Brain-derived neurotrophic factor (BDNF) is a nerve growth factor that has been implicated in the neurobiology of depression. Our group has previously reported an association between a BDNF variant and childhood-onset mood disorder (COMD) in an adult sample from Pittsburgh. We hypothesize that variants at the BDNF locus are associated with COMD. Six BDNF polymorphisms were genotyped in 258 trios having juvenile probands with childhood-onset DSM-IV major depressive or dysthymic disorder. Keywords: neurotrophic factors; mood disorder; childhood-onset; genetic association; haplotype Mood disorders rank fourth among the most significant global public health problems. 1 The prevalence of the juvenile-onset subtype of depressive disorder increases dramatically across the years of childhood and adolescence, with an estimated lifetime prevalence close to 20% by late adolescence. 2 Juvenile-onset mood disorders are associated with serious morbidity, including recurrence, impaired interpersonal functioning, and increased risks of bipolar disorder and suicide. 2,3 The influence of hereditary factors on susceptibility to major depression has been documented based on twin and adoption studies. 4 Twin studies in youth have identified significant heritability for depressive symptoms. 5,6 It has also been proposed that genetic aspects of liability to mood disorder may be more readily identified in families of childhood-and adolescentonset probands. 7 Accordingly, first-degree relatives of childhood-onset mood disorder probands have higher rates of affective disorder than do first-degree relatives of adult-onset mood disorder probands. 8 Evidence from both preclinical and clinical studies implicates brain-derived neurotrophic factor (BDNF) in mood disorders. Altered BDNF expression in stress-related depression via cellular signalling has been described in animal models. Repeated antidepressant administration, including electroconvulsive seizures, is associated with increased hippocampal BDNF expression, neuronal plasticity and neurogenesis. 9-11 Human neuroimaging 12,13 post mortem 14 and clinical [15][16][17] investigations indirectly support the hypothesis that neurotrophic factors play a key role in depression. As well, human linkage studies in
Background/Aims: Inflammatory cytokines induce a behavioral syndrome, known as sickness behavior, that strongly resembles symptoms typically seen in depression. This resemblance has led to the theory that an imbalance of inflammatory cytokine activity may be a contributing factor in depressive disorders. Support for this is found in multiple lines of evidence, such as the effects of cytokines on the activities of the hypothalamic-pituitary-adrenal axis, serotonin and brain-derived neurotrophic factor, and hippocampal function, all of which are implicated in the etiology of depression. In addition, associations between inflammatory activity and depressive symptomology have been documented in a number of studies, and the depressogenic effects of cytokine therapy are well known. Accordingly, given that depression has a substantial genetic basis, genes involved in the regulation of inflammatory cytokine activity are strong candidates for involvement in genetic susceptibility to depressive disorders. Here, we have tested 6 key genes of this type, TNF, IL1A, IL1B, IL6, IL1RN and IL10, as candidates for involvement in childhood-onset mood disorders. Methods: In this study of 384 families, each ascertained through a child with depression diagnosed before the age of 15 years, 11 polymorphisms of known or likely functional significance (coding and regulatory variants) were analyzed. Results: Testing for biased transmission of alleles from parents to their affected offspring, we found no evidence for an association between childhood-onset mood disorders and any of the polymorphisms, either individually or as haplotypes. Conclusion: The present study does not support the involvement of the TNF, IL1A, IL1B, IL6, IL1RN and IL10 variants as major genetic risk factors contributing to early-onset mood disorders.
Extremophile plants are valuable sources of genes conferring tolerance traits, which can be explored to improve stress tolerance of crops. Lepidium crassifolium is a halophytic relative of the model plant Arabidopsis thaliana, and displays tolerance to salt, osmotic and oxidative stresses. We have employed the modified Conditional cDNA Overexpression System to transfer a cDNA library from L. crassifolium to the glycophyte A. thaliana. By screening for salt, osmotic and oxidative stress tolerance through in vitro growth assays and non-destructive chlorophyll fluorescence imaging, 20 Arabidopsis lines were identified with superior performance under restrictive conditions. Several cDNA inserts were cloned and confirmed to be responsible for the enhanced tolerance by analysing independent transgenic lines. Examples include full-length cDNAs encoding proteins with high homologies to GDSL-lipase/esterase or acyl CoA-binding protein or proteins without known function, which could confer tolerance to one or several stress conditions. Our results confirm that random gene transfer from stress tolerant to sensitive plant species is a valuable tool to discover novel genes with potential for biotechnological applications.
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