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.

Meaningfulness and mortality: exploring the sense of coherence in Eastern Finnish men.

AIMS: The sense of coherence scale has been shown to have an epidemiological relationship with mortality. This study aimed to investigate how the three components of sense of coherence (meaningfulness, comprehensibility and manageability) and the individual items of these components relate to mortality. METHODS: Eastern Finnish men (n=2315) aged 42-60 years at baseline in the 1980s completed a 12-item sense of coherence scale and were followed for 25 years, on average, until death or until the end of 2019. Hazard ratios for mortality were calculated using two models: one adjusted for age and the second for an additional 12 mortality risk factors. RESULTS: Of the three sense of coherence components, only meaningfulness was associated with all-cause mortality, and in the fully adjusted model, those in the weakest tertile had a 1.14 (95% confidence interval 1.01-1.29, P=0.042) times higher hazard ratio for mortality than those in the strongest tertile. Of the individual sense of coherence items, only the first question, 'How often do you have the feeling that you really don't care about what is going on around you?', was associated with all-cause mortality, and in the fully adjusted Cox model, the hazard ratio of weak versus strong was 1.18 (95% confidence interval 1.03-1.36, P=0.020). CONCLUSIONS: The sense of coherence component related to meaningfulness, including its first item, 'Caring about what goes on around you', plays a significant role in the association with mortality among middle-aged men in Eastern Finland. This item should be considered a noteworthy patient-reported variable when predicting mortality in public health settings.

Promotive and preventive interventions for mental health and well-being in adult populations: a systematic umbrella review.

Introduction: Mental health disorders are increasing worldwide, leading to significant personal, economic, and social consequences. Mental health promotion and prevention have been the subject of many systematic reviews. Thus, decision makers likely face the problem of going through literature to find and utilize the best available evidence. Therefore, this systematic umbrella review aims to evaluate the effectiveness of interventions for promoting mental health and mental well-being, as well as for the primary prevention of mental health disorders. Methods: Literature searches were performed in APA PsycInfo, Medline, and Proquest Social Science databases from January 2000 to December 2021. The search results were screened for eligibility using pre-defined criteria. The methodological quality of the included reviews was evaluated using the AMSTAR 2 tool. The key findings of the included reviews were narratively synthesized and reported with an emphasis on reviews achieving higher methodological quality. Results: Out of the 240 articles found, 16 systematic reviews and four systematic umbrella reviews were included. The methodological quality of included reviews was low or critically low. Discussion: This review suggests that interventions using cognitive-behavioral therapy and those developing resilience, mindfulness, or healthy lifestyles can be effective in the promotion of mental health and well-being in adult populations. Motivational interviewing may reduce alcohol consumption in young adults. Indicated or selective prevention is likely to be cost-effective compared to universal prevention. Parenting interventions and workplace interventions may be cost-effective in terms of promoting mental health. Due to the low methodological quality of the included reviews and substantial heterogeneity among the reported results, the findings from the reviews we summarized should be interpreted with caution. There is a need for further rigorous, high-quality systematic reviews.

Cortical thickness is inversely associated with transcranial magnetic stimulation-evoked N45 potential among young adults whose heavy drinking began in adolescence.

BACKGROUND: Adolescence is a particularly vulnerable stage of development in terms of the deleterious effects of alcohol. Both lower gray matter (GM) volume and greater GABAergic activity have been associated with chronic alcohol consumption during adolescence. However, the association between these measures has not been investigated. METHODS: In this exploratory study, we compared 26 young adults with a 10year history of heavy alcohol consumption with 21 controls who used little or no alcohol. Simultaneous transcranial magnetic stimulation and electroencephalography were used to assess transcranial magnetic stimulation-evoked N45 potentials, reflecting a balance between GABAergic inhibition and N-methyl-D-aspartate (NMDA) receptor-mediated glutaminergic excitation in the brain. GM thickness was measured from magnetic resonance images and GM and N45 potentials were then correlated. RESULTS: Cortical thickness was significantly lower in several brain regions in the heavy-drinking group than the light-drinking group. The N45 amplitude was significantly larger frontally in the heavy-drinking group. Among heavy drinkers, there were several statistically significant correlations between thinner GM and larger frontal N45 amplitudes that were not detectable in the light-drinking group. The strongest correlations were detected in the frontal and parietal lobes, especially in the left superior frontal gyrus and the left supramarginal gyrus, and in both hemispheres in the superior parietal lobes. CONCLUSIONS: These findings show that a thinner cortex and greater inhibitory neurotransmission are correlated in certain brain regions among young, long-term heavy alcohol users. Studies are needed to explore the possible causal mechanisms underlying these effects.

Change in sense of coherence mediates the association between economic recession and mortality among middle-aged men: A population-based cohort study from Eastern Finland.

A financial recession has been associated with a decrease in all-cause mortality, but little is known about how psychosocial fluctuations in stress tolerance or orientation to life affect this association. Sense of Coherence (SOC) is a core construct in the Salutogenic Model of Health and is determined by generalized resistance resources and measures one's orientation to life by comprehensibility, manageability, and meaningfulness. We followed the mortality of a cohort of middle-aged Finnish men (n = 854) from the 1980s to the end of 2019. The cohort baseline was stratified into four age groups at baseline: 42, 48, 54, and 60. SOC was measured twice, at the baseline and at the 11-year follow-up visit. Between these SOC measurements, Finland confronted a deep financial recession, the effects of which were examined at the follow-up visit by questionnaires related to economic hardship (sum of nine items) and experience of the recession (one item). Using age group, marital status, employment status, and education as covariates, the change in SOC mediated both the economic hardship and the experience of recession relations to mortality: the indirect effects -19.57 (95% CI -43.23 to -0.92), and -26.82 (95% CI -59.52 to -0.61), respectively. Every one-point increase in economic hardship predicted about 2 and a half weeks shorter life expectancy, and those who experienced very strong disadvantages of economic recession had about 3 and a half months lower life expectancy by the end of 2019 than those who fully avoided the disadvantages. Furthermore, the younger age groups, 42 and 48, experienced the recession more severely than the older groups, 54 and 60. We conclude that following how orientation to life changes among middle-aged might be an informative approach after a recession.

Depression and dissociation mediate the association between bullying victimization and self-cutting.

BACKGROUND: Bullying victimization is experienced by more than 10% of children and adolescents worldwide and has been associated with numerous negative mental health consequences, such as depression and dissociation. AIMS: We investigated the association between bullying victimization and self-cutting in a Finnish adolescent population and whether depression and dissociation act as mediators in this association. METHODS: We used cross-sectional questionnaire data from Finnish students (age 13-18; N = 3345; boys n = 1454; girls n = 1891). Logistic regression and mediation analyses were performed. RESULTS: Bullying victimized adolescents were younger, more likely to be afraid to go to school, had fewer friends, felt lonelier, and had a poorer relationship with family members, as well as higher level of depressive and dissociative symptoms compared to non-bullied adolescents. According to logistic regression analysis, the association between bullying and self-cutting remained significant despite all other adjustments besides those for depressive symptoms. In serial mediation analysis, depressive and dissociative symptoms mediated the effect of bullying victimization on self-cutting, regardless of their order in the model. CONCLUSIONS: Self-cutting is more common among bullying victimized adolescents than their peers. The association is mediated by depressive and dissociative symptoms. More studies are needed to clarify the exact mechanisms via which depressive and dissociative symptoms interact with the association between bullying and self-harm.

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.

Externally oriented thinking style increases primary health care use in adolescence.

BACKGROUND: Alexithymia has been related to adult health care use. We investigated the association between alexithymia and the utilization of primary health care services by adolescents and young adults. METHODS: The participants (n = 751, aged 13-18 years) in this 5-year follow-up study were assessed with the 20-item Toronto Alexithymia Scale (TAS-20) and its three subscales, difficulty identifying feelings (DIF), difficulty describing feelings (DDF) and externally oriented thinking (EOT), and the 21-item Beck Depression Inventory (BDI). Primary health care data were gathered from health care centre registers in 2005-10. Generalized linear models and mediation analyses were used. RESULTS: An increase in the TAS-20 total score correlated with a higher number of primary health care and emergency care visits, but in multivariate general linear models, TAS-20 total scores were no longer significant. Younger age, female gender and an increase in the baseline EOT score are associated with a higher number of both primary health care and emergency room visits. In females, a smaller change in the EOT score from baseline to follow-up was associated with a higher number of primary health care visits. In mediation analyses, EOT had a direct effect on a higher number of primary health care and emergency room visits, whereas the BDI score mediated the incremental effect of DIF and DDF on visit numbers. CONCLUSIONS: The results suggest that an EOT style independently increases health care use by adolescents, whereas the effects of difficulties identifying and describing feelings on health care use are mediated by symptoms of depression.

Associations between total dairy, high-fat dairy and low-fat dairy intake, and depressive symptoms: findings from a population-based cross-sectional study.

PURPOSE: Evidence on the association between dairy intake and depression is conflicting. Given numerous dietary guidelines recommend the consumption of low-fat dairy products, this study examined associations between total dairy, high-fat dairy, and low-fat dairy intake and the prevalence of elevated depressive symptoms. Associations between dairy products, which differed in both fat content and fermentation status, and depressive symptoms were also explored. METHODS: This cross-sectional study included 1600 Finnish adults (mean age 63 ± 6 years; 51% female) recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. Dairy intake was assessed using 4-day food records. Elevated depressive symptoms were defined as having a score ≥ 5 on the Diagnostic and Statistical Manual of Mental Disorders-III Depression Scale, and/or regularly using one or more prescription drugs for depressive symptoms. RESULTS: In total, 166 participants (10.4%) reported having elevated depressive symptoms. Using multivariate logistic regression models, intake in the highest tertile of high-fat dairy products (OR 0.64, 95% CI 0.41-0.998, p trend = 0.04) and high-fat non-fermented dairy products (OR 0.60, 95% CI 0.39-0.92, p trend = 0.02) were associated with reduced odds for having elevated depressive symptoms. Whereas no significant association was observed between intake of total dairy, low-fat dairy, or other dairy products, and depressive symptoms. CONCLUSION: Higher intake of high-fat dairy and high-fat non-fermented dairy products were associated with reduced odds for having elevated depressive symptoms in middle-aged and older Finnish adults. Given the high global consumption of dairy products, and widespread burden of depression, longitudinal studies that seek to corroborate these findings are required.

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.

Nonfermented Dairy Intake, but Not Fermented Dairy Intake, Associated with a Higher Risk of Depression in Middle-Age and Older Finnish Men.

BACKGROUND: Despite the putative health benefits of fermented dairy products, evidence on the association between fermented dairy and nonfermented dairy intake, and depression incidence is limited. OBJECTIVES: This study examined cross-sectional and prospective associations between total dairy, fermented dairy, and nonfermented dairy intake with 1) the presence of elevated depressive symptoms and 2) the risk of a future hospital discharge or outpatient diagnosis of depression. METHODS: Data from 2603 Finnish men (aged 42-60 y), recruited as part of the Kuopio Ischaemic Heart Disease Risk Factor Study, were included. Multivariable logistic regression models were used to examine ORs and 95% CIs for elevated depressive symptoms (Human Population Laboratory scale ≥5 points) at baseline. Cox proportional hazards regression models were used to estimate HRs and 95% CIs between dairy categories and risk of depression diagnoses. RESULTS: In cross-sectional analyses, fermented dairy intake in the highest (compared with lowest) tertile was associated with lower odds of having elevated depressive symptoms (adjusted OR: 0.70; 95% CI: 0.52, 0.96). Each 100-g increase in nonfermented dairy intake was associated with higher odds of having elevated depressive symptoms (adjusted OR: 1.06; 95% CI: 1.01, 1.10). During a mean follow-up time of 24 y, 113 males received a diagnosis of depression. After excluding cheese intake, higher fermented dairy intake was associated with a lower risk of depression diagnosis (adjusted HR: 0.62; 95% CI: 0.38, 1.03), which was strengthened after excluding those with elevated depressive symptoms at baseline (adjusted HR: 0.55; 95% CI: 0.31, 0.99), whereas nonfermented dairy intake in the highest tertile was associated with a 2-fold higher risk of depression (adjusted HR: 2.02; 95% CI: 1.20, 3.42). CONCLUSIONS: Fermented dairy and nonfermented dairy intake were differentially associated with depression outcomes when examined cross-sectionally and over a mean period of 24 y. These findings suggest that dairy fermentation status may influence the association between dairy intake and depression in Finnish men. The KIHD study was registered at clinicaltrials.gov as NCT03221127.

Factor Structure, Measurement Invariance, and Abbreviated Versions of The Adolescent Dissociative Experiences Scale (A-DES).

The purpose of this study was to examine the factor structure of the Adolescent Dissociative Experiences Scale (A-DES) questionnaire with item response theory (IRT) methods, including an assessment of measurement invariance with differential item functioning (DIF) analysis. Three abbreviated versions of the A-DES (with 20, 10, and 5 items) were constructed based on the IRT and DIF statistics. The respondents in this population-based study (N = 4,072) were 12- to 19-year-old Finnish junior and senior high school students. A one-factor model of the A-DES was best supported, and the original theoretical four-factor model showed poor fit. The A-DES turned out to have high measurement invariance with respect to age, gender, transgender tendencies, having multiple friends, the use of illegal substances, and experience of being bullied. Compared to the full 30-item A-DES, abbreviated versions of the questionnaire retained acceptable information value and empirical reliability in the clinically relevant range of symptomatology. Further psychometric studies are needed especially with regards to clinical use.

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.

Stability of alexithymia is low from adolescence to young adulthood, and the consistency of alexithymia is associated with symptoms of depression and dissociation.

BACKGROUND: The aims of this study were to investigate the stability of alexithymia from adolescence to young adulthood, as well as the association between alexithymia, peer relationships, and symptoms of depression and dissociation. METHODS: The participants (n = 755, aged 13-18 years) were assessed with self-rated questionnaires and the 20-item Toronto Alexithymia Scale (TAS-20) at baseline in 2005 and on follow-up in 2011. RESULTS: The changes in the TAS-20 total score (t = -12.26) and the scores for its subscales, difficulty identifying feelings (DIF) (t = -4.04), difficulty describing feelings (DDF) (t = -5.10), and externally oriented thinking (EOT) (t = -18.23), were statistically significant (p < 0.001). Effect sizes (Cohen's d) for the change indicating absolute stability were small for DIF (-0.15) and DDF (-0.19), medium for TAS-20 total (-0.45), and large for EOT (-0.66) scores. Moderate correlations in test-retests with Spearman's ρ (TAS-20 total 0.46, DIF 0.41, DDF 0.39, EOT 0.43) indicated relative stability, whereas low intraclass correlation coefficients (ICCs) (respectively 0.41, 0.39, 0.37, 0.37) indicated poor reliability of test-retests. In regression analyses, poor relationships with peers, loneliness, and symptoms of depression and dissociation at baseline associated with alexithymia at baseline and on follow-up. Unlike EOT, increases in the TAS-20 total, DIF, and DDF scores during the 6-year follow-up associated with baseline symptoms of depression and dissociation. CONCLUSIONS: Alexithymia in adolescence is not always a reliable predictor of alexithymia in young adulthood. Mental health symptoms appear to affect the consistency of alexithymia during adolescent development.

Social support may prevent self-cutting in adolescence: A 5-year follow-up study.

Self-cutting is common among adolescents. However, studies examining protective factors are rare. It has been suggested that social support may protect against self-cutting in adolescence. The aim of this study was to investigate the possible association of social relationships with the initiation of self-cutting. METHODS: The participants were community-dwelling Finnish adolescents (N = 4171) aged 13-18 years at baseline. The follow-up assessment was conducted 5 years later (N = 794). Those adolescents who had self-cut before the baseline assessment (N = 134) were excluded from the analysis, leaving a total of 660 participants to be analyzed. In this group, 37 adolescents initiated self-cutting during the 5-year follow-up period and 623 did not. Cox's proportional hazards models were used with several adjustments for possible confounding factors. FINDINGS: A higher age, male gender, good relationships with siblings, weekly meetings with friends, and personal experience of not being lonely associated with the noninitiation of self-cutting during the follow-up period. Good relationships with parents or peers had no association with the initiation of self-cutting. Depressive symptoms mediated the effect of subjective loneliness on initiating self-cutting. CONCLUSIONS: Social support produced by friends may have a protective effect against self-cutting.

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.

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.

Heavy drinking from adolescence to young adulthood is associated with an altered cerebellum.

Excessive alcohol use results in cerebellar damage in adults, but there has been less research on how alcohol use during adolescence affects the cerebellum. In this study, we observed that heavy drinking from adolescence to young adulthood was associated with altered volumes of cerebellar lobules. The study included two groups consisting of 33 heavy-drinking and 25 light-drinking participants. The heavy-drinking participants were highly functional young adults without alcohol use disorder, but with a history of regular heavy alcohol consumption. The participants were 13-18 years old at baseline and were followed for 10 years. At the age of 21-28 years, the participants underwent magnetic resonance imaging (MRI). From the MR images, the cerebellum was segmented into 12 lobules using the CERES pipeline. Heavy drinking did not influence the absolute cerebellar volume, but changes were observed in posterior cerebellar lobules associated with motor and cognitive functions. The absolute volume (p = 0.038) and gray matter volume (p = 0.034) of Crus II (hemispheres combined) were smaller in the heavy-drinking group. Furthermore, the relative volume of the right VIIIB lobule was larger in the HD group (p = 0.036). However, there were no differences in the absolute right VIIIB volumes (p = 0.198) between the groups. Our results suggest changes in the cerebellum in healthy young adults with a history of heavy drinking from adolescence. The exact implications and significance of these findings require further research.