PHLPP1 Regulates Inflammatory Signaling in Degenerated Nucleus Pulposus Cells in Mice and Humans.

Primary hyperhidrosis (PHH) is defined by excess sweating not attributable to any medications or underlying medical conditions and is almost exclusively focal. PHH accounts for approximately 93% of hyperhidrosis cases and significantly detracts from quality of life, causing physical discomfort and impairments in psychological, social, and occupational functioning [–]. PHH is widely prevalent, with a 2016 survey reporting that 4.8% of Americans have hyperhidrosis, and questionnaires in Vancouver, Shanghai, and Japan identified regional prevalence rates of up to 14.5% [–]. Prior research has suggested that autonomic nervous system dysfunction and aberrant emotional control are possible causative factors in PHH and demonstrated that PHH significantly increases the risk of later developing psychiatric comorbidities, including anxiety disorders, depressive disorders, and sleep disorders [, –]. However, associations between PHH and pre-existing psychiatric conditions are not well characterized. Therefore, our objective was to evaluate associations between psychiatric conditions and the development of PHH using a matched case-control approach. A matched case-control study was performed on subjects ≥18 years old diagnosed with PHH using the All of Us Research Program (AoURP), a National Institutes of Health program that prioritizes participant recruitment from demographic groups historically under-represented in research. Systematized Nomenclature of Medicine (SNOMED) diagnostic codes were used to identify participants diagnosed with focal PHH (SNOMED codes 427794001, 303089000, 303090009, 403375001, 403380005, 10677591000119103, 10677631000119103, and 10677671000119100). All assessed PHH were focal, corresponding to “primary focal” hyperhidrosis ( = 1,410) (ex. “primary focal hyperhidrosis”), or focal hyperhidrosis ( = 8) (ex. “hyperhidrosis of axilla”) that were not coded as secondary. SNOMED codes were used to retrieve participant information on the following psychiatric comorbidities: generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), bipolar disorder, schizophrenia, insomnia, restless legs syndrome (RLS), attention-deficit/hyperactivity disorder (ADHD), and posttraumatic stress disorder (PTSD) (respective SNOMED codes 21897009, 191736004, 370143000, 13746004, 58214004, 193462001, 32914008, 406506008, 47505003, and all descendant codes for each). Subjects with PHH were matched 1:5 to controls based on self-reported age, sex, and race using nearest neighbor propensity score matching and inter-group differences were assessed with Fisher’s exact test and Welch two-sample test. Multivariable logistic regressions calculated odds ratios (ORs) and 95% confidence intervals (CIs), using the Benjamini-Hochberg procedure to correct for multiple testing. Age, sex, and race were used as covariates. Conditions corresponding to a false discovery rate of less than 0.05 were considered significant and corrected values were reported. Temporality was established by considering only psychiatric diagnoses made before the time of PHH diagnosis. Assessed studies in the psychiatric literature consider subjects presenting with primary, local, or essential hyperhidrosis, to correspond with our sample.