pituitrin and Bipolar-Disorder

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

Topics: Adjustment Disorders; Amines; Animals; Bipolar Disorder; Body Temperature; Diuretics; Electroencephalography; Extracellular Space; Humans; Iodine; Kidney; Kinetics; Lithium; Nerve Endings; Norepinephrine; Potassium; Rats; Sodium; Vasopressins; Water

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

We have previously studied the genetics of schizophrenia in a large inbred Arab-Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus harbours four strong candidate genes for schizophrenia: atractin (ATRN), pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this study we further explored the association of these genes with schizophrenia in the pedigree and searched for the disease-causing variants. A mutation screening of affected individuals from the pedigree was performed by using intensive sequencing in these four genes of interest. Then, we studied the prevalence of the identified variants in all family members (n=56) as well as in Arab-Israeli nuclear families (n=276) and a Jewish case-control sample (n=545). We also studied the possible functional role of these variants by examining their association with gene expression in the brain (n=104). We identified seven genetic variants in the OXT-AVP cluster in affected individuals from the pedigree. Three of these variants were significantly associated with schizophrenia in this pedigree. A 7-SNP haplotype was also significantly associated with disease. We found significant association of some of these variants in the two samples from the general population. Expression data analysis showed a possible functional role of two of these variants in regulation of gene expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been suggested in the past. This study demonstrates, for the first time, a significant genetic association of these neuropeptides with schizophrenia and strongly supports this hypothesis.

Topics: Adult; Arabs; Bipolar Disorder; Brain; Case-Control Studies; Cohort Studies; Family; Female; Gene Expression Regulation; Haplotypes; Humans; Israel; Jews; Male; Membrane Proteins; Neurophysins; Oxytocin; Pedigree; Phosphotransferases (Alcohol Group Acceptor); Polymorphism, Single Nucleotide; Prevalence; Protein Precursors; Schizophrenia; Vasopressins

A 39-year-old man was hospitalized after divalproate self-poisoning. He presented coma requiring tracheal intubation and mechanical ventilation at 11 hours and central diabetes insipidus. Serum valproic acid concentration was 590 mg/l at 30 hours. Progressive improvement occurred after hydratation and administration of vasopressin.

Topics: Adult; Bipolar Disorder; Coma; Diabetes Insipidus; Fluid Therapy; Humans; Intubation, Intratracheal; Male; Poisoning; Polyuria; Respiration, Artificial; Suicide, Attempted; Valproic Acid; Vasopressins

Renal and metabolic adverse effects of lithium therapy are illustrated by the case report of a manic depressive woman aged 78 years, so treated for about 25 years. Long term lithium therapy with plasma lithium level in the therapeutic range impairs renal concentrating ability in 25-50% of the patients (when the total ingested amount reaches 100-200 mol, 700-1400 g). About 10-15% of the patients have overt nephrogenic diabetes insipidus (NDI) with elevated antidiuretic hormone plasma level and unresponsiveness to desmopressin. In rats, lithium treatment down regulates expression of the main water channel, aquaporin 2, in the renal collecting duct. NDI may be complicated by hypernatremic dehydration if the access to water is restricted, whatever the cause. Treatment of NID is best started with nonsteroidal antiinflammatory drugs, being then substituted for amiloride. Prolonged lithium therapy may induce chronic interstitial nephritis. In some patients this may result in mild or moderate non progressive chronic renal insufficiency. Acute lithium intoxication (with supratherapeutic doses) may be complicated by acute renal failure (ARF); even in the absence of ARF hemodialysis is indicated when plasma lithium level reaches 4 mmol/l or more. Other metabolic adverse effects of lithium therapy include: hypercalcemia due to hyperparathyroidism (in 5-10% of the patients); hypothyroidism (often latent); hyperthyroidism. In conclusion, these renal and metabolic adverse effects are generally mild or moderate, allowing the continuation of lithium therapy in most affected patients.

Topics: Aged; Animals; Antidepressive Agents; Bipolar Disorder; Blood Proteins; Calcitriol; Calcium; Diabetes Insipidus; Electrolytes; Female; Humans; Lithium Carbonate; Parathyroid Hormone; Phosphates; Rats; Thyrotropin; Time Factors; 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

Levels of vasopressin, somatostatin, neurotensin, vasoactive intestinal peptide, corticotrophin-releasing factor and adrenocorticotrophin in CSF were determined in lithium-treated and unmedicated euthymic bipolar patients and controls, in a search for a trait marker in affective disorder. No group differences in levels of these peptides were found. Highly significant positive correlations were found among these peptides (with the exception of neurotensin), suggesting that their presence in CSF is functionally significant, as opposed to the result of random diffusion from the interstitial space of the brain.

Topics: Adrenocorticotropic Hormone; Bipolar Disorder; Corticotropin-Releasing Hormone; Humans; Lithium; Neuropeptides; Neurotensin; Somatostatin; Vasoactive Intestinal Peptide; Vasopressins

Determinations of the affinity constants (KD) and number of binding sites (Bmax) for platelet vasopressin receptors were done in euthymic bipolar patients and normal volunteers. No significant differences were found between these groups. In addition, lithium treatment did not alter these receptor parameters in the bipolar group.

Topics: Adult; Arginine Vasopressin; Bipolar Disorder; Blood Platelets; Female; Humans; Lithium; Male; Receptors, Cell Surface; Receptors, Vasopressin; Vasopressins

Topics: Aldosterone; Bipolar Disorder; Humans; Hydrocortisone; Periodicity; Potassium; Sodium; Sweat; Vasopressins

Animal studies have revealed two important aspects of vasopressin function which make this peptide a suitable candidate for involvement in complex behavioural syndromes: (1) vasopressin deficiency produces deficits of behaviour which are reversed by vasopressin; (2) well-developed systems exist for the distribution of vasopressin throughout the central nervous system (C.N.S.) via either peptidergic neurons or the cerebrospinal fluid (C.S.F.) and provide the means by which vasopressin may regulate cells controlling behavioural or physiological processes. Among the processes which vasopressin can influence are several of significance in the symptom-complex of affective illness, including alterations in memory, changes in pain sensitivity, synchronisation of biological rhythms, the timing and quality of R.E.M. sleep, and the regulation of fluid and electrolyte balance. In addition, vasopressin is functionally linked to monoamine neurotransmitter systems and, like them, is altered by pharmacological agents which affect mood. Some of the pharmacological and clinical data suggest that vasopressin function is diminished in depression and augmented in mania; sometimes, however, alterations in vasopressin function may be detectable only during crucial periods of the manic-depressive cycle. The hypothesis that vasopressin plays a role in disorders of human behaviour, particularly manic-depressive illness, can now be directly tested by radioimmunoassays of vasopressin in C.S.F. and plasma and by the administration of specific vasopressin analogues and inhibitors.

Topics: Affective Symptoms; Bipolar Disorder; Circadian Rhythm; Deamino Arginine Vasopressin; Depression; Endorphins; Homeostasis; Humans; Memory; Nociceptors; Vasopressins

Topics: Bipolar Disorder; Deamino Arginine Vasopressin; Humans; Vasopressins

Topics: Adult; Aged; Bipolar Disorder; Deamino Arginine Vasopressin; Female; Humans; Lithium; Middle Aged; Polyuria; Thirst; Vasopressins

Among 18 patients receiving prophylactic, long-term lithium treatment for manic-depressive psychosis, a high incidence of increased thirst and frequency of micturition (60-70 per cent) was noted on direct questioning. Symptoms arose at varying times after the start of lithium therapy; in no patient did symptoms antedate the use of the drug. Plasma levels of antidiuretic hormone were found, on average, to be higher than in normal control subjects for a given level of plasma osmolality, although the scatter of results was wide. It is suggested that elevation of antidiuretic hormone occurs as a compensatory mechansims for the polyuria which is a common feature of long-term lithium treatment. The more florid form of nephrogenic diabetes insipidus occasionally seen in lithium takers seems likely to be due to a different mechanism from the more common mild polyuria.

Topics: Arginine Vasopressin; Bipolar Disorder; Female; Humans; Lithium; Male; Osmolar Concentration; Urination; Vasopressins

Interaction between lithium+ and water balance was studied in nine patients suffering manic-depressive trouble. Nephrogenic diabetes insipidus with polyuria and polydipsia was induced by Li+ in one case only. No trouble was apparent in eight cases. However, the applied method of investigation by lacking, and next, excess of water, vasopressin and ADH tests, measurements of urinary osmolarity and clearances, showed up a trouble of concentration in four cases, improved by ADH. The Li+ frequently (50%) induces a trouble of urinary concentration, without polyuria; it is brought to light only by biological investigations. Its origin is double, nephrogenic, which is the most important, and central by a pituitary component. In the other hand, the change in water metabolism, studied by the same tests, showed us a decrease of the clearance Li+ after lacking of water (deshydratation), and an increase after water surcharge. That result is not concordant, chiefly in regards to the water surcharge, with former experiments. It appears that our method (division by horary periods for measurement of clearance, study of circadian cycle of urinary Li+) permits some observations more precise than global gathering and measurement of clearances. That method also allows to make evident a circadian cycle of renal clearance of Li+, according to, for some part, with the renal movement of water. That remark would also have some consequence on lithium-therapy practice.

Topics: Bipolar Disorder; Diabetes Insipidus; Humans; Lithium; Osmolar Concentration; Polyuria; Thirst; Vasopressins; Water-Electrolyte Balance

Topics: Bipolar Disorder; Chlorothiazide; Diabetes Insipidus; Evaluation Studies as Topic; Evoked Potentials; Female; Hospitalization; Humans; Kidney Concentrating Ability; Lithium; Middle Aged; Polyuria; Sodium; Somatosensory Cortex; Vasopressins; Water-Electrolyte Balance

Topics: Amino Acid Metabolism, Inborn Errors; Aspartic Acid; Bipolar Disorder; Catatonia; Circadian Rhythm; Cysteine; Humans; Intellectual Disability; Lithium; Mass Spectrometry; Mental Disorders; Metabolism, Inborn Errors; Periodicity; Phenylketonurias; Sleep; Vasopressins

Topics: Adult; Bipolar Disorder; Diabetes Insipidus; Diuresis; Humans; Hypothalamo-Hypophyseal System; Kidney Concentrating Ability; Lithium; Male; Osmosis; Polyuria; Vasopressins; Water Deprivation

The physiological basis for the polyuria and polydipsia occurring in some manic-depressive patients treated with lithium salts was studied in vivo and in vitro. Three lithium-treated polyuric patients, in whom other causes of a concentrating defect were excluded, had abnormal urinary concentrating abilities after a standard water depreviation test. Two of these patients failed to respond to exogenous vasopressin (ADH) and one had a subnormal response. The abilities of these patients to excrete solute-free water (C(H2O)) was comparable to normal subjects during steady-state water diuresis, suggesting no gross abnormalities in sodium transport. However, each of these patients demonstrated abnormally low capacities to reabsorb solute-free water (T(C) (H2O)) under hydropenic conditions after administration of hypertonic saline and vasopressin. These in vivo findings demonstrate at least a nephrogenic basis for the diabetes insipidus syndrome manifested by these three patients. The defect in water transport was further characterized in toad urinary bladders in vitro. Short-circuit current (I) and water flow (W) were studied under basal, ADH-stimulated, and cyclic adenosine 3',5'-monophosphate (c-AMP)-stimulated conditions. Increasing mucosal [Li(+)] progressively inhibited basal I, and both I and W induced by ADH. Significant inhibition of basal and ADH-induced I was observed at mucosal [Li(+)] < 1.1 mEq/liter, and of ADH-induced W at mucosal [Li(+)] = 11 mEq/liter. On the other hand, at these lithium concentrations, neither c-AMP-stimulated W nor I was inhibited. Increasing serosal [Li(+)] produced significant inhibition of basal I only at [Li(+)] at least 50-fold greater than at the mucosal (urinary) surface. These in vitro studies confirm that mucosal lithium inhibits the action of ADH, but not c-AMP. Hence, lithium appears to be a significant inhibitor of ADH-stimulated water flow, probably acts from the urinary surface, and appears to exert its effect at a site biochemically proximal to c-AMP action.

Topics: Adult; Animals; Anura; Biological Transport, Active; Bipolar Disorder; Cyclic AMP; Diabetes Insipidus; Drinking Behavior; Humans; In Vitro Techniques; Kidney; Kidney Concentrating Ability; Lithium; Male; Membrane Potentials; Middle Aged; Osmolar Concentration; Polyuria; Sodium; Urinary Bladder; Vasopressins; Water-Electrolyte Balance

Topics: Bipolar Disorder; Cyclic AMP; Humans; Kidney; Lithium; Vasopressins

The transmucosal potential difference across the rectal mucosa was measured in 30 healthy subjects and in 13 psychiatric patients on lithium treatment for manic-depressive psychosis. It was significantly greater in the lithium-treated patients. A highly significant correlation was found between the potential difference and the serum lithium, and in all eight patients in whom it was measured before and one week after starting lithium treatment a rising potential difference was found. This phenomenon may possibly be explained in terms of resistance of the rectal mucosa to vasopressin.

Topics: Bipolar Disorder; Drug Resistance; Humans; Intestinal Mucosa; Lithium; Membrane Potentials; Rectum; Stimulation, Chemical; Time Factors; Vasopressins

Topics: Adult; Bipolar Disorder; Carbonates; Humans; Kidney Concentrating Ability; Lithium; Male; Middle Aged; Osmolar Concentration; Polyuria; Thirst; Time Factors; Vasopressins; Water Deprivation

Topics: Animals; Bipolar Disorder; Diabetes Insipidus; Female; Humans; Kidney Concentrating Ability; Lithium; Middle Aged; Rats; Vasopressins

Topics: Bipolar Disorder; Depression; Epilepsy; Estrogens; Female; Humans; Hydantoins; Intellectual Disability; Mental Disorders; Mentally Ill Persons; Nitrates; Potassium; Premenstrual Syndrome; Progesterone; Schizophrenia; Thyroid Hormones; Tranquilizing Agents; Vasopressins