The hidden link between circadian entropy and mental health disorders.

The high overlapping nature of various features across multiple mental health disorders suggests the existence of common psychopathology factor(s) (p-factors) that mediate similar phenotypic presentations across distinct but relatable disorders. In this perspective, we argue that circadian rhythm disruption (CRD) is a common underlying p-factor that bridges across mental health disorders within their age and sex contexts. We present and analyze evidence from the literature for the critical roles circadian rhythmicity plays in regulating mental, emotional, and behavioral functions throughout the lifespan. A review of the literature shows that coarse CRD, such as sleep disruption, is prevalent in all mental health disorders at the level of etiological and pathophysiological mechanisms and clinical phenotypical manifestations. Finally, we discuss the subtle interplay of CRD with sex in relation to these disorders across different stages of life. Our perspective highlights the need to shift investigations towards molecular levels, for instance, by using spatiotemporal circadian "omic" studies in animal models to identify the complex and causal relationships between CRD and mental health disorders.

Dynamic Changes of Brain Cilia Transcriptomes across the Human Lifespan.

Almost all brain cells contain primary cilia, antennae-like microtubule sensory organelles, on their surface, which play critical roles in brain functions. During neurodevelopmental stages, cilia are essential for brain formation and maturation. In the adult brain, cilia play vital roles as signaling hubs that receive and transduce various signals and regulate cell-to-cell communications. These distinct roles suggest that cilia functions, and probably structures, change throughout the human lifespan. To further understand the age-dependent changes in cilia roles, we identified and analyzed age-dependent patterns of expression of cilia's structural and functional components across the human lifespan. We acquired cilia transcriptomic data for 16 brain regions from the BrainSpan Atlas and analyzed the age-dependent expression patterns using a linear regression model by calculating the regression coefficient. We found that 67% of cilia transcripts were differentially expressed genes with age (DEGAs) in at least one brain region. The age-dependent expression was region-specific, with the highest and lowest numbers of DEGAs expressed in the ventrolateral prefrontal cortex and hippocampus, respectively. The majority of cilia DEGAs displayed upregulation with age in most of the brain regions. The transcripts encoding cilia basal body components formed the majority of cilia DEGAs, and adjacent cerebral cortices exhibited large overlapping pairs of cilia DEGAs. Most remarkably, specific α/ß-tubulin subunits (TUBA1A, TUBB2A, and TUBB2B) and SNAP-25 exhibited the highest rates of downregulation and upregulation, respectively, across age in almost all brain regions. α/ß-tubulins and SNAP-25 expressions are known to be dysregulated in age-related neurodevelopmental and neurodegenerative disorders. Our results support a role for the high dynamics of cilia structural and functional components across the lifespan in the normal physiology of brain circuits. Furthermore, they suggest a crucial role for cilia signaling in the pathophysiological mechanisms of age-related psychiatric/neurological disorders.