Atypical attentional filtering of visual information in youth with chromosome 22q11.2 deletion syndrome as indexed by event-related potentials.

BACKGROUND: Youth with chromosome 22q11.2 deletion syndrome (22q) face one of the highest genetic risk factors for the development of schizophrenia. Previous research suggests impairments in attentional control and potential interactions with elevated anxiety and reduced adaptive functioning may increase the risk for developing psychosis in this population. Here, we examined how variations in attentional control relate to the presence or severity of psychosis-proneness symptoms in these individuals. METHODS: To achieve this, we measured attentional control in youth (12-18 years) with 22q (N = 35) compared to a typically developing group (N = 45), using a flanker task (the Distractor Target task) while measuring neural activity with event-related potentials. RESULTS: Similar to previous findings observed in people with schizophrenia, greater attentional capture by, and reduced suppression of, non-target flanker stimuli characterized participants with 22q and was indexed by the N2pc (N2-posterior-contralateral) and PD (distractor positivity) components. Although we observed no relationships between these components and measures of psychosis-proneness in youth with 22q, these individuals endorsed a relatively low incidence of positive symptoms overall. CONCLUSIONS: Our results provide neural evidence of an attentional control impairment in youth with 22q that suggests these individuals experience sustained attentional focus on irrelevant information and reduced suppression of distracting stimuli in their environment. Impairments in attentional control might be a valid biomarker of the potential to develop attenuated positive symptoms or frank psychosis in high-risk individuals long before the age at which such symptoms typically arise. The evaluation of such a hypothesis, and the preventive potential for the putative biomarker, should be the focus of future studies.

Brain free water alterations in first-episode psychosis: a longitudinal analysis of diagnosis, course of illness, and medication effects.

BACKGROUND: Multiple lines of evidence suggest the presence of altered neuroimmune processes in patients with schizophrenia (Sz) and severe mood disorders. Recent studies using a novel free water diffusion tensor imaging (FW DTI) approach, proposed as a putative biomarker of neuroinflammation, atrophy, or edema, have shown significantly increased FW in patients with Sz. However no studies to date have investigated the longitudinal stability of FW alterations during the early course of psychosis, nor have studies focused separately on FE psychosis patients with Sz or bipolar disorder (BD) with psychotic features. METHODS: The current study included 188 participants who underwent diffusion magnetic resonance imaging scanning at baseline. Sixty-four participants underwent follow-up rescanning after 12 months. DTI-based alterations in patients were calculated using voxelwise tract-based spatial statistics and region of interest analyses. RESULTS: Patients with FE psychosis, both Sz and BD, exhibited increased FW at illness onset which remained unchanged over the 12-month follow-up period. Preliminary analyses suggested that antipsychotic medication exposure was associated with higher FW in gray matter that reached significance in the BD group. Higher FW in white matter correlated with negative symptom severity. CONCLUSIONS: Our results support the presence of elevated FW at the onset of psychosis in both Sz and BD, which remains stable during the early course of the illness, with no evidence of either progression or remission.

Effects of aging and life-long moderate calorie restriction on IL-15 signaling in the rat white adipose tissue.

OBJECTIVE: Phosphorylation of insulin receptor substrate (IRS) 1 by tumor necrosis factor alpha (TNF-α) has been implicated as a factor contributing to insulin resistance. Administration of IL-15 reduces adipose tissue deposition in young rats and stimulates secretion of adiponectin, an insulin sensitizing hormone that inhibits the production and activity of TNF-α. We aimed at investigating the effects of age life-long moderate calorie restriction (CR) on IL-15 and TNF-α signaling in rat white adipose tissue (WAT). MATERIALS AND METHODS: Thirty-six 8-month-old, 18-month-old, and 29-month-old male Fischer344´Brown Norway F1 rats (6 per group) were either fed ad libitum (AL) or calorie restricted by 40%. The serum levels of IL-15 and IL-15 receptor α-chain (IL-15Rα) were increased by CR controls regardless of age. An opposite pattern was detected in WAT. In addition, CR reduced gene expression of TNF-α and cytosolic IRS1 serine phosphorylation in WAT, independently from age. RESULTS: IL-15 signaling in WAT is increased over the course of aging in AL rats compared with CR rodents. Protein levels of IL-15Rα are greater in WAT of AL than in CR rats independently from age. This adaptation was paralleled by increased IRS1 phosphorylation through TNF-α-mediated insulin resistance. Adiponectin decreased at old age in AL rats, while no changes were evident in CR rats across age groups. CONCLUSIONS: IL-15 signaling could therefore represent a potential target for interventions to counteract metabolic alterations and the deterioration of body composition during aging.

Disrupted GABAergic facilitation of working memory performance in people with schizophrenia.

OBJECTIVES: Gamma-Amiobutyric acid (GABA) is a primary inhibitory neurotransmitter that facilitates neural oscillations that coordinate neural activity between brain networks to facilitate cognition. The present magnetic resonance spectroscopy (MRS) study tests the hypothesis that GABAergic facilitation of working memory is disrupted in people with schizophrenia (PSZ). METHODS: 51 healthy participants and 40 PSZ from the UC Davis Early Psychosis Program performed an item and temporal order working memory (WM) task and underwent resting MRS to measure GABA and glutamate concentrations in dorsolateral prefrontal (DLPFC) and anterior cingulate (ACC) regions of interest. MRS was acquired on a 3 Tesla Siemens scanner and GABA and glutamate concentrations were referenced to creatine. Percent correct on the WM task indexed performance and correlation coefficients examined GABAergic or Glutamatergic facilitation of WM, with Fisher's Z transformation testing for group differences. RESULTS: There were no group differences in GABA or glutamate concentrations, but WM correlations were reversed between groups. In patients, higher DLPFC GABA was associated with worse rather than better WM performance. This pattern was not observed for glutamate or in the ACC. Although under-powered, there was no indication of medication effects. CONCLUSIONS AND RELEVANCE: Results cannot be explained by group differences in DLPFC GABA or glutamate concentrations but, instead, indicate that schizophrenia disrupts the GABAergic facilitation of WM seen in healthy individuals. Results appear to parallel post mortem findings in suggesting that schizophrenia alters the distribution of different classes of GABAergic interneurons rather than producing a general deficit across the total population of neurons.

Behavioral and epigenetic consequences of oxytocin treatment at birth.

Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism.

Memory and cognition in schizophrenia.

Episodic memory deficits are consistently documented as a core aspect of cognitive dysfunction in schizophrenia patients, present from the onset of the illness and strongly associated with functional disability. Over the past decade, research using approaches from experimental cognitive neuroscience revealed disproportionate episodic memory impairments in schizophrenia (Sz) under high cognitive demand relational encoding conditions and relatively unimpaired performance under item-specific encoding conditions. These specific deficits in component processes of episodic memory reflect impaired activation and connectivity within specific elements of frontal-medial temporal lobe circuits, with a central role for the dorsolateral prefrontal cortex (DLPFC), relatively intact function of ventrolateral prefrontal cortex and variable results in the hippocampus. We propose that memory deficits can be understood within the broader context of cognitive deficits in Sz, where impaired DLPFC-related cognitive control has a broad impact across multiple cognitive domains. The therapeutic implications of these findings are discussed.

The birth experience and subsequent maternal caregiving attitudes and behavior: a birth cohort study.

Optimal maternal caregiving is critical for children's healthy development, yet quality of maternal caregiving may be influenced by a negative birth experience. We examined whether the birth experience was associated with maternal caregiving attitudes and behavior throughout the first year. We conducted secondary analysis of the Avon Longitudinal Study of Parents and Children birth cohort on perinatal data. The birth experience was assessed using self-report data on level of support in labor. Maternal caregiving variables were self-report maternal attitudes at one and eight postnatal months, and observed maternal behavior at 12 postnatal months. Data were analyzed using multivariable logistic regression models adjusting for critical covariates at one (N = 4389), eight (N = 4580), and 12 (N = 842) postnatal months. Feeling supported in labor was associated with a report of "immediately falling in love" with one's baby after birth, surveyed at 1 month (adjusted OR 1.41 [95% CI 1.20-1.65]), and with more positive parenting scores at 8 months (adjusted OR 1.56 [95% CI 1.36-1.79]), but not with more positive observed maternal behavior at 12 months. Additional risk factors were identified. Our findings suggest that we may be able to modify the risk of poor postnatal maternal caregiving by supporting women in labor and facilitating a positive birth experience.

I must have missed that: Alpha-band oscillations track attention to spoken language.

Attention is critical to the construction of mental representations of language context during comprehension. We investigated the consequences of momentary lapses in attention during listening comprehension on neural activity and behavior. Participants listened to two full-length stories while EEG was recorded, and afterwards completed multiple choice comprehension questions. Listening was periodically interrupted by attention probes, in which participants were asked whether their attention immediately preceding the probe's appearance was focused on the story. The results showed that (1) participants spent a substantial amount of time off-task, endorsing attention lapses on over 30% of probes; (2) for probes on which an attention lapse was endorsed, later accuracy on comprehension questions querying pre-probe information was decreased; (3) the pre-probe period just before the endorsement of an attention lapse was characterized by a greater percentage of above-threshold oscillations in the alpha-band (8-12 Hz) compared to just prior to the endorsement of on-task or split-attention listening; and (4) when participants made "I have no idea" responses to comprehension questions, their EEG record revealed a greater percentage of above-threshold alpha oscillations during the original presentation of the information queried by the comprehension questions, compared to correct responses or incorrect guesses. These results connect changes in neural activity in the alpha band to episodes of mind-wandering during listening comprehension, and in turn to decreased comprehension accuracy. This demonstrates how alpha can be used to track attentional engagement during language comprehension, and illustrates the dependence of successful language comprehension on attention.

Differential physiological responses to central leptin overexpression in male and female rats.

Brains of females are more sensitive to the acute catabolic actions of leptin. However, sex differences in the long-term physiological responses to central leptin receptor modulation are unknown. Accordingly, we centrally delivered a viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist (Leptin-Antagonist) or a green fluorescence protein (GFP) (Control). We examined chronic changes in body weight and composition in male and female rats. Females displayed greater and sustained responses to Leptin, whereas males rapidly lost physiological effects and developed leptin resistance as confirmed by lower acute leptin-mediated phosphorylation of signal transducer and activator of transcription 3 (P-STAT3). Surprisingly, despite persistent physiological responses, Leptin-females also exhibited reduced acute leptin-mediated P-STAT3, suggesting an onset of leptin resistance near time of death. In line with this interpretation, Leptin-females and Control-females consumed the same amount of food on the last day of the experiment. Both Leptin-Antagonist groups gained similar percentages of their initial body weight and fat mass, whereas only Leptin-Antagonist-females gained lean body mass. Consequently, the lean/fat mass ratio with Leptin-Antagonist was preserved in females and decreased in males, suggesting a deterioration of body composition in males. In summary, the present study establishes that females are more responsive to long-term central leptin overexpression than males and that leptin antagonism has a greater physiological impact in males. The hormone environment may have played a role in these processes; however, future studies are needed to establish whether such physiological responses are mediated by female or male sex hormones.

Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction.

Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days. MTII suppressed appetite in a dose-dependent manner (P < 0.05). Although food intake promptly rose back to control level, body mass was persistently reduced in both MTII groups (P < 0.01). At day 40, both MTII groups displayed lower adiposity than the aCSF animals (P < 0.01). These results show that MTII chronically reduces body mass without the requirement of long-term caloric restriction. Our study proposes that food restriction helps initiate mass loss; however, combined with a secondary pharmacological approach preserving a negative energy balance state over time may help combat obesity.

Impact of schizophrenia on anterior and posterior hippocampus during memory for complex scenes.

OBJECTIVES: Hippocampal dysfunction has been proposed as a mechanism for memory deficits in schizophrenia. Available evidence suggests that the anterior and posterior hippocampus could be differentially affected. Accordingly, we used fMRI to test the hypothesis that activity in posterior hippocampus is disproportionately reduced in schizophrenia, particularly during spatial memory retrieval. METHODS: 26 healthy participants and 24 patients with schizophrenia from the UC Davis Early Psychosis Program were studied while fMRI was acquired on a 3 Tesla Siemens scanner. During encoding, participants were oriented to critical items through questions about item features (e.g., "Does the lamp have a square shade?") or spatial location (e.g., "Is the lamp on the table next to the couch?"). At test, participants determined whether scenes were changed or unchanged. fMRI analyses contrasted activation in a priori regions of interest (ROI) in anterior and posterior hippocampus during correct recognition of item changes and spatial changes. RESULTS: As predicted, patients with schizophrenia exhibited reduced activation in the posterior hippocampus during detection of spatial changes but not during detection of item changes. Unexpectedly, patients exhibited increased activation of anterior hippocampus during detection of item changes. Whole brain analyses revealed reduced fronto-parietal and striatal activation in patients for spatial but not for item change trials. CONCLUSIONS: Results suggest a gradient of hippocampal dysfunction in which posterior hippocampus - which is necessary for processing fine-grained spatial relationships - is underactive, and anterior hippocampus - which may process context more globally - is overactive.

High dietary fructose does not exacerbate the detrimental consequences of high fat diet on basilar artery function.

The objective of the study was to determine the effects of a high fat (HF) diet alone or with high fructose (HF/F) on functional and structural changes in the basilar arteries and cardiovascular health parameters in rats. Male Sprague Dawley rats were fed either a HF (30%) or HF/F (30/40%) diet for 12 weeks. The basilar artery was cannulated in a pressurized system (90 cm H2O) and vascular responses to KCl (30 - 120 mM), endothelin (10(-11) - 10(-7) M), acetylcholine (ACh) (10(-10) - 10(-4) M), diethylamine (DEA)-NONO-ate (10(-10) - 10(-4) M), and papaverine (10(-10) - 10(-4) M) were evaluated. Rats were also monitored for food intake, body weight, blood lipids, blood pressure, and heart rate. At death, asymmetrical dimethyl arginine level (ADMA) and leptin were assayed in serum. Although there was no significant difference in weight gain and food intake, HF and HF/F diets increased body fat composition and decreased the lean mass. HF/F diet accelerated the development of dyslipidemia. Although resting blood pressure remained unchanged, stress caused a significant elevation in blood pressure and a modest increase in heart rate in HF fed rats. Both HF and HF/F diet resulted in decreased response to endothelium-dependent and -independent relaxation, whereas increased basilar artery wall thickness was observed only in HF group. Serum leptin levels positively correlated with wall thickness. Moreover serum ADMA was increased and eNOS immunofluorescence was significantly decreased with both diets. These data suggest that the presence of high fructose in a HF diet does not exacerbate the detrimental consequences of a HF diet on basilar artery function.

BOLD fMRI in awake prairie voles: A platform for translational social and affective neuroscience.

The advancement of neuroscience depends on continued improvement in methods and models. Here, we present novel techniques for the use of awake functional magnetic resonance imaging (fMRI) in the prairie vole (Microtus ochrogaster) - an important step forward in minimally-invasive measurement of neural activity in a non-traditional animal model. Imaging neural responses in prairie voles, a species studied for its propensity to form strong and selective social bonds, is expected to greatly advance our mechanistic understanding of complex social and affective processes. The use of ultra-high-field fMRI allows for recording changes in region-specific activity throughout the entire brain simultaneously and with high temporal and spatial resolutions. By imaging neural responses in awake animals, with minimal invasiveness, we are able to avoid the confound of anesthesia, broaden the scope of possible stimuli, and potentially make use of repeated scans from the same animals. These methods are made possible by the development of an annotated and segmented 3D vole brain atlas and software for image analysis. The use of these methods in the prairie vole provides an opportunity to broaden neuroscientific investigation of behavior via a comparative approach, which highlights the ethological relevance of pro-social behaviors shared between voles and humans, such as communal breeding, selective social bonds, social buffering of stress, and caregiving behaviors. Results using these methods show that fMRI in the prairie vole is capable of yielding robust blood oxygen level dependent (BOLD) signal changes in response to hypercapnic challenge (inhaled 5% CO2), region-specific physical challenge (unilateral whisker stimulation), and presentation of a set of novel odors. Complementary analyses of repeated restraint sessions in the imaging hardware suggest that voles do not require acclimation to this procedure. Taken together, awake vole fMRI represents a new arena of neurobiological study outside the realm of traditional rodent models.

Childbirth and symptoms of postpartum depression and anxiety: a prospective birth cohort study.

We investigated associations between aspects of childbirth and elevated postpartum symptoms of depression and anxiety. We employed secondary analysis of perinatal data (N = 4657-4946) from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Multivariable logistic regression models (adjusted for covariates) examined predictors of elevated symptoms of postpartum depression and anxiety. Predictors included the following: type of delivery (normal physiological vs. interventive non-physiological), immediate postpartum complications, and maternal perception of the recent birth experience. The Edinburgh Postnatal Depression Scale assessed elevated symptoms of depression (score ≥ 13), and the Crown-Crisp Experiential Index assessed elevated symptoms of anxiety (score ≥ 9) at 2 and 8 months after delivery. A more negative perception of the recent birth experience was associated with elevated symptoms of anxiety at 2 months [odds ratio (OR) 1.52, 95 % confidence interval (CI) 1.25-1.85] and 8 months (OR 1.30, 95 % CI 1.06-1.60) postpartum but was not associated with elevated symptoms of depression at either time point. Type of delivery (physiological vs. non-physiological) and immediate postpartum complications were not associated with elevated symptoms of depression or anxiety. Our findings suggest that improving women's childbirth experience may decrease the likelihood of postpartum anxiety, but not postpartum depression.

Interaction between oxytocin receptor DNA methylation and genotype is associated with risk of postpartum depression in women without depression in pregnancy.

Postpartum depression (PPD) affects up to 19% of women, negatively impacting maternal and infant health. Reductions in plasma oxytocin levels have been associated with PPD and heritability studies have established a genetic contribution. Epigenetic regulation of the oxytocin receptor gene (OXTR) has been demonstrated and we hypothesized that individual epigenetic variability at OXTR may impact the development of PPD and that such variability may be central to predicting risk. This case-control study is nested within the Avon Longitudinal Study of Parents and Children and included 269 cases with PPD and 276 controls matched on age group, parity, and presence or absence of depressive symptoms in pregnancy as assessed by the Edinburgh Postnatal Depression Scale. OXTR DNA methylation (CpG site -934) and genotype (rs53576 and rs2254298) were assayed from DNA extracted from blood collected during pregnancy. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of elevated symptoms of PPD with genotype, methylation, and their interaction adjusted for psychosocial factors (n = 500). There was evidence of an interaction between rs53576 and methylation in the OXTR gene amongst women who did not have depression prenatally but developed PPD (p interaction = 0.026, adjusted for covariates, n = 257). Those women with GG genotype showed 2.63 greater odds of PPD for every 10% increase in methylation level (95% CI: 1.37, 5.03), whereas methylation was unrelated to PPD amongst "A" carriers (OR = 1.00, 95% CI: 0.58, 1.73). There was no such interaction among women with PPD and prenatal depression. These data indicate that epigenetic variation that decreases expression of OXTR in a susceptible genotype may play a contributory role in the etiology of PPD.

Deficits in anticipatory but not consummatory pleasure in people with recent-onset schizophrenia spectrum disorders.

The majority of studies examining self-reported anticipatory and consummatory pleasure in schizophrenia, as measured on the Temporal Experience of Pleasure Scale (TEPS), have been conducted on chronically ill people with the disorder. In this study, people with a recent-onset schizophrenia spectrum diagnosis (first psychotic episode within one year of study participation) (n=88) and people without a schizophrenia spectrum diagnosis (n=66) were administered the TEPS. People with a schizophrenia spectrum diagnosis reported significantly lower scores of anticipatory, but not consummatory, pleasure on the TEPS compared to the control group. TEPS anticipatory pleasure scores were also significantly, negatively correlated with negative symptoms, but neither TEPS anticipatory nor consummatory pleasure scores were significantly correlated with functioning measures. Our results replicate previous findings with chronically ill people with schizophrenia on the TEPS.

Is oxytocin a maternal-foetal signalling molecule at birth? Implications for development.

The neuropeptide oxytocin was first noted for its capacity to promote uterine contractions and facilitate delivery in mammals. The study of oxytocin has grown to include awareness that this peptide is a neuromodulator with broad effects throughout the body. Accumulating evidence suggests that oxytocin is a powerful signal to the foetus, helping to prepare the offspring for the extrauterine environment. Concurrently, the use of exogenous oxytocin or other drugs to manipulate labour has become common practice. The use of oxytocin to expedite labour and minimise blood loss improves both infant and maternal survival under some conditions. However, further investigations are needed to assess the developmental consequences of changes in oxytocin, such as those associated with pre-eclampsia or obstetric manipulations associated with birth. This review focuses on the role of endogenous and exogenous oxytocin as a neurochemical signal to the foetal nervous system. We also examine the possible developmental consequences, including those associated with autism spectrum disorder, that arise from exogenous oxytocin supplementation during labour.

Oxytocin and vasopressin systems in genetic syndromes and neurodevelopmental disorders.

Oxytocin (OT) and arginine vasopressin (AVP) are two small, related neuropeptide hormones found in many mammalian species, including humans. Dysregulation of these neuropeptides have been associated with changes in behavior, especially social interactions. We review how the OT and AVP systems have been investigated in Autism Spectrum Disorder (ASD), Prader-Willi Syndrome (PWS), Williams Syndrome (WS) and Fragile X syndrome (FXS). All of these neurodevelopmental disorders (NDD) are marked by social deficits. While PWS, WS and FXS have identified genetic mutations, ASD stems from multiple genes with complex interactions. Animal models of NDD are invaluable for studying the role and relatedness of OT and AVP in the developing brain. We present data from a FXS mouse model affecting the fragile X mental retardation 1 (Fmr1) gene, resulting in decreased OT and AVP staining cells in some brain regions. Reviewing the research about OT and AVP in these NDD suggests that altered OT pathways may be downstream from different etiological factors and perturbations in development. This has implications for ongoing studies of the therapeutic application of OT in NDD. This article is part of a Special Issue entitled Oxytocin and Social Behav.

Cognition in schizophrenia and schizo-affective disorder: impairments that are more similar than different.

BACKGROUND: Cognition is increasingly being recognized as an important aspect of psychotic disorders and a key contributor to functional outcome. In the past, comparative studies have been performed in schizophrenia and schizo-affective disorder with regard to cognitive performance, but the results have been mixed and the cognitive measures used have not always assessed the cognitive deficits found to be specific to psychosis. A set of optimized cognitive paradigms designed by the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium to assess deficits specific to schizophrenia was used to measure cognition in a large group of individuals with schizophrenia and schizo-affective disorder. METHOD: A total of 519 participants (188 with schizophrenia, 63 with schizo-affective disorder and 268 controls) were administered three cognitive paradigms assessing the domains of goal maintenance in working memory, relational encoding and retrieval in episodic memory and visual integration. RESULTS: Across the three domains, the results showed no major quantitative differences between patient groups, with both groups uniformly performing worse than healthy subjects. CONCLUSIONS: The findings of this study suggests that, with regard to deficits in cognition, considered a major aspect of psychotic disorder, schizophrenia and schizo-affective disorder do not demonstrate major significant distinctions. These results have important implications for our understanding of the nosological structure of major psychopathology, providing evidence consistent with the hypothesis that there is no natural distinction between cognitive functioning in schizophrenia and schizo-affective disorder.

Neuroendocrine and behavioural responses to exposure to an infant in male prairie voles.

Paternal behaviour and pair-bond formation are defining characteristics of social monogamy. However, in comparison to pair-bonding, the endocrine factors associated with the male care of young are not well studied. In the present study, plasma concentrations of oxytocin, vasopressin and corticosterone (CORT) were measured in reproductively naïve male prairie voles as a function of exposure to an infant or control manipulations (i.e. handling or exposure to a wooden dowel). Plasma oxytocin concentrations were transiently elevated within 10 min of pup exposure. Although plasma CORT concentration typically increases after handling, after 10 min of pup exposure, the concentration of plasma CORT was not increased, suggesting an attenuation of CORT release by pup exposure. Group differences in the concentrations of plasma hormones were no longer detected at 20 or 60 min after treatment. These patterns of rapid change in the concentrations of plasma oxytocin and CORT were observed in both juvenile and adult males but not detected after control procedures. Plasma vasopressin, assessed only in adult males, did not vary as a function of pup exposure or other manipulations. In the paraventricular nucleus of the hypothalamus, pup exposure also increased activation (as assessed by the measurement of c-Fos) of neurones that stained for either oxytocin or vasopressin, whereas it decreased c-Fos expression in neurones stained for corticotrophin-releasing hormone. In addition, brief pup exposure (20 min) facilitated subsequent partner preference formation when alloparental males and pup attackers were considered as a group. In the context of other studies, these data support the hypothesis that neuroendocrine changes associated with male alloparental behaviour are related to those implicated in pair-bonding.