Elucidating the neurobiological basis of neurodevelopmental and psychiatric conditions (NDPCs) remains challenging because brain alterations vary within diagnoses and overlap across them. Whether diverse alterations follow a systematic organization that may reflect shared vulnerabilities remains unknown. Here, we assembled 10,135 individuals with schizophrenia, autism, bipolar, obsessive-compulsive, generalized anxiety, and major depressive disorders, and 11,998 reference participants across six continents through the ENIGMA consortium. Using normative modeling, we quantified individual deviations in cortical thickness, surface area, and subcortical volumes relative to lifespan reference trajectories (5 to 80 years). We show that structural deviations converged along cortical axes reflecting connectome organization, maturation, and cytoarchitectonic diversity. These axes mirrored typical population variation, but their expression differed across diagnoses and partly scaled with symptom severity. Even rare and highly individualized extreme deviations followed this organization, concentrating in densely connected regions. Finally, brain structural deviations overlapped substantially across diagnoses, while differences between them increased toward the association cortex. Together, we provide large-scale evidence that structural deviations across NDPCs are systematically constrained by the brain's intrinsic architecture. This shared organization provides a framework for reconciling individual variability with transdiagnostic similarities and motivates an integrative, systems-level understanding of mental health.
M. Hettwer, A. Saberi, G. Shafiei et al.· medRxiv· 0 citations
Abstract “Brain health” encompasses key functions such as cognition, emotion, and behaviour, and is increasingly relevant given its role across neurological and psychiatric conditions. One of these, depression is the most common psychiatric comorbidity in people with epilepsy (PWE). When unrecognized and untreated, depression is associated with increased seizure severity and poorer treatment response, significantly impacting patients’ prognosis and quality of life; conversely, the rate of epilepsy is 2-fold higher in individuals with incident depression compared to those without depression. Several studies have confirmed a strong bidirectional relationship between epilepsy and depression; an advisory panel of psychiatrists and neurologists with expertise in epilepsy and mood disorders convened for a virtual meeting held in 2024 to assess the impact of the interplay between these two conditions. A comprehensive, interdisciplinary approach to discussion was adopted to address challenges in diagnosing and managing depression in PWE, focusing on early intervention, patient education, and tailored treatments strategies; additionally, the meeting emphasized the importance of integrated care between neurologists and psychiatrists to address this unmet medical need. The authors identified depression in PWE as being underdiagnosed due to overlapping symptoms, stigma, and limited psychiatric care integration. Management is challenging as some antiseizure medication worsen depression and certain antidepressants may lower the seizure threshold, requiring careful selection and monitoring to balance efficacy and safety. Potential interactions between these medicines underscore the importance of carefully selecting therapeutic combinations to minimize adverse effects. Effective management involves an interdisciplinary approach, integrating neurologists and psychiatrists. Key strategies include early screening, psychoeducation, a personalized approach to pharmacological and nonpharmacological treatment, and increased awareness among healthcare providers, patients, and caregivers regarding the overlap of neurological and psychiatric disorders. Furthermore, educational resources, as well as digital tools, can help inform and educate patients and caregivers on holistic brain health management.
P. Brambilla, R. Kälviäinen, Bettina Schmitz et al.· Neuropsychiatric Disease and...· 0 citations
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