In the last two decades, there has been a growing body of research that identified sex-related differences in attention-deficit hyperactivity disorder (ADHD). Our objective was to quantify whether these sex differences are based on altered functional brain connectivity profiles. In addition, we investigated whether the presence of comorbid disorders, including depression, substance use disorder (SUD) and overweight, influenced these sex differences. A seed-based connectivity analysis of the external globus pallidus (GPe), an important inhibitory relay hub of the fronto-thalamo-striatal-loop, was performed. In a first step, we searched for sex-related differences in ADHD patients (N = 137) and separately in healthy controls (HC) (N = 45), after that, we compared an equal group of HC and ADHD patients to compare sex-related differences in ADHD patients and HC. In a second step, we studied whether the neural basis of comorbidity patterns is different between male and female patients. We observed that male ADHD patients demonstrated a decrease in functional connectivity (FC) from the GPe to the left middle temporal gyrus compared to female ADHD patients. Moreover, within the full ADHD group (N = 137), there was a lower FC in male patients from GPe to the right frontal pole/middle frontal gyrus compared to female patients. Male ADHD patients with depression demonstrated decreased FC from the GPe to parts of the occipital cortex compared to female ADHD patients with depression. No such effect was demonstrated for overweight or SUD. The current study reveals different FC profiles in males and females with ADHD, which are centered around altered connectivity with the GPe. An improved understanding of sex-differences in ADHD, and the role of comorbid disorders, therein can result in improved diagnostic and therapeutic opportunities for ADHD patients.

Clozapine-induced myocarditis (CIM) is among the most important side-effects limiting the use of clozapine as the most effective treatment for schizophrenia and schizoaffective disorder. CIM necessitates immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patient’s psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM has been discussed, with published reports indicating a success rate of approximately 60 %. However, compared to re-challenges after clozapine-induced neutropenia for CIM cases remain considerably more limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis, and clinical management of CIM. Moreover, we review current recommendations for re-challenging patients after CIM. We illustrate these issues using a case presentation with a special focus on the relevance of CRP, troponin, NT-proBNP, therapeutic drug-monitoring and cardiac MRI. Our review and case presentation underscore the importance of swiftly attempting to reinitiate clozapine after CIM given the lack of effective alternatives. Cardiac MRI might aid this strategy due to its high sensitivity for detecting myocardial inflammation. Moreover, both previous findings and our case indicate that using slow dose titration regimes and addressing other risk factors for CIM including concomitant valproate are crucial to ensure a safe and successful re-challenge.