Neuroanatomical abnormalities in fragile X syndrome during the adolescent and young adult years.

Abnormal brain development and cognitive dysfunction have been reported both in children and in adults with fragile X syndrome (FXS). However, few studies have examined neuroanatomical abnormalities in FXS during adolescence. In this study we focus on adolescent subjects with FXS (N = 54) as compared to age- and sex-matched subjects with idiopathic intellectual disability (Comparison Group) (N = 32), to examine neuroanatomical differences during this developmental period. Brain structure was assessed with voxel-based morphometry and independent groups t-test in SPM8 software. Results showed that the FXS group, relative to the comparison group, had significantly larger gray matter volume (GMV) in only one region: the bilateral caudate nucleus, but have smaller GMV in several regions including bilateral medial frontal, pregenual cingulate, gyrus rectus, insula, and superior temporal gyrus. Group differences also were noted in white matter regions. Within the FXS group, lower FMRP levels were associated with less GMV in several regions including cerebellum and gyrus rectus, and less white matter volume (WMV) in pregenual cingulate, middle frontal gyrus, and other regions. Lower full scale IQ within the FXS group was associated with larger right caudate nucleus GMV. In conclusion, adolescents and young adults with FXS demonstrate neuroanatomical abnormalities consistent with those previously reported in children and adults with FXS. These brain variations likely result from reduced FMRP during early neurodevelopment and mediate downstream deleterious effects on cognitive function.

Life Course Challenges Faced by Siblings of Individuals with Schizophrenia May Increase Risk for Depressive Symptoms.

BACKGROUND: Research suggests siblings of individuals with schizophrenia are at a heightened risk for depressive symptomatology. Research has not yet examined whether the strains of growing up with a brother or sister with schizophrenia contribute to this risk. This study examined whether early life course burdens associated with an emerging mental illness, and current objective and subjective caregiver burden predicted depressive symptoms in siblings of individuals with schizophrenia. METHOD: Forty-one siblings of individuals with schizophrenia were recruited from a large study of schizophrenia neurobiology to complete a self-administered questionnaire and a neuropsychological test battery. RESULTS: Early life course burdens and current objective and subjective burdens explained incremental variance in depressive symptoms of siblings of individuals with schizophrenia after accounting for gender and global neurocognitive function. Higher levels of depressive symptoms among siblings were associated with perceptions of being stigmatized by the community (ß=.37, p<.01), and perceiving that the brother or sister's emerging illness negatively impacted the sibling's social life during childhood and adolescence (ß=.39, p<.01). Taking on adult responsibilities while the sibling was growing up was found to be protective against depressive symptoms in adulthood (ß= -.36, p<.01). CONCLUSIONS: Early life course burdens associated with having a sibling with schizophrenia and current subjective burden provide insight into psychosocial factors that may contribute to the risk for depression in this sibling group. Mental health service providers and psychoeducation programs would benefit by considering these factors when developing family-based interventions.

A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans.

Acetylcholine, a major excitatory neurotransmitter in Caenorhabditis elegans, is transported into synaptic vesicles by the vesicular acetylcholine transporter encoded by unc-17. The abnormal behavior of unc-17(e245) mutants, which have a glycine-to-arginine substitution in a transmembrane domain, is markedly improved by a mutant synaptobrevin with an isoleucine-to-aspartate substitution in its transmembrane domain. These results suggest an association of vesicular soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) components with vesicular neurotransmitter transporters.