Tamara Sheinbaum

Positive and negative schizotypy are associated with prodromal and schizophrenia- spectrum symptoms

The present study examined the validity of psychometrically assessed positive and negative schizotypy in a study of 214 Spanish young adults using interview and questionnaire measures of impairment and psychopathology. Schizotypy provides a useful construct for understanding the etiology and development of schizophrenia and related disorders. Recent interview, laboratory, and experience sampling studies have supported the validity of psychometrically assessed positive and negative symptom dimensions. The present study expands on previous findings by examining the validity of these dimensions in a Spanish sample and employing a widely used interview measure of the schizophrenia prodrome. As hypothesized, the positive schizotypy dimension predicted CAARMS ultra high-risk or psychosis threshold status, and both dimensions uniquely predicted the presence of schizophrenia-spectrum personality disorders. Furthermore, positive schizotypy was associated with psychotic-like, paranoid, schizotypal, and mood symptoms, whereas negative schizotypy was associated with interview ratings of negative and schizoid symptoms. The schizotypy dimensions were also distinguished by their associations with self and other schemas. Positive schizotypy was associated with increased negative self and other schemas, whereas negative schizotypy was associated with decreased positive self and other schemas. The findings provide further construct validation of positive and negative schizotypy and support these dimensions as universal constructs.

COMT-by-sex interaction effect on psychosis proneness

Schizotypy phenotypes in the general population share etiopathogenic mechanisms and risk factors with schizophrenia, supporting the notion of psychosis as a continuum ranging from nonclinical to clinical deviance. Catechol-O-methyltransferase (COMT) is a candidate susceptibility gene for schizophrenia that is involved in the regulation of dopamine in the prefrontal cortex. Several recent studies have reported a sex difference in the impact of COMT genotype on psychiatric and cognitive phenotypes and personality traits. The present study investigated the association of COMT Val158Met (rs4680) with psychometric positive and negative schizotypy and psychotic experiences in a sample of 808 nonclinical young adults. The main finding was that sex moderates the association of COMT genotype with the negative dimension of both schizotypy and psychotic experiences. Male subjects carrying the Val allele tended to score higher on the negative dimension of both trait and symptom-like measures. The results from the present study are consistent with recent work suggesting an association between negative schizotypy and diminished prefrontal dopamine availability. They support the idea that a biological differentiation underlies the positive and negative schizotypy dimensions. Additionally, these findings contribute to the growing literature on sex-specific effects of COMT on the predisposition to psychiatric disorders and personality traits.

Fearful attachment mediates the association of childhood trauma with schizotypy and psychotic-like experiences

We examined whether insecure attachment styles mediate the association between childhood trauma and nonclinical psychotic phenomena in 546 young adults. Fearful attachment mediated the associations of physical/emotional trauma with schizotypy, suspiciousness, and psychotic-like experiences. Results support theoretical accounts implicating attachment disruptions in the pathway from childhood adversity to psychosis.

Association between Attachment Prototypes and Schizotypy Dimensions in Two Independent Non-clinical Samples of Spanish and American Young Adults

Attachment theory offers a powerful theoretical framework for elucidating the developmental pathway through which childhood interpersonal trauma confers vulnerability to psychosis. In the present study, the association between attachment and schizotypy was explored in two independent non-clinical samples of Spanish (n=547) and American (n=1425) young adults. Participants completed the Relationship Questionnaire and the Wisconsin Schizotypy Scales. Following attachment theory and cognitive accounts of psychosis, it was hypothesized that preoccupied attachment would be associated with positive schizotypy, dismissing attachment with negative schizotypy, and fearful attachment with both schizotypy dimensions. Results confirmed these predictions, thus supporting the theoretical frameworks invoked. Also, the associations found in these non-clinical samples are consistent with those in clinical psychosis, supporting the continuum model of schizotypy and schizophrenia. Finally, there was cross-cultural consistency of these associations. Overall, the findings support the application of attachment theory for furthering our understanding of whether different insecure styles, characterized by different self and other representations and affect regulation strategies, play a role in the pathways to positive and negative symptoms.

Attachment style predicts affect, cognitive appraisals, and social functioning in daily life

The way in which attachment styles are expressed in the moment as individuals navigate their real-life settings has remained an area largely untapped by attachment research. The present study examined how adult attachment styles are expressed in daily life using experience sampling methodology (ESM) in a sample of 206 Spanish young adults. Participants were administered the Attachment Style Interview (ASI) and received personal digital assistants that signaled them randomly eight times per day for 1 week to complete questionnaires about their current experiences and social context. As hypothesized, participants’ momentary affective states, cognitive appraisals, and social functioning varied in meaningful ways as a function of their attachment style. Individuals with an anxious attachment, as compared with securely attached individuals, endorsed experiences that were congruent with hyperactivating tendencies, such as higher negative affect, stress, and perceived social rejection. By contrast, individuals with an avoidant attachment, relative to individuals with a secure attachment, endorsed experiences that were consistent with deactivating tendencies, such as decreased positive states and a decreased desire to be with others when alone. Furthermore, the expression of attachment styles in social contexts was shown to be dependent upon the subjective appraisal of the closeness of social contacts, and not merely upon the presence of social interactions. The findings support the ecological validity of the ASI and the person-by-situation character of attachment theory. Moreover, they highlight the utility of ESM for investigating how the predictions derived from attachment theory play out in the natural flow of real life.

The Interaction between Childhood Bullying and the FKBP5 Gene on Psychotic-Like Experiences and Stress Reactivity in Real Life

Aim The present study employed Experience Sampling Methodology to examine whether the interaction between childhood bullying and FKBP5 variability (i) is associated with the expression of psychotic-like experiences, paranoia, and negative affect, and (ii) moderates psychotic-like, paranoid, and affective reactivity to different forms of momentary stress (situational and social) in daily life. Methods A total of 206 nonclinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted randomly eight times daily for one week to complete assessments of their current experiences, affect, and stress appraisals. Participants were genotyped for three FKBP5 single nucleotide polymorphisms (SNPs) (rs3800373, rs9296158, and rs1360780) that have been linked to hypothalamus-pituitary-adrenal axis reactivity. Multilevel analyses were conducted to examine the effect of the interaction between childhood bullying and the FKBP5 haplotype derived from these three SNPs. Results The interaction between bullying and the FKBP5 haplotype was associated with positive, but not negative, psychotic-like experiences, paranoia, and negative affect. The bullying x FKBP5 interaction also moderated the association of a social stress appraisal (specifically, being alone because people do not want to be with you) with psychotic-like experiences and negative affect in daily life. Simple slopes analyses indicated that, in all cases, the associations were significantly increased by exposure to bullying in participants with the risk haplotype, but not for those with the non-risk haplotype. Discussion The present study provides the first evidence of the interplay between childhood bullying and FKBP5 variability in the real-world expression of psychosis proneness and social stress reactivity. The findings underscore the importance of investigating how gene-environment interactions are involved in mechanistic pathways to the extended psychosis phenotype and lend further support to the increasing relevance given to socially defeating appraisals in the experience of reality distortion.

Association between RGS4 variants and psychotic-like experiences in nonclinical individuals

The psychosis phenotype is expressed across a continuum known as schizotypy, which ranges from personality variation through subclinical symptoms to severe psychopathology. The study of subclinical manifestations in non-affected individuals minimizes confounding factors associated with the clinical phenotype and facilitates the differentiation of dimension-specific etiological mechanisms. The aim of the present study was to investigate the association between the variation in the regulator of G-protein signaling 4 (RGS4) gene, a putative candidate gene for psychosis previously associated with schizophrenia endophenotypes, and psychotic-like experiences (PLEs). In total, 808 healthy individuals completed the community assessment of psychic experiences (CAPE) to measure positive and negative PLEs and provided a DNA sample. Two RGS4 single-nucleotide polymorphisms (SNPs) (rs951436 [SNP4] and rs2661319 [SNP18]) were genotyped. Analyses of covariance (ANCOVA) were used to explore the association of positive and negative PLEs with RGS4 variation. Our results showed associations of positive and negative PLEs with the two polymorphisms studied: subjects with the T allele (SNP4) and the A allele (SNP18) had higher scores on both the positive and the negative dimensions. Haplotypic analyses supported these results, showing the highest scores in those with the TA haplotype (SNP4-SNP18). The RGS4 variants might exert gene-specific modulating effects on psychosis proneness.

Impact of attachment style on the 1-year outcome of persons with an at-risk mental state for psychosis

Attachment theory provides key elements for understanding the psychosocial vulnerability for and response to the emergence of psychosis. This study examined (1) whether pre-treatment attachment styles are differentially associated with clinical and functional outcome in at-risk mental state (ARMS) for psychosis patients across one year of psychosocial treatment, and (2) whether clinical change is associated with changes in attachment ratings beyond the effect of baseline symptom severity. Thirty-eight ARMS patients (mean age=16.7, S.D.=5.9) identified from a psychosocial needs-adapted treatment were evaluated with the Positive and Negative Syndrome Scale, the Global Assessment of Functioning, and the Relationships Questionnaire. Lower levels of insecure-avoidant attachment predicted better clinical outcomes, whereas higher levels of secure attachment predicted improvement in functioning. A decrease in preoccupied-anxious attachment was associated with symptom amelioration. The findings suggest that the intensity of insecure attachment plays a significant role in the clinical outcome of ARMS patients involved in psychosocial treatment. Reducing the levels of insecure attachment in the therapeutic setting probably favors a better course in the early phases of psychosis. Furthermore, the finding that negative models of the self and others were associated with symptom outcome is consistent with current psychosocial models of psychosis.

Interaction between FKBP5 gene and childhood trauma on psychosis, depression and anxiety symptoms in a non-clinical sample

BACKGROUND Childhood trauma has been associated with a heightened risk for presenting clinical and non-clinical psychopathology in adulthood. Genes related with the stress response, such as the FK506 binding protein 51 (FKBP5), are plausible candidates moderating the effects of childhood trauma on the emergence of such symptoms later on. The present study aimed to explore the moderating role of FKBP5 genetic variability on the association of different types of childhood trauma with subclinical psychosis, depression and anxiety in a non-clinical sample. METHODS Schizotypy, psychotic-like experiences, depression and anxiety symptoms and childhood trauma were assessed in 808 young adults. Two FKBP5 haplotypic blocks were detected: block 1 (rs3800373 - rs9296158 - rs1360780) and block 2 (rs9470080 - rs4713916). Subjects were classified in two groups according to whether they carried or not the risk haplotype previously described in the literature (block 1: CAT and block 2: TA). Linear regression analyses were used to study (i) the main effects of childhood trauma and FKBP5 haplotype blocks and (ii) their interaction effects on the mentioned forms of psychopathology. RESULTS All childhood trauma scales, except sexual abuse, were associated with schizotypy, psychotic-like experiences, depression and anxiety symptoms. None of the analysed symptoms was associated with the main effects of FKBP5 genetic variability. However an interaction effect between block 1 and physical abuse was observed on anxiety, with lower scores in CAT carriers. This effect was driven by SNP 1 and 2. Moreover, an interaction effect between block 2 and physical abuse was identified on the variables tapping depressive and anxiety symptoms. Specifically, non-TA carrier subjects who were exposed to physical abuse were found to be at higher risk for depressive and anxiety symptoms. These effects were driven by SNP 5. No interaction effect was observed for the other variables. CONCLUSIONS Our data suggest that exposure to childhood physical abuse may increase the risk for sub-clinical depressive and anxiety symptoms depending on FKBP5 genetic variability. Further research is needed to better elucidate the role of FKBP5 on mental health in clinical and non-clinical cohorts.

Interview Investigation of Insecure Attachment Styles as Mediators between Poor Childhood Care and Schizophrenia-Spectrum Phenomenology.

Background Insecure attachment styles have received theoretical attention and some initial empirical support as mediators between childhood adverse experiences and psychotic phenomena; however, further specificity needs investigating. The present interview study aimed to examine (i) whether two forms of poor childhood care, namely parental antipathy and role reversal, were associated with subclinical positive and negative symptoms and schizophrenia-spectrum personality disorder (PD) traits, and (ii) whether such associations were mediated by specific insecure attachment styles. Method A total of 214 nonclinical young adults were interviewed for subclinical symptoms (Comprehensive Assessment of At-Risk Mental States), schizophrenia-spectrum PDs (Structured Clinical Interview for DSM-IV Axis II Disorders), poor childhood care (Childhood Experience of Care and Abuse Interview), and attachment style (Attachment Style Interview). Participants also completed the Beck Depression Inventory-II and all the analyses were conducted partialling out the effects of depressive symptoms. Results Both parental antipathy and role reversal were associated with subclinical positive symptoms and with paranoid and schizotypal PD traits. Role reversal was also associated with subclinical negative symptoms. Angry-dismissive attachment mediated associations between antipathy and subclinical positive symptoms and both angry-dismissive and enmeshed attachment mediated associations of antipathy with paranoid and schizotypal PD traits. Enmeshed attachment mediated associations of role reversal with paranoid and schizotypal PD traits. Conclusions Attachment theory can inform lifespan models of how adverse developmental environments may increase the risk for psychosis. Insecure attachment provides a promising mechanism for understanding the development of schizophrenia-spectrum phenomenology and may offer a useful target for prophylactic intervention.