Mothers' and their children's emotional and behavioral symptom trajectories and subsequent maternal adjustment: Twenty-seven years of motherhood.

BACKGROUND: This study aims to describe maternal depressive symptoms (MDS) trajectories in a longitudinal study extending from pregnancy to 27 years after the birth of the firstborn child. We also explored the associations of both MDS trajectories and child internalizing and externalizing problem trajectories with maternal adjustment (adaptive functioning, emotional and behavioral problems). METHODS: The population-based study was conducted in Tampere, Finland, and the sample comprised 356 first-time mothers. MDS were screened with the Edinburgh Postnatal Depression Scale during pregnancy, first week after delivery, 2 and 6 months postnatally, and when the child was 4-5, 8-9, 16-17, and 26-27 years of age. The internalizing and externalizing problems of the children were assessed with the Child Behavior Checklist when the child was 4-5, 8-9, and 16-17 years of age. Maternal adaptive functioning and internalizing and externalizing problems were assessed with the Adult Self Report at 26-27 years after the birth of the first child. Complete follow-up data were available for 168 mothers. RESULTS: We describe a three-group trajectory model of MDS (High Stable, Low Stable, Very Low). Elevated depressive symptom patterns were associated with less optimal maternal outcomes regarding both adaptive and problem dimensions. The child's internalizing and externalizing problem trajectories were associated with maternal internalizing and externalizing problems but not with maternal adaptive functioning. LIMITATIONS: Maternal and child measures were based on maternal reports only. CONCLUSIONS: The interconnectedness of the well-being of the mother and child should be noted in health and mental health services for adults and children.

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.

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.

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.

Adverse childhood experiences and alexithymia in patients with major depressive disorder.

The purpose of the article: Adverse childhood experiences (ACEs) have been postulated to negatively affect the development of emotional regulation. However, little is known about specific associations between ACEs, depressive symptoms, and alexithymia or its components [i.e. difficulty in identifying feelings (DIF), difficulty in describing feelings to others (DDF) and externally-oriented thinking (EOT)] in patients with major depressive disorder (MDD). The aims of the present cross-sectional study were to (1) compare ACEs (emotional neglect, emotional abuse, physical neglect, physical abuse, sexual abuse) between alexithymic and non-alexithymic patients with MDD; (2) explore whether specific ACEs, depressive symptoms or the interaction between sex and depressive symptoms predicted TAS-20 or its components.Materials and Methods: The study sample consisted of 186 psychiatric outpatients with MDD (aged 21-61 years, mean 33.87 years, SD 10.88) recruited from the Department of Psychiatry, Kuopio University Hospital between 2016-2019. Alexithymia and its components were assessed using the 20-item Toronto Alexithymia Scale (TAS-20). ACEs were assessed with the Trauma and Distress Scale (TADS).Results: Almost all patients with alexithymia and 80% of non-alexithymic patients reported that they had experienced emotional abuse or neglect, at least sometimes. Approximately 60% of MDD patients reported having experienced physical neglect and 30% described physical abuse. Emotional and physical abuse and neglect predicted DDF score.Conclusions: These findings suggest that among MDD patients, early experiences of emotional and physical abuse and neglect is associated with difficulties in describing feelings in adulthood.

Decreased serum total cholesterol is associated with a history of childhood physical violence in depressed outpatients.

Associations between adverse childhood experiences (ACEs) and cholesterol in depressed patients are unclear. Therefore, we compared 78 adult outpatients with major depressive disorder (MDD) with (n = 24) or without (n = 54) experiences of physical violence in childhood. Background data were collected with questionnaires, and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured from fasting blood samples. Patients with a history of childhood physical violence had lower levels of TC than the control group. No differences were observed in HDL-C, LDL-C, or low-grade inflammation levels between the two groups. In multivariate models, decreased levels of TC were associated with childhood physical violence, and these associations remained significant after adjustments for age, gender, lifestyle, metabolic condition, socioeconomic situation, psychiatric status, suicidality, low-grade inflammation, the chronicity of depression, medications used and somatic diseases. At the 8-month follow-up, the results were essentially the same when the Trauma and Distress Scale (TADS) was used as the measure of ACEs. The specific mechanisms underlying cholesterol alterations associated with ACEs are a topic for future studies. Better understanding of these mechanisms might lead to possible new interventions in the prevention of adverse health effects resulting from ACEs.

Bifrontal active and sham rTMS in treatment-resistant unipolar major depression.

BACKGROUND AND AIM: Prevention of the recurrence of major depression and its residual symptoms requires effective treatment. Our aim was to study the effects of bifrontal active rTMS controlled by sham rTMS in treatment-resistant unipolar major depressive disorder (MDD). METHODS: Thirty-seven patients with treatment-resistant MDD were randomized into two groups. One group received a total of 30 sessions of active bifrontal rTMS (10 Hz rTMS on left dorsolateral prefrontal cortex (DLPFC) and 1 Hz rTMS on right DLPFC) and the other group received bilateral sham rTMS on five days a week for six weeks. RESULTS: Depressive symptoms significantly improved in both the groups, but without a significant group difference. Furthermore, patients with psychotic depression improved similarly to those with moderate or severe depression. CONCLUSIONS: The results of present study indicate a large sham effect of stimulation treatment. The intensive structured treatment protocol may explain the positive outcome in both the groups. It is important to recognize, appreciate, and utilize placebo effects as a significant means of rehabilitation in psychiatric care.

Global arginine bioavailability ratio is decreased in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is characterized by increased oxidative and nitrosative stress. We compared nitric oxide metabolism, i.e., the global arginine bioavailability ratio (GABR) and related serum amino acids, between MDD patients and non-depressed controls, and between remitted and non-remitted MDD patients. METHODS: Ninety-nine MDD patients and 253 non-depressed controls, aged 20-71 years, provided background data via questionnaires. Fasting serum samples were analyzed using ultra-performance liquid chromatography coupled to mass spectrometry to determine the serum levels of ornithine, arginine, citrulline, and symmetric and asymmetric dimethylarginine. GABR was calculated as arginine divided by the sum of ornithine plus citrulline. We compared the above measures between: 1) MDD patients and controls, 2) remitted (n=33) and non-remitted (n = 45) MDD patients, and 3) baseline and follow-up within the remitted and non-remitted groups. RESULTS: Lower arginine levels (OR 0.98, 95% CI 0.97-0.99) and lower GABR (OR 0.13, 95% CI 0.03-0.50) were associated with the MDD vs. the non-depressed group after adjustments for potential confounders. The remitted group showed a decrease in GABR, arginine, and symmetric dimethylarginine, and an increase in ornithine after the follow-up compared with within-group baseline values. The non-remitted group displayed an increase in arginine and ornithine levels and a decrease in GABR. No significant differences were recorded between the remitted and non-remitted groups. LIMITATIONS: The MDD group was not medication-free. CONCLUSIONS: Arginine bioavailability may be decreased in MDD. This could impair the production of nitric oxide, and thus add to oxidative stress in the central nervous system.

Dietary patterns are associated with the prevalence of alexithymia.

Recent evidence supports the association between healthy dietary patterns and a reduced risk of depression. The objective was: (1) to examine the associations between dietary patterns and alexithymic features; and (2) investigate whether these possible associations are explained by depressive symptoms in a cross-sectional study among the Finnish general population aged 25-65 years. The study population was a part of the population-based Kuopio Depression Study (KUDEP) conducted in central-eastern Finland (n = 1747). Dietary data were collected using a food frequency questionnaire and dietary patterns from 22 predefined food groups, which were extracted by factor analysis. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20) and depression using the 21-item Beck Depression Inventory (BDI-21). Altogether, 173 of the study subjects (9.9%) were alexithymic. Three dietary patterns were identified: "prudent," "Western" and "traditional." Lower scores for a healthy prudent dietary pattern and higher scores for an unhealthy Western dietary pattern were associated with an increased likelihood of belonging to the alexithymic group among subjects with elevated depressive symptoms. Among subjects without depressive symptoms, alexithymia was associated with lower scores in the prudent dietary pattern, but also with higher scores in the traditional dietary pattern. General population subjects with alexithymic features may have unhealthier dietary patterns than non-alexithymic subjects.

Effects of Scheduled Waiting for Psychotherapy in Patients With Major Depression.

The role of nonspecific factors in the outcome of psychotherapy is poorly understood. To study the effects of pretreatment expectancy of scheduled psychotherapy, we examined the effects of an agreed waiting time on the outcome of psychodynamic psychotherapy. Thirty-three treatment-naive outpatients with major depressive disorder were randomly selected to start psychotherapy either directly (DG; n = 17) or after waiting for 6 months (WG; n = 16). In WG, 18% to 60% of the total decline in symptoms took place during the waiting time. After 1 year of active psychotherapy, the anxiety score declined significantly only in WG, and the total length of treatment needed was shorter in WG. No other outcome differences between WG and DG were found. We conclude that scheduled waiting associates with a significant decline in depressive symptoms. Scheduled waiting should be regarded as a preparatory treatment and not as an inert nontreatment control.

Nutritive sucking induces age-specific EEG-changes in 0-24 week-old infants.

Little is known how the brain of the newborn infant responds to the postnatal nutrition and care. No systematic studies exist in which the effects of nutritional and non-nutritional sucking on the brain activity of the infant were compared. We recorded the EEG activity of 40 infants at the ages of 0,6,12 and 24 weeks in four successive behavioral stages: while the infants were hungry and waiting for sucking, during non-nutritional and nutritional sucking, and during satiation after completed feeding. Quantitative EEG analysis was performed using occipital, parietal and central EEG channels. In the newborn infants, a significant reduction in the EEG power was found after nutritional sucking in the all EEG frequency bands studied (1-10Hz), which was paralleled by a significant behavioral alertness decline. This response decayed during the subsequent neonatal period and was completely absent at the age of 12 weeks. In 24-week-old infants, nutritional sucking was accompanied with an increase in rhythmic theta activity during which no significant alertness change took place. Non-nutritional sucking was connected with minor and non-significant effects on the EEG. We conclude that in newborn infants nutritional sucking has a direct effect on the EEG, which has a soothing character and is connected with an alertness decline. In 24-week-old infants the response to nutritional sucking is of a different type and consists of an organized, rhythmical theta activity in the EEG not directly linked with alertness change. Our findings suggest a developmental relationship between nursing and infant brain function with plausible affective and cognitive implications.

Treatment-resistant Major Depressive Disorder with Psychotic Features is Associated with Impaired Processing Speed.

OBJECTIVE: A proportion of patients with major depressive disorder (MDD) show cognitive impairment that is associated with treatment nonresponse and poorer functional recovery. A broader range of cognitive dysfunction has been found to be associated with treatment-resistant depression (TRD) and with the presence of psychotic symptoms. Thus far, the effects of psychotic symptoms on the neuropsychological profile of patients with treatment-resistant MDD have not been investigated. METHOD: In the present study, 44 treatment-resistant MDD patients with (n = 12) or without (n = 32) psychotic symptoms-based on the Structured Clinical Interview (SCID I)-were compared with regard to their clinical status and performance in a neuropsychological test battery. The neuropsychological test battery assessed verbal skills, processing speed, executive functions and memory functions. RESULTS: Patients with psychotic TRD displayed lower performance in processing speed than non-psychotic patients. The group differences were not associated with the severity or pervasiveness of depressive symptoms. The duration of depression (from the onset of depressive symptoms) was longer in the group of non-psychotic TRD patients, but no other group differences with respect to sociodemographic characteristics, age at the onset of symptoms or symptom severity were found. CONCLUSIONS: The results imply that among individuals suffering from MDD, patients with the psychotic subtype who are unresponsive to standard pharmacological and psychosocial treatments have an increased vulnerability to cognitive dysfunction in the area of processing speed. Further research with larger sample size is warranted to determine whether these group differences persist after remission.

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.

Baseline symptom severity predicts serotonin transporter change during psychotherapy in patients with major depression.

AIMS: The role of the serotonin transporter (SERT) in the pathophysiology of depression is unclear and only a few follow-up studies exist. Our aim was to measure changes in SERT availability during psychodynamic psychotherapy in patients with major depression over a follow-up time of 12 or 18 months. METHODS: The patients were studied with iodine-123 labelled 2ß-carbomethoxy-3ß-(4-iodophenyl) serial single-photon emission tomography imaging and clinical rating scales of symptoms. RESULTS: Changes in SERT availability had no correlation with the change of symptoms, but the change of SERT availability during psychotherapy in the midbrain was predicted by the baseline severity of the clinical symptoms measured by the Symptom Checklist Depression Scale and the Symptom Checklist Global Severity Index. With cut-off values applied, it was found that SERT availabilities increased in patients with high baseline symptoms, and decreased in patients with low baseline symptoms. CONCLUSIONS: Together with our earlier finding of decreased SERT in patients with depression, these results indicate a state-dependent and possibly a compensatory role of decreased SERT availability in depression.

Reduced serum adiponectin levels in alexithymia.

OBJECTIVES: Clinical studies have demonstrated that circulating cytokine profiles may differ between alexithymic and non-alexithymic subjects. We examined whether the levels of adiponectin (µg/ml) and resistin (ng/ml) are independently related to alexithymic features in a population-based sample. METHODS: In 2005, clinical data including laboratory assessments were obtained from a sub-sample (n = 308) of the Kuopio Depression Study general population study including subjects aged 25-64 years. Based on the Toronto Alexithymia Scale score in 1998, 1999, 2001 and 2005, a group of subjects with high alexithymic features (n = 85) was formed and compared with non-alexithymic controls (n = 206). RESULTS: Serum adiponectin levels were significantly lower in subjects with alexithymic features than in non-alexithymic control subjects. No difference was found in resistin levels. Similarly, in a logistic regression model adjusted for age, gender and body mass index (BMI), lowered levels of adiponectin, but not resistin, were associated with an increased likelihood of belonging to the group with alexithymic features. Further adjustments for cardiovascular risk factors (i.e. smoking, BMI, metabolic syndrome, alcohol use, and coronary heart disease), depressive symptoms (Hamilton Depression Rating Scale with 17 items) and the use of antidepressants in addition to age and gender did not change these patterns. CONCLUSIONS: Our findings suggest that a disturbed anti-inflammatory balance may characterize alexithymia. In addition, our results widen the concept of alexithymia and highlight the role of immune system alterations and stress in alexithymic individuals.

Self-reported sleep disturbance is associated with elevated levels of PAI-1 in individuals with a recorded history of depressive symptoms.

BACKGROUND: The majority of depressed individuals report insomnia. Self-reported symptoms of insomnia, in particular, more strongly predict adverse health effects than the actual measured sleep time. The physiological alterations in individuals with insomnia are complex, as both autonomic and endocrine dysfunctions are present. Plasminogen activator inhibitor (PAI)-1 is a stress-related acute-phase reactant that has also been suggested to regulate the circadian rhythm and sleep patterns. It has been suggested to contribute to both depressive symptoms and sleep disorders, although data on the relationships between these parameters are scarce. OBJECTIVE: This study examined the role of self-reported sleep disturbance and its association with PAI-1 among individuals with a history of depressive symptoms. METHODS: Differences in the serum levels of PAI-1 between two groups (group 1: moderate to very severe sleep disturbance, n=37; group 2: mild or no sleep disturbance, n = 90) were examined in a population-based sample of individuals with a recorded history of depressive symptoms. RESULTS: Multivariate analysis controlling for potential confounding factors (age, sex, body mass index, depression severity) showed that each 1-unit increase in PAI-1 (µg/mL) increased the likelihood for belonging to the group with moderate to very severe sleep disturbance by 23% (OR = 1.23, C.I. 95% = 1.04-1.45, p = 0.016). This statistical significance remained after additional adjustments for regular smoking and the use of sleep or lipid-lowering medication. CONCLUSION: Our observations may further clarify the physiological alterations related to sleep disturbance in depressive individuals. In the present study, self-reported sleep disturbance in individuals with a recorded history of depressive symptoms was associated with an elevation of PAI-1. This finding may illustrate the association of subjective sleep disturbance with sympathetic activation. Our study highlights the importance of effects of perceived sleep disturbance on individual homeostasis, and may provide potential directions for research on treatment options.

[Glucocorticoids and aetiopathogenesis of depression]. / Glukokortikoidien yhteys masennuksen syntyyn ja oirekuvaan.

Current research interest is increasingly directed towards the role of glucocorticoid actions and inflammation. A failure in the stress system regulation appears to largely characterize depression. New research data have substantially diversified the theoretical concept of association between overactivity of HPA-axis and depression. The glucocorticoid effects are regulated by glucocorticoid reseptor gene polymorphisms, and glucocorticoid resistance is often associated with depression. Moreover, immune system disturbances affect the development of depression, and an altered balance of pro- and anti-inflammatory cytokines is also observable. Treatment methods that follow the new developments of the glucocorticoid theory are being developed.