Patients With Fibromyalgia, Depression, and/or Anxiety and Sex Differences.

Fibromyalgia is a syndrome characterized by chronic widespread pain, with a multifactorial etiopathogenesis and high incidence of neuropsychiatric comorbidity. It has been inaccurately considered a pathological condition affecting only middle-aged women. The study aimed to explore the association of sociodemographic and clinical factors in patients with fibromyalgia with depression and/or anxiety. The present study is an analysis of a cross-sectional study of a secondary source. The prevalence ratio (PR) between the demographic and clinical variables of patients with fibromyalgia and concomitant depression and/or anxiety was calculated. Overall, 1,106 medical records were obtained with a confirmed diagnosis of fibromyalgia between 2010 and 2016; of these, 318 (28.75%) patients had an associated diagnosis of depression and/or anxiety. Approximately 28% women (295 of 1,052) and 42.6% men (23 of 54) suffered from depression and/or anxiety. In the adjusted explanatory model of depression and/or anxiety in patients with fibromyalgia, the relationship between sex (female PR = 0.5 [0.28-0.86]) and low socioeconomic strata (PR = 0.53 [0.33-0.70]) remained constant. In the study population, patients with fibromyalgia belonging to lower social strata were less likely to present with depression and anxiety. The male sex may pose as a risk factor for depression and/or anxiety in patients with fibromyalgia. Fibromyalgia has a huge impact on men's physical as well as mental health.

Deposition of hyperphosphorylated tau in cerebellum of PS1 E280A Alzheimer's disease.

Early-onset familial Alzheimer's disease (AD) caused by presenilin-1 mutation E280A (PS1-E280A) presents wide clinical and neuropathological variabilities. We characterized clinically and neuropathologically PS1-E280A focusing in cerebellar involvement and compared it with early-onset sporadic Alzheimer's disease (EOSAD). Twelve E280A brains and 12 matched EOSAD brains were analyzed for beta-amyloid and hyperphosphorylated tau (pTau) morphology, beta-amyloid subspecies 1-40, 1-42 levels, pTau levels, and expression of stress kinases in frontal cortex and cerebellum. The data were correlated to clinical and genetic findings. We observed higher beta-amyloid load, beta-amyloid 1-42 and pTau concentrations in frontal cortex of PS1-E280A compared with EOSAD. High beta-amyloid load was found in the cerebellum of PS1-E280A and EOSAD patients. In PS1-E280A, beta-amyloid localized to the molecular and Purkinje cell layers, whereas EOSAD showed them in Purkinje and granular cell layers. Surprisingly, 11 out of 12 PS1-E280A patients showed deposition of pTau in the cerebellum. Also, seven out of 12 PS1-E280A patients presented cerebellar ataxia. We conclude that deposition of beta-amyloid in the cerebellum is prominent in early-onset AD irrespective of genetic or sporadic origin. The presence of pTau in cerebellum in PS1-E280A underscores the relevance of cerebellar involvement in AD and might be correlated to clinical phenotype.

A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome.

Human monogenic pain syndromes have provided important insights into the molecular mechanisms that underlie normal and pathological pain states. We describe an autosomal-dominant familial episodic pain syndrome characterized by episodes of debilitating upper body pain, triggered by fasting and physical stress. Linkage and haplotype analysis mapped this phenotype to a 25 cM region on chromosome 8q12-8q13. Candidate gene sequencing identified a point mutation (N855S) in the S4 transmembrane segment of TRPA1, a key sensor for environmental irritants. The mutant channel showed a normal pharmacological profile but altered biophysical properties, with a 5-fold increase in inward current on activation at normal resting potentials. Quantitative sensory testing demonstrated normal baseline sensory thresholds but an enhanced secondary hyperalgesia to punctate stimuli on treatment with mustard oil. TRPA1 antagonists inhibit the mutant channel, promising a useful therapy for this disorder. Our findings provide evidence that variation in the TRPA1 gene can alter pain perception in humans.