Severity of depression and hypothalamic-pituitary-adrenal axis dysregulation: identification of contributing factors

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65507/1/j.1600-0447.1990.tb05465.x.pd

Large Differences in Small RNA Composition Between Human Biofluids.

Extracellular microRNAs (miRNAs) and other small RNAs are implicated in cellular communication and may be useful as disease biomarkers. We systematically compared small RNAs in 12 human biofluid types using RNA sequencing (RNA-seq). miRNAs and tRNA-derived RNAs (tDRs) accounted for the majority of mapped reads in all biofluids, but the ratio of miRNA to tDR reads varied from 72 in plasma to 0.004 in bile. miRNA levels were highly correlated across all biofluids, but levels of some miRNAs differed markedly between biofluids. tDR populations differed extensively between biofluids. Y RNA fragments were seen in all biofluids and accounted for >10% of reads in blood plasma, serum, and cerebrospinal fluid (CSF). Reads mapping exclusively to Piwi-interacting RNAs (piRNAs) were very rare, except in seminal plasma. These results demonstrate extensive differences in small RNAs between human biofluids and provide a useful resource for investigating extracellular RNA biology and developing biomarkers

Plasma postdexamethasone cortisol levels in schizoaffective disorder

The degree of hypothalamic-pituitary-adrenal (HPA) axis dysregulation in depressed patients with schizoaffective disorder was compared to that seen in patients with major depressive disorder with and without delusional features. The frequency of nonsuppression to dexamethasone was similar for all three diagnostic groups. Maximum postdexamethasone plasma cortisol was greater for delusional depressives, but did not differ between patients with major depressive and schizoaffective disorders. Modest correlations were found between postdexamethasone plasma cortisol levels, severity of illness, age, and recent weight loss, for patients with both major depressive disorder and delusional depression. For schizoaffective patients, associations between postdexamethasone plasma cortisol levels and various measures of severity of illness, but not age and recent weight loss, were found. Although HPA axis dysregulation occurs more frequently in all three of the studied diagnostic groups than in normal individuals, factors contributing to this dysregulation may be qualitatively different for schizoaffective patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27102/1/0000094.pd

Dexamethasone suppression test status and severity of depression

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27129/1/0000122.pd

Multiplicity of depressive episodes: Phenomenological and neuroendocrine correlates

Sixty-four patients with a Research Diagnostic Criteria (RDC) diagnosis of major depressive disorder were categorized into three groups based on their number of depressive episodes (DE): Gr 1 (1 DE), n = 16, Gr II (2-4 DE), n = 25; and Gr III (5 or more DE), n = 23. All patients were nonsuppressors after 1 mg dexamethasone suppression test (DST) prior to the start of treatment. Patients were monitored during the course of their treatment using serial Hamilton Depression scores and post-DST plasma cortisol levels. A proportionately equal number of patients in the three groups had a favorable outcome, i.e., the number of depressive episodes did not predict recovery. Despite favorable clinical outcome, patients with higher numbers of depressive episodes had significantly higher post-DST plasma cortisol levels that were above the supressive range (greater than 5 [mu]g/dl). Patients with a higher number of depressive episodes had a significantly shorter duration of index episodes and were younger at first depressive episode than patients in the other two groups. These results, however, were confounded with polarity, with a higher number of bipolars in Gr III than in the other two groups. Results are discussed in light of phenomenological and psychoendocrine findings of earlier studies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28571/1/0000374.pd

Multiple depressive episodes and plasma postdexamethasone cortisol levels

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with major depressive disorder (MDD). To determine whether or not a past history of depressive episodes is associated with this dysregulation, we studied the relationships among number of past depressive episodes, number of previous hospitalizations for depression, and number of years since first depressive episode and biological markers of depression (postdexamethasone plasma cortisol levels and dexamethasone suppressor/nonsuppressor status). No significant relationships were detected.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26723/1/0000273.pd

Postdexamethasone plasma cortisol and [beta]-endorphin levels in depression: Relationship to severity of illness

The hypothalamic-pituitary-adrenal (HPA) axis is dysregulated in many patients with depression, probably at all levels of the axis. To determine if HPA dysregulation is associated with severity of depression, we studied a group of 66 patients with major depressive disorder. Each patient underwent a pretreatment Dexamethasone Suppression Test, with plasma postdexamethasone cortisol determination at 8:00 AM, 4:00 PM, and 11:00 PM. All three postdexamethasone cortisol levels were significantly correlated with the Hamilton Rating Scale for Depression (HRSD) scores. We also examined the "profile" measures of mean, maximum, and minimum of the three cortisol values; again, all three were significantly correlated with HRSD scores. To evaluate associations between clinical severity and HPA dysregulation at the pituitary level, we studied a second group of 44 patients with major depressive disorder. Each had postdexamethasone cortisol determinations at 4:00 PM and 11:00 PM as well as pre- and postdexamethasone [beta]-endorphin determinations at 4:00 PM. The cortisol data from this group followed the same pattern as in the first sample, and there was a significant relationship between HRSD score and degree of [beta]-endorphin nonsuppression as well. These results suggest that severity of depression is one of the determinants of dysregulation at both adrenal and pituitary levels of the HPA axis, accounting for 10%-20% of the observed variance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26603/1/0000144.pd

Positive and negative symptoms in schizophrenia and the dexamethasone suppression test

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28016/1/0000452.pd