Biology subjects

Petrican, R.

Publications and source records attributed to Petrican, R..

5 recordsLinked to original sources

bioRxiv2026

Regional Similarity to Sex-Typical Young Adult Brain Architecture is a Longitudinal Correlate of Neuroinflammation and Depression in Later Adulthood

Lifespan trajectories of psychiatric and neurodegenerative risk show robust overlap and marked sex differences. Nonetheless, their neurobiological underpinnings are still poorly understood. One potential culprit is the predominant categorical definition of sex, which overlooks the tapestry of sex-dependent and sex-independent features recently shown to typify each human brain. Shifting from a holistic, dichotomous approach to regionally specific, continuous assessments of sex differences in brain function could help identify individualized therapeutic targets for both psychiatric and neurological conditions. To probe the psychiatric and neurological relevance of functional alignment with sex-typical brain architecture, we analyzed longitudinal neuroimaging and clinical data from a healthy aging cohort (N = 353, aged 36-87 years). We identified complementary patterns of deviance from sex-typical brain architecture along the canonical sensorimotor-to-association axis, which overlapped areas enriched in microglial genes and genes regulating sex steroid metabolism. The two connectivity patterns differentiated longitudinally between psychiatric symptoms and neurodegeneration as a function sex and age: one connectivity pattern related to more severe future depression in younger women, whereas the second related to later neurodegeneration (higher GFAP and pT217 blood concentration) and poorer fluid cognition (inhibition, episodic memory, processing speed, working memory) in older men. The aforementioned effects showed some context-specificity, as they involved connectivity patterns characterized during awake rest and cognitive control, but not associative memory performance. Taken together, our findings attest to the value of integrating regionally specific, continuous assessments of sex differences in brain function with inflammation-relevant biomarkers in order to support precision medicine approaches across the life course.

neuroscience↗

bioRxiv2026

Alignment with sex-typical brain architecture: Links to mood pathology, sex hormones and transcriptomics of neurodegenerative conditions

Understanding the mechanisms that underpin the pervasive sex bias in risk for specific psychiatric and neurodegenerative conditions could substantially advance efforts promoting personalized medicine. As a first step towards addressing this issue, we applied imaging transcriptomics and multivariate analysis techniques to data from an adolescent sample enriched in anxiety/depression cases, a child sample enriched in attention deficit hyperactivity disorder (ADHD) cases, and adult patients with treatment resistant major depressive disorder (MDD). We tested whether, across sexes, alignment with female-typical, rather than male-typical, patterns of neural functional connectivity (FC) would relate to a diagnosis (adolescent sample) or severity of symptoms (adult sample) associated with internalizing disorders, which tend to be more often diagnosed in females. To provide preliminary evidence on its functional specificity, we compared the sex-aligned FC profile that distinguished neurotypical adolescents from those diagnosed with depression/anxiety against the sex-aligned FC patterns that distinguished neurotypical children from those diagnosed with ADHD. All the analyses controlled for age within each sample and sex. Finally, we examined the spatial overlap between the sex-aligned FC profile linked to an internalizing diagnosis in adolescence and the transcriptomic maps of genes that show sex-dependent dysregulation in neurodegenerative conditions. Across sexes, increasing alignment with female-typical FC patterns, from sensory-perceptual to default mode regions, discriminated between typically developing and anxious/depressed teens and tracked longitudinal fluctuations in depressive symptoms within adult MDD patients. The identified internalizing-related gradient showed a negative correlation with risk for ADHD in the child sample. The brain regions most strongly aligned with female-, rather than male-, typical FC in depression/anxiety overlapped the spatial expression profiles of genes linked to gonadal hormone synthesis, as well as genes dysregulated in female autism spectrum disorder (ASD) and male neurodegenerative conditions, specifically, Alzheimer's Disease (AD), Huntington's Disease (HD) and Multiple Sclerosis (MS). The brain areas most strongly aligned with male-typical, rather than female-typical, FC patterns overlapped the transcriptomic maps of genes related to androgen and estrogen receptors, as well as of genes dysregulated in male ASD and female neurodegenerative conditions (i.e., AD, HD, MS). Our results raise the possibility that the link between mood pathology and neurodegeneration could reflect a partial, regional reversal of sex-normative functional brain profiles.

neuroscience↗

bioRxiv2026

Regional alignment with sex-typical brain architecture, maternal health and environmental enrichment predict psychiatric symptoms in early life

Robust sex differences in brain morphology and function exist from birth onwards. While traditionally conceptualized as categorical, they were recently shown to be best described along a female-to-male continuum. Here, we probed the under-explored implications of this proposal for understanding early life vulnerability to psychiatric conditions with sex-biased prevalence. We analyzed environmental, clinical and resting state functional neuroimaging data from 411 participants in Developing Human Connectome Project (dHCP) and 214 children from the Oregon ADHD 1000 study. In the dHCP, we identified complementary patterns of neonatal alignment with sex-typical young adult architecture, which overlapped areas rich in nicotinic cholinergic receptors and predicted the same psychiatric symptoms across sexes in toddlerhood. Specifically, for association (compared to sensorimotor) areas, greater alignment with female-typical functional connectivity (FC) patterns foreshadowed higher anxiety, whereas greater alignment with male-typical FC patterns forecasted autism-related problems. The latter effect was weaker among toddlers with an older epigenetic age at birth and exposure to fewer maternal health problems, but greater environmental enrichment. In the independent child sample, patterns of alignment with sex-typical FC, overlapping those observed in neonates, distinguished a history of depression and generalized anxiety (greater alignment with female-typical FC) from a history of separation anxiety, behavioral problems and current ADHD (greater alignment with male-typical FC). Our study speaks to the psychiatric relevance of sex-related functional brain architecture from birth onwards, its value in identifying vulnerable youths and its promise in monitoring the success of environmental interventions.

neuroscience↗

bioRxiv2026

Regional similarity to male-typical brain architecture links childhood ADHD to neurophysiological aging in later adulthood

Identifying early life biomarkers of suboptimal aging trajectories could help design interventions to delay or even prevent the onset of pathological conditions in older adulthood. To address this issue, we capitalize on evidence that the prevalence rates and presentation of neurodevelopmental and neurodegenerative conditions tend to vary between males and females, thereby raising the possibility that processes involved in sexual differentiation could help connect brain maturation and aging outcomes. Here, we focus on attention deficit hyperactivity disorder (ADHD), a neurodevelopmental condition with male-biased prevalence, and examine the relevance of its genetic risk and functional brain profile to aging outcomes. We analyzed multimodal data from a child sample enriched in ADHD cases and a neurologically intact adult sample. Among 6-to-12-year-olds (N =522), genetic vulnerability to pathological aging, indexed via polygenic risk scores (PRSs) for Alzheimer's Disease (AD), predicted ADHD diagnosis across sexes, regardless of psychiatric history and PRSs for multiple disorders (including ADHD). Irrespective of age, boys and girls diagnosed with ADHD showed preferential alignment with male-, rather than female-, typical functional connectivity patterns in metabolically active transmodal areas which are enriched in 5-HT2,4, D1, and mGLU5 receptors. In an independent sample aged 36-90 years (N = 345), the ADHD brain profile correlated with higher levels of testosterone, physiological markers of reproductive aging and poorer performance on AD-relevant cognitive tasks among older individuals of either sex. Our results imply that neurodevelopmental conditions could provide insights into vulnerability to suboptimal aging trajectories and could help guide early interventions targeting at-risk individuals.

neuroscience↗

bioRxiv2020

Brain-Environment Alignment during Movie Watching Predicts Cognitive-Affective Function in Adulthood

BOLD fMRI studies have provided compelling evidence that the human brain demonstrates substantial moment-to-moment fluctuations in both activity and functional connectivity patterns. While the role of brain signal variability in fostering cognitive adaptation to ongoing environmental demands is well-documented, the relevance of moment-to-moment changes in functional brain architecture is still debated. To probe the role of architectural variability in naturalistic information processing, we used neuroimaging and behavioural data collected during movie watching by the Cambridge Centre for Ageing and Neuroscience (N = 642, 326 women) and the Human Connectome Project (N = 176, 106 women). Both moment-to-moment and contextual change-evoked architectural variability increased from young to older adulthood. However, coupling between moment-to-moment changes in functional brain architecture and concrete environmental features was stronger at younger ages. Architectural variability (both momentary and context-evoked) was associated with age-distinct profiles of network communication, specifically, greater functional integration of the default mode network in older adulthood, but greater informational flow across neural networks implicated in environmentally driven attention and control (cingulo-opercular, salience, ventral attention) in younger adulthood. Whole-brain communication pathways anchored in default mode regions relevant to episodic and semantic context creation (i.e., angular and middle temporal gyri) contributed to greater brain reconfiguration in response to narrative context changes, as well as stronger coupling between moment-to-moment changes in functional brain architecture and changes in concrete environmental features. Cognitive adaptation was directly linked to levels of brain-environment alignment, but only indirectly associated with levels of architectural variability. Specifically, stronger coupling between moment-to-moment variability in brain architecture and concrete environmental features predicted poorer cognitive adaptation (i.e., fluid IQ) and greater affectively driven environmental vigilance. Complementarily, across the adult lifespan, higher fluid (but not crystallized) IQ was related to stronger expression of the network communication profile underlying momentary and context-based architectural variability during youth. Our results indicate that the adaptiveness of dynamic brain reconfiguration during naturalistic information processing changes across the lifespan due to the associated network communication profiles. Moreover, our findings on brain-environment alignment complement the existing literature on the beneficial consequences of modulating brain signal variability in response to environmental complexity. Specifically, they imply that coupling between moment-to-moment variability in functional brain architecture and concrete environmental features may index a bias towards perceptually-bound, rather than conceptual processing, which hinders affective functioning and strategic engagement with the external environment.

neuroscience↗