Previous studies on the etiology of attention deficit/hyperactivity disorder (ADHD) highlight high heritability, structural/functional brain abnormalities, and dopamine/noradrenaline imbalances, emphasizing gene-environment interactions. While maternal smoking during pregnancy and low-grade peripheral inflammation have been implicated, its neurobiological basis remains incompletely understood. Our aim was to elucidate neuroinflammatory signaling contributing to ADHD and investigate behavioural and molecular changes in a mouse model.

We examined neuroinflammatory signaling using prenatal nicotine exposed (PNE) mice via immunohistochemistry combined with cortical thickness (CT) measurement in the subregions of the prefrontal cortex (PFC). Mice were exposed to nicotine via drinking water containing 300 μg/ml nicotine and 2% sucrose until weaning 2 weeks prior to mating to induce ADHD-like symptoms, as opposed to controls receiving drinking water containing 2% sucrose alone. Behavioral tests were conducted to assess ADHD-like behaviors and accompanying anxiety on postnatal week 5. Inflammatory pathways in the anterior cingulate cortex (ACC), prelimbic cortex (PL) and infralimbic cortex (IL) were examined using Iba-1 and NF-κB immunolabeling, and microglial morphology was analyzed.

Findings showed increased CT, microglial cell number, activity, and NF-κB activation in the ACC, which correlated with attention-related impairment in PNE mice. Increased Iba-1 levels in the PL and IL, along with elevated NF-κB activation in the IL, were observed in PNE mice, which corresponded with a significant increase in anxiety-like behaviors compared to controls. PNE mice also morphologically exhibited microglia activation in all three subregions.

Perinatal nicotine exposure contributes to ADHD development through neuroinflammatory signaling, a common end pathway.

To refine the knowledge on familial transmission, we examined the (shared) familial components among neurodevelopmental problems (i.e. two attention-deficit/hyperactivity–impulsivity disorder [ADHD] and six autism spectrum disorder [ASD] subdomains) and with aggressive behavior, depression, anxiety, and substance use.

Data were obtained from a cross-sectional study encompassing 37 688 participants across three generations from the general population. ADHD subdomains, ASD subdomains, aggressive behavior, depression, anxiety, and substance use were assessed. To evaluate familial (co-)aggregation, recurrence risk ratios (λR) were estimated using Cox proportional hazards models. The (shared) familiality (f2), which is closely related to (shared) heritability, was assessed using residual maximum likelihood-based variance decomposition methods. All analyses were adjusted for sex, age, and age2.

The familial aggregation and familiality of neurodevelopmental problems were moderate (λR = 2.40–4.04; f2 = 0.22–0.39). The familial co-aggregation and shared familiality among neurodevelopmental problems (λR = 1.39–2.56; rF = 0.52–0.94), and with aggressive behavior (λR = 1.79–2.56; rF = 0.60–0.78), depression (λR = 1.45–2.29; rF = 0.43–0.76), and anxiety (λR = 1.44–2.31; rF = 0.62–0.84) were substantial. The familial co-aggregation and shared familiality between all neurodevelopmental problems and all types of substance use were weak (λR = 0.53–1.57; rF = −0.06–0.35).

Neurodevelopmental problems belonging to the same disorder were more akin than cross-disorder problems. That said, there is a clear (shared) familial component to neurodevelopmental problems, in part shared with other psychiatric problems (except for substance use). This suggests that neurodevelopmental disorders, disruptive behavior disorders, and internalizing disorders share genetic and environmental risk factors.

Ensuring a successful transition to Adult Mental Health Services (AMHS) is fundamental for attention deficit/hyperactivity disorder (ADHD) patients to prevent adverse scenarios in adults (e.g., psychiatric disorders, substance or alcohol abuse). Yet, most European nations do not have appropriate transition guidelines and still fail to adequately support transition processes. This study aims to enquire about the current transition paths in Italy and the perceived experiences of the patients and their clinicians.

The present observational study collected 36 interviews with young adults with ADHD who turned 18 between 2017 and 2021. Simultaneously, two questionnaires were filled in by the clinicians (both from paediatric and AMHS) who were involved in their transition paths. These tools collected information about the transition process, the services that cared for the young adults and well-being indicators such as impairment in daily life, employment status and the presence of sentinel events (e.g., critical stage accesses to the emergency room or hospitalizations). Successful and failed referrals were analysed.

A referral to an AMHS was attempted for 16 young adults (8 before age 18 and 8 when turning 18), and 8 patients (22.2% overall) were successfully taken into the care of the AMHS. Twenty patients were not referred since it was deemed unnecessary (N = 6) or because of the lack of specialized services or compliance (N = 14). At the time of the interview, only nine participants were still under AMHS care. Of eleven individuals with a high need for care (identified by the level of impairment, support needs or sentinel events), five were not followed by a mental health professional at the time of the interview.

For the majority of ADHD young adults, a transition path was never started or completed. While this is partly due to mild levels of impairment, in many cases it was difficult to find a service that could care for the adult patient. Only one out of four young adults are successfully transferred to AMHS care. Creating or improving evidence-based transition guidelines should be a priority of the public health system to ensure healthcare for as many patients as possible. The results of this study will converge towards the need for recommendations for the transition of services from adolescence to adulthood for young people with ADHD for Italian clinical practice.

This article presents the results of two studies investigating increased intra-individual variability (IIV) in the performance of individuals with attention deficit hyperactivity disorder (ADHD), in two cognitive domains: numerosity judgments and quantitative and verbal reasoning.

Study 1, a pre-registered experiment, involved approximately 200 participants (42.66% female; mean age: 36.86; standard deviation of age: 10.70) making numerical judgments at two time-points. ADHD-symptom severity was assessed on a continuous scale. In Study 2, we collected the data of approximately 3000 examinees who had taken a high-stakes admissions test for higher education (assessing quantitative and verbal reasoning). The sample comprised only people formally diagnosed with ADHD. The control group consisted of approximately 200 000 examinees, none of whom presented with ADHD.

The results of Study 1 revealed a positive correlation between IIV (distance between judgments at the two time-points) and ADHD symptom severity. The results of Study 2 demonstrated that IIV (distance between the scores on two test chapters assessing the same type of reasoning) was greater among examinees diagnosed with ADHD. In both studies, the findings persisted even after controlling for performance level.

The results indicate that individuals with ADHD, v. those without, exhibit less consistent numerosity judgments and greater fluctuation in performance on verbal and quantitative reasoning. The measurement of the same psychological constructs appears to be less precise among individuals with ADHD compared to those without. We discuss the theoretical contributions and practical implications of our results for two fields: judgment and decision-making, and assessment.

Previous observational epidemiological studies have suggested that coffee consumption during pregnancy may affect fetal neurodevelopment. However, results are inconsistent and may represent correlational rather than causal relationships. The present study investigated whether maternal coffee consumption was observationally associated and causally related to offspring childhood neurodevelopmental difficulties (NDs) in the Norwegian Mother, Father and Child Cohort Study.

The observational relationships between maternal/paternal coffee consumption (before and during pregnancy) and offspring NDs were assessed using linear regression analyses (N = 58694 mother-child duos; N = 22 576 father-child duos). To investigate potential causal relationships, individual-level (N = 46 245 mother-child duos) and two-sample Mendelian randomization (MR) analyses were conducted using genetic variants previously associated with coffee consumption as instrumental variables.

We observed positive associations between maternal coffee consumption and offspring difficulties with social-communication/behavioral flexibility, and inattention/hyperactive-impulsive behavior (multiple testing corrected p < 0.005). Paternal coffee consumption (negative control) was not observationally associated with the outcomes. After adjusting for potential confounders (smoking, alcohol, education and income), the maternal associations attenuated to the null. MR analyses suggested that increased maternal coffee consumption was causally associated with social-communication difficulties (individual-level: beta = 0.128, se = 0.043, p = 0.003; two-sample: beta = 0.348, se = 0.141, p = 0.010). However, individual-level MR analyses that modelled potential pleiotropic pathways found the effect diminished (beta = 0.088, se = 0.049, p = 0.071). Individual-level MR analyses yielded similar estimates (heterogeneity p = 0.619) for the causal effect of coffee consumption on social communication difficulties in maternal coffee consumers (beta = 0.153, se = 0.071, p = 0.032) and non-consumers (beta = 0.107, se = 0.134, p = 0.424).

Together, our results provide little evidence for a causal effect of maternal coffee consumption on offspring NDs.

This study investigated the relationship between various intrapersonal factors and the discrepancy between subjective and objective cognitive difficulties in adults with attention-deficit hyperactivity disorder (ADHD). The first aim was to examine these associations in patients with valid cognitive symptom reporting. The next aim was to investigate the same associations in patients with invalid scores on tests of cognitive symptom overreporting.

The sample comprised 154 adults who underwent a neuropsychological evaluation for ADHD. Patients were divided into groups based on whether they had valid cognitive symptom reporting and valid test performance (n = 117) or invalid cognitive symptom overreporting but valid test performance (n = 37). Scores from multiple symptom and performance validity tests were used to group patients. Using patients’ scores from a cognitive concerns self-report measure and composite index of objective performance tests, we created a subjective-objective discrepancy index to quantify the extent of cognitive concerns that exceeded difficulties on objective testing. Various measures were used to assess intrapersonal factors thought to influence the subjective-objective cognitive discrepancy, including demographics, estimated premorbid intellectual ability, internalizing symptoms, somatic symptoms, and perceived social support.

Patients reported greater cognitive difficulties on subjective measures than observed on objective testing. The discrepancy between subjective and objective scores was most strongly associated with internalizing and somatic symptoms. These associations were observed in both validity groups.

Subjective cognitive concerns may be more indicative of the extent of internalizing and somatic symptoms than actual cognitive impairment in adults with ADHD, regardless if they have valid scores on cognitive symptom overreporting tests.

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.

Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.