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Faizan, M.

Publications and source records attributed to Faizan, M..

2 recordsLinked to original sources

A mechanistic model of threat-driven respiration and its homeostatic recovery in anxiety and depression

Anxiety and depression change how people breathe, often early in the illness, and wearable sensors now allow breathing to be monitored continuously. This work presents, to our knowledge, the first mechanistic model of how the brain's threat response sets breathing rate and depth and how fast breathing recovers after stress. A threat signal from the amygdala, shaped by stimulus magnitude and by cognitive appraisal (coping capacity and perceived stress), drives the breathing-control center that receives lung feedback: stretch receptors slow breathing and airway receptors speed it up. A simple electrical circuit stores the threat signal and expresses recovery as one time constant. We prove the model's key properties, test them under noise and parameter variation, and compare it with chest-belt recordings from 15 adults in the Wearable Stress and Affect Detection (WESAD) study. Breathing rate rose from 18 to 28 and 31 breaths per minute from normal to moderate to severe, an order that held in every test. Recovery took about 3, 10, and 50 seconds, paced by how long the airway-receptor signal lingers in the brainstem, and the circuit followed breathing closely (correlation 0.96-0.98). In WESAD, a spoken stress task raised anxiety and breath depth (p<0.001); speech set the breathing rhythm during the task, and breathing then returned to rest, as the model predicts for healthy people. A compact, provable model links clinical stress measures to the breathing signals that wearables record. It offers measurable targets for monitoring anxiety and depression: how strongly threat drives respiration and how quickly homeostatic regulation restores it.

physiology↗

Isoform-Resolved Genetic Architecture of Epilepsy and SUDEP Reveals Divergent Brain and Heart Channelopathy Signatures

Sudden unexpected death in epilepsy (SUDEP) is the most devastating complication of epilepsy, yet the molecular features distinguishing individuals at risk remain poorly defined. Although epilepsy and SUDEP share substantial genetic overlap, fatal outcomes may arise when shared risk genes are differentially deployed across neuronal and cardiac systems. Here, we identify tissue- and isoform-level regulation as a key determinant of divergence between epilepsy and SUDEP risk. We performed a large-scale integrated analysis of genetic variants reported in epilepsy and SUDEP across 419 sequencing-based studies encompassing 35,659 individuals, and quantified gene-level burden using a Bayesian Poisson-Gamma rate ratio framework. This analysis revealed preferential enrichment of genes related to cardiac electrophysiology and contractile function in SUDEP, whereas epilepsy was dominated by genes involved in neuronal excitability and synaptic signaling. To determine how shared genetic loci are deployed across tissues, we integrated GTEx-based tissue expression profiles with long-read single-cell transcriptomic datasets from human heart and brain to resolve isoform-level expression patterns. These analyses revealed pronounced tissue-specific transcript architectures. Cardiac-associated genes, including HCN4, KCNH2, KCNE1, MYH6, MYO18B, and ATP1A2, showed heart-restricted isoform expression, whereas neuronal genes such as ADGRV1, CACNA1A, GRIN2B, HCN1, HCN2, KCNA1, SCN1A, SCN2A, and SCN8A. Importantly, several shared genes exhibited tissue-partitioned isoform expression, with distinct transcript repertoires in heart and brain, particularly across pathways related to ion transport, signaling, metabolism, and structural organization. Consistent patterns were observed in iPSC-derived cardiomyocytes and neurons, indicating that lineage-dependent deployment of shared genes is preserved in controlled systems. Together, these findings suggest that tissue-specific isoform regulation provides a mechanistic basis linking shared epilepsy genetics to SUDEP susceptibility, whereby the same genetic loci contribute to neuronal dysfunction in epilepsy and to cardiac vulnerability in SUDEP. This positions SUDEP as a neuro-cardiac interface disorder shaped by isoform-level regulatory divergence.

genetics↗