pituitrin and Depressive-Disorder--Major

Although the neurohypophyseal hormones vasopressin (VP) and oxytocin (OT) are mostly known for their role respectively in antidiuresis, and in labour, lactation and maternal behavior, both might exert widespread influences either on emotion and cognition in healthy subjects, showing some gender-related differences. They interact with each other facilitating shifts between positive socially- oriented and defensive states. In fact, VP amplifies the reactivity to stressors showing also beneficial effects on attention, verbal learning as well as memory, whereas OT reduces the amplitude of the stress response, improves emotion processing, and can play a negative effect on memory and verbal learning in healthy individuals. Several data indicate the possible involvement of these neuropeptides in the pathophysiology of psychiatric conditions involving social interactions, such as autism, as well as in schizophrenia and depression. The aim of this paper is to review the literature relating to the role played by neurohypophyseal hormones in neuropsychiatric disorders.. We analyzed the best of published literature dealing with the relationships between neurohypophyseal hormones and neuropsychiatric conditions like autism (AD), major depressive disorder (MDD), bipolar disorder (BD) and schozophrenia, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on December 2017.. Several studies indicate a role played by OT and VP in AD, schizophrenia, MDD and BD. Even if conflicting data have been reported, several mechanisms may be involved in these behavioral diseases, such as differences in aminoacid sequence and peptide biological activity, neurotransmission and genetic disorders involving OT and VP receptors.. The involvment of VP and OT in neurpopsychiatric disorders can support a possible beneficial therapy with OT or with VP antagonists. The target may be obtained using effective drug delivery methods as well as the association with other drugs.

Topics: Affect; Animals; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Humans; Mental Disorders; Oxytocin; Pituitary Gland, Posterior; Schizophrenia; Schizophrenic Psychology; Signal Transduction; Vasopressins

Antidepressant drugs represent the principal form of treatment for major depressive disorder. While there are a plethora of medications available for this task, current drugs have many shortcomings. In the face of these deficiencies there is an ongoing search for new agents. The search has been guided, in part, by drug design based on existing agents and their putative mechanism of action. This has been less than fruitful in addressing inadequacies of existing medications as it has not produced compounds which are novel in terms of pharmacological mechanisms. Recent insights from molecular biological approaches hold promise for the discovery of novel compounds, in particular the so-called neurogenesis hypothesis suggests novel therapeutic approaches. Although significantly modified over the years, the monoamine hypothesis of depression and antidepressant drug action still remains an important driving force behind the development of new compounds. Several recently marketed agents and some in early-phase development tend to conform to these existing mechanistic hypotheses. Clearly the place of these agents in the treatment of depression is dependent on issues such as short- and long-term safety and efficacy. Duloxetine has been developed as a dual monoamine re-uptake inhibitor. Agomelatine is a compound with major effects on the circadian system as well as effects on subtypes of the serotonin receptor system. While the mechanism of action of this compound is not certain, recent evidence would suggest that the drug exerts its effects through antagonist actions at serotonin receptors. Compounds based on the hypothalamic pituitary adrenal axis, substance P antagonism and other neuropeptides have potential application for the treatment of depression but require further development before that potential is realized.

Topics: Acetamides; Depressive Disorder, Major; Duloxetine Hydrochloride; Humans; Hypnotics and Sedatives; Nerve Growth Factors; Selective Serotonin Reuptake Inhibitors; Substance P; Thiophenes; Vasopressins

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.

Topics: Adrenocorticotropic Hormone; Antidepressive Agents; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Fluoxetine; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Receptors, Vasopressin; Vasopressins

Vasopressin 1B (V

Topics: Antidepressive Agents; Depressive Disorder, Major; Double-Blind Method; Humans; Treatment Outcome; Vasopressins

This study investigated the development of hyponatremia and its underlying mechanism in elderly patients prescribed paroxetine. Patients were 15 men and women (mean age, 75.7 +/- 5.3 years) who were participants in a treatment study of late-life depression and who were without medical illness or other medications known to cause hyponatremia or alter antidiuretic hormone (ADH) secretion. Blood samples for measurement of plasma sodium, ADH, blood urea nitrogen (BUN), creatinine, glucose, and osmolality were determined prior to initiation of paroxetine (week 0) and at 2, 4, 6, and 12 weeks of treatment with paroxetine. Hyponatremia (serum sodium < 135 mEq/L) was identified in 6 of 15 patients after 2 weeks of treatment with paroxetine. Despite low plasma osmolality, ADH levels were not suppressed appropriately. Data suggest hyponatremia is a common adverse event in elderly patients prescribed paroxetine and implicates inappropriate secretion of ADH as the potential mechanism.

Topics: Aged; Depressive Disorder, Major; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Male; Osmolar Concentration; Paroxetine; Pilot Projects; Prospective Studies; Selective Serotonin Reuptake Inhibitors; Severity of Illness Index; Vasopressins

The pineal hormone melatonin regulates circadian rhythms, largely by feedback on the central biological clock of the brain, the hypothalamic suprachiasmatic nucleus (SCN). This feedback is mediated by the melatonin receptors, melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). The circadian system may play a role in the pathophysiology of mood disorders, and indeed, melatonin-receptor agonists are considered a potential therapy for depression.. In order to investigate melatonin receptors in the SCN during depression, and their relationship to the major neuropeptides in the SCN, vasopressin (AVP) and vasoactive intestinal peptide (VIP), we studied the SCN in 14 depressed patients (five major depression and nine bipolar disorder) and 14 matched controls by immunocytochemistry.. We show here that hypothalamic MT2 receptor immunoreactivity was limited to SCN, the supraoptic nucleus and paraventricular nucleus. We found that numbers of MT1-immunoreactive (MT1-ir) cells and AVP and/or VIP-ir cells were increased in the central SCN in depression, but numbers of MT2-ir cells were not altered. Moreover, the number of MT1-ir cells, but not MT2-ir cells was negatively correlated with age at onset of depression, while positively correlated with disease duration. CONCLUSION AND LIMITATIONS: Although every post-mortem study has limitations, MT1 receptors appeared specifically increased in the SCN of depressed patients, and may increase during the course of the disease. These changes may be involved in the circadian disorders and contribute to the efficacy of MT agonists or melatonin in depression. Moreover, we suggest that melatonin receptor agonists for depression should be targeted towards the MT1 receptor selectively.

Topics: Aged; Aged, 80 and over; Bipolar Disorder; Case-Control Studies; Circadian Rhythm; Depressive Disorder, Major; Female; Humans; Immunohistochemistry; Male; Melatonin; Middle Aged; Receptor, Melatonin, MT1; Receptor, Melatonin, MT2; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide; Vasopressins

It is well established that the neuropeptide oxytocin (OT) is involved in regulating social behavior, anxiety, and hypothalamic-pituitary-adrenal (HPA) axis physiology in mammals. Because individuals with major depression often exhibit functional irregularities in these measures, we test in this pilot study whether depressed subjects (n=11) exhibit dysregulated OT biology compared to healthy control subjects (n=19). Subjects were hospitalized overnight and blood samples were collected hourly between 1800 and 0900h. Plasma levels of OT, the closely related neuropeptide argine-vasopressin (AVP), and cortisol were quantified. Results indicated that depressed subjects exhibit increased OT levels compared to healthy control subjects, and this difference is most apparent during the nocturnal peak. No depression-related differences in AVP or cortisol levels were discerned. This depression-related elevation in plasma OT levels is consistent with reports of increased hypothalamic OT-expressing neurons and OT mRNA in depressed patients. This present finding is likewise consistent with the hypothesis that dysregulated OT biology may be a biomarker of the emotional distress and impaired social relationships which characterize major depression. Additional research is required to elucidate the role of OT in the pathophysiology of this psychiatric disorder.

Topics: Adult; Depressive Disorder, Major; Female; Humans; Hydrocortisone; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Regression Analysis; Vasopressins

Anxious-retarded depression is a two-dimensionally defined subcategory of depression derived from DSM-IV melancholia. It is related to increased plasma vasopressin, correlative plasma vasopressin and cortisol levels, and a positive family history. We now explored its relation with outcome.. Seventy depressed patients were included to follow-up for two years. Outcome was defined by time until full-remission. Cox regression analyses were used to compare anxious-retarded and non-anxious-retarded patients, as well as melancholic and non-melancholic patients.. Anxious-retarded depression had poor outcome.. The number of patients was relatively small.. The poor outcome of anxious-retarded depression further supports its validity.

Topics: Anxiety; Cross-Sectional Studies; Depressive Disorder, Major; Follow-Up Studies; Humans; Hydrocortisone; Psychomotor Disorders; Surveys and Questionnaires; Vasopressins

An anxious-retarded subtype of depression has been derived from the DSM-IV category of melancholia. It is defined by combined high scores for anxiety and retardation, and is related to family history of depression and increased plasma vasopressin (AVP) levels. Central problems concerning this hypothesized subcategory are whether elevated plasma AVP is related to family history, whether it would be better operationalized by a cut-off level for plasma AVP than as continuous variable, and whether the anxious-retarded phenotype would be better described in terms that account for full variability of mixed anxiety and retardation. A previous study suggested that above-normal plasma AVP was a more useful endophenotypic parameter than plasma AVP as a continuous variable. To answer these and related questions, 81 patients were investigated. Receiver Operating Characteristic analyses yielded a cut-off value of 5.56 pg/ml for above-normal plasma AVP, log-transformed plasma AVP (ln (AVP)) was used as continuous variable, and the correlation between anxiety and retardation was used to account for full variability of the anxious-retarded phenotype. Family history was related to above-normal plasma AVP (n = 16) and non-significantly to ln (AVP). Depression with above-normal plasma AVP, as well as familial depression with above-normal plasma AVP, showed a high correlation between anxiety and retardation, and this correlation was significantly higher than that found in the depressed patient control groups. The data support the delimitation of a largely familial depression with above-normal plasma AVP, vasopressinergic activation of the hypothalamus-pituitary-adrenal axis and a variable anxious-retarded phenotype.

Topics: Adult; Anxiety Disorders; Depressive Disorder, Major; Diagnostic and Statistical Manual of Mental Disorders; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Intellectual Disability; Male; Middle Aged; Phenotype; Pituitary-Adrenal System; Surveys and Questionnaires; Vasopressins

The Wistar-Kyoto (WKY) rat shows signs of persistent activation of the hypothalamic-pituitary-adrenal axis, but the cause and site of this activation is not yet known. Chronically activated corticotrophs generally show blunted adrenocorticotropic hormone (ACTH) response to corticotropin releasing factor (CRF); therefore, the anterior pituitary responsiveness to ACTH secretagogues, CRF and vasopressin, was compared in male WKY and Wistar rats. Anterior pituitary CRF binding and CRF receptor mRNA expression was significantly decreased in WKY rats. ACTH response to CRF or vasopressin was markedly impaired, and vasopressin failed to potentiate the CRF-stimulated ACTH release in cultured WKY anterior pituitary cells. In contrast, CRF and vasopressin alone and in combination stimulated large, concentration-dependent increases in ACTH release in Wistar anterior pituitary cells. By contrast to the decreased ACTH secretory responses, steady-state anterior pituitary pro-opiomelanocortin mRNA levels were approximately 12-fold greater in WKY rats compared to Wistar rats, and they further increased in response to CRF stimulation. These findings suggest that, although the WKY rat corticotroph is under a chronic state of activation or disinhibition, the in vitro secretory responses to classic ACTH secretagogues are impaired.

Topics: Adrenocorticotropic Hormone; Animals; Cells, Cultured; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Gene Expression; Male; Pituitary Gland, Anterior; Pro-Opiomelanocortin; Rats; Rats, Inbred WKY; Rats, Wistar; Receptors, Corticotropin-Releasing Hormone; RNA, Messenger; Species Specificity; Vasoconstrictor Agents; Vasopressins

The hypothalamic neuropeptide arginine vasopressin is thought to play an important role in the pathophysiology of affective disorders and the hyperactivity of the hypothalamic-pituitary-adrenocortical system that frequently accompanies them. Postmortem studies as well as clinical investigations have described elevated levels of vasopressin in the brain and plasma of depressed patients, and this finding has been suggested to contribute to depressive symptomatology.. The case of a 47-year-old patient displaying chronically elevated plasma vasopressin levels due to paraneoplastic vasopressin secretion by an olfactory neuroblastoma and the first episode of major depression is presented.. Depressive symptoms improved markedly after surgical resection of the tumor and subsequent normalization of plasma vasopressin levels. Unexpectedly, neither corticotropin nor cortisol secretion could be stimulated by an intravenous corticotropin-releasing hormone challenge under the condition of chronically elevated plasma vasopressin levels in this patient.. Chronically elevated plasma vasopressin levels may induce depressive symptomatology, and-in contrast to the potent corticotropin secretagogue effects of acute vasopressin administration-lead to a marked desensitization of the hypothalamic-pituitary-adrenocortical system.

Topics: Adrenocorticotropic Hormone; Cerebral Cortex; Depressive Disorder, Major; Esthesioneuroblastoma, Olfactory; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary-Adrenal System; Vasopressins