Early environmental predictors for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and their co-occurrence: The prospective ABIS-Study.

ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.

Breastfeeding decreases the risk of developing psoriasis through to early adulthood.

BACKGROUND: Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections and drug exposure, have been identified. OBJECTIVES: To explore the role of early nutrition as a risk factor for the development of psoriasis. METHODS: Parents in the All Babies in Southeast Sweden (ABIS) prospective birth cohort (n = 16 415) answered questionnaires at birth and when their children were aged 1 and 3 years. A diagnosis of psoriasis was determined from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. RESULTS: Individuals breastfed for < 4 months and who received infant formula before 4 months of age had a higher risk of psoriasis [odds ratio (OR) 1.84 (P = 0.02) and OR 1.88 (P = 0.02), respectively]. At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR 9.61; P = 0.003). In addition, the risk of psoriasis increased following the consumption of a large volume of milk (OR 2.53; P = 0.04). CONCLUSIONS: Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months appears to be protective.

Clinical implications of ADHD, ASD, and their co-occurrence in early adulthood-the prospective ABIS-study.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are childhood-onset disorders associated with functional and psychosocial impairments that may persist into adulthood, leading to serious personal and societal costs. OBJECTIVE: This study aimed to examine the socio-economic difficulties, physical and mental comorbidities, and psycho-social vulnerabilities associated with ADHD, ASD, and their co-occurrence among young adults. METHODS: 16 365 families with children born 1997-1999, were involved in the prospective population-based ABIS study (All Babies in Southeast Sweden). A total of 6 233 ABIS young adults answered the questionnaire at the 17-19-year follow-up and were included in this case-control study. Diagnoses of ADHD and ASD from birth up to 17 years of age were obtained from the Swedish National Diagnosis Register. N=182 individuals received a single diagnosis of ADHD, n=78 of ASD, and n=51 received both diagnoses and were considered the co-occurrence group. Multiple multinomial logistic regression analyses were performed. RESULTS: In the univariate analyses all three conditions were significantly associated with concentration difficulties, worse health quality, lower socio-economic status, lower faith in the future, less control over life, and lower social support. In the adjusted analyses, individuals with ADHD were almost three-times more likely to have less money compared with their friends (aOR 2.86; p < .001), experienced worse sleep quality (aOR 1.50; p = .043) and concentration difficulties (aOR 1.96; p < .001). ASD group were two-fold more likely to experience concentration difficulties (aOR 2.35; p = .002) and tended not to have faith in the future (aOR .63; p = .055), however, showed lesser risk-taking bahaviours (aOR .40; p < .001). Finally, the co-occurrence was significantly associated with unemployment (aOR 2.64; p = .007) and tended to have a higher risk of autoimmune disorders (aOR 2.41; p = .051), however, showed a 51% lower risk of stomach pain (aOR .49; p = .030). CONCLUSIONS: All these conditions significantly deteriorated several areas of life. ADHD/ASD co-occurrence is a heavy burden for health associated with several psychosocial vulnerabilities, that shared a similar morbidity pattern with ADHD although showed less risk cognitive and behavioral profile, similar to the ASD group. Long-term follow-up and support for individuals with these conditions over the life course are crucial.

Excessive hair cortisol concentration as an indicator of psychological disorders in children.

Cortisol in hair is a new biomarker assessing long-term hypothalamic-pituitary-adrenal (HPA) axis activity, which is related to emotion regulation. We compare hair cortisol concentrations (HCC), in clinically referred children with disruptive mood dysregulation disorder (DMDD) (n = 19), children with other types of psychological disorders (n = 48), and healthy subjects (n = 36). We also investigate the association between HCC and irritability, age, and sex. Our results show that children with DMDD or other types of psychological disorders have higher HCC than healthy subjects, p < .001, ηp2 = .39. No difference between children with DMDD and those with other types of psychological disorders was found, p = .91, nor an association between HCC and irritability in the clinical sample, p = .32. We found a significant negative correlation between HCC and age in those with DMDD, r = -0.54, p < .05, but not in the normative sample, r = -0.20, p = .25. No differences in HCC between girls and boys were found in the normative sample, p = .49. Children in need of psychological treatment, including those with DMDD, seem to have dysregulated HPA-axis activity over time. Excessive accumulated cortisol concentrations in hair could be an indicator of a psychological disorder in children.

Cardiovascular and psychosocial risks among patients below age 50 with acute myocardial infarction.

BACKGROUND: Despite improvements in the treatment and prevention of cardiovascular disease since the 1960s, the incidence of cardiovascular diseases among young people has remained the same for many years. This study aimed to compare the clinical and psychosocial attributes of young persons affected by myocardial infarction under the age of 50 years compared to middle-aged myocardial infarction patients 51-65 years old. METHODS: Data from patients with a documented STEMI or NSTEMI elevated acute myocardial infarction in the age groups up to 65 years, were collected from cardiology clinics at three hospitals in southeast Sweden. The Stressheart study comprised a total of 213 acute myocardial infarction patients, of which n = 33 (15.5%) were under 50 years of age and n = 180 (84.5%) were middle-aged, (51-65 years). These acute myocardial infarction patients filled in a questionnaire at discharge from the hospital and further information through documentation of data in their medical records. RESULTS: Blood pressure was significantly higher in young compared to middle-aged patients. For diastolic blood pressure (p = 0.003), systolic blood pressure (p = 0.028), and mean arterial pressure (p = 0.005). Young AMI patients had a higher (p = 0.030) body mass index (BMI) than the middle-aged. Young AMI patients were reported to be more stressed (p = 0.042), had more frequently experienced a serious life event the previous year (p = 0.029), and felt less energetic (p = 0.044) than middle-aged AMI patients. CONCLUSIONS: This study revealed that persons under the age of 50 affected by acute myocardial infarction exhibit traditional cardiovascular risk factors like high blood pressure, and higher BMI, and were more exposed to some psychosocial risk factors. The risk profile of young persons under age 50 affected by AMI was in these respects more exaugurated than for middle-aged persons with AMI. This study underlines the importance of the early discovery of those at increased risk and encourages preventative actions to focus on both clinical and psychosocial risk factors.

Hair cortisol as a biomarker of chronic stress in preadolescents: influence of school context and bullying.

Bullying has been identified as the most common form of aggression and a major source of stress among children and adolescents. The main objective of this study was to analyze the association that school context in general and bullying in particular might have with hair cortisol concentration (HCC), examining the effect of executive function and sex on this association. The study included 659 11-year-old preadolescents from the cohorts of Gipuzkoa and Sabadell of the INMA (INfancia y Medio Ambiente-Children and Environment) project. We gathered information about school-related factors (bullying, school environment, problems with peers and academic performance) and executive function (risky decision-making). Hair samples were collected to measure cortisol concentrations and Structural Equation Modeling was used to examine associations between school-related factors, executive function and HCC. Results showed that being involved as a bully/victim was related to higher HCC and, higher HCC was associated with poorer executive function. This study may contribute to a better understanding of the consequences that chronic exposure to a stressful factors may have on preadolescents' health and developmental outcomes. Besides, our results are relevant for designing programs for prevention and intervention, which could modify individual physiological responses to stress and reduce the effects of stress on the health.

Decreased Testosterone Levels Precede a Myocardial Infarction in Both Men and Women.

The potential role of the hormone testosterone in the risk for myocardial infarction is investigated in this study of middle-aged men and women compared with a large random control sample from the general population. Radioimmunoassay was used to measure testosterone levels in hair, approximately 1 month and 3 months before an ST-elevation or non-ST-elevation acute myocardial infarction. Mean testosterone levels were measured for middle-aged men and women (n = 168) with diagnosed myocardial infarction (the acute myocardial infarction [AMI] cases). As controls, n = 3,150 randomly selected subjects from the general population of similar age were measured at 1 time point. No significant difference in testosterone levels in hair was found 3 months before AMI for men and women compared with the controls. However, 1 month before AMI, the testosterone levels were decreasing (p <0.001) for both men (from 2.84 to 2.10 pg/mg) and women (from 1.43 to 1.10 pg/mg), indicating that a decrease in testosterone concentrations precedes a severe cardiac event. Conventional cardiovascular risk factors were tested as confounders but did not alter this tendency. The AMI cases were also compared with a randomly selected second control group from the general population (n = 205), for whom comparable segmental hair analyses were conducted. A tendency of some decreasing testosterone levels, also in the small control group, was only significant for men. This control group was a small sample, and there might be some natural biologic variation in testosterone levels over time. This study indicates that decreased testosterone levels may be among the pathophysiological processes preceding myocardial infarction and merits further investigation.

Chronic social instability stress down-regulates IL-10 and up-regulates CX3CR1 in tumor-bearing and non-tumor-bearing female mice.

Extensive literature has reported a link between stress and tumor progression, and between both of these factors and mental health. Despite the higher incidence of affective disorders in females and the neurochemical differences according to sex, female populations have been understudied. The aim of this study was therefore to analyze the effect of stress on tumor development in female OF1 mice. For this purpose, subjects were inoculated with B16F10 melanoma cells and exposed to the Chronic Social Instability Stress (CSIS) model. Behavioral, neurochemical and neuroendocrine parameters were analyzed. Female mice exposed to CSIS exhibited reduced body weight and increased arousal, but there was no evidence of depressive behavior or anxiety. Exposure to CSIS did not affect either corticosterone levels or tumor development, although it did provoke an imbalance in cerebral inflammatory cytokines, decreasing IL-10 expression (IL-6/IL-10 and TNF-α/IL-10); chemokines, increasing CX3CR1 expression (CX3CL1/CX3CR1); and glucocorticoid receptors, decreasing GR expression (MR/GR). In contrast, tumor development did not alter body weight and, although it did alter behavior, it did so to a much lesser extent. Tumor inoculation did not affect corticosterone levels, but increased the MR/GR ratio in the hippocampus and provoked an imbalance in cerebral inflammatory cytokines and chemokines, although differently from stress. These results underscore the need for experimental approaches that allow us to take sex differences into account when exploring this issue, since these results appear to indicate that the female response to stress is mediated by mechanisms different from those often proposed in relation to male mice.

Do prepubertal hormones, 2D:4D index and psychosocial context jointly explain 11-year-old preadolescents' involvement in bullying?

BACKGROUND: Bullying is a type of aggressive behavior that occurs repeatedly and intentionally in school environments and where there is a power imbalance. The main objective of this study was to analyze the association that hormones and the psychosocial context jointly have with bullying behavior. METHOD: Participants were 302 11-year-old preadolescents from the Gipuzkoan cohort of the INMA Project. Bullying was assessed using the Olweus Bully/victim Questionnaire. Prenatal sexual hormones were assessed by calculating 2D:4D ratio and in order to measure prepubertal testosterone and cortisol levels saliva samples were collected within a week of each other. Additionally, various psychosocial factors were evaluated: executive function, family context, school environment and social context. To analyze our complex hypothesis, six metamodels were tested using structural equation modeling. RESULTS: In relation to victims, results showed that victimization was related to worse school environment' perception in boys, and higher stress and conflict in the family in girls. In the case of their involvement in bullying as a bully, lower salivary cortisol levels, worse school environment' perception and lower peers and social support was related to being more frequently involved as a bully in boys, while having more family stress and conflict was related with being a bully in girls. CONCLUSIONS: This approach makes it possible not only to explore the different biological and psychosocial factors affect bullying behavior, but also to explore associations between the predictor variables.

Behavioral coping strategies predict tumor development and behavioral impairment after chronic social stress in mice.

The aims of this study were to identify behavioral strategies to cope with social defeat, evaluate their impact on tumor development and analyze the contributions of both to changes in physiology and behavior produced by chronic defeat stress. For this purpose, OF1 mice were inoculated with B16F10 melanoma cells and subjected to 18 days of repeated defeat stress in the presence of a resident selected for consistent levels of aggression. Combined cluster and discriminant analyses of behavior that manifested during the first social interaction identified three types of behavioral profiles: active/aggressive (AA), passive/reactive (PR) and an intermediate active/non-aggressive (ANA) profile. Animals that showed a PR coping strategy developed more pulmonary metastases at the end of the social stress period than animals in other groups. The ANA but not AA group also showed higher tumor metastases than non-stressed subjects. In addition, the ANA group differed from the other groups because it displayed the highest corticosterone levels after the first interaction. Chronic stress reduced sucrose consumption, which indicates anhedonia, in all the stressed groups. However, the PR subjects exhibited a longer immobility time and swam for less time than other subjects in the forced swim test (FST), and they travelled a shorter distance in the open field test (OFT). In this test, the ANA group also travelled smaller distances than the non-stressed group, but the difference was more moderate. In contrast, tumor development but not stress increased behaviors associated with anxiety in the OFT (e.g., time in the center) in all tumor-bearing subjects. In summary, although the effects of social stress and tumor development on behavior were rather moderate, the results indicate the importance of behavioral coping strategies in modulating the effects of chronic stress on health.

Social instability in female rodents as a model of stress related disorders: A systematic review.

The risk of developing stress related disorders such as depression is two times higher in women than in men, and social stress is considered the principal etiology for this disorder. Social defeat animal model is the most common procedure to induce social stress in male rodents, but the stressful stimulus and the stress response can be different for each sex. In this regard, social defeat stress model does not fit the social nature of females, and according to the emerging evidence, the social instability stress (SIS) model could be a suitable procedure to investigate this stress related disorder in females. This study aims to systematically review the effects of SIS on physiological and behavioral parameters involved in the pathophysiology of depression, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method on PubMed, Medline and Web of Science. Seventeen studies met the inclusion criteria. The reported physiological measures comprised the hypothalamic-pituitary-adrenal axis activity, neurotrophic factors, immune and monoaminergic systems, vasopressin and oxytocin receptors, sex hormone levels and estrus cycle, while main behavioral measures involved sucrose preference test, forced swimming test, elevated plus maze, open field test and social interaction. This systematic review revealed a wide variability on the social instability regimen and on the measured variables. However, all studies agree that SIS model can elicit behavioral and physiological alteration involved in stress related disorders, with HPA axis hyperactivity, increased anxiety-like behavior and disrupted reward system being the most repeated outcomes. A unified SIS application criterion is required in order to obtain consistent data and elucidate the underlying mechanisms of anxiety and depression in females.

Biological Sex Differences in Depression: A Systematic Review.

Depression is the leading cause of disability worldwide, and its prevalence is 2 times higher in women than in men. There is, however, a lack of data on sex-specific pathophysiology of this disorder. The purpose of this systematic review is to identify the biological sex differences found in major depressive disorder (MDD) in studies published in the last 10 years. We conducted a literature search using the Medline, PsycInfo, PubMed, and Web of Science databases, selecting English-language studies that included physiological measures compared by sex in addition to MDD. We identified 20 relevant studies, which consisted primarily of mixed methodology and samples. The reported physiological measures comprised a variety of serum biomarkers, gene mRNA expression, and brain activity. Findings suggest different biological patterns in those with MDD depending on sex. Specifically, women presented higher levels of inflammatory, neurotrophic, and serotonergic markers and a stronger correlation between levels of some inflammatory and neurotrophic factors and the severity of symptoms. This review provides information about possible different biological patterns for women and men with depressive disorder and may have important implications for treatment. Future research should include homogeneous samples; make comparisons based on sex, control sex hormone fluctuations and pharmacological treatment; and use consistent criteria for evaluating psychobiological changes in MDD.

Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.

Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1ß and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.