It is well recognized that Attention-deficit/hyperactivity disorder (ADHD) is associated with heightened risk for common psychiatric disorders; early identification and treatment of ADHD may help reduce some of this risk. However, the substantially increased risk of bipolar disorder, psychosis, and schizophrenia (hereafter psychotic disorders) is often overlooked (odds ratios 4.7-8.9). Given how common ADHD is, there is growing pressure for greater involvement of primary care services, especially for less complex forms of ADHD. However, those at highest risk for transition to a psychotic disorder need to be prioritised for secondary care follow up. Currently it is unknown how to stratify ADHD according to risk or indeed why only some develop a psychotic disorder. This perspective examines key hypotheses that may explain why transition occurs only in a subset of individuals. One hypothesis is that features suggestive of ADHD may represent early manifestations of psychotic disorders, although direct support for this is limited. The potential role of ADHD treatment is also considered; current data indicate that therapeutic use of methylphenidate is not associated with increased risk of psychotic disorders, while uncertainty remains for amphetamines. The possible mediating roles of ADHD-evoked environmental exposures are discussed, but evidence for mediation is lacking. We also consider the evidence that ADHD and psychotic disorders result from shared underlying neurodevelopmental processes. We highlight key clinical implications for screening and monitoring individuals with ADHD for psychotic disorders and consider what factors may help in weighting risk. Finally, we identify important evidence gaps for future research.

Diagnosis and treatment monitoring of attention-deficit/hyperactivity disorder (ADHD) largely rely on subjective assessments, highlighting the need for objective markers. Voice features and speech embeddings represent promising candidates, as they may offer an objective, scalable and clinically valuable complement to current practice. Yet it remains largely unclear which features are most informative for distinguishing ADHD and monitoring treatment effects, and which speech tasks best elicit these differences. Twenty-seven children with ADHD and 27 age-matched neurotypical controls completed six speech tasks across two study visits. Children with ADHD were unmedicated at baseline and were assessed under prescribed methylphenidate treatment at follow-up, whereas controls underwent repeated assessment without intervention. Established acoustic voice features and high-dimensional speech embeddings were extracted and analysed using linear mixed models to examine baseline group differences and group-by-time interaction effects reflecting medication-associated change patterns. At baseline, children with ADHD showed a lower and more variable pitch (F0 mean, F0 variability), altered spectral properties (MFCC1/MFCC2 variability), and reduced rhythmic stability (variability of voiced-segment length) compared to controls. Group-by-time interaction effects indicated medication-associated modulation in the ADHD group, including reduced loudness variability and normalization of first formant bandwidth toward control values. Speech embeddings (Whisper but not WavLM) showed FDR-significant baseline and interaction effects. Free speech tasks, particularly picture description, yielded the most robust and consistent effects. These findings support further investigation of speech-based measures as potential digital biomarkers in ADHD, with picture description emerging as a particularly promising task for future clinical assessment protocols.Clinical trial registration: German Clinical Trials Registry, registration no. DRKS00030766, Registration Date: 12 December 2022. Available: https://drks.de/search/en/trial/DRKS00030766.

The prevalence of ADHD is increasing rapidly, and lisdexamfetamine is increasingly popular, but few studies investigate its safety. We performed a sequence symmetry analysis (SSA) using Danish register data to identify potential ADRs associated with lisdexamfetamine in 2013-2023. Outcomes were incident prescriptions or incident discharge diagnoses. We calculated trend-adjusted sequence ratios (SR) with 95% confidence intervals (CI). We additionally performed two comparator SSAs for the same outcomes following incident use of stimulants (methylphenidate and dexamfetamine) or non-stimulants (guanfacine and atomoxetine). This study is reported according to RECORD-PE guidelines. We included 48 740 incident lisdexamfetamine users with a median age of 24 years (IQR 16-35). SRs were calculated for 1426 exposure-diagnosis and 1337 exposure-prescription pairs. The 50 highest SRs from each category were evaluated. Among these, 28 exposure-outcome combinations had a 95% CI lower bound above 1. Of the 100 outcomes, 33 were considered known ADRs, while 60 were previously unknown. Two outcomes indicating increased urinary symptoms were identified ('hematuria', SR: 1.88 [95% CI: 1.25; 2.85] and 'other urinary symptoms', SR: 1.63 [1.20; 2.23]). We also identified serious gastrointestinal outcomes as a potential safety alert. Further investigation into these symptoms as potential ADRs is warranted.

Attention-deficit hyperactivity disorder (ADHD) and conduct disorder (CD) are diagnoses that are frequently comorbid. CD is characterised by persistent dissocial, aggressive, and defiant behaviors that defy age-appropriate expectations. This is the case of a 15-year-old male adoptee referred to Tier 3 Child and Adolescent Mental Health Service (CAMHS) for severe aggression, impulsivity, and domestic violence. The patient exhibited coercive control toward his mother, physical violence involving weapons, and property damage, necessitating police involvement and risking family placement breakdown. Following a failure of psychosocial interventions, the patient underwent the Quantified Behavioral (Qb) Test and Conners-4 assessments and review by a consultant psychiatrist confirming ADHD and conduct disorder diagnosis. Methylphenidate was initiated and titrated to 36mg daily. Outcomes were significant. Within one month, antisocial behaviors reduced markedly. At seven months, domestic violence had ceased, and social care involvement ended. The patient successfully completed his General Certificates of Secondary Education (GCSE). Repeat testing on medication showed normalisation of scores: QbTest activity dropped to the 23rd percentile and impulsivity to the 21st percentile. Crucially, parent-rated Conners-4 scores for CD dropped to zero. This case highlights the importance of identifying and treating underlying ADHD in adolescents presenting with severe conduct issues. Higher doses of methylphenidate are often cited as beneficial for CD symptom reduction; this patient achieved remission of aggression at 36mg/day. The case shows that delaying ADHD diagnosis in favor of solely managing behavioral conduct symptoms can risk education and family stability. Treating the ADHD effectively mitigated the emotional dysregulation and violence and reduced the negative impact on this patient during a crucial period of his life as he was completing high school. This case highlights the importance of considering comorbid ADHD and CD in patients presenting with impulsive behaviours and aggression as their primary presenting complaints. Appropriate management with methylphenidate could have a significant therapeutic effect on these patients and their antisocial behaviours.

Psychostimulants such as methylphenidate (MPH) and modafinil (MOD) are effective in attention-deficit/hyperactivity disorder and narcolepsy but may induce behavioral activation, anxiety-like responses, and cognitive alterations, particularly under stress. Buspirone (BUS), a nonsedative anxiolytic acting as a partial 5-HT1A receptor agonist, may influence stimulant-related behavioral effects. This study evaluated whether BUS modifies behavioral outcomes induced by chronic MPH and MOD administration in rats exposed to repeated restraint stress. Adult male Sprague-Dawley rats received oral MPH (10 mg/kg), MOD (75 mg/kg), BUS (10 mg/kg), or their combinations for 35 days under restrained or nonrestrained conditions. Behavioral assessments included locomotor activity, exploratory performance (open-field and head-dip tests), and memory evaluation using passive avoidance and Morris water maze paradigms. MPH and MOD alone increased locomotor activity and altered exploratory behavior, with effects influenced by stress conditions. BUS coadministration attenuated stimulant-induced hyperactivity and modulated exploratory responses. BUS alone reduced passive avoidance latency, which may reflect anxiolytic effects rather than impaired memory, while combined treatment indicated modulation of stimulant-associated cognitive outcomes. BUS may reduce stimulant-induced behavioral activation under stress, suggesting its potential as an adjunct to improve the behavioral tolerability of psychostimulant therapy.

Idiopathic hypersomnia (IH) is a chronic central disorder of hypersomnolence characterized by excessive daytime sleepiness despite adequate or prolonged sleep, with potentially substantial effects on occupational functioning, cognition, and driving safety. Pharmacologic management may be challenging when treatment is limited by inadequate efficacy or adverse effects. We report a young woman with severe hypersomnolence and a diagnosis of IH supported by clinical history and objective sleep testing. Multiple sleep latency testing demonstrated a mean sleep latency of one minute and 22 seconds, with no sleep-onset rapid eye movement periods (SOREMPs). Her Epworth Sleepiness Scale (ESS) score was 18/24, and symptoms included prolonged sleep duration, extended daytime naps, occupational impairment, and drowsy driving. Modafinil initially produced substantial benefit but subsequently lost efficacy despite dose escalation. Sequential trials of armodafinil, solriamfetol, mixed amphetamine salts, and methylphenidate were limited by tachycardia, inadequate efficacy or poor tolerability, paranoia, and persistent late-day sleepiness, respectively. Lower-sodium oxybate was subsequently initiated at 3 g once nightly but was reduced to 2.25 g because of significant nausea. With slower, individualized titration to 5.5 g once nightly, the patient reported substantial improvement in daytime sleepiness and functioning. Her ESS score decreased from 18/24 to 4/24, scheduled methylphenidate and caffeine were no longer required, and daytime napping was markedly reduced. This case illustrates the challenges of longitudinal pharmacologic management of IH and highlights the importance of individualized treatment selection, tolerability-guided oxybate titration, and assessment of functional outcomes beyond standardized sleepiness scores.

Attention-deficit/hyperactivity disorder (ADHD) has been increasingly associated with chronic inflammation and may contribute to early cardiovascular risk. Although subclinical atherosclerosis has been documented in drug-naive children with ADHD, whether methylphenidate treatment status is associated with differences in subclinical atherosclerotic markers remains unknown. This study aimed to evaluate the association between methylphenidate treatment status and subclinical atherosclerosis in children and adolescents with ADHD. This cross-sectional comparative observational study enrolled 65 MPH-treated and 65 medication-naïve children and adolescents aged 8-17 years with a DSM-5 diagnosis of ADHD. Subclinical atherosclerosis was evaluated echocardiographically through measurements of carotid intima-media thickness (cIMT), epicardial adipose tissue (EAT) thickness, and periaortic adipose tissue (PAT) thickness. Group differences were analyzed using multivariate analysis of covariance (MANCOVA) and subsequent analyses of covariance (ANCOVA), adjusting for age, sex, body mass index, mean blood pressure, and total cholesterol. Following covariate adjustment, PAT thickness was the only parameter that remained significantly higher in the medication-naïve group compared to the MPH-treated group; adjusted differences in cIMT and EAT thickness did not reach statistical significance. Within the MPH-treated group, methylphenidate dose was positively correlated with EAT and PAT thickness, duration of treatment was associated with PAT thickness, and duration of ADHD symptoms was correlated with all three echocardiographic parameters. In this cross-sectional comparative study, medication-naïve children and adolescents with ADHD had higher periaortic adipose tissue thickness compared to methylphenidate-treated patients, independent of major cardiovascular confounders, whereas no significant adjusted differences were observed for cIMT or EAT thickness. The positive associations between methylphenidate dose, treatment duration, and vascular risk markers within the treated group highlight the importance of cardiovascular monitoring in children receiving long-term MPH treatment. These findings should be interpreted within the limitations of the cross-sectional design, which precludes causal inference, and the observed associations may reflect residual confounding rather than direct effects of methylphenidate treatment status on subclinical atherosclerosis.