Rosana Shuhama

Animal defense strategies and anxiety disorders

Anxiety disorders are classified according to symptoms, time course and therapeutic response. Concurrently, the experimental analysis of defensive behavior has identified three strategies of defense that are shared by different animal species, triggered by situations of potential, distal and proximal predatory threat, respectively. The first one consists of cautious exploration of the environment for risk assessment. The associated emotion is supposed to be anxiety and its pathology, Generalized Anxiety Disorder. The second is manifested by oriented escape or by behavioral inhibition, being related to normal fear and to Specific Phobias, as disorders. The third consists of disorganized flight or complete immobility, associated to dread and Panic Disorder. Among conspecific interactions lies a forth defense strategy, submission, that has been related to normal social anxiety (shyness) and to Social Anxiety Disorder. In turn, Posttraumatic Stress Disorder and Obsessive-Compulsive Disorder do not seem to be directly related to innate defense reactions. Such evolutionary approach offers a reliable theoretical framework for the study of the biological determinants of anxiety disorders, and a sound basis for psychiatric classification.

Caracterização clínica e psicossocial da clientela de um ambulatório de esterilidade

The objective of this study was to describe the demographic, clinical and psychosocial characteristics of Sterility Clinic outpatients and to identify motivation for psychological care. It is a retrospective study, conducted using 50 couples, interviewed at the beginning of the medical inquiry process. Eighty percent of the couples were in their first marriage, 64% had been married for up to 8 years, 72% had no children and 78% had been trying to conceive for up to 6 years. The causes of infertility were unknown in thirty-six percent

Behavioral and neuroimaging responses induced by mental imagery of threatening scenarios

Functional neuroimaging studies have shown that actual situations of uncertain or distant threats increase the activity of forebrain regions, whereas proximal threats increase the activity of the dorsal midbrain. This experiment aimed at testing the hypothesis that brain activity elicited by imagined scenarios of threats with two different magnitudes, potential and imminent, resembles that found in response to actual threats. First, we measured subjective responses to imagined scenarios of potential and imminent threats compared with neutral and pleasant scenarios. The same scenarios were used as a paradigm in a functional magnetic resonance imaging experiment. Behavioral results show that the scenarios draw a gradient of hedonic valence and arousal dimensions. Both potential and imminent threat scenarios increased subjective anxiety; the imminent threat scenario also increased feelings of discomfort and bodily symptoms. The functional magnetic resonance imaging results revealed modulations of BOLD signal in the ventromedial prefrontal cortex by potential threat and in the periaqueductal gray matter by imminent threat. These results agree with previously reported evidence using actual threat situations, indicating that mental imagery is a reliable method for studying the functional neuroanatomy of relevant behavioral processes.

Low plasma concentrations of N -methyl- d -aspartate receptor subunits as a possible biomarker for psychosis

BACKGROUND N-methyl-d-aspartate receptor (NMDAR) has been largely implicated in the neurobiology of schizophrenia and other psychosis. Aiming to evaluate their potential as peripheral biomarkers for psychosis, we quantified the plasma concentrations of NR1 and NR2 NMDAR subunits of first-episode psychosis patients in their first contact with mental health services due to psychotic symptoms, compared with siblings and matched community-based controls. METHODS The quantifications of NR1 and NR2 plasma concentrations were performed by ELISA. Data were analysed by nonparametric tests and Receiver Operating Curve (ROC) analysis. RESULTS We included 166 first-episode psychosis patients (mean age = 30.3 ± 12.2 years; 64% men), with the diagnosis of schizophrenia spectrum (n = 84), bipolar disorder (n = 51) and psychotic depression (n = 31), 76 siblings (mean age = 31.5 ± 11.0 years; 30.3% men) and 166 healthy community-based controls (mean age = 31.4 ± 12.0 years; 63.9% men). NMDAR subunits were significantly lower in patients compared with siblings and controls (p < 0.001), except by NR1 plasma concentrations of bipolar patients compared with siblings and controls. NR1 plasma concentrations lower than 17.65 pg/ml (AUC = 0.621) showed sensitivity of 42.8%, specificity of 84.3%, positive predictive value (PPV) of 73.2% and negative predictive value (NPV) of 59.6%. Individuals with NR2 plasma concentrations lower than 2.92 ng/ml (AUC = 0.801) presented a 10.61-fold increased risk of psychosis, with a sensibility of 71.9%, specificity of 80.6%, PPV of 79.0% and NPV of 73.9%. CONCLUSIONS This is the first study reporting the measurement and the reduction of NR1 and NR2 NMDAR subunits plasma concentrations in psychiatric disorders. In particular, the NR2 subunit may be a possible plasma biomarker for psychosis.

F23. LOW-GRADE INFLAMMATORY PROFILE IN FIRST-EPISODE PSYCHOSIS: RESULTS FROM THE STREAM STUDY IN BRAZIL

Abstract Background The inflammatory hypothesis of schizophrenia suggests that abnormalities in inflammatory factors may contribute to the onset of this disease early in adulthood. Nevertheless, no study has investigated possible effects of shared environment by looking at cytokine levels in healthy siblings of first-episode psychosis patients (FEP). The aim of this study was to investigate inflammatory cytokine (IL-6, IL-10, TNF-a) abnormalities in a sizeable epidemiological-based sample of FEP patients, their healthy siblings and population-based controls. Methods This study is part of the epidemiological investigation “Schizophrenia and Other Psychoses Translational Research: Environment and Molecular Biology” (STREAM), conducted in Ribeirão Preto (São Paulo, Brazil) and surrounding area, which is part of the international consortium “European Network of National Schizophrenia Networks Studying Gene-Environment Interactions” (EU-GEI). We recruited a total sample of 507 participants, composed by 166 FEP patients (64% males; mean age: 30.3 ± 12.2), 76 siblings (30.3% males; mean age: 31.5 ± 11.0) and 265 population-based controls (50.2% males; mean age: 31.7 ± 11.2). Plasma cytokines IL-6, TNF-a and IL-10 were analysed by Multiplex Bead Array (Luminex xMap technology). We performed the multivariate general linear model (GLM) analysis with age as covariate, cytokines as dependent variables and diagnostic group and sex as explanatory variables. Results We found significant differences between the three groups [F (6,994) = 10.864; p < 0.001] in the plasma concentration of all the three cytokines (p < 0.001), independent of the sex of the participants (p = 0.115; interaction diagnosis & sex p = 0.115). FEP patients had significantly higher levels of IL-6, TNF-a, and IL-10 when compared to controls (p < 0.001 for all). When compared to their siblings, patients had higher levels of both TNF-a and IL-10 (p < 0.05 for both), and a trend to IL-6 (p = 0.058), whereas siblings did not differ from controls for any of the three cytokines analysed (p > 0.05 for all). Discussion This is the first study conducted in the South hemisphere to demonstrate the low-grade inflammatory profile in FEP patients, compared to their siblings and community-based controls. The fact that IL-6, TNF-a and IL-10 are all higher in the FEP group than their healthy siblings and community-based controls suggests the synergism of individual vulnerability factors in the development of this inflammatory profile.

A Method for Simultaneous Evaluation of Muscular and Neural Prepulse Inhibition

Prepulse inhibition (PPI) test has been widely used to evaluate sensorimotor gating. In humans, deficits in this mechanism are measured through the orbicularis muscle response using electromyography (EMG). Although this mechanism can be modulated by several brain structures and is impaired in some pathologies as schizophrenia and bipolar disorder, neural PPI evaluation is rarely performed in humans. Since eye blinks are a consequence of PPI stimulation, they strongly contaminate the electroencephalogram (EEG) signal. This paper describes a method to reduce muscular artifacts and enable neural PPI assessment through EEG in parallel to muscular PPI evaluation using EMG. Both types of signal were simultaneously recorded in 22 healthy subjects. PPI was evaluated by the acoustical startle response with EMG and by the P2-N1 event-related potential (ERP) using EEG in Fz, Cz, and Pz electrodes. In order to remove EEG artifacts, Independent Component Analysis (ICA) was performed using two methods. Firstly, visual inspection discarded components containing artifact characteristics as ocular and tonic muscle artifacts. The second method used visual inspection as gold standard to validate parameters in an automated component selection using the SASICA algorithm. As an outcome, EEG artifacts were effectively removed and equivalent neural PPI evaluation performance was obtained using both methods, with subjects exhibiting consistent neural as well as muscular PPI. This novel method improves PPI test, enabling neural gating mechanisms assessment within the latency of 100–200 ms, which is not evaluated by other sensory gating tests as P50 and mismatch negativity.

Cannabis use as a risk factor for psychotic-like experiences: A systematic review of non-clinical populations evaluated with the Community Assessment of Psychic Experiences

Epidemiological data have provided evidence that psychotic‐like experiences (PLEs) can occur in the general population, not necessarily accompanied by the impairment and suffering observed in formal psychiatric diagnoses. According to the psychosis continuum hypothesis, PLEs would be subject to the same risk factors as frank psychosis. The aim of this review was to summarize observational studies that evaluated cannabis use as a risk factor for PLEs as determined by the Community Assessment of Psychic Experiences in non‐clinical samples. The instrument composed of 3 dimensions—positive, negative and depressive—is a scale specifically designed to assess the occurrence, frequency and impact of PLEs in non‐clinical population.

What we imagine is what we do? A critical overview about mental imagery as a strategy to study human defensive responses

&NA; There is not a single and perfect instinctive behavior to react to threatening situations. However, the study of particular features of these situations suggests the existence of prototypical emotional reactions and associated defensive behaviors. Since all living beings are subjected to common evolutionary pressures, such as predation and conspecific competition, it is plausible that there is conservation of some basic defensive responses in their behavioral repertoire. The choice for approaching or withdrawing from a given situation depends, among others things, on environmental features, including the threat intensity and the distance from the source of the threat. If these basic responses were conserved in humans, they should be expressed in ways similar to those observed in non‐human animals. Due to ethical reasons and easy application, mental imagery has been used to test this hypothesis. The studies included in this review point to the validity of this method, with both self‐report and neurophysiological findings corroborating the hypothesis under scrutiny. Despite the need for additional investigation to deal with some limitations, the information obtained with this method can help to a better understanding of the conditions that provoke specific defensive behaviors and related emotions. This knowledge may also contribute to identify vulnerability factors for fear/anxiety‐related disorders.

Simultaneous evaluation of prepulse inhibition with EMG and EEG using advanced artifact removal techniques

Prepulse inhibition (PPI) consists of a reduction of the acoustic startle reflex (SR) magnitude (measured with EMG) when a startling stimulus is preceded by a non-startling one. This behavior has been extensively investigated in studies related to schizophrenia, since sensory-motor deficit plays a central role in its pathophysiology. However, the same auditory stimuli that trigger the SR also provoke intense auditory evoked responses (AEP), which can be measured with EEG. Comparing these two types of responses, acquired simultaneously, is a great opportunity to investigate the dependence and interdependence of their neural pathways. Nonetheless, so far very few studies have dared to perform such simultaneous recordings, because SR produces strong eye blinks and muscle contraction artifacts that contaminate EEG electrodes placed on the scalp. In this study we investigated the possibility of simultaneously obtaining both the acoustic SR (using EMG) and the AEP (using EEG) measures, through the use of advanced artifact removal techniques, to better characterize PPI in healthy humans.

Poster #T217 PRELIMINARY SAMPLE DESCRIPTION OF FIRST EPISODE PSYCHOSIS IN A BRAZILIAN LARGE CATCHMENT AREA

chotic experiences and dependent stressful life events (bivariate heritabilities = 42–86%). Analyses indicated familial influences with hallucinations, and grandiosity and delusion, as it was not possible to differentiate between genetic and common environmental effects. Discussion: Further to stressful life events being an environmental risk, individuals may have a genetic propensity for dependent stressful life events and positive psychotic experiences via a gene-environment correlation.