oxytocin and Cognition-Disorders

Schizophrenia is a disabling, heterogeneous disorder with clinical features that can be parsed into three domains: positive symptoms, negative symptoms, and cognitive deficits. Current antipsychotic drugs produce fairly robust clinical benefit against positive symptoms but typically have minimal therapeutic effects on negative symptoms and cognitive deficits. Oxytocin (OT) is a nonapeptide that, in addition to its role as a hormone regulating peripheral reproductive-relevant functions, acts as a neurotransmitter in the brain. Several lines of preclinical and clinical research suggest that the OT system may play a role in regulating the expression of schizophrenia spectrum disorders and that targeting the central OT system may yield novel treatments to address these symptoms. In this review, we summarize the extant preclinical and clinical evidence relevant to the role of OT in schizophrenia with particular emphasis on its putative therapeutic effects on each of the three above-mentioned clinical domains.

Topics: Animals; Brain; Cognition; Cognition Disorders; Disease Models, Animal; Humans; Oxytocin; Schizophrenia; Schizophrenic Psychology

Schizophrenia is a heterogeneous, debilitating disorder characterized by three distinct sets of clinical features: positive symptoms, negative symptoms, and cognitive deficits. Extant antipsychotic drugs have been most successful at treating the positive symptoms of patients with schizophrenia but have minimal therapeutic effects on negative symptoms and cognitive deficits, which are the symptoms that best predict the poor prognosis of these patients. Therefore, there has been a major effort towards identifying compounds that alleviate these symptoms. Oxytocin (OT) is a nonapeptide that regulates peripheral reproductive-relevant functions, and also acts as a neurotransmitter in the brain. Converging evidence from both preclinical and clinical research suggests that OT may have therapeutic efficacy for the positive symptoms, negative symptoms, and cognitive deficits of schizophrenia. In the majority of the small, randomized, placebo-controlled clinical trials conducted to date, OT has shown particular promise in its potential to treat the intractable negative symptoms and social cognitive deficits exhibited by most of the patients with this debilitating disorder. In this leading article, we summarize the clinical evidence relevant to (1) endogenous OT and schizophrenia, and (2) the putative therapeutic effects of OT on each of the three clinical domains.

Topics: Animals; Antipsychotic Agents; Brain; Cognition Disorders; Humans; Oxytocin; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology

Oxytocin is a nonapeptide mammalian hormone, best known for its role in childbirth, parturition and lactation. It has been implicated in the control of social behaviors and relationships, such as monogamy or promiscuous behaviors. The putative involvement of oxytocin in schizophrenia was first postulated following several pioneer reports of oxytocin use in schizophrenia and observations of increased oxytocin levels in the cerebrospinal fluid of schizophrenic patients, although this latter finding has subsequently been challenged. More recently, oxytocin plasma levels have been found to be decreased in schizophrenic individuals, particularly in those exhibiting hyponatremic polydipsia and emotional dysregulation. Some authors report that intranasal oxytocin administration to schizophrenic patients may reduce symptomatology. The aim of the present paper was to review studies investigating symptomatology, social cognition and emotion recognition changes in DSM-IV-TR schizophrenic patients, after administration of intranasal oxytocin at different doses. Literature search was conducted in March, 2012. PubMed and Scopus databases were used to find studies for inclusion in the systematic review. Oxytocin may represent an important novel adjunctive treatment for patients with schizophrenia. However, some limitations of current studies cannot be overlooked and further investigations are certainly needed.

Topics: Administration, Intranasal; Animals; Cognition Disorders; Humans; Interpersonal Relations; Oxytocin; Schizophrenia

Only few substances have achieved such a great prominence in recent years as the hypothalamic neuropeptide oxytocin, which is also widely known as the love hormone. Oxytocin is a potent neuromodulator which can improve social cognitive functions including empathy, trust, cooperation and social learning. However, oxytocin can also promote negative social behavior and increase poor memory and feelings of fear in social situations. Positive data from initial clinical trials give rise to the hope that oxytocin will prove to be a substance which is suitable for targeted treatment of poor social-cognitive behavior in neuropsychiatric diseases. This review article summarizes the most important recent preclinical and clinical human studies and discusses the findings presented with respect to current concepts of personal and contextual influences.

Topics: Cognition Disorders; Evidence-Based Medicine; Humans; Neurotransmitter Agents; Oxytocin; Social Behavior Disorders

With the growing mechanistic understanding of higher brain functions like learning and memory, vigilance and social cognition, new pharmacological approaches for the treatment of psychiatric disorders arise. Substances used as neuroenhancers for the improvement of cognitive or emotional functions in healthy subjects might provide novel pharmacological opportunities in psychiatry. Intriguingly, drugs like modafinil, D-cycloserine or oxytocin have shown significant improvements in key symptoms in several psychiatric disorders. When used as augmentation strategies, they could either directly interfere with psychopathological impairments or improve response to other treatment modalities like psychotherapy or psychopharmacological drugs. While initial studies yielded promising results, further research on beneficial or adverse effects is required.

Topics: Brain; Central Nervous System Stimulants; Cognition Disorders; Cycloserine; Emotions; Humans; Interpersonal Relations; Learning; Mental Disorders; Oxytocin; Psychotherapy

Building on animal research, the past decade has witnessed a surge of interest in the effects of oxytocin on social cognition and prosocial behavior in humans. This work has generated considerable excitement about identifying the neurochemical underpinnings of sociality in humans, and discovering compounds to treat social functioning deficits. Inspection of the literature, however, reveals that the effects of oxytocin in the social domain are often weak and/or inconsistent. We propose that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals. We show how this approach can improve understanding of extant research, suggest novel mechanisms through which oxytocin might operate, and refine predictions about oxytocin pharmacotherapy.

Topics: Animals; Brain; Cognition Disorders; Humans; Oxytocin; Social Behavior

Topics: Aged; Aging; Cognition Disorders; Humans; Middle Aged; Oxytocin; Vasopressins

Topics: Animals; Behavior, Animal; Cognition; Cognition Disorders; Electroconvulsive Therapy; Humans; Memory; Mental Disorders; Neurophysins; Oxytocin; Pituitary Hormones, Posterior; Vasopressins

Social cognition is impaired in people with schizophrenia and these deficits are strongly correlated with social functioning. Oxytocin is a hypothalamic peptide that contributes to maternal infant bonding and has diverse pro-social effects in adults. This study tested the hypothesis that 12weeks of intranasal oxytocin will improve social cognitive function in outpatients with schizophrenia and schizoaffective disorder. Sixty-eight eligible participants were randomized to oxytocin (24IU twice daily) or placebo. Social cognitive function was assessed using the Emotion Recognition-40, Brüne Theory of Mind, Reading the Mind in the Eyes test, Trustworthiness task and Ambiguous Intentions Hostility Questionnaire at baseline, 6weeks and 12weeks. In addition, social function was assessed using the Specific Levels of Functioning Scale and a role-play test, and psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Fifty-five participants completed the 12-week trial. The study found no evidence for a differential advantage of oxytocin over placebo on social cognition. Among secondary outcomes, there was a modest advantage for oxytocin over placebo on a component of social functioning, although there was also evidence that the placebo group outperformed the oxytocin group on the role-play task. No between-group differences emerged on measures of psychopathology in pre-specified comparisons, but oxytocin showed significant within-group reduction in PANSS negative symptoms and significant between-group improvement in negative symptoms in the schizophrenia subgroup. Further testing is needed to clarify whether oxytocin has therapeutic potential for social cognitive deficits and/or negative symptoms in people with schizophrenia.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Cognition Disorders; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Outcome Assessment, Health Care; Oxytocin; Psychiatric Status Rating Scales; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Social Behavior; Young Adult

Topics: Adolescent; Adult; Chronic Disease; Cognition Disorders; Female; Humans; Neuropsychological Tests; Oxytocin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Vasopressins; Young Adult

Many with schizophrenia experiences deficits in social cognition, neurocognition and metacognition. Yet the biological mechanisms which may underpin these cognitive deficits are poorly understood. Two candidate causes of these deficits are disturbances in oxytocin (OT) and vasopressin (VP). To explore this we assessed plasma OT and VP in 34 schizophrenia patients and 31 healthy controls. We also concurrently assessed social cognition using the Reading the Mind from the Eyes test, neurocognition using the Wisconsin Card Sorting Test and metacognition using the Metacognitive Assessment Scale-Abbreviated. Group comparisons revealed lower plasma OT levels in the schizophrenia group. Plasma VP levels did not differ between groups. Correlations revealed that lower levels of OT were associated with poorer levels of metacognitive functioning in the schizophrenia group but not poorer social cognition or neurocognition. In a stepwise multiple regression, plasma OT level, neurocognition and social cognition contributed uniquely to the prediction of metacognition in the schizophrenia group. Results may suggest that disturbance in OT is linked with deficits in metacognition and may interact with other forms of cognitive deficits, interfering with the person's abilities to form a complex and integrated sense of self and others.

Topics: Adult; Case-Control Studies; Cognition; Cognition Disorders; Female; Humans; Male; Metacognition; Neuropsychological Tests; Oxytocin; Schizophrenia; Schizophrenic Psychology; Social Behavior; Social Perception; Vasopressins; 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

Because brain development continues during adolescence, the effects of chronic stress on hippocampal changes that occur during that period are permanent. Oxytocin, which is synthesized in the hypothalamus and has many receptors in brain regions, including the hippocampus, may affect learning-memory. This study aimed to investigate chronic restraint stress on hippocampal functions, and hippocampal vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in adolescent male and female rats and the role of oxytocin in these effects.. Experimental groups included control, stress+oxytocin, and stress+saline groups. Restraint stress was applied to all the stress groups for 1 h/day, for 7 days. Learning-memory tests were performed after the 7th day.. In the stress+oxytocin groups, the process of finding the platform was shorter than in others groups. The stress+saline groups spent less time, whereas the stress+oxytocin groups spent more time, on the target quadrant in the probe trial. In the stress+oxytocin groups thigmotaxis time (indicating anxiety) decreased, but VEGF and BDNF levels increased. A positive correlation was found between VEGF and BDNF levels and the time spent within the target quadrant.. The results indicate that impaired hippocampal learning and memory loss due to chronic restraint stress can be positively affected by intranasal oxytocin.

Topics: Animals; Anxiety; Brain-Derived Neurotrophic Factor; Cognition Disorders; Female; Hippocampus; Hypothalamus; Learning; Male; Maze Learning; Memory; Oxytocin; Rats; Rats, Wistar; Vascular Endothelial Growth Factor A

The neurological basis for autism is still not fully understood, and the role of the interaction between neuro-inflammation and neurotransmission impairment needs to be clearer. This study aims to test the possible association between impaired levels of gamma aminobutyric acid (GABA), serotonin, dopamine, oxytocin, and interferon-γ-induced protein-16 (IFI16) and the severity of social and cognitive dysfunctions in individuals with autism spectrum disorders.. GABA, serotonin, dopamine, oxytocin, and IFI16 as biochemical parameters related to neurochemistry and inflammation were determined in the plasma of 52 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) or social responsiveness scale (SRS), and compared to 30 age- and gender-matched control samples.. The data indicated that Saudi patients with autism have remarkably impaired plasma levels of the measured parameters compared to age and gender-matched controls. While serotonin in platelet-free plasma and dopamine did not correlated with the severity in social and cognitive dysfunction, GABA, oxytocin, and IFI16 were remarkably associated with the severity of both tested scores (SRS and CARS).. The relationship between the selected parameters confirms the role of impaired neurochemistry and neuro-inflammation in the etiology of autism spectrum disorders and the possibility of using GABA, oxytocin, and IFI16 as markers of autism severity. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis.

Topics: Area Under Curve; Biomarkers; Child; Child Development Disorders, Pervasive; Child, Preschool; Cognition Disorders; Enzyme-Linked Immunosorbent Assay; Humans; Male; Mitochondrial Proteins; Neurotransmitter Agents; Oxytocin; Statistics as Topic

To determine the incidence of moderate to severe neonatal encephalopathy (NE) and neonatal seizures without encephalopathy, and the association with metabolic acidemia. Secondly, to investigate the occurrence of suboptimal intrapartum care and its impact on neonatal outcome.. Clinical audit.. Two university hospitals in Sweden.. Neonates ≥34 weeks with moderate or severe NE and neonatal seizures alone, i.e. without encephalopathy, from a population of 71 189 births, where umbilical blood gases were routinely analyzed.. Neonates were categorized depending on the presence of metabolic acidemia at birth by umbilical artery pH < 7.00, base deficit ≥12 mmol/L. Records were audited for suboptimal care and a decision was made on whether management was assessed to have impacted neonatal outcome.. Encephalopathy and seizures alone.. We identified 80 neonates with NE and 30 with seizures alone, of which 48 (60%) and none, respectively, had metabolic acidemia. Suboptimal care could be assessed in 77 and occurred in 28 (36%) NE cases and in one neonate with seizures alone (p < 0.001). In 47 NE cases with metabolic acidemia, suboptimal care occurred in 22 (47%) vs. 6/30 (20%) without metabolic acidemia (p = 0.02). Suboptimal care had an impact on outcome in 18/77 (23%) NE cases but in no cases with seizures alone.. Suboptimal care was commonly seen with NE, particularly in neonates with metabolic acidemia, and also affected neonatal outcome. No such associations were found in neonates with seizures alone.

Topics: Acidosis; Blood Gas Analysis; Cardiotocography; Cerebral Palsy; Child Behavior Disorders; Child, Preschool; Clinical Audit; Cognition Disorders; Fetal Blood; Humans; Incidence; Infant, Newborn; Intellectual Disability; Mental Disorders; Oxytocics; Oxytocin; Perinatal Care; Quality of Health Care; Retrospective Studies; Seizures; Speech Disorders; Sweden; Vacuum Extraction, Obstetrical

Social cognitive impairment is related to poor social functioning in schizophrenia. This impairment includes both deficits in emotion perception and theory of mind (ToM), and cognitive biases including attributional bias and jumping to conclusions. Oxytocin (OXT) is a hormone that has been implicated in human social behavior, and that has also been associated with regulation of inflammation. In a cross-sectional study involving 60 patients with schizophrenia and 20 healthy controls, we examined associations between OXT and social cognitive capacity and bias. Secondary analyses examined associations between OXT and inflammation. We found significant correlations between OXT and social cognitive bias in the control group and in patients with delusions, but not in patients without delusions. Social cognitive capacity only correlated significantly with OXT in patients with delusions. A correlation between OXT and inflammation was observed only in patients without delusions. Findings suggest that OXT may be implicated in social cognition both in controls and in patients with delusions, but that this association may be blunted in patients without delusions. Inflammation appears to be related to OXT rather independently of social cognition. Future longitudinal and intervention studies with OXT are needed to clarify causality in the identified associations.

Topics: Adult; Cognition Disorders; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Neuropsychological Tests; Oxytocin; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Social Behavior; Statistics as Topic

Until recently, the social cognitive impairment in schizophrenia has been underappreciated and remains essentially untreated. Deficits in emotional processing, social perception and knowledge, theory of mind, and attributional bias may contribute to functional social cognitive impairments in schizophrenia. The amygdala has been implicated as a key component of social cognitive circuitry in both animal and human studies. In addition, structural and functional studies of schizophrenia reproducibly demonstrate abnormalities in the amygdala and dopaminergic signaling. Finally, the neurohormone oxytocin plays an important role in multiple social behaviors in several mammals, including humans. We propose a model of social cognitive dysfunction in schizophrenia and discuss its therapeutic implications. The model comprises abnormalities in oxytocinergic and dopaminergic signaling in the amygdala that result in impaired emotional salience processing with consequent social cognitive deficits.

Topics: Amygdala; Animals; Cognition Disorders; Dopamine; Emotions; Humans; Models, Psychological; Oxytocin; Schizophrenia; Schizophrenic Psychology; Social Behavior; Social Perception

Prader-Willi syndrome (PWS) is a complex neurogenetic disorder with considerable clinical variability that is thought in large part to be the result of a hypothalamic defect. PWS results from the absence of paternal expression of imprinted genes localized in the 15q11-q13 region; however, none of the characterized genes has so far been shown to be involved in the etiology of PWS. Here, we provide a detailed investigation of a mouse model deficient for NECDIN: Linked to the mutation, a neonatal lethality of variable penetrance is observed. Viable NECDIN: mutants show a reduction in both oxytocin-producing and luteinizing hormone-releasing hormone (LHRH)-producing neurons in hypothalamus. This represents the first evidence of a hypothalamic deficiency in a mouse model of PWS. NECDIN:-deficient mice also display increased skin scraping activity in the open field test and improved spatial learning and memory in the Morris water maze. The latter features are reminiscent of the skin picking and improved spatial memory that are characteristics of the PWS phenotype. These striking parallels in hypothalamic structure, emotional and cognitive-related behaviors strongly suggest that NECDIN is responsible for at least a subset of the multiple clinical manifestations of PWS.

Topics: Animals; Cognition; Cognition Disorders; Disease Models, Animal; Gonadotropin-Releasing Hormone; Hypothalamus; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurons; Nuclear Proteins; Oxytocin; Prader-Willi Syndrome; Psychomotor Performance