oxytocin 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

Hippocrates attributed women's high emotionality - hysteria - to a 'wandering womb'. Although hysteria diagnoses were abandoned along with the notion that displaced wombs cause emotional disturbance, recent research suggests that elevated levels of oxytocin occur in both bipolar disorder and endometriosis, a gynecological condition involving migration of endometrial tissue beyond the uterus. We propose and evaluate the hypothesis that elevated oxytocinergic system activity jointly contributes to bipolar disorder and endometriosis. First, we provide relevant background on endometriosis and bipolar disorder, and then we examine evidence for comorbidity between these conditions. We next: (1) review oxytocin's associations with personality traits, especially extraversion and openness, and how they overlap with bipolar spectrum traits; (2) describe evidence for higher oxytocinergic activity in both endometriosis and bipolar disorder; (3) examine altered hypothalamic-pituitary-gonadal axis functioning in both conditions; (4) describe data showing that medications that treat one condition can improve symptoms of the other; (5) discuss fitness-related impacts of endometriosis and bipolar disorder; and (6) review a pair of conditions, polycystic ovary syndrome and autism, that show evidence of involving reduced oxytocinergic activity, in direct contrast to endometriosis and bipolar disorder. Considered together, the bipolar spectrum and endometriosis appear to involve dysregulated high extremes of normally adaptive pleiotropy in the female oxytocin system, whereby elevated levels of oxytocinergic activity coordinate outgoing sociality with heightened fertility, apparently characterizing, overall, a faster life history. These findings should prompt a re-examination of how mind-body interactions, and the pleiotropic endocrine systems that underlie them, contribute to health and disease.

Topics: Adult; Bipolar Disorder; Endometriosis; Female; Humans; Oxytocin; Pelvic Floor Disorders; Peritoneal Diseases; Personality; Social Behavior

There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.

Topics: Animals; Bipolar Disorder; Humans; Metabolic Syndrome; Oxytocin; Psychotic Disorders; Schizophrenia; Treatment Outcome

We aimed to compare neuropeptide levels between patients with major psychiatric disorders and healthy controls and examine their association with symptoms and cognitive function.. The participants were 149 patients with schizophrenia, 115 patients with bipolar disorder (BD), 186 unremitted patients with major depressive disorder (MDD), and 350 healthy controls. Psychiatric (schizophrenic, manic, and depressive) symptoms, sleep state, and cognitive (premorbid intelligence quotient, general cognitive, and memory) functions were evaluated. A multiplex immunoassay kit was used to measure cerebrospinal fluid (CSF) and plasma α-melanocyte-stimulating hormone (MSH), β-endorphin, neurotensin, oxytocin, and substance P levels.. The verification assay revealed that CSF α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were too low to be reliably measured, while plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels could be successfully measured. Plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were not significantly different between patients with schizophrenia, BD, or MDD and healthy controls. Plasma α-MSH, β-endorphin, neurotensin, oxytocin, and substance P levels were not significantly correlated with psychiatric symptom scores in patients with schizophrenia, BD, or MDD and cognitive function scores in patients or healthy controls.. Our data suggest that plasma neuropeptide levels do not elucidate the involvement of neuropeptides in the pathology of schizophrenia, BD, or MDD.

Topics: alpha-MSH; beta-Endorphin; Bipolar Disorder; Depressive Disorder, Major; Humans; Immunoassay; Neurotensin; Oxytocin; Schizophrenia; Substance P

The aim of this study was to evaluate serum heat shock protein 70 (HSP70) and oxytocin levels, attachment and perceived social support levels in adolescents with parental bipolar disorder (BD) and Schizophrenia (SCZ).. This study included 9 adolescents with SCZ parents, 30 adolescents with BD parents and 31 healthy adolescents. Brief Symptom Inventory (BSI), Relationship Scale Questionnaire-Adolescent Form (RSQ-A) and Multidimensional Scale of Perceived Social Support (MSPSS) were administered to all participants. In addition, serum HSP-70 and oxytocin levels were evaluated.. There was no significant difference between the groups in terms of attachment style, psychiatric symptoms and perceived social support. Serum HSP-70 levels were found to be lower in adolescents whose parents had BD. Serum oxytocin levels of the SCZ group were significantly lower than those of the BD group.. HSP-70 level was found to be lower in adolescents with BD parents. Oxytocin level was found to be lower in adolescents with SCZ parents. These findings suggest that HSP-70 and oxytocin may be a marker of early life stress in adolescents with parental psychopathology. However, studies are needed to evaluate the relationship between attachment, oxytocin and HSP-70 in adolescents exposed to parental psychopathology in early life.

Topics: Adolescent; Bipolar Disorder; HSP70 Heat-Shock Proteins; Humans; Oxytocin; Parents; Schizophrenia

Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice.. Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls.. Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way.. Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD.. National Natural Science Foundation of China (81971268, 82101592).

Topics: Animals; Bipolar Disorder; Corticotropin-Releasing Hormone; Depressive Disorder, Major; Female; Male; Mice; Oxytocin; RNA, Messenger

The oxytocin (OXT) and dopamine systems synergistically facilitate striatal reactivity. Abnormal striatal activation has repeatedly been observed in patients with bipolar disorder (BD); however, such abnormality remains unclear in BD II. Here we aimed to investigate whether the corticostriatal connectivity was altered and the possible relationships among corticostriatal connectivity, OXT, and dopamine systems in BD II. Twenty-five BD II patients, as defined by the DSM-V, and 29 healthy controls (HC) were enrolled in this study. Plasma OXT was measured and striatal dopamine transporter (DAT) availability was assessed using [

Topics: Bipolar Disorder; Brain; Dopamine; Humans; Magnetic Resonance Imaging; Oxytocin

Many single nucleotide polymorphisms (SNPs) have been identified for Bipolar disorder (BD), but association between SNPs and BD can vary depending on the population tested. SNPs rs10994336 and rs9804190 in ANK3 and rs1006737 in CACNA1C have emerged as the most highly replicated SNPs significantly associated with BD. The aim of the present study was to assess the association of these SNPs with BD in the Pakistani population, which has never before been examined. A total of 120 BD and 120 control individuals from Pakistan were examined in this analysis. Genotyping results indicated that rs1006737 in CACNA1C was significantly associated with BD, while rs10994336 or rs9804190 in ANK3 was not significant when examined individually. However, risk score assessment found that the presence of two or more risk alleles was significantly associated with disease, indicating that risk alleles from ANK3 and CACNA1C may additively contribute to BD. A protein-protein interaction network was generated using STRING to probe the relationship between ANK3 and CACNA1C interactors and their associations with BD. While none of the interactors are directly linked to BD, they play a role in pathways linked to BD, including oxytocin and dopamine signaling pathways. Collectively, these results reveal a significant association of CACNA1C with BD among the Pakistani population, extending results from other ethnic groups to the Pakistani population for the first time.

Topics: Adult; Alleles; Ankyrins; Bipolar Disorder; Calcium Channels, L-Type; Case-Control Studies; Dopamine; Ethnicity; Female; Genetic Predisposition to Disease; Genotyping Techniques; Humans; Male; Oxytocin; Pakistan; Polymorphism, Single Nucleotide; Protein Binding; Signal Transduction

There is growing interest in oxytocin as a putative treatment for various psychiatric disorders including major depressive disorder, bipolar disorder and schizophrenia/schizoaffective disorder. However, potential alterations in the endogenous brain oxytocin system in these disorders are poorly characterized. Brain expression of oxytocin and its receptor genes in patients with these psychiatric disorders has not been well studied outside the hypothalamus. We measured expression of mRNA for oxytocin and its receptor in the dorsolateral prefrontal cortex of postmortem brains using quantitative polymerase chain reaction in a total of 581 individuals. These individuals either were diagnosed with major depressive disorder (n = 135), bipolar disorder (n = 57), schizophrenia/schizoaffective disorder (n = 169), or were control subjects, defined as individuals with no lifetime history of any of these disorders (n = 220). Diagnoses of major depressive disorder and bipolar disorder were associated with significantly increased oxytocin receptor mRNA levels in the dorsolateral prefrontal cortex. This finding is discussed in light of the extant literature on the dysregulation of oxytocin signaling in individuals with major psychiatric disorders.

Topics: Adult; Autopsy; Bipolar Disorder; Brain; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Male; Middle Aged; Oxytocin; Prefrontal Cortex; Psychotic Disorders; Receptors, Oxytocin; RNA, Messenger; Schizophrenia

Oxytocin may play a role in mood regulation. Research has shown the plasma oxytocin level of patients with bipolar I disorder (BD I) during a manic episode was significantly higher than that of BD I patients of other statuses, and also that of healthy subjects. However, whether or not a difference in the level of oxytocin exists between patients with major depressive disorder (MDD) and those with BD II is unclear. This study aimed to investigate the plasma oxytocin levels in MDD and BD II patients in a depressive episode. 119 healthy controls, 135 BD II patients, and 97 MDD patients were enrolled. All of the BD II and MDD patients were drug-naïve, with baseline depressive status 17-item Hamilton Depression Rating Scale scores >15. The plasma oxytocin level of the BD II patients was significantly higher than that of the MDD patients and controls at baseline. After treatment, the plasma oxytocin level of the BD II patients increased significantly; however, in the MDD group, the oxytocin level decreased slightly after treatment. Our findings suggested more significant plasma oxytocin dysregulation in the patients in the BD II group than in the MDD patients and controls, both before and after treatment.

Topics: Adult; Affect; Bipolar Disorder; Depression; Depressive Disorder, Major; Female; Humans; Male; Oxytocin; Psychiatric Status Rating Scales

Neuroendocrine biomarkers have long been studied in the context of electroconvulsive therapy (ECT). We prospectively assessed serum oxytocin change and moderators thereof in an exploratory study of patients receiving ECT.. Serum oxytocin concentrations were assessed immediately before and 1 to 3 minutes after the first ECT in 33 patients with schizophrenia (n = 14), other nonaffective psychosis (n = 6), mania (n = 10), and depression (n = 3) who received 6 to 7 bitemporal, brief-pulse ECTs. Change in serum oxytocin was assessed in the sample as a whole, and as a function of age, sex, diagnosis, and treatment response. The primary outcome was change in serum oxytocin in the overall sample.. There was much variation across patients; oxytocin concentrations increased marginally by a mean (standard deviation) (M [SD]) of 6.4 (82.7) pg/mL (P = 0.43). The M (SD) change was -8.2 (85.0) pg/mL in patients with schizophrenia and other nonaffective psychoses (P = 0.84). There was no significant correlation between change in Brief Psychiatric Rating Scale scores and change in oxytocin concentrations in patients with schizophrenia, other nonaffective psychoses, and mania (ρ = 0.10, P = 0.61). Serum oxytocin rose in men, after ECT, and fell in women (P = 0.01).. Change in serum oxytocin immediately after the first ECT in a course may not be a useful biomarker of ECT action. This is the first report on the subject in a sample comprising mostly patients with nonaffective psychosis and mania rather than depression. We discuss our findings in the light of previous research and offer general conclusions about the field.

Topics: Adolescent; Adult; Age Factors; Aged; Biomarkers; Bipolar Disorder; Depressive Disorder, Major; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Oxytocin; Prospective Studies; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Sex Factors; Treatment Outcome; Young Adult

We tested the hypothesis that perinatal oxytocin, given to pregnant women to induce labor, is related to offspring bipolar disorder (BP) and worse childhood cognitive performance among offspring. We also tested the association between childhood cognition and later BP.. A population-based birth cohort derived from the Child Health and Development Study (CHDS) which included nearly all pregnant women receiving obstetric care from the Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) between 1959 and 1966. Prospectively obtained medical and offspring cognitive performance were used. Potential cases with BP from the cohort were identified by database linkages. This protocol identified 94 cases who were matched 1:8 to controls.. Perinatal oxytocin was associated with a 2.4 times increased odds of later BP. Oxytocin was also associated with decreased performance on the Raven Matrices, but not on the Peabody Picture Vocabulary Test (PPVT). Childhood cognition was not associated with later BP.. Loss to follow-up must be considered in all birth cohort studies. In addition, the childhood cognitive battery did not include tests related to multiple domains of cognition which have been associated with later BP. A third limitation is the modest sample size of those exposed to oxytocin.. This study provides evidence for a potentially important perinatal risk factor for BP and cognitive impairment in childhood. While the association between perinatal oxytocin and offspring BP must be viewed cautiously until further studies can attempt to replicate the result, it lends support to the broader view that neurodevelopmental factors contribute to BP.

Topics: Administration, Intranasal; Adult; Bipolar Disorder; Case-Control Studies; Child; Cognition; Cognition Disorders; Female; Humans; Intelligence Tests; Oxytocics; Oxytocin; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors; Young Adult

There is evidence to suggest that oxytocin is effective in stabilizing mood in humans. Lower plasma oxytocin levels have been reported in patients with major depression. The objective of this study was to investigate serum oxytocin levels during manic and depressive episodes and in the remission period in patients with bipolar disorder. Twenty-two patients in manic episode, 21 in depressive episode, and 24 in remission at the initial phase, ranging from 18 to 65 years of age, who were diagnosed with BD Type I and 24 healthy individuals were included in this study. Blood samples were collected from subjects in the morning at the beginning of the study. A second blood sampling was obtained from manic and depressive patients after response to treatment. MANCOVA was performed to compare the oxytocin values of the groups. The serum oxytocin levels of patients in manic episode were statistically significantly higher than those of the depressive episode and remission groups and of the healthy subjects. The serum oxytocin levels of patients in the depressive episode group and in the remission group were statistically significantly higher than those of the control group. The serum oxytocin levels of the manic episode and depressive episode patients after response to treatment were statistically significantly higher than those of the control group, and there was no statistically significant difference between the patient groups in serum oxytocin levels. The higher oxytocin levels observed in patient groups, compared to the controls, before and after response to treatment suggest that oxytocin may be a trait marker in BD.

Topics: Adolescent; Adult; Aged; Biomarkers; Bipolar Disorder; Body Mass Index; Depression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Oxytocin; Psychiatric Status Rating Scales; Smoking; Socioeconomic Factors; Young Adult

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

We studied the concentration of neurophysin I (hNPI) and II (hNPII), the hypothalamo-pituitary carriers of vasopressin and oxytocin, in CSF of depressed and schizophrenic patients and age matched controls. Mean hNPI values were lower and mean hNPII values greater in schizophrenics than in controls. Lower hNPI values were observed in unipolar patients than in controls. In bipolar patients however, higher hNPI values were present. Significantly higher hNPII values were observed in bipolar patients than in controls; no difference was present between unipolars and controls. A positive correlation was observed with age in controls and bipolars for hNPII. These data emphasize the interest of studying the neurohypophysal function in affective illness and in schizophrenia.

Topics: Adult; Aged; Arginine Vasopressin; Bipolar Disorder; Depressive Disorder; Female; Humans; Male; Middle Aged; Neurophysins; Oxytocin; Schizophrenia

Topics: Affective Disorders, Psychotic; Bipolar Disorder; Cystinyl Aminopeptidase; Female; Humans; Neurophysins; Oxytocin; Pregnancy; Puerperal Disorders