Life Course Challenges Faced by Siblings of Individuals with Schizophrenia May Increase Risk for Depressive Symptoms. Mental health in family medicine ; 12 (1): 147-151
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.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.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 (=.37, p<.01), and perceiving that the brother or sister's emerging illness negatively impacted the sibling's social life during childhood and adolescence (=.39, p<.01). Taking on adult responsibilities while the sibling was growing up was found to be protective against depressive symptoms in adulthood (= -.36, p<.01).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.
View details for PubMedID 27175217
A genetic interaction between the vesicular acetylcholine transporter VAChT/UNC-17 and synaptobrevin/SNB-1 in C. elegans NATURE NEUROSCIENCE 2006; 9 (5): 599-601
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.
View details for DOI 10.1038/nn1685
View details for Web of Science ID 000237417200007
View details for PubMedID 16604067
Defective slow inactivation of sodium channels contributes to familial periodic paralysis NEUROLOGY 1999; 52 (7): 1447-1453
To evaluate the effects of missense mutations within the skeletal muscle sodium (Na) channel on slow inactivation (SI) in periodic paralysis and related myotonic disorders.Na channel mutations in hyperkalemic periodic paralysis and the nondystrophic myotonias interfere with the normally rapid inactivation of muscle Na currents following an action potential. This defect causes persistent inward Na currents that produce muscle depolarization, myotonia, or onset of weakness. Distinct from fast inactivation is the process called SI, which limits availability of Na channels on a time scale of seconds to minutes, thereby influencing muscle excitability.Human Na channel cDNAs containing mutations associated with paralytic and nonparalytic phenotypes were transiently expressed in human embryonic kidney cells for whole-cell Na current recording. Extent of SI over a range of conditioning voltages (-120 to +20 mV) was defined as the fraction of Na current that failed to recover within 20 ms at - 100 mV. The time course of entry to SI at -30 mV was measured using a conditioning pulse duration of 20 ms to 60 seconds. Recovery from SI at -100 mV was assessed over 20 ms to 10 seconds.The two most common hyperkalemic periodic paralysis (HyperPP) mutations responsible for episodic attacks of weakness or paralysis, T704M and M1592V, showed clearly impaired SI, as we and others have observed previously for the rat homologs of these mutations. In addition, a new paralysis-associated mutant, I693T, with cold-induced weakness, exhibited a comparable defect in SI. However, SI remained intact for both the HyperPP/paramyotonia congenita (PMC) mutant, A1156T, and the nonparalytic potassium-aggravated myotonia (PAM) mutant, V1589M.SI is defective in a subset of mutant Na channels associated with episodic weakness (HyperPP or PMC) but remains intact for mutants studied so far that cause myotonia without weakness (PAM).
View details for Web of Science ID 000079903200025
View details for PubMedID 10227633
A role for endothelial NO synthase in LTP revealed by adenovirus-mediated inhibition and rescue SCIENCE 1996; 274 (5293): 1744-1748
Pharmacological studies support the idea that nitric oxide (NO) serves as a retrograde messenger during long-term potentiation (LTP) in area CA1 of the hippocampus. Mice with a defective form of the gene for neuronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neurons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane protein were used to demonstrate that membrane-targeted eNOS is required for LTP. The membrane localization of eNOS may optimally position the enzyme both to respond to Ca2+ influx and to release NO into the extracellular space during LTP induction.
View details for Web of Science ID A1996VW71200071
View details for PubMedID 8939872