Emotional side-effects of SSRIs are a robust phenomenon, prominent in some people's thoughts about their medication, having a demonstrable impact on their functioning and playing a role in their decision-making about antidepressant adherence.

Fragile X syndrome (FXS) has a characteristic cognitive "signature" that by late childhood includes core weaknesses in attention and working memory (WM), but their earlier developmental trajectories remain uncharted. Using a combined cross-sectional and prospective longitudinal design, we tested whether early profiles of attention and WM impairment in FXS indicate developmental freeze or developmental change. In Study 1, 26 young boys with FXS and 55 typically developing (TD) boys completed two experimental paradigms designed to assess cognitive aspects of attention and WM, in addition to behavioral indices of inattention and hyperactivity. Study 2 mapped longitudinal changes in 21 children with FXS and 21 TD children. In Study 1, significant weaknesses emerged for boys with FXS, with no substantial improvement over chronological age. Mapping performance against mental age level revealed delay, but it also yielded a similar attention and WM profile to TD boys. In Study 2, longitudinal improvements for boys with FXS paralleled those in TD children. In conclusion, cognitive attention and WM, although delayed in FXS, reveal developmental change, rather than "arrest." Our findings underscore the need for going beyond cross-sectional group comparisons and gross behavioral indices to map cognitive changes longitudinally in developmental disorders.

Very long chain fatty acids (VLCFAs) are essential building blocks for synthesis of the ceramides and sphingolipids required for nerve, skin and retina function and 3-keto acyl-CoA synthases (ELOVL elongases) perform the first step in the FA elongation cycle. Although ELOVLs are implicated in common diseases including insulin resistance, hepatic steatosis and Parkinson's, their underlying molecular mechanisms are unknown. Here we report the structure of the human ELOVL7 elongase, which includes an inverted transmembrane barrel structure surrounding a 35 Å long tunnel containing a covalently-attached product analogue. The structure reveals the substrate binding sites in the tunnel and an active site deep in the membrane including the canonical ELOVL HxxHH sequence. This indicates a ping-pong mechanism for catalysis, involving unexpected covalent histidine adducts. The unusual substrate-binding arrangement and chemistry suggest mechanisms for selective ELOVL inhibition, relevant for diseases where VLCFAs accumulate such as X-linked adrenoleukodystrophy. MainThe seven human 3-keto acyl-CoA synthases (elongation of very long chain fatty acids proteins: ELOVL1-7 elongases) catalyse the first, rate-limiting step in the cycle that adds two carbon units to the acyl chains of fatty acids (FAs) with 12 or more carbons per chain (Fig. 1a).These long and very long chain FAs (LCFAs: 12C:20C and VLCFAs: >20C) 1,2 are the precursors for synthesis of ceramides, sphingolipids and sphingolipid signalling molecules 3 .VLCFAs are essential for the myelin sheaths of nerves 4,5 , the skin permeability barrier 6,7 , retina 8 and liver function 4,9 . Mutations in ELOVL elongases cause severe genetic diseases