Polymorphisms in corticotrophin-releasing hormone-proopiomalanocortin (CRH-POMC) system genes: Neuroimmune contributions to psoriasis disease.

BACKGROUND: Skin is a target organ and source of the corticotropin-releasing hormone-proopiomelanocortin (CRH-POMC) system, operating as a coordinator and executor of responses to stress. Environmental stress exacerbates and triggers inflammatory skin diseases through modifying the cellular components of the immune system supporting the importance of CRH-POMC system in the pathogenesis of psoriasis. The aim of this study was to analyse the association of CRH-POMC polymorphisms with psoriasis and evaluate transcript expression of lesional psoriatic and normal skin in RNA-seq data. METHODS: Samples of 104 patients with psoriasis and 174 healthy controls were genotyped for 42 single nucleotide polymorphisms (SNPs) of CRH-POMC using Applied Biosystems SNPlex™ method. The transcript quantification was performed using Salmon software v1.3.0. RESULTS: This study demonstrated the associations between melanocortin 1 receptor (MC1R) polymorphisms rs2228479, rs3212369, dopachrome tautomerase (DCT) polymorphisms rs7987802, rs2031526, rs9524501 and psoriasis in the Tatar population. Very strong association was evident for the SNP rs7987802 in the DCT gene (pc = 5.95е-006) in psoriasis patients. Additionally, the haplotype analysis provided AT DCT (rs7992630 and rs7987802) and AGA MC1R (rs3212358, 2228479 and 885479) haplotypes significantly associated (pc ˂ 0.05) with psoriasis in the Tatar population, supporting the involvement of DCT and MC1R to the psoriasis susceptibility. Moreover, MC1R-203 and DCT-201 expression levels were decreased in psoriasis lesional skin compared with healthy control skin. CONCLUSIONS: This study is the first to identify genetic variants of the MC1R and DCT genes significantly associated with psoriasis in Tatar population. Our results support potential roles of CRH-POMC system genes and DCT in the pathogenesis of psoriasis.

Role of cardiometabolic risk in the association between accumulation of affective symptoms across adulthood and mid-life cognitive function: national cohort study.

BACKGROUND: Affective symptoms are associated with cognition in mid-life and later life. However, the role of cardiometabolic risk in this association has not been previously examined. AIMS: To investigate how cardiometabolic risk contributes to associations between affective symptoms and mid-life cognition. METHOD: Data were used from the National Child Development Study (NCDS), a sample of people born in Britain during one week in 1958. Measures of immediate and delayed memory, verbal fluency and information processing speed and accuracy were available at age 50. Affective symptoms were assessed at ages 23, 33 and 42 years and a measure of accumulation was derived. A cardiometabolic risk score was calculated from nine cardiometabolic biomarkers at age 44. Path models were run to test these associations, adjusting for sex, education, socioeconomic position and affective symptoms at age 50. RESULTS: After accounting for missing data using multiple imputation, path models indicated significant indirect associations between affective symptoms and mid-life immediate memory (ß = -0.002, s.e. = 0.001, P = 0.009), delayed memory (ß = -0.002, s.e. = 0.001, P = 0.02) and verbal fluency (ß = -0.002, s.e. = 0.001, P = 0.045) through cardiometabolic risk. CONCLUSIONS: These findings suggest that cardiometabolic risk may play an important role in the association between affective symptoms and cognitive function (memory and verbal fluency). Results contribute to understanding of biological mechanisms underlying associations between affective symptoms and cognitive ageing, which can have implications for early detection of, and intervention for, those at risk of poorer cognitive outcomes.

Bidirectional relation between affective symptoms and cognitive function from middle to late adulthood: a population-based birth cohort study.

OBJECTIVES: There is an association between affective symptoms and cognition. However, the direction of this association remains unclear. This study aimed to test bidirectional relationships between affective symptoms and cognition from middle to late adulthood. METHOD: Data were available from the MRC National Survey of Health and Development (NSHD), a prospective birth cohort of 5362 people born in 1946. Affective symptoms and cognition were measured at ages 53, 60-64, and 69. Latent scores of affective symptoms were derived and cross-lagged models were fitted for affective symptoms with verbal memory and processing speed. RESULTS: Results revealed an inverse cross-sectional association between affective symptoms and verbal memory (ß=-0.18, SE=0.04, p<.001) and processing speed (ß=-0.13, SE=0.06, p=.05) at age 53, but not at ages 60-64 or 69. Affective symptoms at age 53 predicted lower verbal memory at age 60-64 (ß=-0.58, SE=0.27, p=.03), and affective symptoms at age 60-64 predicted lower verbal memory (ß=-0.64, SE=0.29, p=.03) and processing speed (ß=-1.27, SE=0.41, p=.002) at age 69. Verbal memory and processing speed did not predict subsequent affective symptoms. CONCLUSION: Affective symptoms predict poorer verbal memory and processing speed over a period of 16 years, but not vice versa.

Accumulation of affective symptoms and midlife cognitive function: The role of inflammation.

BACKGROUND: The aim of the present study was to test whether C-Reactive Protein (CRP), a proxy measure of inflammation, is elevated in people with higher childhood and adulthood affective symptoms and whether elevated CRP predicts midlife cognitive function. METHODS: Data were used from the National Child Development Study (n = 6276). Measures of memory, verbal fluency, information processing speed and accuracy were available in midlife (age 50). Affective symptoms were assessed in childhood (ages 7, 11, 16) and in adulthood (ages 23, 33, 42, 50). The level of plasma CRP was measured at age 44. Pathway models, unadjusted and fully adjusted for sex, education, childhood socioeconomic position, childhood cognitive ability and affective symptoms at age 50, were fitted to test direct associations between affective symptoms and midlife cognitive function, and indirect associations via the inflammatory pathway (CRP level). RESULTS: In a fully adjusted model, there were significant indirect associations between adulthood affective symptoms and immediate memory (ß = -0.01, SE = 0.003, p = .03) and delayed memory (ß = -0.01, SE = 0.004, p = .03) via CRP. In addition, there were significant indirect associations between affective symptoms in childhood and immediate memory (ß = -0.001, SE = 0.00, p = .03) and delayed memory (ß = -0.001, SE = 0.001, p = .03), via adulthood affective symptoms and associated CRP. Independent of CRP, there was a significant direct association between adulthood affective symptoms and information processing errors (ß = 0.47, SE = 0.21, p = .02). There were no direct or indirect associations between affective symptoms and verbal fluency or information processing speed. CONCLUSIONS: CRP at age 44 is elevated in people with higher affective symptoms from age 7 to 42, and elevated CRP is associated with poorer immediate and delayed memory at age 50.

Affective symptoms across the life course and resilience in cognitive function.

Background: Little is known about what factors can modify the relationship between affective symptoms and cognitive function across the life course.Aim: To investigate a number of factors that can contribute to resilience in cognitive function in relation to affective symptoms, using data from the National Child Development Study.Subjects and methods: Adult affective symptoms were measured using the Malaise Inventory Scale (ages 23, 33, 42 and 50). Measures of immediate and delayed memory, verbal fluency and information processing accuracy (age 50) were used to derive measures of resilience in cognitive function-better than predicted cognition, when accounting for experiences of affective symptoms. Factors contributing to resilience in cognitive function were informed by a literature review and included sex, childhood cognitive ability, education, household socio-economic position (SEP), midlife SEP, and APOE genotype. Linear regression and structural equation modelling approaches were used for analyses.Results: Higher childhood cognitive ability, educational level, midlife SEP and female sex contributed to better than predicted cognitive function in relation to affective symptoms (i.e. resilience), with particularly consistent effects for memory. No effects on resilience were revealed for APOE genotype.Conclusion: Understanding factors contributing to resilience in cognitive function in those with affective symptoms can inform interventions to promote healthy cognitive ageing for those at risk.

Longitudinal associations of affective symptoms with mid-life cognitive function: evidence from a British birth cohort.

BACKGROUND: Affective disorders are associated with poorer cognition in older adults; however, whether this association can already be observed in mid-life remains unclear. AIMS: To investigate the effects of affective symptoms over a period of 30 years on mid-life cognitive function. First, we explored whether timing (sensitive period) or persistence (accumulation) of affective symptoms predicted cognitive function. Second, we tested how different longitudinal trajectories of affective symptoms were associated with cognitive function. METHOD: The study used data from the National Child Development Study. Memory, verbal fluency, information processing speed and accuracy were measured at age 50. Affective symptoms were measured at ages 23, 33, 42 and 50 and used to derive longitudinal trajectories. A structured modelling approach compared a set of nested models in order to test accumulation versus sensitive period hypotheses. Linear regressions and structural equation modelling were used to test for longitudinal associations of affective symptoms with cognitive function. RESULTS: Accumulation of affective symptoms was found to be the best fit for the data, with persistent affective symptoms being associated with poorer immediate memory (b = -0.07, s.e. = 0.03, P = 0.01), delayed memory (b = -0.13, s.e. = 0.04, P < 0.001) and information processing accuracy (b = 0.18, s.e. = 0.08, P = 0.03), but not with information processing speed (b = 3.15, s.e. = 1.89, P = 0.10). Longitudinal trajectories of repeated affective symptoms were associated with poorer memory, verbal fluency and information processing accuracy. CONCLUSIONS: Persistent affective symptoms can affect cognitive function in mid-life. Effective management of affective disorders to prevent recurrence may reduce risk of poor cognitive outcomes and promote healthy cognitive ageing. DECLARATION OF INTEREST: None.

Research Review: Childhood chronic physical illness and adult emotional health - a systematic review and meta-analysis.

BACKGROUND: Childhood chronic physical illness is associated with a greater vulnerability for emotional problems (i.e. depression and anxiety) in childhood. However, little is known about life-long effects of childhood chronic physical illness on mental health. The present study aims to systematically review evidence for associations between eight chronic physical illnesses with childhood onset (arthritis, asthma, cancer, chronic renal failure, congenital heart disease, cystic fibrosis, type 1 diabetes, and epilepsy) and adult emotional problems. METHODS: A database search of MEDLINE, PsycARTICLES, PsycINFO, and ScienceDirect was undertaken, and random effects meta-analyses were used to synthesise evidence from eligible studies. RESULTS: In total, 37 studies were eligible for the systematic review (n = 45,733) and of these, 34 studies were included in the meta-analyses (n = 45,358). There were overall associations between childhood chronic physical illness and adult depression (OR = 1.31; 95% CI [1.12, 1.54]) and anxiety (OR = 1.47; 95% CI [1.13, 1.92]). Separate meta-analyses for childhood asthma, type 1 diabetes and cancer were also conducted, with cancer being significantly associated with adult depression (OR = 1.19; 95% CI [1.00, 1.42]). CONCLUSIONS: The effects of childhood chronic physical illness on the risk of emotional problems persist beyond childhood and adolescence. Mental health prevention and intervention strategies targeting children with chronic physical illnesses can have long-term benefits.

Pubertal maturation and affective symptoms in adolescence and adulthood: Evidence from a prospective birth cohort.

The higher prevalence of affective symptoms among women compared to men emerges in adolescence, and it has been associated with pubertal maturation. However, it remains unclear whether pubertal timing has long-term influences on affective symptoms. Using data from the British 1946 birth cohort, we investigated whether pubertal timing was associated with affective symptoms over the life course, distinguishing those with symptoms in adolescence only, symptoms in adulthood only, and symptoms in both adolescence and adulthood. In females, there was no evidence that early pubertal maturation was a risk factor for affective symptoms. However, those with particularly late menarche (≥15 years) showed a lower risk of adult-onset affective symptoms (odds ratio = 0.54, 95% confidence interval = 0.31, 0.95). This effect of late pubertal timing was not explained by a range of sociobehavioral factors. In contrast, in males, late pubertal timing was associated with increased risk of adolescent-onset affective symptoms that tracked into adulthood (odds ratio = 2.10, 95% confidence interval = 1.44, 3.06). This effect was partly explained by low prepubertal body mass index. Sex-specific effects of pubertal timing on the long-term risk of affective symptoms might be due to different effects of gonadal hormonal on the central nervous system, as well as different social experiences during puberty.

Maternal caregiving and girls' depressive symptom and antisocial behavior trajectories: an examination among high-risk youth.

Past research has identified maternal depression and family of origin maltreatment as precursors to adolescent depression and antisocial behavior. Caregiving experiences have been identified as a factor that may ameliorate or accentuate adolescent psychopathology trajectories. Using a multilevel approach that pools the unique attributes of two geographically diverse, yet complementary, longitudinal research designs, the present study examined the role of maternal caregiver involvement as a factor that promotes resilience-based trajectories related to depressive symptoms and antisocial behaviors among adolescent girls. The first sample comprises a group of US-based adolescent girls in foster care (n = 100; mean age = 11.50 years), each of whom had a history of childhood maltreatment and removal from their biological parent(s). The second sample comprises a group of UK-based adolescent girls at high familial risk for depression (n = 145; mean age = 11.70 years), with all girls having biological mothers who experienced recurrent depression. Analyses examined the role of maternal caregiving on girls' trajectories of depression and antisocial behavior, while controlling for levels of co-occurring psychopathology at each time point. Results suggest increasing levels of depressive symptoms for girls at familial risk for depression but decreasing levels of depression for girls in foster care. Foster girls' antisocial behavior also decreased over time. Maternal caregiver involvement was differentially related to intercept and slope parameters in both samples. Results are discussed with respect to the benefits of applying multilevel (multisample, multiple outcome) approaches to identifying family-level factors that can reduce negative developmental outcomes in high-risk youth.

Predictors of treatment outcome of psychological therapies for common mental health problems (CMHP) in older adults: A systematic literature review.

Identifying factors that impact psychological treatment outcomes in older people with common mental health problems (CMHP) has important implications for supporting healthier and longer lives. The aim of the present study was to synthesise the evidence on predictors of psychological treatment outcomes in older people (aged 65+). PubMed, Scopus, Web of Science and PsycINFO were searched and 3929 articles were identified and screened, with 42 studies (N = 7978, M age = 68.9, SD age = 2.85) included: depression: k = 21, anxiety: k = 11, panic disorder: k = 3, mixed anxiety & depression: k = 3, PTSD: k = 2, various CMHP: k = 2, with CBT being the most common treatment (71%). The review identified 28 factors reported as significant predictors of treatment outcome in at least one study, across different domains: psychosocial (n = 9), clinical (n = 6), treatment-related (n = 6), socio-demographic (n = 4), neurobiological (n = 3). Homework completion was the most consistent predictor of positive treatment outcome. Baseline symptom severity was the most frequently studied significant predictor and across all conditions, with higher baseline symptom severity largely linked to worse treatment outcomes. No significant effects on treatment outcome were reported for gender, income and physical comorbidities. For a large majority of factors evidence was mixed or inconclusive. Further studies are required to identify factors affecting psychological treatment outcomes, which will be important for the development of personalised treatment approaches.

"I felt I needed help, but I did not get any": A multiple stakeholder qualitative study of risk and protective factors, and barriers to addressing common mental health problems among perinatal adolescents in Malawi.

Common mental health problems (particularly depression and anxiety) are common among adolescents during the perinatal period. Previous research has identified the distinctive needs of this group and called for contextually appropriate psychosocial interventions. The current study conducted in Malawi aimed to explore risk and protective factors for common mental health problems, and barriers to accessing mental health care, among perinatal adolescents, to develop a contextually relevant intervention for preventing and treating perinatal depression and anxiety. An exploratory qualitative study was conducted in antenatal and postnatal clinics in Zomba district, Malawi in January-March 2022. In-depth individual interviews were completed with perinatal adolescents aged ≤19 (n = 14); their family members (n = 4); and healthcare workers (n = 8). Interview data were subjected to thematic framework analysis. Data were organised around two themes: "psychosocial risk and protective factors" (potential causes of common mental health problems among adolescents); and "health care services" (maternal and mental health services available, and adolescents' experiences of using these services). Interventions need to go beyond targeting symptoms of depression and anxiety to addressing the wider contextual risk factors and barriers to care at the different socioecological levels.

Psychoeducation as an active ingredient for interventions for perinatal depression and anxiety in youth: a mixed-method systematic literature review and lived experience synthesis.

BACKGROUND: Psychoeducation is a common element in psychological interventions for youth depression and anxiety, but evidence about its use with youth perinatally is limited. AIMS: This review aims to understand outcomes and mechanisms of psychoeducation for the indicated prevention and treatment of perinatal depression and anxiety in youth. METHOD: For this review, we synthesised published quantitative and qualitative evidence. Seven databases (ASSIA, Medline, PubMed, PsycINFO, PsycArticles, Scopus and Web of Science) were searched for studies published before 10 August 2021. We also had consultations with a youth advisory group (N = 12). RESULTS: In total, 20 studies met the inclusion criteria. Seven quantitative studies examined multicomponent interventions that included psychoeducation, and one study evaluated psychoeducation as a standalone intervention for postnatal depression. Multicomponent interventions showed significant effects on postnatal depression in two out of six studies, as well as being effective at reducing prenatal anxiety in one study. Standalone psychoeducation for postnatal depression was also effective in one study. Evidence from 12 qualitative studies, corroborated by commentaries from the youth advisory group, suggested that psychoeducation could increase knowledge about symptoms, generate awareness of relevant services and enhance coping. CONCLUSIONS: Psychoeducation may be an important foundational ingredient of interventions for perinatal depression and, potentially, anxiety in adolescents and young adults through stimulating help-seeking and self-care.

Life course trajectories of affective symptoms and their early life predictors.

Background: Life course trajectories of affective symptoms (depression and anxiety) are heterogenous. However, few studies have investigated the role of early life risk factors in the development of these trajectories. The present study aimed to: (1) derive latent trajectories of affective symptoms over a period of more than 50 years (ages 13-69), and (2) examine early life risk factors for associations with specific life course trajectories of affective symptoms. Method: Participants are from the MRC National Survey of Health and Development (NSHD) (n = 5,362). Affective symptoms were measured prospectively at ages 13, 15, 36, 43, 53, 60-64 and 69. A latent variable modelling framework was implemented to model longitudinal profiles of affective symptoms. Twenty-four prospectively measured early life predictors were tested for associations with different symptom profiles using multinomial logistic regression. Results: Four life course profiles of affective symptoms were identified: (1) absence of symptoms (66.6% of the sample); (2) adolescent symptoms with good adult outcome (15.2%); (3) adult symptoms only (with no symptoms in adolescence and late life) (12.9%); (4) symptoms in adolescence and mid adulthood (5.2%). Of the 24 early life predictors observed, only four were associated with life course trajectories, with small effect sizes observed. Conclusions: People differ in their life course trajectories of anxiety and depression symptoms and that these differences are not largely influenced by early life factors tested in this study.

Salivary cortisol in longitudinal associations between affective symptoms and midlife cognitive function: A British birth cohort study.

Affective disorders are associated with accelerated cognitive ageing. However, current understanding of biological mechanisms which underlie these observed associations is limited. The aim of this study was to test: 1) Whether cortisol acts as a pathway in the association between depressive or anxiety symptoms across adulthood and midlife cognitive function; 2) Whether cortisol is associated with later depressive or anxiety symptoms, and cognitive function. Data were used from the National Child Development Study (NCDS), a sample of infants born in mainland UK during one week of 1958. A measure of the accumulation of affective symptoms was derived from data collected from age 23 to 42 using the Malaise Inventory Scale. Salivary cortisol measures were available at age 44-45. Cognitive function (memory, fluency, information processing) and affective symptoms were assessed at the age of 50. Path models were run to test whether salivary cortisol explained the longitudinal association between depressive or anxiety disorder symptoms and cognitive function. Direct effects of affective symptoms are shown across early to middle adulthood on cognitive function in midlife (memory and information processing errors). However, there were no effects of affective symptoms on cognitive function through cortisol measures. Additionally, cortisol measures were not significantly associated with subsequent affective symptoms or cognitive function at the age of 50. These results do not provide clear evidence to suggest that cortisol plays a role in the association between affective symptoms and cognitive function over this period of time. These findings contribute to our understanding of how the association between affective symptoms and cognitive function operates over time.

Association between adolescent emotional problems and metabolic syndrome: the modifying effect of C-reactive protein gene (CRP) polymorphisms.

Depression is associated with the development of the metabolic syndrome, and both depression and metabolic syndrome are associated with markers of systemic inflammation, such as C-reactive protein (CRP). We examined associations between affective status in adolescence and adulthood, and the metabolic syndrome at age 53 years in a large representative British birth cohort. We also investigated whether two CRP gene polymorphisms (rs1205 and rs3093068) were associated with affective status and the metabolic syndrome, and whether the association between affective status and the metabolic syndrome was modified by these CRP polymorphisms. Women, but not men, with emotional problems in adolescence were more likely to have the metabolic syndrome (OR=1.53, 95% CI: 1.04, 2.26), although this sex difference was not statistically significant (p=0.22). The CRP SNPs were not associated with affective status or the metabolic syndrome, but the association of adolescent emotional problems with the metabolic syndrome was stronger in those who were homozygous for the major allele (C) of rs1205 (OR=1.83, 95% CI: 1.17, 2.86) than in carriers of the T allele (OR=1.01, 95% CI: 0.66, 1.55) (p=0.05 for gene by affective status interaction). This interaction was stronger when considering adolescent emotional problems as a continuous variable (p=0.003). Adolescent emotional problems play an important role in the development of the metabolic syndrome later in life, particularly in those homozygous for the major allele of CRP rs1205. These findings may highlight new ways of identifying people with emotional problems at high risk of developing the metabolic syndrome, which is of great importance for the management of the physical health of these patients.

Childhood socio-economic position and affective symptoms in adulthood: The role of neglect.

BACKGROUND: Childhood neglect is more common within low-income families and can have long-term effects on mental health. Despite this, the extent to which it can mediate the well documented longitudinal inverse relationship between childhood socio-economic position (SEP) and adult affective symptoms is yet to be investigated. METHOD: Data (9595 males and 8959 females) from participants of the National Child Development Study (NCDS) were used to investigate the extent to which prospectively measured neglect mediates the relationship between SEP (age 11) and affective symptoms (ages 23 and 50). RESULTS: Neglect partially mediated the relationship between childhood SEP and affective symptoms at ages 23 (b = -0.02, [-0.02, -0.02]) and 50 (b = -0.02, [-0.02, -0.01]), after controlling for other family-related adversities. In addition, gender moderated the direct effect of SEP on affective symptoms at both ages 23 (b = -0.06, t = -4.87, [-0.08, -0.03]) and 50 (b = -0.05, t = -3.86, [-0.07, -0.02]), with the relationship being stronger for females; but did not moderate the indirect effect of neglect at either age 23 (b = 0.01, t = 1.09 [-0.01, 0.02]) or 50 (b = 0.00, t = -0.60 [-0.02, 0.01]). CONCLUSIONS: Neglect in childhood should be viewed as having serious implications for the mental health of both men and women. Greater investments into social support interventions that reduce incidences of neglect are also warranted.

Childhood neglect and trajectories of affective symptoms throughout adulthood: A British birth cohort study.

BACKGROUND: Childhood maltreatment, including neglect, can affect an individual's mental health. However, there is a gap in current literature investigating the long-term, dynamic effects of childhood neglect on adult affective symptoms (AS). METHOD: Data were used from the National Child Development Study (a British 1958 birth cohort). Childhood neglect was prospectively measured at ages 7 and 11. Five distinct trajectories of AS have been derived previously, using data from the Malaise Inventory Scale (at ages 23, 33, 42 and 50): 'no symptoms', 'persistent mild/moderate symptoms', 'low and increasing symptoms', 'high and increasing symptoms' and 'high and decreasing symptoms' (John et al., 2019). Multinomial logistic regressions were used to explore whether childhood neglect was associated with AS trajectory membership, while adjusting for a number of covariates. RESULTS: Results revealed that childhood neglect was significantly associated with 'high and decreasing', 'high and increasing' and 'persistent mild/moderate' AS trajectories from young adulthood through midlife. There was no association with the 'low and increasing' AS trajectory. When testing for at age specific effects, neglect experienced at age 7 only, or at age 11 only, was predictive of 'high and decreasing symptoms' trajectory, whereas neglect experienced at both ages was predictive of 'persistent mild/moderate symptoms' trajectory. CONCLUSIONS: Childhood neglect has negative long-lasting effects on trajectories of adult mental health. This finding has important implications for early intervention for individuals who have experienced childhood neglect.

The Bipolar Association Case-Control Study (BACCS) and meta-analysis: No association with the 5,10-Methylenetetrahydrofolate reductase gene and bipolar disorder.

Bipolar disorder (BD) is a complex genetic disease for which the underlying pathophysiology has yet to be fully explained. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in folate-mediated one-carbon metabolism and folate deficiency can be associated with psychiatric symptoms. A single base variant in MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme and has recently been implicated in BD. We conducted an association study of this polymorphism in 897 patients with bipolar I or bipolar II disorder, and 1,687 healthy control subjects. We found no evidence for genotypic or allelic association in this sample. We also performed a meta-analysis of our own, and all published data, and report no evidence for association. Our findings suggest that the MTHFR C677T polymorphism is not involved in the genetic etiology of clinically significant BD.

Internalizing symptoms and working memory as predictors of mathematical attainment trajectories across the primary-secondary education transition.

The transition from primary to secondary education is a critical period in early adolescence which is related to increased anxiety and stress, increased prevalence of mental health issues, and decreased maths performance, suggesting it is an important period to investigate maths attainment. Previous research has focused on anxiety and working memory as predictors of maths, without investigating any long-term effects around the education transition. This study examined working memory and internalizing symptoms as predictors of children's maths attainment trajectories (age 7-16) across the transition to secondary education using secondary longitudinal analysis of the Avon Longitudinal Study of Parents and Children (ALSPAC). This study found statistically significant, but very weak evidence for the effect of internalizing symptoms and working memory on maths attainment. Greater parental education was the strongest predictor, suggesting that children of parents with a degree (compared with those with a CSE) gain the equivalent of almost a year's schooling in maths. However, due to methodological limitations, the effects of working memory and internalizing symptoms on attainment cannot be fully understood with the current study. Additional research is needed to further uncover this relationship, using more time-appropriate measures.

Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case-control study (BACCS).

Recent studies suggest a degree of overlap in genetic susceptibility across the traditional categories of schizophrenia and bipolar disorder. There is some evidence for an association of the dystrobrevin binding protein 1 gene (DTNBP1) with schizophrenia, and, thus, this gene has also become a focus of further investigation in bipolar disorder (BD). The aim of our study is to explore the association of DTNBP1 with BD and with a sub phenotype, presence/absence of psychotic symptoms, in a sample of 515 patients with BD (ICD10/DSMIV) and 1,316 ethnically matched control subjects recruited from the UK. Seven DTNBP1 SNPs: rs2743852 (SNP C), rs760761 (P1320), rs1011313 (P1325), rs3213207 (P1635), rs2619539 (P1655), rs16876571 and rs17470454 were investigated using the SNPlex genotyping system and 1 SNP (rs2619522) genotypes were imputed. Association analyses were conducted in a sample of 452 cases and 956 controls. We found significant differences in genotypic and allelic frequencies of rs3213207 and rs760761 of DTNBP1 between bipolar patients and controls. We also showed a global haplotypic association and an association of a particular haplotype with BD. Our results are consistent with previous studies in term of a general association between DTNBP1 and bipolar disorder and provide additional evidence that a portion of the genotypic overlap between schizophrenia and bipolar affective disorder is attributable to this gene.