pituitrin and Depressive-Disorder

The therapies of mood and anxiety disorders are not solved, because current antidepressants have delayed onset of therapeutic action and a significant number of patients are non-responsive. Research on the field was leaning towards neuropeptides as therapeutic targets. Vasopressin (VP) is a hot candidate, as beyond its peripheral actions VP is implicated in interneuronal communication and modulates the hypothalamo-pituitary-adrenal (HPA), the key stress axis, as well as behavioural functions. Affective disorders are stress related disorders and the most frequently occurring abnormality in depressed subjects is hyperactivity of the HPA. VP with nucleus paraventricularis hypothalami origin is a direct adrenocorticotrophin secretagogue through its V1b receptor. VP seems to have special importance under prolonged stress conditions, which are known to be strong predictive factor of depressive disorder and can induce depressive-like symptoms. Preclinical and clinical data summarized in this review underline the importance of VP in the development of anxiety- and depressive-like symptoms. Orally active nonpeptiderg V1b antagonists were developed and seemed to have effective anxiolytic and antidepressant profile in preclinical studies, which was not fully confirmed by clinical observations. It seems that V1a receptors on special brain areas could have same importance. Taken together current knowledge strongly implies an importance of vasopressinergic regulation in affective disorders and consider VP as endogenous anxiogenic/depressogenic substance. However, wide range of side effects could develop as a result of an intervention on the VP system; therefore there is a need for area-specific targeting of VP receptors (e.g. with modified nanoparticles).

Topics: Animals; Anti-Anxiety Agents; Antidepressive Agents; Antidiuretic Hormone Receptor Antagonists; Anxiety; Anxiety Disorders; Depression; Depressive Disorder; Diabetes Insipidus; Disease Models, Animal; Humans; Hypothalamo-Hypophyseal System; Inappropriate ADH Syndrome; Mice; Mice, Inbred BALB C; Mice, Knockout; Molecular Targeted Therapy; Mood Disorders; Pituitary-Adrenal System; Rats; Rats, Brattleboro; Rats, Mutant Strains; Receptors, Vasopressin; Stress, Psychological; Vasopressins

Affective disorders comprise mood disorders such as unipolar depression and anxiety disorders, including generalized anxiety, post-traumatic stress disorder, panic, phobia and obsessive-compulsive disorder. The etiology of these disorders is related to stress. Further, they are characterized by alterations of the hypothalamus-pituitary-adrenal (HPA) axis function, controlling the endocrine response to stress. Vasopressin is a nonapeptide that is mainly expressed and/or released in the hypothalamus and the pituitary, but also in other brain areas particularly in limbic regions. It strongly contributes to the endocrine and neural response to stress. Therefore, it has been suggested that vasopressin may be involved in affective disorders. Here, we review both clinical and preclinical data that investigated this hypothesis. Several studies show an increased plasmatic level of vasopressin in anxiety disorders as well as in unipolar depression. Further, a single nucleotide polymorphism (SNP) of the vasopressin V(1b) receptor has been found to protect against depression. Preclinical data are convergent with the clinical findings. For example, Brattleboro rats, that display decreased vasopressin function, show reduced anxiety, reduced depressive-like behavior and decreased HPA function. Rats selected for high anxiety behavior exhibit increased HPA function related to a SNP in the vasopressin locus resulting in an overexpression of vasopressin. Antagonism of the V(1b) receptor decreases anxiety and depressive-like behaviors in rodents, as well as HPA responsivity to stress. Taken together, these data indicate that affective disorders may be related to excessive vasopressin function and consequently that a treatment with vasopressin receptor antagonists may be an effective treatment.

Topics: Animals; Anxiety Disorders; Depressive Disorder; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Receptors, Vasopressin; Vasopressins

Affective disorders tend to be chronic and life-threatening diseases: suicide is estimated to be the cause of death in 10-15% of individuals with major depressive disorders. Major depression is one of the most prevalent and costly brain diseases with up to 20% of the worldwide population suffering from moderate to severe forms of the disease. Only 50% of individuals with depression show full remission in response to currently available antidepressant drug therapies which are based on serendipitous discoveries made in the 1950s. Previously underestimated, other severe depression-associated deleterious health-related effects have increasingly been recognized. Epidemiological studies have provided substantial evidence that patients with depression have a 2-4-fold increased risk both of developing cardiovascular disease and of mortality after experiencing a myocardial infarction. The majority of patients suffering from affective disorders have measurable shifts in their stress hormone regulation as reflected by elevated secretion of central and peripheral stress hormones or by altered hormonal responses to neuroendocrine challenge tests. In recent years, these alterations have increasingly been translated into testable hypotheses addressing the pathogenesis of illness. Refined molecular technologies and the creation of genetically engineered mice have allowed to specifically target individual genes involved in regulation of corticotropin releasing factor (CRF) and vasopressin (AVP) system elements. The cumulative evidence makes a strong case implicating dysfunction of these systems in the etiology and pathogenesis of depression and pathological anxiety. Translation of these advances into novel therapeutic strategies has already been started.

Topics: Animals; Anxiety Disorders; Corticotropin-Releasing Hormone; Depressive Disorder; Humans; Hypothalamo-Hypophyseal System; Mutation; Pituitary-Adrenal System; Receptors, Corticotropin-Releasing Hormone; Receptors, Vasopressin; Vasopressins

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis characterized by hypercortisolism, adrenal hyperplasia and abnormalities in negative feedback is the most consistently described biological abnormality in melancholic depression. Corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) are the main secretagogues of the HPA/stress system. Produced in the parvicellular division of the hypothalamic paraventricular nucleus the release of these peptides is influenced by inputs from monoaminergic neurones. In depression, anterior pituitary CRH1 receptors are down-regulated and response to CRH infusion is blunted. By contrast, vasopressin V3 receptors on the anterior pituitary show enhanced response to AVP stimulation and this enhancement plays a key role in maintaining HPA overactivity.

Topics: Adrenocorticotropic Hormone; Depressive Disorder; Feedback, Physiological; Glucocorticoids; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Neurons; Pituitary-Adrenal System; Receptors, Vasopressin; Stress, Psychological; Vasopressins

Topics: Clinical Trials as Topic; Depressive Disorder; Dopamine; Electromagnetic Fields; Humans; Stress, Psychological; Synaptic Transmission; Vasopressins

The clinical utility of the tests of hypothalamic-pituitary-adrenocortical function discussed in this article are still to be ascertained. As with the dexamethasone suppression test, reviewed elsewhere in this issue, the application of other basal and challenge tests have furthered our understanding of the character of observed hypothalamic-pituitary-adrenocortical function in psychiatric patients. Hypothalamic-pituitary-adrenocortical physiology is complex and plastic and cannot be understood in terms of oversimplified explanations or concepts. Repeated measures over time, involving multiple assessments of axis activity, are essential in understanding the modulating effects of prior activity of the system (induced by endogenous regulatory systems or by superimposed environmental stressors) on the current function of the various levels in this closed-loop axis, where all parts influence the function of the remainder. From such an appreciation and understanding of this system can come more simplified assessments of its function, which would allow application to clinical psychiatry.

Topics: Adrenocorticotropic Hormone; Body Fluids; Corticotropin-Releasing Hormone; Depressive Disorder; Estrenes; Humans; Hypothalamo-Hypophyseal System; Metyrapone; Mifepristone; Physostigmine; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Vasopressins

The 41-amino acid CRF fulfils all the criteria for a corticotrophin releasing factor, although considerable evidence suggests that other factors, particularly VP, also play a physiologically significant role in controlling ACTH release. Although human CRF has now been identified as a 41-residue peptide, most studies to date have used oCRF-41 in their exploration of the physiology and pathology of the hypothalamic--pituitary--adrenal axis. Low doses of oCRF-41 appear to be safe, and for specific tests of the readily-releasable pool of ACTH and related peptides 100 micrograms is a practical dose for most purposes. Although serious side-effects have only been noted at doses above 100 micrograms, it is reasonable to monitor all patients administered CRF-41 with great care, and in particular to be alert to hypotension, especially in patients with corticosteroid deficiency. There is little doubt that, in combination with the standard insulin-tolerance test, the CRF test is a useful means of diagnosing hypothalamic or portal dysfunction in patients with secondary adrenal failure. However, in the diagnosis and differential diagnosis of Cushing's syndrome, the role of the CRF test remains unclear. In normal subjects, a high basal cortisol level usually inhibits the response to CRF, such that a greatly enhanced response is suggestive of pituitary-dependent Cushing's syndrome. In patients with diagnosed ACTH-dependent Cushing's syndrome, an absent response to CRF predisposes towards an ectopic source of ACTH. However, there are exceptions in all directions, and it is uncertain whether the CRF test will prove of greater value than the traditional procedures, such as the dexamethasone suppression test. The differential diagnosis of depression and Cushing's disease may be its greatest value. In terms of treatment, there are as yet few data on the usefulness of CRF in expediting recovery of the pituitary-adrenal axis following long-term suppression, such as in patients with Cushing's syndrome treated by removal of a unilateral adenoma or trans-sphenoidal microadenomectomy. It is possible that such treatment may eventually be a useful application of CRF, although data are not yet available.

Topics: Acetylcholine; Acromegaly; Adrenocorticotropic Hormone; Animals; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Depressive Disorder; Diagnosis, Differential; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Immunologic Techniques; Kinetics; Models, Biological; Pituitary-Adrenal System; Stress, Physiological; Vasopressins

Topics: Animals; Anticonvulsants; Antipsychotic Agents; Depressive Disorder; Drug Therapy, Combination; Endorphins; Enkephalins; Humans; Mental Disorders; Naloxone; Naltrexone; Nerve Tissue Proteins; Pituitary Hormones; Psychotropic Drugs; Schizophrenia; Substance-Related Disorders; Vasopressins

Topics: Aged; Alzheimer Disease; Animals; Brain; Cholecystokinin; Depressive Disorder; Endorphins; Female; Humans; Male; Mental Disorders; Middle Aged; Nerve Tissue Proteins; Neurotransmitter Agents; Schizophrenia; Substance P; Vasopressins

Dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis is related to melancholic or endogenous depression; however, the strength of this relationship depends on the definition of the specific depression subcategory. A two-dimensionally defined subcategory, anxious-retarded depression, is related to melancholic depression. Since arginine vasopressin (AVP) activates the HPA axis, and both major depression and the melancholic subcategory are associated with elevated plasma AVP levels, we investigated whether the plasma AVP level is also elevated in anxious-retarded depression, melancholic depression and anxious-retarded melancholic depression, and whether plasma AVP and cortisol levels are correlated in these subcategories. A total of 66 patients with major depression not using oral contraception were investigated. Patients with anxious-retarded depression had a highly significant AVP-cortisol correlation, while no such correlation was found in patients with nonanxious-retarded depression. Log-transformed mean plasma AVP values were higher in patients with anxious-retarded depression than in patients with nonanxious-retarded depression. Patients with anxious-retarded melancholic depression also had a significantly elevated level of plasma AVP and a highly significant correlation between plasma AVP and cortisol levels. The correlation was low in patients with melancholic depression. Anxious-retarded depression may be a useful refinement of the melancholic subcategory with regard to dysregulation of the HPA axis and plasma AVP release.

Topics: Adult; Anxiety; Biomarkers; Cross-Over Studies; Depressive Disorder; Female; Follow-Up Studies; Humans; Hydrocortisone; Male; Middle Aged; Prospective Studies; Psychiatric Status Rating Scales; Vasopressins

Major depression is associated with significant disturbance in hypothalamic-pituitary-adrenal axis functioning, including blunted release of ACTH in response to CRH infusion. Eight melancholic depressives and eight matched healthy comparison subjects underwent, in random order, the following challenges: placebo, CRH, CRH + DDAVP. Blood for ACTH and cortisol estimation was drawn at -15, 0, 15, 30, 45, 60, 90, and 120 min. A blunted release of ACTH, in response to CRH challenge, was observed in depression (P < 0.01), whereas maximal cortisol responses in both groups were similar, despite elevated baseline levels in depression (P < 0.05). The combined CRH/DDAVP infusion produced similar ACTH and cortisol release in both groups. These results suggest that melancholic depression is associated with enhanced pituitary vasopressinergic responsivity.

Topics: Adrenocorticotropic Hormone; Adult; Corticotropin-Releasing Hormone; Deamino Arginine Vasopressin; Depressive Disorder; Female; Humans; Hydrocortisone; Male; Middle Aged; Single-Blind Method; Vasopressins

Animal studies suggest that vasopressin has cognitive-enhancing properties and oxytocin may have amnestic effects. A clinical report suggests that the acute increase in oxytocin-associated neurophysin predicts clinical response to electroconvulsive therapy (ECT) in depressed patients.. Medication-free patients with major depression were randomized to receive right unilateral or bilateral ECT administered with electrical stimulus intensity at either just above seizure threshold or at 150% above seizure threshold. The associations between plasma vasopressin, oxytocin, ECT treatment parameters, clinical outcome, and cognitive effects were assessed.. The sample comprised 55 patients. At the second ECT, patients receiving ECT at 150% above initial seizure threshold had significantly greater increases in plasma vasopressin than patients receiving low-dose ECT (ps < .01-.04), with no effects of electrode placement. At the second and ninth ECT treatments, the vasopressin or oxytocin surges were not associated with clinical improvement, seizure duration, time to orientation, or memory test performance. There were inverse trend-level associations between the acute surge in oxytocin levels at the ninth ECT and clinical response, contradicting a report in the literature.. Overall, these findings do not support the hypothesis that diencephalic seizure propagation is central to the mechanism of action of ECT.

Topics: Cognition; Depressive Disorder; Double-Blind Method; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Vasopressins

The aim of the present study was to evaluate the association of neuro-otological examination, blood tests, and scoring questionnaire data with treatment-resistant intractability of persistent dizziness in Ménière's disease.. We managed 1520 successive vertigo/dizziness patients at the Vertigo/Dizziness Center in Nara Medical University from May 2014 to April 2018. Five hundred and twenty-two patients were diagnosed with Ménière's disease (522/1520; 34.3%) according to the 2015 diagnostic guideline of the International Classification of Vestibular Disorders. Among the patients with Ménière's disease there were 102 with intractable rotatory vertigo attacks for more than 3-6 months (102/522; 19.5%), including 20 bilateral cases (20/102; 19.6%), and 88 with intractable unremitting floating sensation rather than rotatory vertigo attacks for more than 3-6 months (88/522; 16.9%), including 28 bilateral cases (28/88; 31.8%). Sixty out of 88 cases with intractable unremitting floating sensation were unilateral and were enrolled for hospitalization to undergo neuro-otological examinations including pure-tone audiometry (PTA), the caloric test (C-test), vestibular evoked cervical myogenic potentials (cVEMP), subjective visual vertical (SVV) test, glycerol test (G-test), electrocochleogram (ECoG), inner ear magnetic resonance imaging (ieMRI), blood tests including anti-diuretic hormone (ADH) and bone alkaline phosphatase (BAP), and self-rating questionnaires of depression score (SDS). Data are presented as positive (+) ratios of the number of patients with examination and questionnaire data outside of the normal range.. The ratios (+) were as follows: C-test=33.3% (20/60), cVEMP=25.0% (15/60), SVV=50.0% (30/60), G-test=55.0% (33/60), ECoG=63.3% (38/60), ieMRI=86.7% (52/60), ADH=35.0% (21/60), BAP=11.7% (7/60), and SDS=40.0% (24/60). Multivariate regression analysis revealed that the periods of persistent dizziness were significantly longer in unilateral Ménière's patients with C-test(+), SVV(+), and SDS(+) compared with those with negative findings. Additionally, the periods in bilateral cases were significantly longer than those in unilateral ones.. Although approximately 70% of patients with Ménière's disease are usually treatable through the appropriate conservative medical therapy, the presence of canal paresis, gravity-sensitive dysfunction, neurosis/depression, and bilaterality may make the persistent dizziness intractable and may thus require additional treatments.

Topics: Adult; Alkaline Phosphatase; Audiometry, Evoked Response; Audiometry, Pure-Tone; Caloric Tests; Depressive Disorder; Dizziness; Ear, Inner; Female; Gravitation; Humans; Magnetic Resonance Imaging; Male; Meniere Disease; Mental Disorders; Middle Aged; Multivariate Analysis; Regression Analysis; Semicircular Canals; Vasopressins; Vestibular Evoked Myogenic Potentials

Alterations in peripheral sex hormones may play an important role in sex differences in terms of stress responses and mood disorders. It is not yet known whether and how stress-related brain systems and brain sex steroid levels fluctuate in relation to changes in peripheral sex hormone levels, or whether the different sexes show different patterns. We aimed to investigate systematically, in male and female rats, the effect of decreased circulating sex hormone levels following gonadectomy on acute and chronic stress responses, manifested as changes in plasma and hypothalamic sex steroids and hypothalamic stress-related molecules.. Experiment (Exp)-1: Rats (14 males, 14 females) were gonadectomized or sham-operated (intact); Exp-2: gonadectomized and intact rats (28 males, 28 females) were exposed to acute foot shock or no stressor; and Exp-3: gonadectomized and intact rats (32 males, 32 females) were exposed to chronic unpredictable mild stress (CUMS) or no stressor. For all rats, plasma and hypothalamic testosterone (T), estradiol (E2), and the expression of stress-related molecules were determined, including corticotropin-releasing hormone, vasopressin, oxytocin, aromatase, and the receptors for estrogens, androgens, glucocorticoids, and mineralocorticoids.. Surprisingly, no significant correlation was observed in terms of plasma sex hormones, brain sex steroids, and hypothalamic stress-related molecule mRNAs (p > 0.113) in intact or gonadectomized, male or female, rats. Male and female rats, either intact or gonadectomized and exposed to acute or chronic stress, showed different patterns of stress-related molecule changes.. Diminished peripheral sex hormone levels lead to different peripheral and central patterns of change in the stress response systems in male and female rats. This has implications for the choice of models for the study of the different types of mood disorders which also show sex differences.

Topics: Animals; Aromatase; Brain; Corticotropin-Releasing Hormone; Depression; Depressive Disorder; Estradiol; Female; Gonadal Steroid Hormones; Hypothalamus; Male; Orchiectomy; Ovariectomy; Oxytocin; Rats; Rats, Sprague-Dawley; Receptors, Steroid; Sex Characteristics; Sex Factors; Stress, Physiological; Testosterone; Vasopressins

Adolescence is a period of substantial neuroplasticity in stress regulatory neurocircuits. Chronic stress exposure during this period leads to long-lasting changes in neuroendocrine function and emotional behaviors, suggesting adolescence may be a critical period for development of stress vulnerability. This study investigated the effects of exposure to 14 days of chronic variable stress (CVS) in late-adolescent (pnd 45-58) female rats on neuroendocrine function, neuropeptide mRNA expression and depressive-like behavior in adolescence (pnd 59) and in adulthood (pnd 101). Adult females exposed to CVS in adolescence have a blunted hypothalamo-pituitary-adrenocortical (HPA) axis in response to a novel stressor and increased immobility in the forced swim test. Blunted HPA axis responses were accompanied by reduced vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus (PVN), suggesting decreased central drive. Adolescent females tested immediately after CVS did not exhibit differences in stress reactivity or immobility in the forced swim test, despite evidence for enhanced central HPA axis drive (increased CRH mRNA expression in PVN). Overall, our study demonstrates that exposure to chronic stress in adolescence is sufficient to induce lasting changes in neuroendocrine drive and behavior, potentially altering the developmental trajectory of stress circuits as female rats age into adulthood.

Topics: Adrenocorticotropic Hormone; Animals; Corticosterone; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Hypothalamo-Hypophyseal System; Paraventricular Hypothalamic Nucleus; Pituitary Gland; Pituitary-Adrenal System; Pregnancy; Rats; Rats, Sprague-Dawley; Stress, Physiological; Vasopressins

The present study was designed to reveal possible common and specific neuroendocrine mechanisms of depression and anxiety-like states in rodents. Animal models of depression and anxiety (in particular, posttraumatic stress disorder, PTSD) were applied including the learned helplessness and the stress-restress paradigms, respectively. Immunocytochemical staining revealed that depressive- and anxiety-like states in animals were accompanied by the rise in corticotropin-releasing hormone (CRH) immunoreactivity in the parvocellular division of the hypothalamic paraventricular nucleus (PVN). Decrease in vasopressin-immunoreactivity in early period of depressive-like state development was followed by the normalization of vasopressin content in the hypothalamic PVN in delayed period. Increased CRH and vasopressin immunoreactivity in the magnocellular part of the PVN in delayed period of anxiety-like state development was detected only in the stress-restress paradigm. These results suggest that CRH hyperdrive in the parvocellular PVN appears to be a common neuroendocrine abnormality for depressive- and anxiety-like states in animals, while over-expression of CRH and vasopressin in the magnocellular PVN represents a specific feature of anxiety/PTSD-like state.

Topics: Animals; Anxiety Disorders; Corticotropin-Releasing Hormone; Depressive Disorder; Disease Models, Animal; Helplessness, Learned; Immunohistochemistry; Male; Paraventricular Hypothalamic Nucleus; Rats; Rats, Wistar; Restraint, Physical; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

Many psychiatric disorders are a result of a disturbance in or exhaustion of the human stress response system. It is striking that many of these disorders such as depression, anxiety disorders and post-traumatic stress and somatoform and dissociative disorders are more prevalent in women. There are various explanations for this differing prevalence: it can be attributed to molecular, genetic, neurophysiological, relational and neurohormonal differences. Among the topics discussed are differences in exposure to chronic and traumatic stressors, the role of vasopressin and oxytocin in recovery and neurophysiological differences, the differentiating effect of hormones and neuropeptides such as oxytocin and vasopressin, the tend and befriend response and factors such as abuse and attachment disruption in early childhood.

Topics: Anxiety Disorders; Chronic Disease; Depressive Disorder; Dissociative Disorders; Female; Genetic Predisposition to Disease; Humans; Male; Oxytocin; Prevalence; Sex Factors; Stress Disorders, Post-Traumatic; Stress, Psychological; Vasopressins

We investigated the influence of a representative classical benzodiazepine on the regulation of the hypothalamic-pituitary-adrenocortical (HPA) axis activity both under basal conditions and stress. Adult male Wistar rats were intravenously administered with temazepam (0.5, 1, and 3 mg/kg body weight) and plasma concentrations of corticotropin (ACTH) and vasopressin (AVP) were measured in blood samples collected via chronically implanted jugular venous catheters. Simultaneously, the release of AVP within the hypothalamic paraventricular nucleus (PVN) was monitored via microdialysis. Plasma AVP levels remained unaffected by the different treatment conditions. Temazepam blunted the stressor exposure-induced secretion of ACTH in a dose-dependent manner. Concurrently, and also in a dose-dependent manner temazepam enhanced the intra-PVN release of AVP, known to originate from magnocellular neurons of the hypothalamic neurohypophyseal system. Furthermore, temazepam did not affect the in vitro secretion of ACTH from the adenohypophyseal cells. Taken together, the results of this study suggest that temazepam modulates the central nervous regulation of the HPA axis by altering intra-PVN AVP release. An increasingly released AVP of magnocellular origin seems to provide a negative tonus on ACTH secretion most probably via inhibiting the release of ACTH secretagogues from the median eminence into hypophyseal portal blood.

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Animals; Anxiety Disorders; Depressive Disorder; Disease Models, Animal; Dose-Response Relationship, Drug; Extracellular Fluid; GABA Modulators; Hypothalamo-Hypophyseal System; Male; Median Eminence; Microdialysis; Paraventricular Hypothalamic Nucleus; Pituitary Gland; Pituitary-Adrenal System; Rats; Rats, Wistar; Stress, Psychological; Temazepam; Vasopressins

A 71-year old man with failed back syndrome was admitted to hospital with oliguria that had occurred 4 days after his dose of paroxetine had been increased to 40 mg x day(-1). Laboratory data on admission revealed hyponatremia (124 mmol x l(-1)), low serum osmolarity (267 mOsm x l(-1)) with a normal level of serum antidiuretic hormone (1.7 pg x ml(-1)), and concentrated urine (430 mOsm x l(-1)). He was diagnosed as having syndrome of inappropriate secretion of antidiuretic hormone, associated with paroxetine; this drug was discontinued immediately after admission. The hyponatremia was treated with saline infusion, water restriction, and furosemide; serum sodium level returned to normal on hospital day 5. Paroxetine is being increasingly used for depression and chronic pain management because of its favorable side-effect profile; however, we should be alert to hyponatremia in patients on paroxetine by carrying out periodic monitoring of serum electrolytes, especially in elderly patients.

Topics: Aged; Antidepressive Agents, Second-Generation; Chronic Disease; Depressive Disorder; Electrolytes; Humans; Hyponatremia; Inappropriate ADH Syndrome; Intervertebral Disc Displacement; Male; Pain; Paroxetine; Sodium; Spinal Stenosis; Vasopressins

Earlier work has shown that plasma vasopressin levels of depressed patients were higher than those of healthy controls. The aim of the present study was to determine whether plasma vasopressin levels were correlated to parameters of the circadian rhythm. Forty-one patients with major depression and twenty-five controls participated in a case-control design under natural circumstances in a field study to investigate plasma vasopressin levels three times daily, circadian motor activity, and the 24-h periodicity of body temperature for five consecutive 24-h periods. Temperature measurements consisted of at least five, but mostly six or more measurements every 24 h. Twenty-two percent of the patients, but none of the controls lacked 24-h periodicity of body temperature. In melancholic patients increased vasopressin levels in plasma correlated with a weak 24-h periodicity of body temperature. The role of vasopressin is discussed in the light of the present findings.

Topics: Adult; Aged; Body Temperature; Case-Control Studies; Circadian Rhythm; Depressive Disorder; Female; Humans; Male; Middle Aged; Vasopressins

Hyponatremia is an uncommon but widely reported complication of selective serotonin uptake inhibitors (SSRIs), and most of the case reports involve elderly patients. The presentation is usually that of SIADH, but the underlying mechanism leading to the syndrome is poorly understood. Since the use of SSRIs is becoming more popular among elderly depressed patients and because of the potentially serious consequence of hyponatremia, psychiatrists should be alert to the development of the complication and familiarize themselves with its diagnosis and treatment. We report two elderly patients who were identified to have hyponatremia after the commencement of paroxetine. This illustrates the need for monitoring of plasma sodium level if a patient's clinical condition deteriorates. Other factors possibly related to the hyponatremia are discussed and a review of the diagnosis and management of SSRI-related hyponatremia is included.

Topics: Aged; Depressive Disorder; Female; Humans; Hyponatremia; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sodium; Vasopressins

The effect of amitriptyline upon hypothalamic-pituitary-adrenal [HPA]-system-regulating neuropeptides (corticotropin-releasing hormone [CRH], vasopressin, somatostatin) was studied in a group of depressed elderly patients and controls. A first lumbar puncture was performed in 37 depressed in-patients. This was followed by a 6-week medication phase with amitriptyline. Upon its completion a second cerebrospinal fluid (CSF) sample was obtained in 18 of these 37 patients. In 25 healthy controls a first lumbar puncture was done eleven of these individuals agreed to take 75 mg/d amitriptyline for 6 weeks and to participate in the follow-up CSF study. Within the group of depressed patients amitriptyline led to a significant decrease of CSF CRH in treatment responders only (F1, 16 = 5.2; P < 0.02). Also, in normal controls CSF CRH concentration tended to decrease with amitriptyline treatment (t-test; P < 0.09). No effects of amitriptyline upon vasopressin or somatostatin were observed. In normal controls (r = 0.4; P < 0.02) and in patients (r = 0.4; P < 0.03) age correlated positively with baseline CSF somatostatin. A trend for CSF CRH to increase with aging was found only in controls (r = 0.3; P < 0.09); patients did not show a significant association here. Finally, CSF neuropeptide concentration at baseline did not differ between the group of depressed patients and healthy controls. Our study corroborates the evolving concept that antidepressants effect various components of the HPA system with the net result of a reduction in its activity. In addition, we found CSF CRH and CSF somatostatin concentrations to be better reflections of age than of depression and, finally, that during aging and during depression the HPA system changes in similar directions.

Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Antidepressive Agents, Tricyclic; Corticotropin-Releasing Hormone; Depressive Disorder; Female; Humans; Male; Middle Aged; Somatostatin; Vasopressins

The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with neuropsychiatric lupus (NP-SLE) is rare. We report a case of SIADH associated with the new onset of SLE in an 88-yr-old female. The unique features of this case include the extreme age of onset of SLE presenting with neuropsychiatric manifestations and positive antiribosomal P antibody titres. Both the NP manifestations of SLE and SIADH were highly correlated with the SLE disease activity. This case illustrates a novel presentation of NP-SLE with SIADH which may develop due to antibody-mediated hypothalamic dysfunction.

Topics: Aged; Aged, 80 and over; Aldosterone; Antibodies, Antinuclear; Brain; Complement C3; Complement C4; Depressive Disorder; Female; Humans; Hyponatremia; Inappropriate ADH Syndrome; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Protozoan Proteins; Renin; Ribosomal Proteins; Vasopressins

Topics: Depressive Disorder; Humans; Testosterone; Vasopressins

A blunted thyrotropin (TSH) response is a predictor of a good response to antidepressant drug treatment in depressives and neuroleptic treatment in paraphrenic patients (Larger et al 1986). The aim of the following study was to elucidate possible relationships between different endocrine systems and to shed light on the pathogenetic hypotheses of TSH-blunting. In order to evaluate especially hypothalamic activity in severe depression we were interested in the vasopressin system as another hormonal system underlying hypothalamic control. Thirty-four patients who met the criteria for major depression according to DSM-III-R were subjected to the thyrotropin-releasing hormone (TRH) test. We also took baseline readings of the cortisol, neurophysinI (hNpI, reflecting vasopressin plasma levels), and neurophysinII (hNpII, reflecting oxytocin plasma levels) levels. Likelihood ratio tests were done with logistic regression models to analyze the phenomenon of TSH-blunting. We observed that the likelihood of a blunted TSH response increases with higher levels of hNpI and low levels of cortisol, but is unrelated to hNpII levels.

Topics: Adult; Depressive Disorder; Female; Humans; Hydrocortisone; Hypothalamus; Male; Middle Aged; Neurophysins; Oxytocin; Personality Inventory; Reference Values; Thyrotropin; Thyrotropin-Releasing Hormone; Vasopressins

The hypothesis that the release of vasopressin-associated neurophysin (hNpI) or oxytocin-associated neurophysin (hNpII) is modified by a course of electroconvulsive therapy (ECT) was tested by the measurement of serum neurophysins before and after the first and last ECTs given to 17 unipolar depressed patients. Neither basal nor ECT-induced neurophysin release changed between the first and last ECTs. Data from the present study were combined with data from a previous published study to provide a sample of 29 unipolar depressed patients. In this extended sample, the release of hNpII after the first ECT was significantly correlated with improvement in symptoms of depression over a course of ECT as measured by the Hamilton Rating Scale for Depression and the Montgomery-Asberg Depression Rating Scale.

Topics: Adult; Aged; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Vasopressins

Topics: Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Oxytocin; Vasopressins

Basal plasma vasopressin-neurophysin (hNpI) was estimated in 50 drug-free neuropsychiatric patients classified according to the Research Diagnostic Criteria. The hNpI concentration was higher in the 5 manics (0.76 +/- 0.15 ng/ml) than in the 16 schizophrenics (0.53 +/- 0.08), 12 minor depressed (0.54 +/- 0.06) and 17 major depressed (0.48 +/- 0.10; p less than 0.05). Thus, those results confirm our initial observation of an increased vasopressinergic function in the manic compared to the depressed phase in one bipolar patient. Whether this increase in the vasopressin release is a consequence of the neuropsychiatric disorders or initiates and/or participates in their pathophysiology remains to be elucidated. The hypothetic consequence on water metabolism of such an increase remains also to be defined.

Topics: Adolescent; Adult; Bipolar Disorder; Depression; Depressive Disorder; Humans; Middle Aged; Neurophysins; Psychotic Disorders; Schizophrenia; Vasopressins

Topics: Adrenocorticotropic Hormone; Corticotropin-Releasing Hormone; Depressive Disorder; Dexamethasone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Immune Tolerance; Lymphocyte Activation; Pituitary-Adrenal System; Receptors, Glucocorticoid; Vasopressins

Topics: Adrenocorticotropic Hormone; Animals; Circadian Rhythm; Corticotropin-Releasing Hormone; Cushing Syndrome; Depressive Disorder; Drug Synergism; Humans; Hydrocortisone; Peptides; Pro-Opiomelanocortin; Vasopressins

Topics: Arginine Vasopressin; Deamino Arginine Vasopressin; Depressive Disorder; Double-Blind Method; Electroconvulsive Therapy; Humans; Memory; Memory, Short-Term; Mental Recall; Vasopressins; Verbal Learning