pituitrin and Psychotic-Disorders

Novel molecular genetic approaches, at genome-scale in different species allowed characterizing genes that have undergone recent selection. The interest in this research field is not limited to the natural curiosity about our evolutionary past, but it is also to identify novel susceptibility genes for neuropsychiatic disorders by pointing specific human traits, such as behavioral and cognitive abilities. Hypotheses have been proposed to relate specific psychiatric disorders to the origin of modern humans, as evidenced by the theory of Crow about schizophrenia. In the present review, we will focus on genes that underwent positive selection in humans or displayed a human specific evolutionary pattern and which were reported as associated with psychiatric disorders. This will include the (1) DRD4 gene associated with attentiondeficit/ hyperactivity disorder, located in a locus that underwent a positive selection; the (2) GABRB2 gene, a gene associated with schizophrenia and recently reported as the target of a positive selection; (3) MARK1, a candidate gene for autism that was reported as displaying a signature of adaptative evolution in the human lineage, and (4) the ADH and ALDH2 genes which are associated with alcoholism, and for which evidence of positive selection was identified in the human lineage since the divergence between humans and chimpanzees. Identification of novel candidate genes based on recent evolution selection, coupled to genome-wide strategies designed to detect rare structural variants, could lead to a better knowledge of the molecular mechanisms of neurodevelopmental disorders and might therefore help to develop new medical chemistry.

Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Animals; Antipsychotic Agents; Drug Discovery; Evolution, Molecular; Humans; Neurophysins; Primates; Protein Precursors; Protein Serine-Threonine Kinases; Psychotic Disorders; Receptors, Dopamine D4; Receptors, GABA-A; RNA Interference; Vasopressins

Topics: Adaptation, Psychological; Appetite; Biological Evolution; Blood Pressure; Body Temperature Regulation; Brain; Carboxypeptidases; Cell Count; Central Nervous System Diseases; Chemical Phenomena; Chemistry, Physical; Chromaffin Granules; Dissection; Electrophysiology; Histocytochemistry; Humans; Immunochemistry; Learning; Memory; Nerve Tissue Proteins; Neural Pathways; Neuroanatomy; Pain; Peptides; Psychotic Disorders; Radioimmunoassay; Receptors, Cell Surface; Stereotaxic Techniques; Tissue Distribution; Vasopressins

Topics: Adrenal Cortex Hormones; Androgens; Animals; Biological Clocks; Catatonia; Catecholamines; Circadian Rhythm; Electroencephalography; Estrogens; Female; History, 19th Century; History, 20th Century; Humans; Light; Lithium; Menstruation; Psychotic Disorders; Sexual Behavior, Animal; Thyroid Gland; Vasopressins

The effect of lithium on the urine concentrating response to antidiuretic hormone (ADH) and the excretion of ADH has been studied in rats and man. The maximum urine osmolarity following 18 h dehydration and Pitressin (5 u) was decreased in three out of four patients during lithium treatment compared to their response to the same test in the absence of lithium. In a fifth patient, tested only during lithium treatment, the urine remained hypotonic to plasma throughout this test. Lithium increased the excretion of ADH in non-polyuric patients from 9-22 mu/24 h in the absence of lithium to 36-202 mu/24 - during lithium treatment. In four patients with lithium-induced polyuria, a diuretic acting on the distal tubules, clorexolone, reduced the polyuria. Lithium increased urine volume and the excretion of ADH in four rats receiving lithium in their diet. The response to exogenous ADH was decreased during lithium administration.

Topics: Animals; Clinical Trials as Topic; Deamino Arginine Vasopressin; Dose-Response Relationship, Drug; Humans; Kidney Concentrating Ability; Lithium; Polyuria; Psychotic Disorders; Rats; Vasopressins

Psychosis refers to a mental health condition characterized by a loss of touch with reality, comprising delusions, hallucinations, disorganized thought, disorganized behavior, catatonia, and negative symptoms. A first-episode psychosis (FEP) is a rare condition that can trigger adverse outcomes both for the mother and newborn. Previously, we demonstrated the existence of histopathological changes in the placenta of pregnant women who suffer an FEP in pregnancy. Altered levels of oxytocin (OXT) and vasopressin (AVP) have been detected in patients who manifested an FEP, whereas abnormal placental expression of these hormones and their receptors (OXTR and AVPR1A) has been proven in different obstetric complications. However, the precise role and expression of these components in the placenta of women after an FEP have not been studied yet. Thus, the purpose of the present study was to analyze the gene and protein expression, using RT-qPCR and immunohistochemistry (IHC), of OXT, OXTR, AVP, and AVPR1a in the placental tissue of pregnant women after an FEP in comparison to pregnant women without any health complication (HC-PW). Our results showed increased gene and protein expression of OXT, AVP, OXTR, and AVPR1A in the placental tissue of pregnant women who suffer an FEP. Therefore, our study suggests that an FEP during pregnancy may be associated with an abnormal paracrine/endocrine activity of the placenta, which can negatively affect the maternofetal wellbeing. Nevertheless, additional research is required to validate our findings and ascertain any potential implications of the observed alterations.

Topics: Female; Humans; Infant, Newborn; Oxytocin; Placenta; Pregnancy; Psychotic Disorders; Receptors, Oxytocin; Vasopressins

Few studies have addressed likely gene × gene (ie, epistatic) interactions in mediating risk for schizophrenia. Using a preclinical genetic approach, we investigated whether simultaneous disruption of the risk factors Neuregulin-1 (NRG1) and Disrupted-in-schizophrenia 1 (DISC1) would produce a disease-relevant phenotypic profile different from that observed following disruption to either gene alone. NRG1 heterozygotes exhibited hyperactivity and disruption to prepulse inhibition, both reversed by antipsychotic treatment, and accompanied by reduced striatal dopamine D2 receptor protein expression, impaired social cognition, and altered glutamatergic synaptic protein expression in selected brain areas. Single gene DISC1 mutants demonstrated a disruption in social cognition and nest-building, altered brain 5-hydroxytryptamine levels and hippocampal ErbB4 expression, and decreased cortical expression of the schizophrenia-associated microRNA miR-29b. Co-disruption of DISC1 and NRG1, indicative of epistasis, evoked an impairment in sociability and enhanced self-grooming, accompanied by changes in hypothalamic oxytocin/vasopressin gene expression. The findings indicate specific behavioral correlates and underlying cellular pathways downstream of main effects of DNA variation in the schizophrenia-associated genes NRG1 and DISC1.

Topics: Amphetamines; Animals; Behavior, Animal; Brain; Disease Models, Animal; Endophenotypes; Epistasis, Genetic; Female; Grooming; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Nesting Behavior; Neuregulin-1; Oxytocin; Prepulse Inhibition; Psychomotor Agitation; Psychotic Disorders; Schizophrenia; Social Behavior; Vasopressins

In women with chronic schizophrenia, higher levels of peripheral oxytocin have been associated with lower levels of positive but not negative symptoms. Sex-specific associations between endogenous levels of oxytocin (OT) and arginine vasopressin (AVP) with clinical symptoms and cognition in untreated early course patients have not been examined.. Clinical ratings and neuropsychological testing were performed in thirty-eight acutely ill, unmedicated first-episode schizophrenia patients (14 women, 24 men). Serum hormone assays were obtained in patients and thirty-eight demographically similar healthy controls.. Patients demonstrated increased AVP levels compared to controls (p = 0.01). Higher AVP levels were associated with greater positive symptoms (r = 0.58, p = 0.03) and worse verbal learning (r = -0.63, p = 0.02) in female, but not male, patients. OT levels did not statistically differ between patients and controls, and were unrelated to clinical symptoms or cognition in patients.. Results suggest an association of endogenous AVP with increased positive symptom severity and worse cognition in untreated female, but not male, schizophrenia patients. Findings support the role of neuroendocrine alterations in acute psychosis and the importance of examining sex-specific neuroendocrine alterations early in the course of schizophrenia.

Topics: Acute Disease; Adolescent; Adult; Analysis of Variance; Female; Humans; Learning Disabilities; Linear Models; Male; Neuropsychological Tests; Oxytocin; Psychiatric Status Rating Scales; Psychotic Disorders; Sex Characteristics; Vasopressins; Verbal Learning; Young Adult

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: Atrial Natriuretic Factor; Diuresis; Humans; Hyponatremia; Psychotic Disorders; Vasopressins

Water intoxication is a serious problem in many patients with chronic psychiatric illness. In an effort to determine the mechanism of this disorder, we investigated the osmoregulation of water intake and antidiuretic function in psychiatric patients with polydipsia and hyponatremia and in matched controls with psychiatric illness but neither polydipsia nor hyponatremia. We found that a water load suppressed plasma osmolality and vasopressin and urine osmolality in both groups, but that urinary dilution and free water clearance were impaired in the patients with hyponatremia, even though plasma levels of vasopressin and solute clearance were similar in the two groups. Moreover, during water loading and infusion of hypertonic saline, the plasma level of vasopressin was higher at any given plasma osmolality in the test patients than in the controls, indicating a downward resetting of the osmostat. Patients' estimates of the amount of water they desired were shown to correlate significantly with the amount of water consumed and, at any given level of plasma osmolality, appeared to be higher in the test patients than in the controls. We conclude that psychiatric patients with polydipsia and hyponatremia have unexplained defects in urinary dilution, the osmoregulation of water intake, and the secretion of vasopressin.

Topics: Adult; Body Water; Drinking; Female; Humans; Hyponatremia; Kidney Concentrating Ability; Male; Osmolar Concentration; Psychotic Disorders; Urine; Vasopressins; Water-Electrolyte Balance

A case of tuberculous Addison's disease presenting with psychosis, profound hyponatraemia, and detectable plasma antidiuretic hormone is reported. Clinical and biochemical improvement after corticosteroid replacement was followed by relapse with further psychosis and inappropriate antidiuretic hormone secretion: both were promptly reversed by demethylchlortetracycline. The association of psychological symptoms with Addison's disease, the role of anti-diuretic hormone secretion in Addison's disease, and the inter-relationship between Addison's disease, psychosis and anti-diuretic hormone secretion are discussed.

Topics: Addison Disease; Body Weight; Demeclocycline; Fludrocortisone; Humans; Hydrocortisone; Inappropriate ADH Syndrome; Male; Middle Aged; Psychotic Disorders; Vasopressins; Water Intoxication

Topics: Humans; Psychotic Disorders; Vasopressins

We have reviewed 14 cases of water intoxication in psychiatric patients. In these cases the possibility of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected or diagnosed. The SIADH should be suspected in psychotic patients who drink water excessively, develop seizures, disorientation and deterioration of mental status.

Topics: Adult; Compulsive Behavior; Drinking; Female; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Neurocognitive Disorders; Psychotic Disorders; Psychotropic Drugs; Sodium; Vasopressins; Water Intoxication

Plasma antidiuretic hormone (ADH) measured by radioimmunoassay was higher in acutely psychotic subjects than in acutely anxious nonpsychotic subjects or normal subjects. ADH was not elevated in acutely anxious nonpsychotic subjects. ADH was positively correlated with degree of psychosis. Normal osmolar and volume regulatory mechanisms did not seem responsible for the ADH elevations in the psychotic subjects. Because ADH is both produced in the hypothalamus and can be accurately measured in blood, this substance may prove particularly valuable in the study of psychiatric disorders.

Topics: Anxiety; Humans; Osmolar Concentration; Pilot Projects; Psychiatric Status Rating Scales; Psychotic Disorders; Radioimmunoassay; Sodium; Vasopressins

A review of the literature and the three presented cases indicate that multiple factors are often involved in the development of water intoxication in the psychotic. Although the syndrome of inappropriate secretion of antidiuretic hormones (SIADH) is one of these factors, it is usually associated with other causes of the SIADH. Evidence is lacking that the SIADH is an essential feature of a psychotic illness.

Topics: Delusions; Drinking Behavior; Fluphenazine; Humans; Hydrochlorothiazide; Male; Middle Aged; Psychotic Disorders; Sodium; Vasopressins; Water Intoxication

The authors describe three postmenopausal women with agitated psychotic depression, increased water ingestion, and electrolyte values consistent with the syndrome of inappropriate antidiuretic hormone (ADH) secretion. They hypothesize that this clinical triad represents a syndrome reflecting underlying dysfunction of the hypothalamus and limbic system of the brain. The diagnosis of inappropriate ADH in one of the patients was directly confirmed by a recently developed serum radioimmunoassay.

Topics: Acute Disease; Adult; Drinking; Female; Humans; Hypothalamus; Limbic System; Middle Aged; Psychotic Disorders; Radioimmunoassay; Syndrome; Vasopressins

Topics: Diabetes Insipidus; Diabetes Insipidus, Neurogenic; Diagnosis, Differential; Humans; Infusions, Parenteral; Pharmacology; Psychotic Disorders; Sodium Chloride; Thirst; Vasopressins; Water

Topics: Blood Pressure; Blood Pressure Determination; Humans; Pharmaceutical Preparations; Psychotic Disorders; Vasopressins