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

Profound Changes in Dopaminergic Neurotransmission in the Prefrontal Cortex in Response to Flattening of the Diurnal Glucocorticoid Rhythm: Implications for Bipolar Disorder

Patients with bipolar disorder have abnormalities in glucocorticoid secretion, dopaminergic neurotransmission, and prefrontal cortical function. We hypothesized that the flattening of the diurnal glucocorticoid rhythm, commonly seen in bipolar disorder, modulates dopaminergic neurotransmission in the prefrontal cortex (PFC) leading to abnormalities in prefrontally mediated neurocognitive functions. To address this hypothesis, we investigated the effects of a flattened glucocorticoid rhythm on (i) the release of dopamine in the PFC and (ii) the transcription of genes in the ventral tegmental area (VTA) coding for proteins involved in presynaptic aspects of dopaminergic neurotransmission. Male rats were treated for 13–15 days with corticosterone (50??g/ml in the drinking water) or vehicle (0.5% ethanol). Corticosterone treatment resulted in marked adrenal atrophy and flattening of the glucocorticoid rhythm as measured by repeated blood sampling. Animals treated with corticosterone showed markedly enhanced basal dopamine release in the PFC as measured by microdialysis in the presence of a dopamine reuptake inhibitor. Depolarization-evoked release was also enhanced, suggesting that the corticosterone effect on basal release did not result from an increase in the neuronal firing rate. Local blockade of terminal D2 autoreceptors failed to normalize release to control values, suggesting that the enhanced release was not because of reduced autoreceptor sensitivity. In situ hybridization histochemistry showed that mRNAs coding tyrosine hydroxylase and the vesicular monoamine transporter 2 were elevated in the VTA of corticosterone-treated rats. Our data show that flattening of the glucocorticoid rhythm increases dopamine release in the PFC possibly as a result of increased synthesis and vesicular storage. This provides a mechanistic explanation for prefrontal dysfunction in bipolar and other affective disorders associated with glucocorticoid dysrhythmia