95% CI = 0.62-1.05) than in those investigating general or student populations, and in studies with a majority of male rather than female participants. These findings suggest a strong overall association between alexithymia and substance use and a very strong association among clinical patient populations. The association may be stronger with the emotion-related dimensions than with the cognition-related dimension of alexithymia. As nearly all the studies were cross-sectional, more longitudinal studies are needed.

Cerebrospinal fluid dynamics in idiopathic intracranial hypertension: a literature review and validation of contemporary findings.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a rare disease of unknown aetiology related possibly to disturbed cerebrospinal fluid (CSF) dynamics and characterised by elevated intracranial pressure (ICP) causing optic nerve atrophy if not timely treated. We studied CSF dynamics of the IIH patients based on the available literature and our well-defined cohort. METHOD: A literature review was performed from PubMed between 1980 and 2020 in compliance with the PRISMA guideline. Our study includes 59 patients with clinical, demographical, neuro-ophthalmological, radiological, outcome data, and lumbar CSF pressure measurements for suspicion of IIH; 39 patients had verified IIH while 20 patients did not according to Friedman's criteria, hence referred to as symptomatic controls. RESULTS: The literature review yielded 19 suitable studies; 452 IIH patients and 264 controls had undergone intraventricular or lumbar CSF pressure measurements. In our study, the mean CSF pressure, pulse amplitudes, power of respiratory waves (RESP), and the pressure constant (P0) were higher in IIH than symptomatic controls (p < 0.01). The mean CSF pressure was higher in IIH patients with psychiatric comorbidity than without (p < 0.05). In IIH patients without acetazolamide treatment, the RAP index and power of slow waves were also higher (p < 0.05). IIH patients with excess CSF around the optic nerves had lower relative pulse pressure coefficient (RPPC) and RESP than those without (p < 0.05). CONCLUSIONS: Our literature review revealed increased CSF pressure, resistance to CSF outflow and sagittal sinus pressure (SSP) as key findings in IIH. Our study confirmed significantly higher lumbar CSF pressure and increased CSF pressure waves and RAP index in IIH when excluding patients with acetazolamide treatment. In overall, the findings reflect decreased craniospinal compliance and potentially depleted cerebral autoregulation resulting from the increased CSF pressure in IIH. The increased slow waves in patients without acetazolamide may indicate issues in autoregulation, while increased P0 could reflect the increased SSP.

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.

Depression and loneliness may have a direct connection without mediating factors.

PURPOSE OF THE ARTICLE: There is growing interest in loneliness and its various adverse effects on mental and physical health. While depression is one of the adverse health effects associated with loneliness, there have been some limitations in previous studies: 1) Research has mostly been carried out either in depressed patient samples or in general population samples with depressive symptoms as an outcome, 2) the follow-up times have been rather short, and 3) the mechanisms through which loneliness associates with depression are still unclear. MATERIALS AND METHODS: We examined the association between loneliness and incident depression and possible mechanisms underlying this association in a population-based sample of middle-aged men (N = 2339; mean age 53; mean follow-up time 23.5 years). The association between loneliness and depression was explored with Cox proportional hazard analysis, and mediation analyses were performed with the PROCESS macro for SPSS. We used 13 health and lifestyle-related variables as covariates for adjustments in multivariate models and as mediators in simple mediation models. RESULTS: Those with depression as an outcome (n = 99) had significantly higher loneliness scale scores at baseline, and baseline loneliness was associated with depression, despite adjustments for potential confounding factors. No mediating factors were observed. CONCLUSIONS: There was a strong direct association between loneliness and the incidence of depression. Based on our results, we encourage future researchers to look for possible mediators in wider range of variables.

Comparison of the level of allostatic load between patients with major depression and the general population.

OBJECTIVE: We compared the level of allostatic load (AL) between patients with major depressive disorder (MDD) and non-depressed controls using two definitions of AL: continuous AL scores (AL index) and clinically significant high AL (≥4). We examined whether MDD was associated with AL independent of basic socioeconomic (age, sex, cohabiting status and level of education) and lifestyle factors (smoking and alcohol use). METHODS: The MDD patient sample consisted of 177 psychiatric outpatients (mean age 33.7, SD 10.7 years), who were recruited from the Department of Psychiatry at Kuopio University Hospital, Finland, in 2016-19. The non-depressed controls (n = 228, mean age 49.8, SD 10.1 years) lived in the municipality of Lapinlahti, Finland. Ten biomarkers were used to construct the two AL variables. These indicators were systolic and diastolic blood pressure, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine, waist circumference, body mass index (BMI) and C-reactive protein (CRP). RESULTS: The mean AL scores did not significantly differ between MDD patients (2.97) and non-depressed controls (3.12), thus it was not associated with MDD in univariate analysis. In multivariate models a higher AL index was associated with a 1.42 to 1.82 times higher likelihood of belonging to the MDD group. Furthermore, we found that high AL (i.e. AL ≥ 4) was associated with MDD, with the likelihood ranging between 2.27 and 2.96 compared with the non-depressed controls in multivariate models. CONCLUSIONS: Even young adult patients with MDD appear to display clinically significant, high AL compared with non-depressed controls. Thus, it is important to pay attention to the somatic health of depressed patients in addition to their mental health.

The impact of postpartum depressive symptoms on self-reported infant health and analgesic consumption at the age of 12 months: A prospective cohort study.

The infants of mothers with elevated depressive symptoms (EDS) postpartum appear to be at increased risk of somatic health problems during their first 12 months of life in low- and lower-middle-income countries. However, in higher-income countries, knowledge of this association is scarce. We sought to examine whether maternal reports of infant health problems, adherence to vaccination schedules and analgesic supply to the infant during the first 12 months of life differ between mothers with and without postpartum EDS. Altogether, 969 women who were enrolled in the Kuopio Birth Cohort study (www.kubico.fi) during 2012-2017 were included in this investigation. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale during pregnancy (1st and/or 3rd trimester) and at eight weeks postpartum. Infant health data were collected as a part of a 12-month online follow-up questionnaire for mothers and were based on self-reports of either maternal observations or physician-determined diagnoses. Postpartum EDS were associated with a 2- to 5-fold increased likelihood of abnormal crying and paroxysmal wheezing (based on parental observations), as well as gastroesophageal reflux and food allergy (based on physician-determined diagnoses). Mothers with postpartum EDS also supplied their infants with analgesic medication for longer periods. Adherence to vaccination schedules was similar between the examined groups. In conclusion, infants of mothers with postpartum EDS may be more likely to experience health problems or to be perceived by their mother as having health problems, and thus receive more medications.

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.

The role of the microbiome in the neurobiology of social behaviour.

Microbes colonise all multicellular life, and the gut microbiome has been shown to influence a range of host physiological and behavioural phenotypes. One of the most intriguing and least understood of these influences lies in the domain of the microbiome's interactions with host social behaviour, with new evidence revealing that the gut microbiome makes important contributions to animal sociality. However, little is known about the biological processes through which the microbiome might influence host social behaviour. Here, we synthesise evidence of the gut microbiome's interactions with various aspects of host sociality, including sociability, social cognition, social stress, and autism. We discuss evidence of microbial associations with the most likely physiological mediators of animal social interaction. These include the structure and function of regions of the 'social' brain (the amygdala, the prefrontal cortex, and the hippocampus) and the regulation of 'social' signalling molecules (glucocorticoids including corticosterone and cortisol, sex hormones including testosterone, oestrogens, and progestogens, neuropeptide hormones such as oxytocin and arginine vasopressin, and monoamine neurotransmitters such as serotonin and dopamine). We also discuss microbiome-associated host genetic and epigenetic processes relevant to social behaviour. We then review research on microbial interactions with olfaction in insects and mammals, which contribute to social signalling and communication. Following these discussions, we examine evidence of microbial associations with emotion and social behaviour in humans, focussing on psychobiotic studies, microbe-depression correlations, early human development, autism, and issues of statistical power, replication, and causality. We analyse how the putative physiological mediators of the microbiome-sociality connection may be investigated, and discuss issues relating to the interpretation of results. We also suggest that other candidate molecules should be studied, insofar as they exert effects on social behaviour and are known to interact with the microbiome. Finally, we consider different models of the sequence of microbial effects on host physiological development, and how these may contribute to host social behaviour.