A life-course and time perspective on the construct validity of psychological distress in women and men. Measurement invariance of the K6 across gender

<p>Abstract</p> <p>Background</p> <p>Psychological distress is a widespread indicator of mental health and mental illness in research and clinical settings. A recurrent finding from epidemiological studies and population surveys is that women report a higher mean level and a higher prevalence of psychological distress than men. These differences may reflect, to some extent, cultural norms associated with the expression of distress in women and men. Assuming that these norms differ across age groups and that they evolve over time, one would expect gender differences in psychological distress to vary over the life-course and over time. The objective of this study was to investigate the construct validity of a psychological distress scale, the K6, across gender in different age groups and over a twelve-year period.</p> <p>Methods</p> <p>This study is based on data from the Canadian National Population Health Survey (C-NPHS). Psychological distress was assessed with the K6, a scale developed by Kessler and his colleagues. Data were examined through multi-group confirmatory factor analyses. Increasing levels of measurement and structural invariance across gender were assessed cross-sectionally with data from cycle 1 (n = 13019) of the C-NPHS and longitudinally with cycles 1 (1994-1995), 4 (2000-2001) and 7 (2006-2007).</p> <p>Results</p> <p>Higher levels of measurement and structural invariance across gender were reached only after the constraint of equivalence was relaxed for various parameters of a few items of the K6. Some items had a different pattern of gender non invariance across age groups and over the course of the study. Gender differences in the expression of psychological distress may vary over the lifespan and over a 12-year period without markedly affecting the construct validity of the K6.</p> <p>Conclusions</p> <p>This study confirms the cross-gender construct validity of psychological distress as assessed with the K6 despite differences in the expression of some symptoms in women and in men over the life-course and over time. Findings suggest that the higher mean level of psychological distress observed in women reflects a true difference in distress and is unlikely to be gender-biased. Gender differences in psychological distress are an important public health and clinical issue and further researches are needed to decipher the factors underlying these differences.</p

PABPN1 gene therapy for oculopharyngeal muscular dystrophy

International audienceOculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant, late-onset muscle disorder characterized by ptosis, swallowing difficulties, proximal limb weakness and nuclear aggregates in skeletal muscles. OPMD is caused by a trinucleotide repeat expansion in the PABPN1 gene that results in an N-terminal expanded polyalanine tract in polyA-binding protein nuclear 1 (PABPN1). Here we show that the treatment of a mouse model of OPMD with an adeno-associated virus-based gene therapy combining complete knockdown of endogenous PABPN1 and its replacement by a wild-type PABPN1 substantially reduces the amount of insoluble aggregates, decreases muscle fibrosis, reverts muscle strength to the level of healthy muscles and normalizes the muscle transcriptome. The efficacy of the combined treatment is further confirmed in cells derived from OPMD patients. These results pave the way towards a gene replacement approach for OPMD treatment

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans