Imre Kiss

Sharing secrets: Oxytocin and trust in schizophrenia

Abstract Previous studies indicated that oxytocin plays an important role in human trust, which is impaired in patients with severe mental disorders. In this study, we measured plasma oxytocin levels in patients with schizophrenia (n=50) and in healthy controls (n=50) after neutral and trust-related interpersonal interactions. Trust-related interactions were associated with increased oxytocin levels in controls. This effect was absent in patients with schizophrenia. Low oxytocin levels measured after trust-related interactions significantly predicted the negative symptoms of schizophrenia but were not related to positive symptoms, depression, anxiety, and neuropsychological functions. These results suggest that decreased trust-related oxytocin release is related to the negative symptoms and may be associated with social withdrawal, isolation, and flattened affect in schizophrenia.

Anomalous visual experiences, negative symptoms, perceptual organization and the magnocellular pathway in schizophrenia: a shared construct?

BACKGROUNDnSchizophrenia is associated with impaired visual information processing. The aim of this study was to investigate the relationship between anomalous perceptual experiences, positive and negative symptoms, perceptual organization, rapid categorization of natural images and magnocellular (M) and parvocellular (P) visual pathway functioning.nnnMETHODnThirty-five unmedicated patients with schizophrenia and 20 matched healthy control volunteers participated. Anomalous perceptual experiences were assessed with the Bonn Scale for the Assessment Basic Symptoms (BSABS). General intellectual functions were evaluated with the revised version of the Wechsler Adult Intelligence Scale. The 1-9 version of the Continuous Performance Test (CPT) was used to investigate sustained attention. The following psychophysical tests were used: detection of Gabor patches with collinear and orthogonal flankers (perceptual organization), categorization of briefly presented natural scenes (rapid visual processing), low-contrast and frequency-doubling vernier threshold (M pathway functioning), isoluminant colour vernier threshold and high spatial frequency discrimination (P pathway functioning).nnnRESULTSnThe patients with schizophrenia were impaired on test of perceptual organization, rapid visual processing and M pathway functioning. There was a significant correlation between BSABS scores, negative symptoms, perceptual organization, rapid visual processing and M pathway functioning. Positive symptoms, IQ, CPT and P pathway measures did not correlate with these parameters. The best predictor of the BSABS score was the perceptual organization deficit.nnnCONCLUSIONSnThese results raise the possibility that multiple facets of visual information processing deficits can be explained by M pathway dysfunctions in schizophrenia, resulting in impaired attentional modulation of perceptual organization and of natural image categorization.

Oxytocin response in a trust game and habituation of arousal

Oxytocin may be implicated in various sophisticated human processes, including attachment, trust, social perception, memory, and fear regulation. In this study, we explored the relationship between plasma oxytocin level measured after a task requiring intimate trust (secret sharing) and habituation of autonomic arousal (skin conductance response) in sixty healthy volunteers. Results revealed that oxytocin was elevated in the trust-related condition relative to a neutral baseline. In a cognitive stress condition (mental arithmetic task), there was no significant oxytocin elevation relative to the neutral condition. After controlling for age, gender, education, state anxiety and depression, we found a significant positive relationship between trust-related oxytocin level and habituation of autonomic arousal. This relationship was absent in the case of neutral (trust-unrelated) oxytocin level. These results suggest that the habituation of autonomic arousal is closely related to oxytocin released during trust-related social interactions.

A polymorphism of the neuregulin 1 gene(SNP8NRG243177/rs6994992) affects reactivity to expressed emotion in schizophrenia

A single nucleotide polymorphism of the neuregulin 1 gene (SNP8NRG243177/rs6994992) increases the risk of psychosis, affects prefrontal activation and structural connectivity in the brain, and is related to the expression of a specific neuregulin 1 isoform. The purpose of this study was to investigate the interaction between this polymorphism and reactivity to psychosocial stress. Two hundred patients with schizophrenia were genotyped. The patients and one of their family members participated in neutral and conflict‐related interactions in which the number of relatives criticisms and patients unusual thoughts was assessed. Patients with the risk T/T genotype expressed more unusual thoughts than C‐carriers (C/T and C/C) during conflict‐related interactions but not during neutral interactions. Two controls polymorphisms of the neuregulin 1 gene (rs10954867 and rs7005288) showed no such effect. These results raise the possibility that there is a significant gene by environment interaction regarding SNP8NRG243177/rs6994992 and psychosocial stress.

When doors of perception open: Visual contrast sensitivity in never-medicated, first-episode schizophrenia

Schizophrenia is characterized by impaired visual contrast sensitivity and anomalous perceptual experiences. The aim of this study was to investigate these phenomena in unmedicated patients with first-episode schizophrenia. Visual contrast sensitivity was measured with pulsed-pedestal and steady-pedestal tests, which bias information processing toward the parvocellular and magnocellular pathways, respectively. Anomalous perceptual experiences were investigated with the Structured Interview for Assessing Perceptual Anomalies (SIAPA). Results revealed that patients with schizophrenia (n = 20) exhibited increased contrast sensitivity values on the magnocellular test relative to the control participants (n = 20). In the parvocellular condition, there was no significant difference between the two groups. The higher magnocellular contrast sensitivity values were associated with increased visual SIAPA scores, especially at the two lowest spatial frequencies (0.25 and 0.5 cycles/degree). These results indicate the heightened sensitivity of magnocellular pathways in unmedicated first-episode schizophrenia, which may contribute to anomalous perceptual experiences and sensory overloading.

Perceptual and cognitive effects of antipsychotics in first-episode schizophrenia: The potential impact of GABA concentration in the visual cortex

Schizophrenia is characterized by anomalous perceptual experiences (e.g., sensory irritation, inundation, and flooding) and specific alterations in visual perception. We aimed to investigate the effects of short-term antipsychotic medication on these perceptual alterations. We assessed 28 drug-naïve first episode patients with schizophrenia and 20 matched healthy controls at baseline and follow-up 8 weeks later. Contrast sensitivity was measured with steady- and pulsed-pedestal tests. Participants also received a motion coherence task, the Structured Interview for Assessing Perceptual Anomalies (SIAPA), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Proton magnetic resonance spectroscopy was used to measure gamma-aminobutyric acid (GABA) levels in the occipital cortex (GABA/total creatine [Cr] ratio). Results revealed that, comparing baseline and follow-up values, patients with schizophrenia exhibited a marked sensitivity reduction on the steady-pedestal test at low spatial frequency. Anomalous perceptual experiences were also significantly ameliorated. Antipsychotic medications had no effect on motion perception. RBANS scores showed mild improvements. At baseline, but not at follow-up, patients with schizophrenia outperformed controls on the steady-pedestal test at low spatial frequency. The dysfunction of motion perception (higher coherence threshold in patients relative to controls) was similar at both assessments. There were reduced GABA levels in schizophrenia at both assessments, which were not related to perceptual functions. These results suggest that antipsychotics dominantly affect visual contrast sensitivity and anomalous perceptual experiences. The prominent dampening effect on low spatial frequency in the steady-pedestal test might indicate the normalization of putatively overactive magnocellular retino-geniculo-cortical pathways.

CD 38 expression, attachment style and habituation of arousal in relation to trust-related oxytocin release ☆

Oxytocin plays an important role in human attachment, trust, social perception, memory, and fear regulation. Evidence suggests that CD38, a regulator of oxytocin release, may also be critical in these processes. The purpose of this study was to investigate the predictors of plasma oxytocin level measured after a task requiring intimate trust (secret sharing), modeling psychotherapeutic processes, and a neutral social interaction. Results revealed that peripheral CD38 expression positively predicted both trust-related and trust-unrelated oxytocin levels. In addition, habituation of arousal, as measured by skin conductance response, and attachment anxiety also emerged as predictors of oxytocin level in the trust-related condition. These results suggest that CD38 plays a general role in oxytocin secretion, whereas habituation of arousal and attachment anxiety are specifically related to situations involving intimate trust.

Spatial frequency processing in schizophrenia: Trait or state marker?

B. F. ODonnell et al. found impaired discrimination performances at low and medium spatial frequencies in patients with schizophrenia. In this study, the authors replicated this finding in a group of remitted, unmedicated, and highly functioning outpatients with spared IQ and attentional functions. However, the deficit was restricted to low spatial frequencies (0.5 cycles/degree), which suggests that this deficit is a trait marker of schizophrenia.

Decreased peripheral expression of neuregulin 1 in high-risk individuals who later converted to psychosis.

Efforts to identify individuals with high psychosis risk have focused on biological markers that show a marked association with later conversion to full-blown psychosis. Hall et al. (2006) found that a variant in the human neuregulin 1 (NRG1) promoter region is associated with increased development of psychotic symptoms in high-risk individuals. These results were replicated in a Hungarian sample (Kéri et al., 2009). NRG1 plays an important role in neurodevelopment and synaptic plasticity by the regulation of glutamatergic and gamma-amynobutiric acidergic (GABAergic) neurons, and its risk variants are related to altered gene expression in postmortem brain tissue (Law et al., 2006). Previous studies demonstrated decreased peripheral NRG1expression in schizophrenia (Chagnon et al., 2008; Zhang et al., 2008), but it is not clear whether these changes can reliably predict psychosis conversion in high-risk individuals. In order to elucidate this issue, we enrolled 97 help-seeking individuals who visited the outpatient units of the University of Szeged, Bács-Kiskun Country Hospital, and Semmelweis University, Hungary. The control group included 50 healthy volunteers with a negative family history for psychotic disorders. Ultra-high-risk status was evaluated using the Comprehensive Assessment of At-Risk Mental States (CAARMS) (McGorry et al., 2003; for a study description, see Kéri et al., 2009). For the measurement of NRG1 isoforms, we adopted the protocol of Zhang et al. (2008). Blood was drawn from the cubital vein into a sterile plastic tube. Total RNA was extracted and reverse transcribed into first-strand cDNA. Two isoforms of NRG1 were measured using semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) (glial growth factor-2 [GGF2, type II] and heregulin beta 3 [HRG-beta3, type I]; upstream primer: 5′CTTTCTTGTTGCTGCATCTCC-3′; downstream primer: 5′-CACCCTTTTCAGGATGTGGT-3′). Glyceraldehyde-3-Phosphate Dehydrogenase (G3PDH) was the internal control because its level is unchanged in schizophrenia (upstream primer: 5′-ACCACAGTCCATGCCATCAC3′; downstream primer: 5′-TCCACCACCCTGTTGCTGTA-3′). We used cDNA for amplification with upstream and downstream primers of NRG1 and G3PDH, Taq DNA polymerase, dNTP, and PCR buffer. The protocol of the DNA thermal cycler included the following steps: initial denaturation at 95 °C for 5 min, cycles at 94 °C for 45 s, annealing at 65 °C (G3PDH at 62 °C) for 30 s, and extension at 72 °C for 90 s (35 cycles for NRG1 and 30 for G3PDH). Following the electrophoresis of the PCR products (2.0% agarose gel containing ethidium bromide), the optical density of NRG1 (type I and III combined) and G3PDH mRNA was determined. The ratio of the NRG1 and G3PDH mRNA optical density was the dependent measure (Zhang et al., 2008).