The clinical course of major depressive disorder (MDD) is heterogeneous, and early-onset MDD often has a more severe and complex clinical course. Our goal was to determine whether polygenic scores (PGSs) for psychiatric disorders are associated with treatment trajectories in early-onset MDD treated in secondary care.

Data were drawn from the iPSYCH2015 sample, which includes all individuals born in Denmark between 1981 and 2008 who were treated in secondary care for depression between 1995 and 2015. We selected unrelated individuals of European ancestry with an MDD diagnosis between ages 10–25 (N = 10577). Seven-year trajectories of hospital contacts for depression were modeled using Latent Class Growth Analysis. Associations between PGS for MDD, bipolar disorder, schizophrenia, ADHD, and anorexia and trajectories of MDD contacts were modeled using multinomial logistic regressions.

We identified four trajectory patterns: brief contact (65%), prolonged initial contact (20%), later re-entry (8%), and persistent contact (7%). Relative to the brief contact trajectory, higher PGS for ADHD was associated with a decreased odds of membership in the prolonged initial contact (odds ratio = 1.06, 95% confidence interval = 1.01–1.11) and persistent contact (1.12, 1.03–1.21) trajectories, while PGS-AN was associated with increased odds of membership in the persistent contact trajectory (1.12, 1.03–1.21).

We found significant associations between polygenic liabilities for psychiatric disorders and treatment trajectories in patients with secondary-treated early-onset MDD. These findings help elucidate the relationship between a patient's genetics and their clinical course; however, the effect sizes are small and therefore unlikely to have predictive value in clinical settings.

Maternal vitamin-D and omega-3 fatty acid (DHA) deficiencies during pregnancy have previously been associated with offspring neurodevelopmental traits. However, observational study designs cannot distinguish causal effects from confounding.

First, we conducted Mendelian randomisation (MR) using genetic instruments for vitamin-D and DHA identified in independent genome-wide association studies (GWAS). Outcomes were (1) GWAS for traits related to autism and ADHD, generated in the Norwegian mother, father, and child cohort study (MoBa) from 3 to 8 years, (2) autism and ADHD diagnoses. Second, we used mother–father–child trio-MR in MoBa (1) to test causal effects through maternal nutrient levels, (2) to test effects of child nutrient levels, and (3) as a paternal negative control.

Associations between higher maternal vitamin-D levels on lower ADHD related traits at age 5 did not remain after controlling for familial genetic predisposition using trio-MR. Furthermore, we did not find evidence for causal maternal effects of vitamin-D/DHA levels on other offspring traits or diagnoses. In the reverse direction, there was evidence for a causal effect of autism genetic predisposition on lower vitamin-D levels and of ADHD genetic predisposition on lower DHA levels.

Triangulating across study designs, we did not find evidence for maternal effects. We add to a growing body of evidence that suggests that previous observational associations are likely biased by genetic confounding. Consequently, maternal supplementation is unlikely to influence these offspring neurodevelopmental traits. Notably, genetic predisposition to ADHD and autism was associated with lower DHA and vitamin-D levels respectively, suggesting previous associations might have been due to reverse causation.

Copy number variants (CNVs) are large changes in the structure of DNA. Certain rare CNVs are associated with elevated chance of neurodevelopmental conditions and difficulties (NDs), including autism spectrum disorder (ASD) and intellectual disability, alongside various physical health complications. Currently, CNV testing in children with NDs is only recommended under limited circumstances, in part because their impact on outcomes and prognosis remains unknown. We aimed to investigate whether individuals with NDs in childhood, with and without rare pathogenic CNVs, differ in terms of functional outcomes in early adulthood.

Pathogenic CNV carriers were identified in the Avon Longitudinal Study of Parents and Children (ALSPAC), a UK birth cohort of individuals born in 1991–1992. Individuals with the following childhood NDs were identified through parent-reported diagnostic interviews and questionnaires, and assessment with the child: Attention Deficit Hyperactivity-Disorder (ADHD), ASD, reading difficulties, coordination difficulties, language difficulties, and chronic tics. Outcomes were measured at age 25 and included: presence of an emotional disorder, being in receipt of sickness/disability benefit, ability to make and maintain friendships, not being in education, employment, or training (NEET), and self-reported life satisfaction. We will use logistic regression to measure the association between carrying a pathogenic CNV and each functional outcome in ALSPAC. Sensitivity analyses will be conducted on all large (>250kb), rare (<1%) CNVs, as opposed to only pathogenic CNVs.

983 individuals with probable NDs (39.4% female, n = 387) were identified in ALSPAC, including 495 people with ASD, 163 with ADHD, 16 with Tourette's syndrome, 210 with reading difficulties, 295 with language difficulties, and 166 with coordination difficulties. Many individuals met criteria for more than one ND.

43 (4.4%) of individuals with an ND carried a pathogenic CNV. CNV carrier status amongst individuals with a ND was not associated with sex (4.4% of females vs 4.4% of males, OR = 1.007 [0.539–1.882] p = 0.981). Analysis of CNV carrier status on outcomes in NDs will be conducted between February and April 2024.

Evidence in support of poorer outcomes in CNV carriers could suggest that neurodiverse young people with CNVs may benefit from intervention to improve outcomes, and thus more individuals may benefit from genetic testing. Conversely, evidence indicating that CNVs do not impact outcomes may suggest that current clinical guidelines are appropriate within the current research landscape, and that further research is needed to understand the impact of carrying a pathogenic CNV in young people with NDs.

Sex differences in the prevalence of ADHD are well reported in the literature, with childhood ADHD being diagnosed 7–8 times more frequently in males than females, despite a population sex ratio of 3–4:1. A recent consensus statement argued that ADHD is under-identified and under-diagnosed in the UK, and this is especially concerning with regards to females. This systematic review aims to investigate specific symptoms characterising the manifestation of ADHD in females compared with both males with ADHD and females without ADHD.

A systematic search of eligible studies was conducted using predefined search criteria across six databases (Ovid MEDLINE, Ovid EMBASE, Ovid APA PsycINFO, ProQuest, EBSCO ERIC and EBSCO British Education Index), in line with a registration protocol on PROSPERO. Eligible studies included those with statistical analysis comparing ADHD, impact or co-occurring mental health difficulties at the item level, which compared ADHD symptoms in both sexes, or contrasted females with and without ADHD. Studies that exclusively reported total scores without item-level statistical results were excluded. A total of 5,378 articles were identified in the search and 13 studies met the criteria for inclusion.

Outcomes from 13 studies were analysed thematically. 7 studies looked at ADHD at an item level, while 7 studies explored disparities in impairment or other items. Of the eligible studies, 12 compared males and females with ADHD and 4 compared females with and without ADHD. 7 studies focussed on children with ADHD and 6 on adults. Preliminary results from 3 studies of ADHD symptoms in children indicated sex differences in hyperactive and impulsive symptoms: males were more likely to exhibit symptoms such as fidgeting and difficulty remain seated, while females exhibited higher rates of excessive talking and interrupting. Sex differences in impairment showed mixed results. Females with ADHD endorsed self-reported items related to mind-wandering and parent-reported impairment, including friendship difficulties, more than females without ADHD. Overall, the analysis of the results suggested that most studies do show some sex differences in ADHD and impairment items.

While current studies of individuals diagnosed with ADHD highlight important sex differences, the limited number of direct investigations and predominant focus on total symptoms underscore the need for further research. Item-level analysis of symptoms and their impact is essential in exploring how sex influences the associations between ADHD, risk factors and functional outcomes. Recognising potential sex differences is essential for improving ADHD assessment in females and later life outcomes.

Emotional problems, especially anxiety, have become increasingly common in recent generations. Few population-based studies have examined trajectories of emotional problems from early childhood to late adolescence or investigated differences in psychiatric and functional outcomes.

Using the Avon Longitudinal Study of Parents and Children (ALSPAC, n = 8286, 50.4% male), we modeled latent class growth trajectories of emotional problems, using the parent-reported Strength and Difficulties Questionnaire emotional scale (SDQ-E) on seven occasions (4–17 years). Psychiatric outcomes in young adulthood (21–25 years) were major depressive disorder (MDD), generalized anxiety disorder (GAD), and self-harm. Functional outcomes were exam attainment, educational/occupational status, and social relationship quality.

We identified four classes of emotional problems: low (67.0%), decreasing (18.4%), increasing (8.9%), and persistent (5.7%) problems. Compared to those in the low class, individuals with decreasing emotional problems were not at elevated risk of any poor adult outcome. Individuals in the increasing and persistent classes had a greater risk of adult MDD (RR: 1.59 95% CI 1.13–2.26 and RR: 2.25 95% CI 1.49–3.41) and self-harm (RR: 2.37 95% CI 1.91–2.94 and RR: 1.87 95% CI 1.41–2.48), and of impairment in functional domains. Childhood sleep difficulties, irritability, conduct and neurodevelopmental problems, and family adversity were associated with a persistent course of emotional problems.

Childhood emotional problems were common, but those whose symptoms improved over time were not at increased risk for adverse adult outcomes. In contrast, individuals with persistent or adolescent-increasing emotional problems had a higher risk of mental ill-health and social impairment in young adulthood which was especially pronounced for those with persistent emotional problems.

It is well-known that childhood attention-deficit hyperactivity disorder (ADHD) is associated with later adverse mental health and social outcomes. Patient-based studies suggest that ADHD may be associated with later cardiovascular disease (CVD) but the focus of preventive interventions is unclear. It is unknown whether ADHD leads to established cardiovascular risk factors because so few cohort studies measure ADHD and also follow up to an age where CVD risk is evident.

To examine associations between childhood ADHD problems and directly measured CVD risk factors at ages 44/45 years in a UK population-based cohort study (National Child Development Study) of individuals born in 1958.

Childhood ADHD problems were defined by elevated ratings on both the parent Rutter A scale and a teacher-rated questionnaire at age 7 years. Outcomes were known cardiovascular risk factors (blood pressure, lipid measurements, body mass index and smoking) at the age 44/45 biomedical assessment.

Of the 8016 individuals assessed both during childhood and at the biomedical assessment 3.0% were categorised as having childhood ADHD problems. ADHD problems were associated with higher body mass index (B = 0.92 kg/m2, s.d. = 0.27–1.56), systolic (3.5 mmHg, s.d. = 1.4–5.6) and diastolic (2.2 mmHg, s.d. = 0.8–3.6) blood pressure, triglyceride levels (0.24 mol/l, s.d. = 0.02–0.46) and being a current smoker (odds ratio OR = 1.6, s.d. = 1.2–2.1) but not with LDL cholesterol.

Childhood ADHD problems predicted multiple cardiovascular risk factors by mid-life. These findings, when taken together with previously observed associations with cardiovascular disease in registries, suggest that individuals with ADHD could benefit from cardiovascular risk monitoring, given these risk factors are modifiable with timely intervention.

Current psychiatric diagnoses, although heritable, have not been clearly mapped onto distinct underlying pathogenic processes. The same symptoms often occur in multiple disorders, and a substantial proportion of both genetic and environmental risk factors are shared across disorders. However, the relationship between shared symptoms and shared genetic liability is still poorly understood.

Well-characterised, cross-disorder samples are needed to investigate this matter, but few currently exist. Our aim is to develop procedures to purposely curate and aggregate genotypic and phenotypic data in psychiatric research.

As part of the Cardiff MRC Mental Health Data Pathfinder initiative, we have curated and harmonised phenotypic and genetic information from 15 studies to create a new data repository, DRAGON-Data. To date, DRAGON-Data includes over 45 000 individuals: adults and children with neurodevelopmental or psychiatric diagnoses, affected probands within collected families and individuals who carry a known neurodevelopmental risk copy number variant.

We have processed the available phenotype information to derive core variables that can be reliably analysed across groups. In addition, all data-sets with genotype information have undergone rigorous quality control, imputation, copy number variant calling and polygenic score generation.

DRAGON-Data combines genetic and non-genetic information, and is available as a resource for research across traditional psychiatric diagnostic categories. Algorithms and pipelines used for data harmonisation are currently publicly available for the scientific community, and an appropriate data-sharing protocol will be developed as part of ongoing projects (DATAMIND) in partnership with Health Data Research UK.

Reviewing notes & drug charts for 6 months duration (Jan to June 2010) for all the inpatients (74) on the 6 Forensic wards at the Littlemore Hospital

Findings:

1. - 3 patients were found (Zopiclone 7.5)

2. - PRN basis

3. - Insomnia: recorded on charts only

4. - Non pharmacologic measures: 1

5. - Documentation: 1

6. - Max duration: No

7. - Revision: No

1. - Hypnotics are rarely used in Forensic units

2. - Only used for couple of days

3. - Zopiclone mainly used

4. - No switching

5. - Documentation: rare

Recommendations:

1. - Non pharmacological (sleep hygiene)

2. - Document entry in notes (medical+ nursing)

3. - Max duration 2 weeks (NICE)

4. - Larger scale (General wards)

1. - Forensic patients:HDAT & RT

2. - Standards followed by Trust

3. - Forensic patients supervised at all times

4. - On call doctor??

5. - Sleep Hygiene encouragement

Attention-deficit hyperactivity disorder (ADHD) is associated with later depression and there is considerable genetic overlap between them. This study investigated if ADHD and ADHD genetic liability are causally related to depression using two different methods.

First, a longitudinal population cohort design was used to assess the association between childhood ADHD (age 7 years) and recurrent depression in young-adulthood (age 18–25 years) in N = 8310 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). Second, two-sample Mendelian randomization (MR) analyses examined relationships between genetic liability for ADHD and depression utilising published Genome-Wide Association Study (GWAS) data.

Childhood ADHD was associated with an increased risk of recurrent depression in young-adulthood (OR 1.35, 95% CI 1.05–1.73). MR analyses suggested a causal effect of ADHD genetic liability on major depression (OR 1.21, 95% CI 1.12–1.31). MR findings using a broader definition of depression differed, showing a weak influence on depression (OR 1.07, 95% CI 1.02–1.13).

Our findings suggest that ADHD increases the risk of depression later in life and are consistent with a causal effect of ADHD genetic liability on subsequent major depression. However, findings were different for more broadly defined depression.

Attention deficit hyperactivity disorder (ADHD) is highly heritable and is associated with lower educational attainment. ADHD is linked to family adversity, including hostile parenting. Questions remain regarding the role of genetic and environmental factors underlying processes through which ADHD symptoms develop and influence academic attainment.

This study employed a parent-offspring adoption design (N = 345) to examine the interplay between genetic susceptibility to child attention problems (birth mother ADHD symptoms) and adoptive parent (mother and father) hostility on child lower academic outcomes, via child ADHD symptoms. Questionnaires assessed birth mother ADHD symptoms, adoptive parent (mother and father) hostility to child, early child impulsivity/activation, and child ADHD symptoms. The Woodcock–Johnson test was used to examine child reading and math aptitude.

Building on a previous study (Harold et al., 2013, Journal of Child Psychology and Psychiatry, 54(10), 1038–1046), heritable influences were found: birth mother ADHD symptoms predicted child impulsivity/activation. In turn, child impulsivity/activation (4.5 years) evoked maternal and paternal hostility, which was associated with children's ADHD continuity (6 years). Both maternal and paternal hostility (4.5 years) contributed to impairments in math but not reading (7 years), via impacts on ADHD symptoms (6 years).

Findings highlight the importance of early child behavior dysregulation evoking parent hostility in both mothers and fathers, with maternal and paternal hostility contributing to the continuation of ADHD symptoms and lower levels of later math ability. Early interventions may be important for the promotion of child math skills in those with ADHD symptoms, especially where children have high levels of early behavior dysregulation.

Few personalised medicine investigations have been conducted for mental health. We aimed to generate and validate a risk tool that predicts adult attention-deficit/hyperactivity disorder (ADHD).

Using logistic regression models, we generated a risk tool in a representative population cohort (ALSPAC – UK, 5113 participants, followed from birth to age 17) using childhood clinical and sociodemographic data with internal validation. Predictors included sex, socioeconomic status, single-parent family, ADHD symptoms, comorbid disruptive disorders, childhood maltreatment, ADHD symptoms, depressive symptoms, mother's depression and intelligence quotient. The outcome was defined as a categorical diagnosis of ADHD in young adulthood without requiring age at onset criteria. We also tested Machine Learning approaches for developing the risk models: Random Forest, Stochastic Gradient Boosting and Artificial Neural Network. The risk tool was externally validated in the E-Risk cohort (UK, 2040 participants, birth to age 18), the 1993 Pelotas Birth Cohort (Brazil, 3911 participants, birth to age 18) and the MTA clinical sample (USA, 476 children with ADHD and 241 controls followed for 16 years from a minimum of 8 and a maximum of 26 years old).

The overall prevalence of adult ADHD ranged from 8.1 to 12% in the population-based samples, and was 28.6% in the clinical sample. The internal performance of the model in the generating sample was good, with an area under the curve (AUC) for predicting adult ADHD of 0.82 (95% confidence interval (CI) 0.79–0.83). Calibration plots showed good agreement between predicted and observed event frequencies from 0 to 60% probability. In the UK birth cohort test sample, the AUC was 0.75 (95% CI 0.71–0.78). In the Brazilian birth cohort test sample, the AUC was significantly lower –0.57 (95% CI 0.54–0.60). In the clinical trial test sample, the AUC was 0.76 (95% CI 0.73–0.80). The risk model did not predict adult anxiety or major depressive disorder. Machine Learning approaches did not outperform logistic regression models. An open-source and free risk calculator was generated for clinical use and is available online at https://ufrgs.br/prodah/adhd-calculator/.

The risk tool based on childhood characteristics specifically predicts adult ADHD in European and North-American population-based and clinical samples with comparable discrimination to commonly used clinical tools in internal medicine and higher than most previous attempts for mental and neurological disorders. However, its use in middle-income settings requires caution.

Previous studies find that both schizophrenia and mood disorder risk alleles contribute to adult depression and anxiety. Emotional problems (depression or anxiety) begin in childhood and show strong continuities into adult life; this suggests that symptoms are the manifestation of the same underlying liability across different ages. However, other findings suggest that there are developmental differences in the etiology of emotional problems at different ages. To our knowledge, no study has prospectively examined the impact of psychiatric risk alleles on emotional problems at different ages in the same individuals.

Data were analyzed using regression-based analyses in a prospective, population-based UK cohort (the National Child Development Study). Schizophrenia and major depressive disorder (MDD) polygenic risk scores (PRS) were derived from published Psychiatric Genomics Consortium genome-wide association studies. Emotional problems were assessed prospectively at six time points from age 7 to 42 years.

Schizophrenia PRS were associated with emotional problems from childhood [age 7, OR 1.09 (1.03–1.15), p = 0.003] to mid-life [age 42, OR 1.10 (1.05–1.17), p < 0.001], while MDD PRS were associated with emotional problems only in adulthood [age 42, OR 1.06 (1.00–1.11), p = 0.034; age 7, OR 1.03 (0.98–1.09), p = 0.228].

Our prospective investigation suggests that early (childhood) emotional problems in the general population share genetic risk with schizophrenia, while later (adult) emotional problems also share genetic risk with MDD. The results suggest that the genetic architecture of depression/anxiety is not static across development.