Neus Barrantes-Vidal

Early adversity and 5-HTT/BDNF genes: new evidence of gene-environment interactions on depressive symptoms in a general population.

BACKGROUND Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene x environment (GxE) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms. METHOD A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample. RESULTS Total childhood adversity (beta=0.27, p<0.001), childhood sexual abuse (CSA; beta=0.17, p<0.001), childhood emotional abuse (beta=0.27, p<0.001) and childhood emotional neglect (beta=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001). CONCLUSIONS Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Anxiety and depression symptoms in psychometrically identified schizotypy.

The neurodevelopmental vulnerability for schizophrenia appears to be expressed across a dynamic continuum of adjustment referred to as schizotypy. This model suggests that nonpsychotic schizotypic individuals should exhibit mild and transient forms of symptoms seen in full-blown schizophrenia. Given that depression and anxiety are reported to be comorbid with schizophrenia, the present study examined the relationship of psychometrically defined schizotypy with symptoms of depression and anxiety in a college student sample (n=1258). A series of confirmatory factor analyses indicated that a three-factor solution of positive schizotypy, negative schizotypy, and negative affect provided the best solution for self-report measures of schizotypy, anxiety, and depression. As hypothesized, the model indicated that symptoms of depression and anxiety are more strongly associated with the positive-symptom dimension of schizotypy than with the negative-symptom dimension. This is consistent with studies of schizophrenic patients and longitudinal findings that positive-symptom schizotypes are at risk for both mood and non-mood psychotic disorders, while negative-symptom schizotypes appear more specifically at risk for schizophrenia-spectrum disorders.

Neurocognitive, behavioural and neurodevelopmental correlates of schizotypy clusters in adolescents from the general population

Abstract Introduction : Studies on the neurocognitive correlates of schizotypy dimensions have found inconsistent results. This might stem from the fact that correlational methods, in contrast to cluster analysis, do not account for the possibility that a subject presents high scores on more than one dimension simultaneously. We aimed to establish clusters of normal adolescents based on schizotypy dimensions and compare them on neurocognitive, behavioural, and neurodevelopmental markers. Methods : Two hundred seventy normal adolescents from the general population (mean age 13.4, SD=0.72) attending obligatory education were evaluated. Results : A K-means iterative cluster analysis was performed with the Perceptual Aberration, Revised Social Anhedonia and Physical Anhedonia Scales. A forced four-cluster model yielded the following clusters: ‘negative schizotypy’, ‘high or mixed schizotypy’, ‘positive schizotypy’, and ‘normal scorers’. Comparisons with ANOVAs showed that ‘high schizotypes’ performed poorly on neurocognition (Wechsler Intelligence Scales for Children-Revised (WISC-R) and Verbal Fluency (FAS)) and obtained the highest teacher ratings (TRF) of behavioural problems. ‘Negative schizotypes’ had the worst WCST results and more dermatoglyphic abnormalities. Both clusters had more neurological soft signs than ‘normal scorers’ and ‘positive schizotypes’. Conclusions : Our results with community adolescents found the same cluster structure than the previous cluster analytic studies conducted in adult college subjects. Furthermore, we showed differences among them on neurocognitive and malneurodevelopment markers consistent with the adult literature on schizotypy.

The Role of Schizotypy in the Study of the Etiology of Schizophrenia Spectrum Disorders

Schizotypy provides a useful construct for understanding the development of schizophrenia spectrum disorders. As research on the epidemiology of psychotic symptoms and clinical risk for psychosis has expanded, conceptual challenges have emerged to comprehend the nature and borders of the space comprised between personality variation and psychosis. Schizotypy is considered in light of these more recent constructs. It is suggested that rather than being superseded by them due to their higher specificity and predictive power for transition to psychosis, schizotypy integrates them as it constitutes a dynamic continuum ranging from personality to psychosis. The advantages of schizotypy for studying schizophrenia etiology are discussed (eg, it facilitates a developmental approach and the identification of causal, resilience, and compensating factors and offers a multidimensional structure that captures etiological heterogeneity). An overview of putative genetic, biological, and psychosocial risk factors is presented, focusing on communalities and differences between schizotypy and schizophrenia spectrum disorders. The found notable overlap supports etiological continuity, and, simultaneously, differential findings appear that are critical to understanding resilience to schizophrenia. For example, discrepant findings in genetic studies might be interpreted as suggestive of sets of independent genetic factors playing a differential role in schizotypy and schizophrenia: some would influence variation specifically on schizotypy dimensions (ie, high vs low schizotypy, thereby increasing proneness to psychosis), some would confer unspecific liability to disease by impacting neural properties and susceptibility to environmental factors (ie, high vs low resilience to disorder) and some might contribute to disease–specific characteristics. Finally, schizotypy’s promise for studying gene-environment interactions is considered.

Schizotypy: Looking Back and Moving Forward

This article introduces and reviews the history of the construct of schizotypy for the special section appearing in the journal. Schizotypy offers a useful construct for understanding the etiology, development, and expression of schizophrenia-spectrum psychopathology and a unifying construct for linking a broad continuum of clinical and subclinical manifestations. The article reviews the descriptive psychopathology roots of schizotypy, Meehl and Claridges classical formulations of the construct (including the debate about dimensional vs taxonic structure), and the need for a comprehensive, multidimensional model of schizotypy. The article briefly reviews the wide empirical literature supporting schizotypy and also examines several criticisms and misconceptions about the construct and research methods used to assess it. Finally, the article offers several suggested goals for future schizotypy research.

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.

The expression of positive and negative schizotypy in daily life: An experience sampling study

BACKGROUND Psychometrically identified positive schizotypy and negative schizotypy are differentially related to psychopathology, personality and social functioning. However, little is known about the experience and expression of schizotypy in daily life and the psychological mechanisms that trigger psychotic-like experiences. METHOD The present study employed experience sampling methodology (ESM) to assess positive and negative schizotypy in daily life in a non-clinical sample of 412 young adults. ESM is a structured diary technique in which participants are prompted at random times during the day to complete assessments of their current experiences. RESULTS As hypothesized, positive schizotypy was associated with increased negative affect, thought impairment, suspiciousness, negative beliefs about current activities and feelings of rejection, but not with social disinterest or decreased positive affect. Negative schizotypy, on the other hand, was associated with decreased positive affect and pleasure in daily life, increased negative affect, and decreases in social contact and interest. Both positive schizotypy and negative schizotypy were associated with the desire to be alone when with others. However, this was moderated by anxiety in positive schizotypy and by diminished positive affect in negative schizotypy. CONCLUSIONS The results support the construct validity of a multidimensional model of schizotypy and the ecological validity of the positive and negative schizotypy dimensions. ESM appears to be a promising method for examining the daily life experiences of schizotypic individuals.

Putative role of the COMT gene polymorphism (Val158Met) on verbal working memory functioning in a healthy population.

Working memory has been described as a neurocognitive probe of prefrontal brain functioning. Genetic variability related with catechol‐O‐methyltransferase (COMT) gene (Val158Met polymorphism) has received increasing attention as a possible modulator of working memory tasks in both schizophrenic patients and healthy subjects, although inconsistencies across studies have been found. This may be related to the existence of different working memory components, processes and modalities, which may have different sensitivities to subtle changes in dopamine levels and, therefore, the effect of the underlying COMT Val158Met genetic variability. To test this out a large sample of 521 healthy individuals from the general population were tested on the WCST and three working memory tasks that cover the assessment of verbal and spatial working modalities as well as different components and processes (Letter and Number Sequencing, CPT‐IP, Backwards Visual Span). All individuals were genotyped for the rs4680 (Val158Met) polymorphism at the COMT gene. Met carriers showed near‐significant better performance in the LNS compared with Val/Val individuals (F = 3.9, df = 1, P = 0.046). Moreover, the analysis for linear trend found that Met allele carriers showed significantly better performance than Val/Val individuals (B = 0.58 P = 0.031), although evidence for a linear trend was not found. None of the WCST indices differed among genotypes. Consistent with the hypothesis that Val158Met polymorphism (COMT gene) might account for individual differences on dopamine‐dependent prefrontally related neurocognitive functions, the Letter‐Number Sequencing task, which requires not only maintenance but also active manipulation of information seemed to be more sensitive to the disadvantageous Val/Val genotype in a large non‐clinical sample.

Psychopathology, social adjustment and personality correlates of schizotypy clusters in a large nonclinical sample

INTRODUCTION Correlational methods, unlike cluster analyses, cannot take into account the possibility that individuals score highly on more than one symptom dimension simultaneously. This may account for some of the inconsistency found in the literature of correlates of schizotypy dimensions. This study explored the clustering of positive and negative schizotypy dimensions in nonclinical subjects and whether schizotypy clusters have meaningful patterns of adjustment in terms of psychopathology, social functioning, and personality. METHODS Positive and negative schizotypy dimensional scores were derived from the Chapman Psychosis-Proneness Scales for 6137 college students and submitted to cluster analysis. Of these, 780 completed the NEO-PI-R and Social Adjustment Scale-self report version, and a further 430 were interviewed for schizophrenia-spectrum, mood, and substance use psychopathology. RESULTS Four clusters were obtained: low (nonschizotypic), high positive, high negative, and mixed (high positive and negative) schizotypy. The positive schizotypy cluster presented high rates of psychotic-like experiences, schizotypal and paranoid symptoms, had affective and substance abuse pathology, and was open to experience and extraverted. The negative schizotypy cluster had high rates of negative and schizoid symptoms, impaired social adjustment, high conscientiousness and low agreeableness. The mixed cluster was the most deviant on almost all aspects. CONCLUSIONS Our cluster solution is consistent with the limited cluster analytic studies reported in schizotypy and schizophrenia, indicating that meaningful profiles of schizotypy features can be detected in nonclinical populations. The clusters identified displayed a distinct and meaningful pattern of correlates in different domains, thus providing construct validity to the schizotypy types defined.

Neurological soft signs in psychometrically identified schizotypy

Patients with schizophrenia often exhibit structural brain abnormalities, as well as neurological soft signs (NSS), consistent with its conceptualization as a neurodevelopmental disorder. NSS are mild, presumably nonlocalizing, neurological impairments that are inferred from performance deficits in domains such as sensory integration, motor coordination, and motor sequencing. The vulnerability for schizophrenia is presumed to be expressed across a broad continuum of impairment referred to as schizotypy. It is hypothesized that nondisordered people along the schizotypy continuum should exhibit elevated rates of NSS. The present study examined the relation of psychometrically identified positive and negative schizotypy with NSS using the Neurological Evaluation Scale in a nonclinically ascertained sample of young adults (n=177). As hypothesized, negative, but not positive, schizotypy was related to increased NSS in tasks that assessed fine and gross motor coordination, motor sequencing, eye movement abnormalities, and memory recall. However, positive schizotypy was associated with increased NSS in tasks related to sensory integration dysfunction. In general, the positivexnegative schizotypy interaction term was unrelated to individual NSS tasks. The findings support: a) the theory that the vulnerability for schizophrenia is expressed across a broad continuum of subclinical and clinical impairment referred to as schizotypy; b) the multidimensional structure of schizotypy; and c) the notion that schizotypy is an appropriate construct for understanding the etiology and development of schizophrenia-spectrum disorders.