Previous evidence suggests that early life complications (ELCs) interact with polygenic risk for schizophrenia (SCZ) in increasing risk for the disease. However, no studies have investigated this interaction on neurobiological phenotypes. Among those, anomalous emotion-related brain activity has been reported in SCZ, even if evidence of its link with SCZ-related genetic risk is not solid. Indeed, it is possible this relationship is influenced by non-genetic risk factors. Thus, this study investigated the interaction between SCZ-related polygenic risk and ELCs on emotion-related brain activity.

169 healthy participants (HP) in a discovery and 113 HP in a replication sample underwent functional magnetic resonance imaging (fMRI) during emotion processing, were categorized for history of ELCs and genome-wide genotyped. Polygenic risk scores (PRSs) were computed using SCZ-associated variants considering the most recent genome-wide association study. Furthermore, 75 patients with SCZ also underwent fMRI during emotion processing to verify consistency of their brain activity patterns with those associated with risk factors for SCZ in HP.

Results in the discovery and replication samples indicated no effect of PRSs, but an interaction between PRS and ELCs in left ventrolateral prefrontal cortex (VLPFC), where the greater the activity, the greater PRS only in presence of ELCs. Moreover, SCZ had greater VLPFC response than HP.

These results suggest that emotion-related VLPFC response lies in the path from genetic and non-genetic risk factors to the clinical presentation of SCZ, and may implicate an updated concept of intermediate phenotype considering early non-genetic factors of risk for SCZ.

Attention deficit hyperactivity disorder (ADHD) is increasingly diagnosed in adults. People with intellectual disability have higher rates of ADHD yet there is little evidence on the presentation and pharmacological treatment of ADHD in this population or how this differs from the general population.

Retrospective cohort study using data from electronic health records. Adults with intellectual disability newly diagnosed with ADHD between 2007 and 2022 were matched to adults with ADHD without intellectual disability and their clinical features and treatments were compared.

A total of 159 adults with ADHD and intellectual disability and 648 adults with ADHD without intellectual disability formed the dataset. Adults with intellectual disability had higher rates of psychiatric co-morbidity and spent more time under mental health services than those without intellectual disability. They were more likely to have recorded agitation, aggression, hostility, and mood instability, and less likely to have poor concentration recorded in the 12 months prior to the diagnosis of ADHD. Following diagnosis, people with intellectual disability were significantly less likely to be prescribed any medication for ADHD than controls without intellectual disability (adjusted odds ratio 0.60, 95% confidence interval 0.38–0.91), and were less likely to be prescribed stimulants (27.7% v 46.0%, p < 0.001).

The presence of behaviors that challenge in adults with intellectual disability may indicate co-occurring ADHD. Further work to define the safety and efficacy of medication for ADHD in adults with intellectual disability is needed to understand differences in prescription rates and to avoid inequities in care outcomes.

Emotion regulation tendencies are well-known transdiagnostic markers of psychopathology, but their neurobiological foundations have mostly been examined within the theoretical framework of cortical–subcortical interactions.

We explored the connectome-wide neural correlates of emotion regulation tendencies using functional and diffusion magnetic resonance images of healthy young adults (N = 99; age 20–30; 28 females). We first tested the importance of considering both the functional and structural connectome through intersubject representational similarity analyses. Then, we employed a canonical correlation analysis between the functional–structural hybrid connectome and 23 emotion regulation strategies. Lastly, we sought to externally validate the results on a transdiagnostic adolescent sample (N = 93; age 11–19; 34 females).

First, interindividual similarity of emotion regulation profiles was significantly correlated with interindividual similarity of the functional–structural hybrid connectome, more so than either the functional or structural connectome. Canonical correlation analysis revealed that an adaptive-to-maladaptive gradient of emotion regulation tendencies mapped onto a specific configuration of covariance within the functional–structural hybrid connectome, which primarily involved functional connections in the motor network and the visual networks as well as structural connections in the default mode network and the subcortical–cerebellar network. In the transdiagnostic adolescent dataset, stronger functional signatures of the found network were associated with higher general positive affect through more frequent use of adaptive coping strategies.

Taken together, our study illustrates a gradient of emotion regulation tendencies that is best captured when simultaneously considering the functional and structural connections across the whole brain.

Effort-based decision-making has been proposed as a potential mechanism contributing to transdiagnostic motivational deficits in psychotic disorder and bipolar disorder. However, very limited information is available about deficits in effort-cost-decision-making in the early stages of psychotic disorder and no study has investigated effort allocation deficits before the onset of bipolar disorder. Our aim was to investigate effort-based-decision-making in ultra-high-risk for psychosis (UHR-P) and bipolar disorder (UHR-BD).

Effort-cost decision-making performance was evaluated in UHR-P (n = 72) and UHR-BD (n = 68) and healthy controls (n = 38). Effort-Expenditure for Reward Task (EEfRT) was used.

Compared to controls, both UHR-P and UHR-BD groups were associated with a reduced possibility to choose the harder task when the reward magnitudes and/or the likelihood of receiving the reward were high. In both groups, effort allocation abnormalities were associated with poor social functioning.

The current findings suggest that difficulties in effort-cost computation are transdiagnostic markers of illness liability in psychotic and bipolar disorders. In early intervention services, effort-based decision-making abnormalities should be considered as a target for interventions to manage motivational deficits in individuals at high risk for psychosis and BD.