Heterozygous STUB1 mutation causes familial ataxia with cognitive affective syndrome (SCA48).

OBJECTIVE: To describe a new spinocerebellar ataxia (SCA48) characterized by early cerebellar cognitive-affective syndrome (CCAS) and late-onset SCA. METHODS: This is a descriptive study of a family that has been followed for more than a decade with periodic neurologic and neuropsychological examinations, MRI, brain SPECT perfusion, and genetic analysis. Whole exome sequencing was performed in 3 affected and 1 unaffected family member and subsequently validated by linkage analysis of chromosome 16p13.3. RESULTS: Six patients fully developed cognitive-affective and complete motor cerebellar syndrome associated with vermian and hemispheric cerebellar atrophy, suggesting a continuum from a dysexecutive syndrome slowly evolving to a complete and severe CCAS with late truncal ataxia. Three presymptomatic patients showed focal cerebellar atrophy in the vermian, paravermian, and the medial part of cerebellar lobes VI and VII, suggesting that cerebellar atrophy preceded the ataxia, and that the neurodegeneration begins in cerebellar areas related to cognition and emotion, spreading later to the whole cerebellum. Among the candidate variants, only the frameshift heterozygous c.823_824delCT STUB1 (p.L275Dfs*16) pathogenic variant cosegregated with the disease. The p.L275Dfs*16 heterozygous STUB1 pathogenic variant leads to neurodegeneration and atrophy in cognition- and emotion-related cerebellar areas and reinforces the importance of STUB1 in maintaining cognitive cerebellar function. CONCLUSIONS: We report a heterozygous STUB1 pathogenic genetic variant causing dominant cerebellar ataxia. Since recessive mutations in STUB1 gene have been previously associated with SCAR16, these findings suggest a previously undescribed SCA locus (SCA48; MIM# 618093).

Effects of the Financial Crisis on Psychotropic Drug Consumption in a Cohort from a Semi-Urban Region in Catalonia, Spain.

PURPOSE: Evidence of whether the recent economic crisis has or has not had an effect on psychotropic drug consumption is very scarce. Our objective was to determine if there had in fact been an increase in psychotropic drug use as a result of the financial crisis. METHODS: In our study a retrospective cohort (between January 1, 2005, and December 31, 2012) was made up of individuals from the general population in a region in the northeast of Catalonia, Spain. We specified a generalized linear mixed model along with combined 'selection on observables' as (propensity scoring) matching and 'selection on unobservables' as (random coefficient) the panel data model methods, and performed inferences using a Bayesian framework. RESULTS: In the period following the economic crisis (post 2009), there was an increase in the consumption of psychotropic drugs which was significantly higher among those who had already been consuming psychotropic drugs prior to 2009 and those most likely to be unemployed. The increase was of greater significance when consumption was measured by the number of drugs being taken, rather than by the defined daily dose (DDD), with the greatest increase occurring in 2011; the very year in which Spain was most affected by the crisis. CONCLUSIONS: Once the financial crisis had ended, there was an increase in the severity, rather than the intensity, of mental health disorders in individuals who had already had disorders before the crisis. This increase occurred in those most likely to be unemployed, and the severity was accentuated in the toughest year of the economic crisis.