Biological correlates of the Newcastle Scale in depressive illness: a multivariate approach.

Rapid eye movement latency (RL), delta max thyroid-stimulating hormone (dmTSH) and 1600 (DST16) and 2300 (DST23) post-dexamethasone cortisol values were determined in a group of 93 depressed patients who were assessed with the Newcastle Endogenous Depression Diagnostic Index (NEDDI). After the effects of age, gender and severity of illness were controlled for, stepwise multiple regression showed that depressive psychomotor activity and weight loss were the 2 NEDDI items most contributing to explain DST23 variance, as was depressive psychomotor activity for dmTSH variance. When the depressive sample was dichotomized according to the presence of these 2 items, the 2 groups had significantly different DST16, DST23, dmTSH and RL values. This suggests that weight loss, agitation and retardation could represent a core feature of a biologically mediated depressive subtype.Journal ArticleFLWNAinfo:eu-repo/semantics/publishe

Aberrant nocturnal cortisol and disease progression in women with breast cancer

PURPOSE: While a relationship between disruption of circadian rhythms and the progression of cancer has been hypothesized in field and epidemiologic studies, it has never unequivocally demonstrated. We determined the circadian rhythm of cortisol and sleep in women with advanced breast cancer (ABC) under the conditions necessary to allow for the precise measurement of these variables. METHODS: Women with ABC (n=97) and age-matched controls (n=24) took part in a 24-hour intensive physiological monitoring study involving polysomnographic sleep measures and high density plasma sampling. Sleep was scored using both standard clinical metrics and power spectral analysis. Three-harmonic regression analysis and functional data analysis were used to assess the 24-hour and sleep-associated patterns of plasma cortisol, respectively. RESULTS: The circadian pattern of plasma cortisol as described by its timing, timing relative to sleep, or amplitude was indistinguishable between women with ABC and age-matched controls (p's>0.11, t-tests). There was, however, an aberrant spike of cortisol during the sleep of a subset of women, during which there was an 8-fold increase in the amount of objectively-measured wake time (p<0.004, Wilcoxon Signed-Rank). This cortisol aberration was associated with cancer progression such that the larger the aberration, the shorter the disease-free interval (time from initial diagnosis to metastasis; r=−0.30, p=0.004; linear regression). The same aberrant spike was present in a similar percent of women without ABC and associated with concomitant sleep disruption. CONCLUSIONS: A greater understanding of this sleep-related cortisol abnormality, possibly a vulnerability trait, is likely important in our understanding of individual variation in the progression of cancer

Differential Association of Circadian Genes with Mood Disorders: CRY1 and NPAS2 are Associated with Unipolar Major Depression and CLOCK and VIP with Bipolar Disorder

Disruptions in circadian rhythms have been described in mood disorders (MD), but the involvement of genetic variation in genes pertaining to the molecular circadian machinery in the susceptibility to MD has not been conclusively determined. We examined 209 single-nucleotide polymorphisms (SNPs) covering 19 circadian genes (ADCYAP1, ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CRY2, CSNK1E, DBP, NPAS2, NR1D1, PER1, PER2, PER3, RORA, TIMELESS, VIP, and VIPR2) in a sample of 534 MD patients (335 with unipolar major mood depression (MDD) and 199 with bipolar disorder (BD)) and 440 community-based screened controls. Nominally, statistically significant associations were found in 15 circadian genes. The gene-wide test, corrected for the number of SNPs analyzed in each gene, identified significant associations in CRY1 (rs2287161), NPAS2 (rs11123857), and VIPR2 (rs885861) genes with the combined MD sample. In the MDD subsample, the same SNPs in CRY1 and NPAS2 of the combined sample remained associated, whereas in the BD subsample CLOCK (rs10462028) and VIP (rs17083008) were specifically associated. The association with an SNP located 3′ near CRY1 gene in MDD remained statistically significant after permutation correction at experiment level (p=0.007). Significant additive effects were found between the SNPs that were statistically significant at the gene-wide level. We also found evidence of associations between two-marker haplotypes in CRY1 and NPAS2 genes and MD. Our data support the contribution of the circadian system to the genetic susceptibility to MD and suggest that different circadian genes may have specific effects on MD polarity