The mediating role of health behaviors in the association between depression, anxiety and cancer incidence: an individual participant data meta-analysis.

BACKGROUND: Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers). METHODS: Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs). RESULTS: Smoking (HRs range 1.04-1.10) and physical inactivity (HRs range 1.01-1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03-1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01). CONCLUSIONS: Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

Sex differences in modifiable risk factors for stroke incidence and recurrence: the UCC-SMART study.

BACKGROUND AND PURPOSE: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. METHODS: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. RESULTS: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27-0.88; and RD 1.39; CI - 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23-0.80; and RD 9.05; CI 2.78-15.32). CONCLUSIONS: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention.

Association of amyloid-beta with depression or depressive symptoms in older adults without dementia: a systematic review and meta-analysis.

Several lines of evidence have indicated that depression might be a prodromal symptom of Alzheimer's disease (AD). This systematic review and meta-analysis investigated the cross-sectional association between amyloid-beta, one of the key pathologies defining AD, and depression or depressive symptoms in older adults without dementia. A systematic search in PubMed yielded 689 peer-reviewed articles. After full-text screening, nine CSF studies, 11 PET studies, and five plasma studies were included. No association between amyloid-beta and depression or depressive symptoms were found using cerebrospinal fluid (CSF) (0.15; 95% CI: -0.08; 0.37), positron emission topography (PET) (Cohen's d: 0.09; 95% CI: -0.05; 0.24), or plasma (-0.01; 95% CI: -0.23; 0.22). However, subgroup analyses revealed an association in plasma studies of individuals with cognitive impairment. A trend of an association was found in the studies using CSF and PET. This systematic review and meta-analysis suggested that depressive symptoms may be part of the prodromal stage of dementia.

Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis.

Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.

Depression, anxiety, and the risk of cancer: An individual participant data meta-analysis.

BACKGROUND: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. METHODS: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). RESULTS: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06-1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04-1.23). CONCLUSIONS: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. PREREGISTRATION NUMBER: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.

Late-life depression, allostatic load, and risk of dementia: The AGES-Reykjavik study.

BACKGROUND: The current study aimed to assess if the relation between depression and dementia could be explained by allostatic load (AL) profiles, as well as assessing their risk on incident all-cause dementia, Alzheimer's disease (AD), and non-AD dementias. METHODS: The study included individuals without dementia at baseline from the population-based AGES-Reykjavik Study. Depressive symptoms assessed with the Geriatric Depression Scale-15 and AL markers were collected at baseline. Latent profile analysis (LPA) was performed on the AL markers. Incident dementia was measured during 12-years of follow-up. Cox regressions adjusted for AL profiles were performed to evaluate if AL could explain the relation between depressive symptoms and incident dementia. Additional Cox regressions exploring the interaction with depressive symptoms and AL profiles were also performed. RESULTS: LPA revealed four profiles based on AL factors: 'Low cardiovascular dysregulation' (43 %), 'Average' (42 % prevalence), 'High cardiovascular dysregulation' (11 %), and 'Multisystem dysregulation' (4 %). Cox regression analyses found an increased risk for dementia in the 'Multisystem dysregulation' group (HR 1.72; 95 % CI 1.26-2.33), as well as for AD (HR 1.75; 95 % CI: 1.12-2.71) and non-AD dementias (HR 1.87; 95 % CI: 1.23-2.84). AL profiles did not mediate the risk of all-cause dementia with depressive symptoms; however, there was evidence of additive interaction with depressive symptoms and the 'Multisystem dysregulation' profile and all-cause dementia (RERI 0.15; 95 % CI 0.03-0.26). CONCLUSION: AL profiles and depressive symptoms were independently related to dementia. Individuals with multisystem dysregulation could be more susceptible to the negative effects of depressive symptomology on incident dementia.

The experienced positive and negative influence of HIV on quality of life of people with HIV and vulnerable to HIV in the Netherlands.

This qualitative study aimed to explore the experienced influence of HIV on the quality of life (QoL) of people with HIV (PHIV) and key populations without but are vulnerable to HIV in the Netherlands. We conducted and thematically analyzed interviews with 29 PHIV and 13 participants from key populations without HIV (i.e., men who have sex with men). PHIV and key populations shared positive meaningful experiences regarding HIV, i.e., feeling grateful for ART, life, and the availability of PrEP, being loved and supported in the light of HIV, and providing support to the community. Negative predominant experiences regarding HIV were described by both PHIV and key populations as the negative effects of ART, challenges with regards to disclosing HIV, social stigmatization, and self-stigma. It remains important to support HIV community organizations in their efforts to reduce social stigmatization and to continue improving biomedical interventions for HIV.

The perceived impact of an HIV cure by people living with HIV and key populations vulnerable to HIV in the Netherlands: A qualitative study.

Introduction: When an HIV cure becomes available, it will have consequences for people living with HIV (PLHIV) and key populations who are vulnerable to HIV. This qualitative study aimed to explore the perceived impact of two HIV cure scenarios (post-treatment control when HIV is suppressed without the need for ongoing antiretroviral treatment (ART) and complete HIV elimination) on the quality of life of PLHIV and key populations living without HIV in the Netherlands. Methods: Participants were purposefully sampled from the Amsterdam Cohort Studies, the AGEhIV Cohort Study, the outpatient clinic of the University Medical Centre Utrecht and the Dutch HIV Association to increase variability. Semi-structured in-depth interviews were conducted between October 2020 and March 2021 and thematically analysed. Results: Of the 42 interviewed participants, 29 were PLHIV and 13 represented key populations (i.e., men who have sex with men and people injecting drugs). Both PLHIV and participants from vulnerable key populations hoped that a cure would result in normalization of their lives by removing the need to disclose HIV, reducing stigma and guilt, increasing independence of ART, and liberating sexual behaviour. Both groups believed only HIV elimination could accomplish this desired impact. Conclusions: While the post-treatment control scenario seems a more plausible outcome of current HIV cure research, our findings highlight that participants may not perceive it as a true cure. Involvement of PLHIV and vulnerable key populations in devising acceptable and feasible experimental approaches to HIV cure is essential to ensure their future successful implementation.

Time for change: Transitions between HIV risk levels and determinants of behavior change in men who have sex with men.

As individual sexual behavior is variable over time, the timing of interventions might be vital to reducing HIV transmission. We aimed to investigate transitions between HIV risk levels among men who have sex with men (MSM), and identify determinants associated with behavior change. Participants in a longitudinal cohort study among HIV-negative MSM (Amsterdam Cohort Studies) completed questionnaires about their sexual behavior during biannual visits (2008-2017). Visits were assigned to different HIV risk levels, based on latent classes of behavior. We modelled transitions between risk levels, and identified determinants associated with these transitions at the visit preceding the transition using multi-state Markov models. Based on 7,865 visits of 767 participants, we classified three risk levels: low (73% of visits), medium (22%), and high risk (5%). For MSM at low risk, the six-month probability of increasing risk was 0.11. For MSM at medium risk, the probability of increasing to high risk was 0.08, while the probability of decreasing to low risk was 0.33. For MSM at high risk, the probability of decreasing risk was 0.43. Chemsex, erection stimulants and poppers, high HIV risk perception, and recent STI diagnosis were associated with increased risk at the next visit. High HIV risk perception and young age were associated with decreasing risk. Although the majority of MSM showed no behavior change, a considerable proportion increased HIV risk. Determinants associated with behavior change may help to identify MSM who are likely to increase risk in the near future and target interventions at these individuals, thereby reducing HIV transmission.

Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

OBJECTIVES: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer. METHODS: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2). CONCLUSION: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.

The Rhythm of Risk: Sexual Behaviour, PrEP Use and HIV Risk Perception Between 1999 and 2018 Among Men Who Have Sex with Men in Amsterdam, The Netherlands.

HIV risk perception plays a crucial role in the uptake of preventive strategies. We investigated how risk perception and its determinants changed between 1999 and 2018 in an open, prospective cohort of 1323 HIV-negative men who have sex with men (MSM). Risk perception, defined as the perceived likelihood of acquiring HIV in the past 6 months, changed over time: being relatively lower in 2008-2011, higher in 2012-2016, and again lower in 2017-2018. Irrespective of calendar year, condomless anal intercourse (AI) with casual partners and high numbers of partners were associated with higher risk perception. In 2017-2018, condomless receptive AI with a partner living with HIV was no longer associated with risk perception, while PrEP use and condomless AI with a steady partner were associated with lower risk perception. We showed that risk perception has fluctuated among MSM in the past 20 years. The Undetectable equals Untransmittable statement and PrEP coincided with lower perceived risk.

Longitudinal Patterns of Sexually Transmitted Infection Risk Based on Psychological Characteristics and Sexual Behavior in Heterosexual Sexually Transmitted Infection Clinic Visitors.

BACKGROUND: Great heterogeneity in sexually transmitted infections (STI) risk exists, and investigating individual-level characteristics related to changes in STI risk over time might facilitate the development and implementation of effective evidence-based behavior change interventions. The aim of this study was to identify longitudinal patterns of STI risk based on psychological and behavioral characteristics. METHODS: A longitudinal study was conducted among heterosexual STI clinic visitors aged 18 to 24 years. Latent classes based on behavioral and psychological characteristics at baseline, and transitions from 1 latent class to another at 3-week, 6-month, and 1-year follow-up, were identified using latent transition analysis. RESULTS: Four latent classes were identified that could be differentiated by psychological and behavioral characteristics and STI risk: overall low-risk (10%), insecure high-risk (21%), condom-users (38%), and confident high-risk (31%). Although the majority of the total study population did not move to another latent class over time, the size of the overall low-risk group increased from 10% at baseline to 30% after 1 year. This was mainly due to transitions from the insecure high-risk, condom-users, and confident high-risk class at 3-week follow-up to the overall low-risk class at 6-month follow-up. CONCLUSIONS: Distinct subgroups among heterosexual STI clinic visitors can be differentiated from each other by multiple psychological and behavioral characteristics, and these characteristics reflecting the risk of acquiring STI are consistent over the course of 1 year in most individuals. An integral approach, adapting behavioral interventions to match multiple psychological and behavioral characteristics of high-risk subgroups, might be more effective in controlling STI transmission.

Impact of sexual trajectories of men who have sex with men on the reduction in HIV transmission by pre-exposure prophylaxis.

Changes in sexual risk behavior over the life course in men who have sex with men (MSM) can influence population-level intervention efficacy. Our objective was to investigate the impact of incorporating sexual trajectories describing long-term changes in risk levels on the reduction in HIV prevalence by pre-exposure prophylaxis (PrEP) among MSM. Based on the Amsterdam Cohort Study data, we developed two models of HIV transmission in a population stratified by sexual behavior. In the first model, individuals were stratified into low, medium and high risk levels and did not change their risk levels. The second model had the same stratification but incorporated additionally three types of sexual behavior trajectories. The models assumed universal antiretroviral treatment of HIV+ MSM, and PrEP use by high risk HIV- MSM. We computed the relative reduction in HIV prevalence in both models for annual PrEP uptakes of 10% to 80% at different time points after PrEP introduction. We then investigated the impact of sexual trajectories on the effectiveness of PrEP intervention. The impact of sexual trajectories on the overall prevalence and prevalence in individuals at low, medium and high risk levels varied with PrEP uptake and time after PrEP introduction. Compared to the model without sexual trajectories, the model with trajectories predicted a higher impact of PrEP on the overall prevalence, and on the prevalence among the medium and high risk individuals. In low risk individuals, there was more reduction in prevalence during the first 15 years of PrEP intervention if sexual trajectories were not incorporated in the model. After that point, at low risk level there was more reduction in the model with trajectories. In conclusion, our study predicts that sexual trajectories increase the estimated impact of PrEP on reducing HIV prevalence when compared to a population where risk levels do not change.

Sexual risk behaviour trajectories among MSM at risk for HIV in Amsterdam, the Netherlands.

OBJECTIVE: Sexual risk behaviour changes during a person's life course. Insights in sexual risk behaviour trajectories of MSM may provide starting points for the timing of HIV prevention methods. We aimed to study longitudinal trajectories of sexual risk behaviour predictive of HIV acquisition from sexual debut onwards. DESIGN: A longitudinal study among 815 HIV-negative participants of the Amsterdam Cohort Studies (ACS) who completed extensive questionnaires about their sexual behaviour every 6 months between 2007 and 2017. METHODS: A comprehensive behavioural risk score predictive of HIV seroconversion was developed. On the basis of this risk score, linear trajectories of sexual risk behaviour and MSM group membership were estimated using latent class growth mixture modelling. Associations between longitudinal trajectories and demographic and psychosocial factors were examined. RESULTS: Three trajectories of sexual risk behaviour were identified, which were labelled Low risk (90.3% of the sample), Falling high risk (6.5%) and Rising high risk (3.3%). MSM following the Falling high risk (20.5%) and Rising high risk (25.0%) trajectories were more likely to acquire HIV during follow-up. The Falling high risk trajectory was associated with younger age at sexual debut, fewer steady partnerships and high percentages of substance use. The Rising high-risk trajectory was associated with increasing percentages of substance use over time. CONCLUSION: MSM follow different trajectories of changing sexual risk behaviour over time. Early identification of MSM following a trajectory of falling or rising high-risk behaviour and adequate timing of individual-based preventive interventions may reduce HIV transmission.

Cognitive functioning in children with internalising, externalising and dysregulation problems: a population-based study.

Psychiatric symptoms in childhood are closely related to neurocognitive deficits. However, it is unclear whether internalising and externalising symptoms are associated with general or distinct cognitive problems. We examined the relation between different types of psychiatric symptoms and neurocognitive functioning in a population-based sample of 1177 school-aged children. Internalising and externalising behaviour was studied both continuously and categorically. For continuous, variable-centred analyses, broadband scores of internalising and externalising symptoms were used. However, these measures are strongly correlated, which may prevent identification of distinct cognitive patterns. To distinguish groups of children with relatively homogeneous symptom patterns, a latent profile analysis of symptoms at age 6 yielded four exclusive groups of children: a class of children with predominantly internalising symptoms, a class with externalising symptoms, a class with co-occurring internalising and externalising symptoms, that resembles the CBCL dysregulation profile and a class with no problems. Five domains of neurocognitive ability were tested: attention/executive functioning, language, memory and learning, sensorimotor functioning, and visuospatial processing. Consistently, these two different modelling approaches demonstrated that children with internalising and externalising symptoms show distinct cognitive profiles. Children with more externalising symptoms performed lower in the attention/executive functioning domain, while children with more internalising symptoms showed impairment in verbal fluency and memory. In the most severely affected class of children with internalising and externalising symptoms, we found specific impairment in the sensorimotor domain. This study illustrates the specific interrelation of internalising and externalising symptoms and cognition in young children.

The Stability of Problem Behavior Across the Preschool Years: An Empirical Approach in the General Population.

This study examined the stability of internalizing and externalizing problems from age 1.5 to 6 years, while taking into account developmental changes in the presentation of problems. The study comprised a population-based cohort of 7,206 children (50.4 % boys). At ages 1.5, 3, and 6 years, mothers reported on problem behavior using the Child Behavior Checklist/1.5-5 (CBCL/1.5-5). At each age we performed latent profile analysis on the CBCL/1.5-5 scales. Latent transition analysis (LTA) was applied to study the stability of problem behavior. Profiles of problem behavior varied across ages. At each age, 82-87 % of the children did not have problems whereas approximately 2 % showed a profile of co-occurring internalizing and externalizing problems. This profile was more severe (with higher scores) at 6 years than at earlier ages. A predominantly internalizing profile only emerged at 6 years, while a profile with externalizing problems and emotional reactivity was present at each age. LTA showed that, based on profiles at 1.5 and 3 years, it was difficult to predict the type of profile at 6 years. Children with a profile of co-occurring internalizing and externalizing problems early in life were most likely to show problem behavior at 6 years. This study shows that the presentation of problem behavior changes across the preschool period and that heterotypic continuity of problems is very common among preschoolers. Children with co-occurring internalizing and externalizing problems were most likely to show persisting problems. The use of evidence-based treatment for these young children may prevent psychiatric problems across the life course.

Preterm Birth and Adult Wealth: Mathematics Skills Count.

Each year, 15 million babies worldwide are born preterm. Preterm birth is associated with adverse neurodevelopmental outcomes across the life span. Recent registry-based studies suggest that preterm birth is associated with decreased wealth in adulthood, but the mediating mechanisms are unknown. This study investigated whether the relationship between preterm birth and low adult wealth is mediated by poor academic abilities and educational qualifications. Participants were members of two British population-based birth cohorts born in 1958 and 1970, respectively. Results showed that preterm birth was associated with decreased wealth at 42 years of age. This association was mediated by decreased intelligence, reading, and, in particular, mathematics attainment in middle childhood, as well as decreased educational qualifications in young adulthood. Findings were similar in both cohorts, which suggests that these mechanisms may be time invariant. Special educational support in childhood may prevent preterm children from becoming less wealthy as adults.

Why Mothers and Young Children Agree or Disagree in Their Reports of the Child's Problem Behavior.

This study examined multiple determinants of discrepancies between mother and child reports of problem behavior. In 5,414 6-year-olds, child problem behavior was assessed by self-report using the Berkeley Puppet Interview and by maternal report using the Child Behavior Checklist. Patterns in mother-child reports were modeled using latent profile analysis. Four profiles, differing in problem level, and the direction and magnitude of mother-child discrepancies, were identified: one profile representing agreement (46%), another representing slight discrepancies (30%), and two representing higher problem levels and more discrepancies. In the latter two profiles either children (11%) or mothers (13%) reported more problems. Compared to the first profile, the second was predominantly characterized by a positive family environment, the third by child cognitive difficulties, and the fourth by harsh discipline and poor family functioning. Knowledge about specific child/family characteristics that contribute to mother-child discrepancies can help to interpret informants' reports and to make diagnostic decisions.

Maternal LC-PUFA status during pregnancy and child problem behavior: the Generation R Study.

BACKGROUND: Omega 3 (n-3) and 6 (n-6) long-chain polyunsaturated fatty acids (LC-PUFAs) and the n-3:n-6 ratio are important for brain development. Whether maternal LC-PUFA status during pregnancy affects risk of problem behavior in later childhood is unclear. METHODS: Within a population-based cohort, we measured maternal plasma docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA) concentrations and n-3:n-6-ratio in mid-pregnancy. Child emotional and behavioral problems at 6 y of age were assessed by parents (child behavior checklist), teachers (teacher report form), and combined parent/teacher report. RESULTS: Higher maternal DHA and n-3:n-6 ratio were associated with fewer child emotional problems using parent (odds ratio (OR)DHA = 0.82; 95% confidence interval (CI): 0.70, 0.96; P = 0.02 and OR(n-3:n-6) = 0.83; 95% CI: 0.71, 0.96; P = 0.01; n = 5,307) and combined parent/teacher scores (ORDHA = 0.79; 95% CI: 0.66, 0.95; P = 0.01 and OR(n-3:n-6) = 0.77; 95% CI: 0.65, 0.92; P < 0.01; n = 2,828). Higher AA was associated with more child behavioral problems using teacher (OR = 1.10; 95% CI: 1.00, 1.20; P = 0.04; n = 3,365) and combined parent/teacher scores (OR = 1.12; 95% CI: 1.02, 1.22; P = 0.02; n = 2,827). Maternal EPA was not associated with child problem behavior. CONCLUSION: Indications of associations of maternal LC-PUFA status with child emotional and behavioral problems were found. Future research is needed to identify LC-PUFA-sensitive periods of fetal brain development by including multiple assessments of prenatal LC-PUFA status.

Nonverbal intelligence in young children with dysregulation: the Generation R Study.

Children meeting the Child Behavior Checklist Dysregulation Profile (CBCL-DP) suffer from high levels of co-occurring internalizing and externalizing problems. Little is known about the cognitive abilities of these children with CBCL-DP. We examined the relationship between CBCL-DP and nonverbal intelligence. Parents of 6,131 children from a population-based birth cohort, aged 5 through 7 years, reported problem behavior on the CBCL/1.5-5. The CBCL-DP was derived using latent profile analysis on the CBCL/1.5-5 syndrome scales. Nonverbal intelligence was assessed using the Snijders Oomen Nonverbal Intelligence Test 2.5-7-Revised. We examined the relationship between CBCL-DP and nonverbal intelligence using linear regression. Analyses were adjusted for parental intelligence, parental psychiatric symptoms, socio-economic status, and perinatal factors. In a subsample with diagnostic interview data, we tested if the results were independent of the presence of attention deficit hyperactivity disorder (ADHD) or autism spectrum disorders (ASD). The results showed that children meeting the CBCL-DP (n = 110, 1.8%) had a 11.0 point lower nonverbal intelligence level than children without problems and 7.2-7.3 points lower nonverbal intelligence level than children meeting other profiles of problem behavior (all p values <0.001). After adjustment for covariates, children with CBCL-DP scored 8.3 points lower than children without problems (p < 0.001). The presence of ADHD or ASD did not account for the lower nonverbal intelligence in children with CBCL-DP. In conclusion, we found that children with CBCL-DP have a considerable lower nonverbal intelligence score. The CBCL-DP and nonverbal intelligence may share a common neurodevelopmental etiology.