Obesity, depressive symptoms, and periodontitis are major worldwide health concerns. Despite separate studies on both illnesses, no research has directly examined the link between depressive symptoms and periodontitis in obese people. Given the close correlation between obesity and chronic illnesses, as well as the possibility of a bidirectional impact between depressive symptoms and periodontitis, this study aims to investigate the link between depressive symptoms and periodontitis in an obese population.

This study analyzed data from the NHANES database (2009-2014), including 4,820 persons aged 30 years or older with a BMI over 30. The severity of periodontitis was assessed by clinical attachment loss and probing depth, while symptoms of depressive symptoms were measured using the PHQ-9 questionnaire. After gender, age, race, education, ratio of family income to poverty, sleep duration, diabetes, and cardiovascular illnesses were controlled for, the independent connection between depressive symptoms and periodontitis was investigated using multivariable logistic regression.

The modified models indicated a significant negative correlation between depressive symptoms and periodontitis (effect size: -0.13, 95% CI: -0.24 to -0.01, p = 0.0266), indicating that depressive symptoms may operate as a protective factor against periodontitis. Interaction studies did not indicate substantial impact modification by factors like age, gender, or education level.

This study is the first investigation demonstrating a negative link between depressive symptoms and periodontitis in obese persons, indicating a significant interaction between mental health and dental health in this demographic. The results highlight the importance of comprehensive psychological and oral health care in obese individuals, providing a new avenue for future research and therapeutic applications.

To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines.

Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis.

In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P < 0.05). The plasma corticosterone and ACTH levels were significantly higher in the CVS-A (537.42 ± 32.95, 44.44 ± 6.54 pg/mL) and CVS-B (655.07 ± 30.82, 65.46 ± 4.44 pg/mL) groups than in the control group (46.96 ± 13.29, 8.51 ± 1.35 pg/mL, P < 0.05). Notably, the ratio of corticosterone to ACTH was significantly increased in the CVS-A group only. Rats exposed to CVS displayed significantly increased expression of IL-2 and IFN-γ in the plasma and distal colon compared to the control group, whereas this effect was significantly attenuated in the CVS-B group.

These results suggest that concurrent sweet food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

Chronic voluntary running of mice is known to increase the circadian peak of plasma corticosterone without change in the level of adrenocorticotropic hormone (ACTH). In order to investigate how chronic exercise modulates the circadian HPA axis, we used two weeks of voluntary wheel running of mice and confirmed the significant increase of the circadian peak of plasma corticosterone without alteration in ACTH level. To elucidate the mechanisms of exercise modulation on corticosterone synthesis, we first examined the levels of transcripts involved in corticosterone synthesis of the adrenal gland. Among them, only steroidogenic acute regulatory protein (StAR), the rate-limiting factor that transfers substrate cholesterol into inner mitochondrial membrane, showed significantly higher expression in the exercise group. Since the splanchnic nerve input to the adrenal gland has been reported as a factor involved in the direct modulation of corticosterone synthesis, we next examined the expression levels of enzymes for the catecholamine synthesis as indices of sympatho-adrenomedullary activity. We found that the only rate-limiting enzyme, tyrosine hydroxylase (TH), was significantly higher in the adrenals of exercise group. In addition to the increment of StAR and TH mRNA in response to the chronic exercise, surprisingly, we found only these factors showed the circadian variation in its expression levels that was correlated to the circadian rhythm of corticosterone. Chronic exercise seems to alter the circadian corticosterone synthesis, at least partially via altering the levels of circadian-regulated transcripts, StAR and TH of the adrenal gland.

Glucocorticoids released by stress bind to glucocorticoid (GR) and/or mineralocorticoid receptors (MR) to exert negative feedback of subsequent hypothalamic-pituitary-adrenal (HPA) responses to stress. Feedback inhibition is implicated in habituation of HPA activity to repeated exposure to the same (homotypic) stressor. We hypothesized that the posterior paraventricular thalamus (pPVTh) is a site where corticosterone acts to exert negative feedback during repeated stress and that is important for habituation. As previously reported, the pPVTh inhibits HPA responses to homotypic and heterotypic stressors in repeatedly, but not acutely, stressed rats. We conducted a series of experiments involving intra-pPVTh administration of MR and/or GR agonists or antagonists during different time frames over 8 d of restraint. MR exist in the pPVTh, as do GR as shown by our immunocytochemical results. Acute intra-pPVTh injection of MR and/or GR antagonist before the eighth restraint did not alter expression of habituation. Because habituation may develop before d 8, we manipulated GR and MR in the pPVTh throughout 8 d of stress using intra-pPVTh corticosterone implants, which enhanced habituation on d 8 without affecting acute stress responses. Conversely, daily intra-pPVTh injections of GR and MR antagonists on d 1-7 of restraint prevented habituation on d 8. These data suggest that corticosterone released during repeated stress can act at GR and MR in the pPVTh to inhibit HPA responses to homotypic stress. We also found that some GR-containing cells in the pPVTh project to the medial prefrontal cortex and basolateral amygdala, suggesting that pPVTh-induced inhibition of HPA activity is potentially mediated by its projections to these select limbic structures.

Previous experiments in rats suggest that hypothalamic-pituitary-adrenal (HPA) axis over-responsiveness, which leads to increased secretion of immunoregulatory glucocorticoid hormones, increases periodontal disease susceptibility, whereas HPA axis under-responsiveness is associated with increased resistance to the disease. The present study was designed to investigate whether MK-801 (dizocilipine malate), an antagonist of the glutamate receptor N-methyl-D-aspartate (NMDA) in the brain, which has been found to play an important role in the regulation of the HPA axis, would influence the outcome of experimental ligature-induced periodontal disease in a rat model.

Experimental periodontal disease was induced in periodontal disease susceptible and HPA axis high-responding Fischer 344 rats 2 days before chronic treatment with MK-801(1 mg/kg intraperitoneally). The periodontal breakdown was assessed after the ligatures had been in place for 23 days. Following intraperitoneal Gram-negative bacterial lipopolysaccharide stimulation (Escherichia coli, 250 microg/kg), concentrations of glucocorticoid receptors (GRs) in the hippocampus, and levels of the cytokine tumour necrosis factor alpha (TNF-alpha), as well as the HPA axis-derived hormone corticosterone, were measured in serum.

Compared to vehicle-treated controls, MK-801-treated rats had significantly increased periodontal tissue destruction (p < 0.01). MK-801-treated rats also showed significantly increased expression of GRs in the hippocampus (p < 0.05), elevated levels of corticosterone (p < 0.001) and reduced levels of TNF-alpha (p < 0.01) in serum 2 h after lipopolysaccharide stimulation.

These findings may implicate glutamate receptor-dependent mechanisms in periodontal disease, and support the concept of a bidirectional immune-brain-immune regulatory network with importance for periodontal health and disease.

Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P=0.02) and genotype (P=0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P=0.04). In both patient-control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key biological abnormalities described in major depressive disorder, occurring in 30-50% of depressed subjects. Corticotropin-releasing hormone (CRH) and vasopressin (AVP) are the main regulators of this stress system, with the two neuropeptides acting synergistically in bringing about adrenocorticotropin (ACTH) release from the anterior pituitary and cortisol from the adrenal gland. Based on the demonstration of elevated cerebrospinal fluid levels of CRH in depressives, and other evidence, it has been postulated that excess CRH and the resultant increased HPA forward drive form the basis of neuroendocrine dysregulation in depression. However, there is an accumulating body of evidence to support a significant role for AVP in the regulation of pituitary-adrenal activity in health and also in depressive disorder. This review, based on a Medline search from 1980 to 2001, focuses on the functional neuroanatomy, receptor pharmacology, VP synergism with CRH, and the data from clinical and pre-clinical studies that support an important role for AVP in the pathophysiology of major depression. We suggest that future antidepressants may target the vasopressinergic system.

The hippocampus, which is a brain structure involved in learning and memory processes, plays a key role in the feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis and autonomic sympathetic nervous system, and the subsequent secretion of immuno-modulatory hormones in response to pathogenic microorganisms. Dysregulation of these brain-neuroendocrine-immune regulatory networks, which act in concert to maintain homeostasis, is found to be of critical importance to the host defence against pathogens, as well as susceptibility to diseases, including periodontal disease. The present study was designed to determine the effects of hippocampal lesioning on the progression of periodontitis. Experimental ligature-induced periodontitis was induced in 16 Wistar rats, which were bilaterally lesioned in their hippocampal region with an aspiration technique that is well documented to impair learning and memory, as well as in 15 sham-operated control rats. The disease progression was evaluated radiographically and histometrically. The results revealed that the hippocampal lesioned rats developed significantly more destruction of the periodontium than did the sham-operated controls. This finding supports recent studies that indicate that inappropriate brain-neuroendocrine regulation of inflammatory responses to infectious agents may play an important role in disease susceptibility and progression.

Clinical observations and epidemiological studies suggest that experiences of negative life events, especially those manifested as depression, may contribute to an increased susceptibility to periodontal disease.

In the present study, the prevalence of some negative life events and psychological factors and their relation to periodontal disease were investigated. The sample consisted of individuals 50-80 years of age from an extensive cross-sectional epidemiological study performed in 1993 in the city of Jönköping, Sweden.

298 dentate individuals from the Jönköping study were randomly selected. Clinical and radiographic examinations included registration of the number of existing teeth, plaque index, gingival index, pocket depth, and alveolar bone loss. In addition, a questionnaire about socioeconomic status, life events, and psychological and stress-related factors was used.

The results revealed that, in addition to the well-documented periodontal disease risk factors such as increased age, oral hygiene status, and smoking, the loss of a spouse (being a widow or widower) and the personality trait of exercising extreme external control were also associated with severe periodontal disease.

The findings support recent studies suggesting that traumatic life events such as the loss of a spouse may increase the risk for periodontal disease. Above all, the present results indicate that an individual's ability to cope with stressful stimuli (coping behavior), as measured by the beliefs of locus of control of reinforcements may play a role in the progression of periodontal disease.

Socially subordinate female common marmoset monkeys undergo pronounced, chronic reductions in basal plasma cortisol levels, which appear to result both from socially induced suppression of reproductive hormones and from direct effects of social subordination. In this study, we tested the hypothesis that this cortisol suppression is mediated by reduced adrenocortical responsiveness to adrenocorticotropic hormone (ACTH). Dominant, subordinate, and ovariectomized females were given dexamethasone (5 mg/kg, IM), followed the next morning by human ACTH(1-39) (10 microg/kg, IV) or sterile saline (0.5 ml/kg, IV); blood samples were collected at -20 through 150 min from ACTH or saline treatment and assayed for cortisol. ACTH, but not saline, caused a marked elevation of plasma cortisol levels. Prior to ACTH treatment, dominant females tended to have higher dexamethasone-suppressed cortisol levels than subordinate and ovariectomized females. After ACTH treatment, dominant females had significantly higher cortisol concentrations, as well as higher peak and net integrated cortisol responses to ACTH, than did subordinate and ovariectomized animals; the latter two groups showed comparable cortisol responses to ACTH. These results suggest that dampened adrenocortical responsiveness to ACTH contributes to chronic reductions in cortisol levels in subordinate female marmosets and may be mediated by suppression of reproductive hormones.

Periodontal disease is a bacterial dental plaque-induced destructive inflammatory condition of the tooth-supporting tissues, which is thought to be mediated by T lymphocytes secreting T helper 2 (Th2) cytokines, resulting in recruitment of high numbers of antibody-producing B lymphocytes/plasma cells as well as polymorphonuclear leucocytes (PMN) secreting tissue-destructive components, such at matrix metalloproteinases and reactive oxygen metabolites into the gingival connective tissues. One treatment strategy may be to down-regulate the Th2 response to those dental plaque microorganisms which induce the destructive inflammatory response. In this study we have examined the effects of a potent down-regulator of Th2 responses on ligature-induced periodontal disease in an experimental rat model. A single s.c. injection into Wistar rats of 0.1 or 1 mg of SRL172, a preparation of heat-killed Mycobacterium vaccae (NCTC 11659), 13 days before application of the ligature, significantly reduced the subsequent destruction of the tooth-supporting tissues, as measured by loss of periodontal attachment fibres (P < 0.001) and bone (P < 0.002). This protective effect occurred not only on the experimental (ligatured) side but also on the control unligatured side. SRL172 has undergone extensive toxicological studies and safety assessments in humans, and it is suggested that it may provide a safe and novel therapeutic approach to periodontal disease.

There is evidence that the endogenous opioid system (EOS) is involved in the modulation of mood and neuroendocrine function. Furthermore, the possible involvement of the EOS in major depression has been postulated, although a clear role has not been established.

The affective and endocrine responses to naloxone administration in seven female depressives and in seven matched controls and their diurnal variations were investigated. Subjects had an i.v. bolus of either 0.2 mg/kg naloxone or saline at two time points (09:00 or 18:00 h) and for 2 days in a single-blind, cross-over design.

The basal cortisol plasma levels, both in the morning and in the afternoon, showed higher values (P<0.05) in the depressives. There was a naloxone-induced increase in the adrenocorticotrophic hormone (ACTH), cortisol, and luteinizing hormone (LH) plasma levels, plus a subjective dysphoric effect in both groups. The depressives showed a greater dysphoric effect both in the morning and afternoon (P<0.05), and a blunted cortisol response in the afternoon (P<0.05). There were no differences between groups or time of day in the ACTH or LH responses.

The sample size was small, but by studying each patient as their own control, plus a matched control for every patient, softens this effect. Finding patients with a major depressive episode free of medication is difficult, and this aspect contributes to the size of the sample.

These results suggest that opioid mechanisms may be involved in the HPA axis changes and possibly in mood changes found in depression. The discrepancy between increased sensitivity in depression to mood changes and decreased change in cortisol may indicate a ceiling effect for the latter.

The bilateral olfactory bulbectomy resulted in significantly higher plasma concentration of corticosterone, but not of ACTH in basal conditions and much higher plasma ACTH and corticosterone concentrations after 15 min of immobilization stress than were observed in sham-operated animals. Daily treatment with fluoxetine-a specific serotonin reuptake inhibitor-(15 mg/kg/day) had no effect on basal ACTH and corticosterone concentrations in OB rats. Fluoxetine treatment caused lower levels of ACTH, but not of corticosterone secretion, in response to immobilization stress. Bulbectomy significantly reducing 5-HT concentration in the amygdala. Stress increased serotonergic activity in the hypothalamus but not in the amygdala of OB rats. Chronic fluoxetine treatment of both unstressed and stressed OB rats resulted in a lower turnover rate in the two structures. Our results suggest that the hypercorticosteronemia observed after bulbectomy in unstressed OB rats is independent of the serotonergic system in both hypothalamus and amygdala. In contrast, they also demonstrate hypothalamic 5-HT changes in the HPA hyperactivity of OB rats in response to stress. Chronic fluoxetine treatment may normalize pituitary ACTH secretion in response to stress, possibly desensitization of the 5-HT receptors in the hypothalamus due to 5-HT being move available at the synapses.

Persistent hypothalamo-pituitary adrenal axis dysregulation occurs in up to 40% of patients who have suffered a stroke. The degree of hypercortisolemia is partly determined by the size and site of the vascular lesion. Adrenocortical hyperactivity begins almost immediately after a cerebrovasacular infarct but is persistent in an important subgroup of patients. In the early poststroke period (1 day to 1 month) high corticosteroid levels correlate with the presence of an acute confusional state. In the medium term (1 month to 1 year) hypercortisolemia is associated with the development of a major depressive episode and also relates to functional outcome and survival. Neuroanatomical deficits (particularly in the frontal or medial temporal lobes), age of onset, cognitive impairment, and reduced functional status may act as maintaining factors in both the poststroke depression and the adrenocortical hyperactivity. Patients with persisting hypercortisolemia, with or without depression or cognitive impairment, have a worse prognosis with an increased mortality rate. The mechanism for this effect may involve induced hyperglycemia or direct glucocorticoid neurotoxicity, which impairs the brain's capacity for recovery. It is suggested that the cautions use of antiglucocorticoid strategies may be of value in the medical management of the neuropsychiatric complications that follow cerebrovascular accidents.

New mothers are more attracted to the body odor of newborn infants than are nonmothers. In this study we investigated the relation of postpartum hormones and of prior experience with infants to this enhanced maternal attraction to infant odors. New mothers were asked to complete a hedonics task, using a pleasantness scale to provide an attraction score to different odorants presented on a cotton substrate in a 1-pt Baskin-Robbins container. Mothers were "blind" to the contents of the container. Participants also completed an extensive set of 100-item likert scales concerning their attitudes toward infants, care taking, own maternal adequacy, and other interpersonal relations. Mothers were videotaped interacting with their infants and provided salivary samples prior to the interaction. Salivary samples were assayed by radioimmunoassay (RIA) for salivary concentrations of cortisol, progesterone, and testosterone. Results show that first-time mothers with higher cortisol concentrations were more attracted to their own infant's body odor. Mothers with higher cortisol levels were also better able to recognize their own infants' odors. While cortisol was not related to attitudinal measures of maternal responsiveness, mothers with more prior experience interacting with infants exhibited both more attraction to infant odors and more positive maternal attitudes. Together, prior maternal experience and postpartum cortisol explain a significant proportion of the variance in mothers' attraction to newborn infant odors. These relations are discussed in terms of the variety of "meanings" cortisol could have during the postpartum period.

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0.05 microgram/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0.044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

It is generally assumed that adrenocorticotrophic hormone (ACTH) is responsible for the modulation of glucocorticoid secretion from the adrenal cortex. However, under resting or basal conditions, cortisol secretion in the human may be controlled by noradrenergic nerves which regulate adrenal responsivity to ACTH. This hypothesis explains a variety of descrepant observations and is supported by evidence from several biological disciplines. If confirmed, the implications of this model for our understanding of the principal 'stress' hormone would be profound.

Chronic fatigue syndrome (CFS) is a disorder characterized by severe physical and mental fatigue and fatiguability of central rather than peripheral origin. We hypothesized that CFS is mediated by changes in hypothalamopituitary function and so measured the adrenocorticotrophic hormone (ACTH), cortisol, growth hormone, and prolactin responses to insulin-induced hypoglycemia, and the ACTH, cortisol, and prolactin responses to serotoninergic stimulation with dexfenfluramine in nondepressed CFS patients and normal controls. We have shown attenuated prolactin responses to hypoglycemia in CFS. There was also a greater ACTH response and higher peak ACTH concentrations (36.44 +/- 4.45 versus 25.60 +/- 2.78 pg ml), whereas cortisol responses did not differ, findings that are compatible with impaired adrenal cortical function. This study provided evidence for both pituitary and adrenal cortical impairment in CFS and further studies are merited to both confirm and determine more precisely their neurobiological basis so that rational treatments can be evolved.

Whereas much is known about the function of the hypothalamic-pituitary-adrenal (HPA) axis during environmental stress and in psychiatric disorders, little is known about the relation of individual differences in basal HPA-functioning to individual differences in healthy psychological functioning. In the present study, we recruited 37 healthy young men and examined the relations of hardiness, self-esteem and hypomanic personality--dispositions that moderate the effects of psychosocial stress on depressive reactions and health--to circulating levels of cortisol and beta-endorphin at rest. High self-esteem, hardiness and affective stability were associated with higher plasma cortisol levels and less psychological distress. Additionally, affective stability was associated with higher levels of beta-endorphin. The present findings suggest that individual differences in basal HPA-function are associated with individual differences in psychological functioning following stress.

1. Corticotropin-releasing hormone (ovine CRH, 100 micrograms intravenous bolus) was given to 63 unipolar depressed inpatients following the 1 mg overnight dexamethasone suppression test (DST). The depressed patients included 18 minor, 24 simple major and 21 melancholic subtypes. 2. Baseline or postdexamethasone plasma levels of intact adrenocorticotropic hormone (ACTH), beta-endorphin/beta-lipotropin (beta END/beta LPH), cortisol, and dexamethasone were measured, as well as the post DST+CRH hormone responses. 3. CRH administration 9.5 hr after dexamethasone resulted in a significant enhancement of ACTH, beta END/beta LPH and cortisol secretion. The post DST+CRH ACTH and beta END/beta LPH- but not cortisol-values exceeded their baseline hormone levels. The post DST+CRH ACTH--but not beta END/beta LPH or cortisol-levels were significantly higher in major depressives compared to minor depressives. The post DST+CRH ACTH and beta END/beta LPH--but not cortisol-levels were significantly higher in DST nonsuppressors than suppressors. The post DST+CRH ACTH levels were significantly and positively related to severity of illness. 4. The results provide evidence that the pathophysiology underlying the abnormal DST+CRH and DST tests in melancholia is localized at the pituitary level and may consist of a CRH-driven breakthrough of corticotropic cell secretion synergized by central and peripheral agents, in conjunction with a decrease in glucocorticoid feedback suppressibility.

This is a review of psychosomatic interactions between affective disorders (depressive and anxiety disturbances, irritable mood) and endocrine disease. Particular reference is made to stressful life events in the pathogenesis of endocrine disease, psychopathology of hormonal disturbances, and pathophysiology of hypothalamic-pituitary-adrenal axis function in depression and Cushing's disease. These psychosomatic interactions may lead to appraisal of common etiological mechanisms in endocrine and psychiatric disorders, of the value of retaining the category of organic affective syndromes in psychiatric classification, and of the need for research on quality-of-life measures in endocrine disease. The establishment of "psychoendocrine units," where both endocrinologists and psychiatrists should work, is advocated. Such psychoendocrine units may serve and benefit clinical populations who currently defy traditional medical subdivisions.

CRH seems to be of fundamental importance in depressive illness. Melancholic depressed patients, with a syndrome of hyperarousal, have increased activity of CRH-producing neurones. Conversely, there is evidence to support the notion that patients with atypical depression, a syndrome of hypoarousal, have decreased activity of CRH-producing neurones. CRH-induced kindling is a possible model for the natural history of depressive illness. Finally, effective treatments for depressive illness, such as tricyclic antidepressants, decrease CRH production, and drugs, such as carbamazepine, effective in preventing the recurrence of affective disorder, also decrease CRH production. Interestingly, these drugs are not particularly effective in the treatment of atypical depression, which seems to be related not to an activation of CRH-producing neurones, but rather to a decrease of CRH secretion.

"A neuroendocrine hypothesis to explain the clinical activity of convulsive therapy is described. The hypothesis is based on the diabetes/insulin model and suggests that hypothalamic dysfunction with an insufficiency of a mood-maintaining peptide is the basis for affective disorders. Repeated seizures enhance the production and release of the hypothalamic peptide antidepressin - the active principle that relieves both neuroendocrine and behavioral abnormalities.

There is current controversy over the mechanisms underlying hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in depression. Pro-gamma-melanocyte-stimulating hormone (MSH), a portion of the N-terminal region of pro-opiomelanocortin, has been shown to act synergistically with adrenocorticotropic hormone (ACTH) in stimulating corticosteroid secretion both in vitro and in vivo. Pro-gamma-MSH and ACTH plasma levels were measured in 30 drug-free male patients with a DSM-IIIR major depressive disorder and 21 healthy controls. The baseline levels were similar in the two groups. After single-dose metyrapone stimulation, both hormones increased, but pro-gamma-MSH was significantly higher in control subjects than in depressives. After overnight 1-mg dexamethasone, ACTH was significantly less suppressed in depressives than controls. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH and be more complex than previously reported.