Prior studies assessing the relation between negative affective traits and cortisol have yielded inconsistent results. Two studies assessed the relation between individual differences in ...repressive-defensiveness and basal salivary cortisol levels. Experiment 1 assessed midafternoon salivary cortisol levels in men classified as repressors, high-anxious, or low-anxious. In Experiment 2, more rigorous controls were applied as salivary cortisol levels in women and men were assessed at 3 times of day on 3 separate days. In both studies, as hypothesized, repressors and high-anxious participants demonstrated higher basal cortisol levels than low-anxious participants. These findings suggest that both heightened distress and the inhibition of distress may be independently linked to relative elevations in cortisol. Also discussed is the possible mediational role of individual differences in responsivity to, or mobilization for, uncertainty or change.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Hypersecretion of corticotropin-releasing hormone (CRH) and resulting hypercortisolism have been implicated in the pathogenesis of major depression. To test this CRH hypersecretion hypothesis, ...cerebrospinal fluid (CSF) was continuously withdrawn from 11:00
am to 5:00
pm via an indwelling subarachnoid catheter (placed at 8:00
am), and immunoreactive CRH concentrations were determined at 10-min intervals in 10 depressed patients, the majority of whom exhibited at least one “atypical” symptom, and in 15 normal volunteers. CSF CRH was low, plasma adrenocorticotropin (ACTH) tended to be low, and plasma cortisol was normal in the depressed patients. Also, tobacco smokers had lower CSF CRH than nonsmokers. CRH increased acutely in response to lumbar puncture, had a brief half-life, showed rapid variability in concentration over time, and displayed a diurnal concentration rhythm that was preserved in fasting individuals and in most depressed patients. CSF CRH did not correlate with plasma ACTH or cortisol; this and its rapidly fluctuating levels suggest a primarily extrahypothalamic origin of lumbar CSF CRH.
The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was ...investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
Cognitive therapy (CT) for depression has generated considerable interest in recent years. Comparisons with tricyclic pharmacotherapy in nonbipolar outpatients have suggested that (a) CT may be ...roughly comparable in the treatment of the acute episode; (b) combined CT-pharmacotherapy does not appear to be clearly superior to either modality (although indications of potential enhancement do exist to justify additional studies with larger samples), and (c) treatment with CT during the acute episode (either alone or with medications) may reduce the risk of subsequent relapse following termination. Nonetheless, for a variety of reasons (e.g., limitations in study design and execution, inadequate design power, and possible differential retention), these conclusions can be considered only suggestive at this time. More than a decade after the publication of the first controlled study involving CT, the approach remains a promising, but not adequately tested, alternative to pharmacotherapy in the treatment of depression.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Corticotropin-releasing hormone (CRH) is a neuropeptide thought to play a role in appetite regulation. In this report, we used a serial cerebrospinal fluid (CSF) sampling technique to examine the ...relationship between CSF CRH, plasma ACTH and cortisol and perceptions of hunger and satiety in fasting and sated volunteers. CSF was withdrawn continuously from 11:00 AM to 5:00 PM via an indwelling subarachnoid catheter. Blood was withdrawn every 10 min via an antecubital vein catheter. Fed subjects received a meal at 1:00 PM. Subjects who were fed had lower post-prandial ratings on hunger scales and higher ratings on satiety scales. Fed subjects also had slightly lower levels of CSF CRH after feeding. Furthermore, fed subjects had higher ACTH and cortisol concentrations in the first 3 h; by the fourth h the opposite was true. Our findings do not support the hypothesis that CNS CRH is a central satiety factor in the human. Instead our findings of slightly diminished CSF CRH levels after feeding may be accounted for by the rises in glucocorticoids and their associated negative feedback effects on CNS CRH. Alternatively, our findings could also reflect changes in CRH levels associated with feeding in multiple brain areas and in the spinal cord with the net effect being in the negative direction.
The finding of a diminished TSH response to exogenously administered TRH in a significant proportion of depressed patients has now been established as one of the most reproducible findings in ...biological psychiatry. More than 50 reports, in which more than 1000 patients have been studied, reveal that the TSH response is blunted in approximately 25% of patients with major depression. TSH blunting is clearly not specific for depression, because it also has been observed in mania, alcoholism, and borderline personality disorder. It is doubtful that TSH blunting represents a non-specific response to mental stress: it was found only rarely in schizophrenic patients, and the TSH response to in vivo flooding therapy in phobic patients was normal. In both depression and alcoholism, TSH blunting has been reported to be sometimes a state marker and sometimes a trait marker, i.e. the fault was found to persist into remission in more than half the patients. In both conditions, TSH blunting was unrelated to the patients' age, body weight, height, body surface, thyroid status, and serum cortisol concentrations. It also is unlikely that TSH blunting was due to increased dopaminergic inhibition of thyrotroph cells: serum prolactin concentrations in TSH blunters were found to be normal, and pretreatment with haloperidol had no effect on either basal TSH levels or TSH blunting. In depression, TSH blunting was not associated with previous drug intake, dexamethasone suppression test abnormalities, or variables of biogenic amine metabolism, nor did it usefully segregate between primary and secondary depression or between unipolar and bipolar subgroups. Preliminary evidence suggests that TSH blunting in depression may be related to duration of illness, history of violent suicide attempts, and a reduced 24 h TSH secretion. In alcoholism, TSH blunting was unrelated to family or personal history of depression and duration of abstinence. With reference to clinical utility, TSH blunting may aid in assessing the response to antidepressant treatment, predicting outcome to such treatment, assessing the risk for violent suicide attempts, and describing relationships between different psychiatric populations (e.g. depression and alcoholism).
CRH, a hypothalamic peptide that is the most potent ACTH secretagogue known, also appears to be produced in the cerebral cortex and spinal cord. Depressed patients have blunted responses to exogenous ...CRH and normal to high concentrations of CRH immunoreactivity in single morning samples of lumbar cerebrospinal fluid (CSF). Although these data suggest that depression may be associated with hypersecretion of CRH, it has also been postulated that central nervous system insufficiency of CRH might have a pathophysiological role in certain depressive syndromes. We continuously sampled lumbar CSF via indwelling subarachnoid catheters from 1100-1700 h and measured CRH at 10-min intervals in depressed patients and normal subjects. A standardized mixed liquid meal was administered at 1300 h. CSF CRH was strikingly reduced in depressed patients compared to normal subjects 4.2 +/- 1.1 pmol/L vs. 13 +/- 2.1 pmol/L (mean +/- SEM), respectively, P less than 0.01 by Wilcoxon test. CSF CRH concentrations rose progressively during the experiment in both groups, suggesting a diurnal rhythm and, possibly, response to a test meal. CRH had a very brief half-life in CSF (less than 10 min), suggesting that the spinal cord is the origin of CRH in lumbar CSF. The rapid transients in CSF CRH concentration demonstrate that single samples provide very limited information. There were no intraindividual correlations between CSF CRH concentrations and those of either plasma ACTH or cortisol, both of which rose in response to eating. The present data show that impaired central nervous system secretion of CRH can exist during states of severe depression.
Facial expression in schizophrenia Earnst, Kelly S.; Kring, Ann M.; Kadar, Michael A. ...
Biological psychiatry (1969),
09/1996, Volume:
40, Issue:
6
Journal Article
We evaluated 20 patients with Cushing's disease (i.e., Cushing's syndrome due to ACTH-secreting pituitary microadenoma) and 20 patients with Major Depressive Disorder (MDD) using the Structured ...Clinical Interview for DSM-III-R (SCID) and Research Diagnostic Criteria. The diagnosis of Generalized Anxiety Disorder (GAD) was most common in Cushing's disease (79%), followed by MDD (68%), and Panic Disorder (PD) including subthreshold PD (53%). The combination of MDD and GAD and/or PD was also common in Cushing's disease (63%). Behavioral symptoms, if present, usually first occurred at or after the onset of the first physical symptoms. However, the onset of PD was associated with more chronic stages of Cushing's disease. In both Cushing's disease and MDD, more female than male relatives suffered from MDD, whereas more male than female relatives suffered from substance abuse. The data demonstrate a syndrome of anxious depression in patients with active Cushing's disease; such comorbidility has not been previously noted. The data also point to intriguing epidemiological, clinical, and biological associations between Cushing's disease, MDD and substance abuse.
Thirty-nine patients with major depression were studied to determine the differential effects of desipramine (DMI) and fluoxetine (FLU) on thyroid hormones. Twenty-six percent showed some abnormality ...in baseline thyroid hormone levels. There were no demonstrable differences for any of the thyroid indices from baseline to the 3- or 6-week samples for the total group or for either drug by repeated measures analysis of variance. There was a significant group by time interaction for total thyroxine (TT4) between the drug treatment groups, which was caused by a small but significant increase in TT4 in the DMI sample. Correlations were performed between the change in hormones over the 6 week period and treatment response. There was a significant association between a decline in triiodothyronine (T3) levels and response to FLU but not DMI. The implications of these findings for the pathophysiology of depression and antidepressant drug mechanisms are discussed.
