Associations between schizotypal features and indicators of neurological and morphological abnormalities

OBJECTIVE: Limited research suggests that subtle neurological and morphological abnormalities that have been documented in patients with schizophrenia also may be associated with schizotypal traits in non-psychiatric samples. Based on the notion that neurological soft signs (NSS) may mark a genetic diathesis, this study hypothesized that NSS scores would be related to the level of schizotypy in relatives of schizophrenia patients and in controls. Additionally, associations between MPA scores and schizotypy were explored in these two groups. METHOD: Twenty-six first-degree relatives of schizophrenia patients and 38 controls with no personal or family history of psychosis were assessed for schizotypy using the Structured Clinical Interview for DSM-IV Axis II Disorders schizotypal personality disorder module, as well as the self-administered Schizotypal Personality Questionnaire. The Neurological Evaluation Scale and a structured examination for MPAs also were administered. RESULTS: Mean schizotypy scores did not differ between relatives and controls. Both NSS and MPAs were associated with the level of interviewer-assessed schizotypal features in controls but not in relatives of patients with schizophrenia. NSS and MPAs were not associated with self-reported schizotypy in either group. CONCLUSIONS: These findings demonstrate that both NSS and MPAs are associated with interview-based schizotypal traits, at least in non-psychiatric participants. Future research should seek to replicate these results in other samples of relatives and controls.     

Neurological signs in parents of schizophrenic patients

The importance of neurological abnormalities in relatives of schizophrenic patients is not completely clear and has been questioned. The hypothesis that neurological abnormalities are trait markers for a vulnerability to develop schizophrenia was tested in 32 parents of patients with schizophrenia and 34 healthy controls. A comprehensive and standardized neurological assessment battery was used. The examiners were blind as to whether they tested a parent of a patient or a healthy control. Four function domains were investigated; higher cerebral functions, cranial nerve functions, general motor functions and gait. There were no significant differences between parents of patients and healthy controls on any of the neurological function domains, or on the total number of neurological abnormalities. No difference was found between parents with a positive family history of schizophrenia spectrum disorders, parents with a negative family history and controls. Results suggest that the neurological functions investigated are not related to a genetic liability to develop schizophrenia.     

Association of schizotypy with striatocortical functional connectivity and its asymmetry in healthy adults

Altered striatocortical functional connectivity has been suggested to be a trait marker of schizophrenia spectrum disorders, including schizotypal personality. In the present study, we examined the association between schizotypal personality traits and striatocortical functional connectivity in a sample of healthy adults. The German version of the Schizotypal Personality Questionnaire was obtained from N = 111 participants recruited from the general public. Resting‐state functional magnetic resonance imaging scans were acquired at 3T. Six striatal seed regions in each hemisphere were defined and striatocortical resting‐state functional connectivity (rsFC) as well as its lateralization indices was calculated. Regression analysis showed that schizotypy scores, especially from the positive dimension, were positively correlated with rsFC between ventral striatum and frontal cortex and negatively associated with rsFC between dorsal striatum and posterior cingulate. No significant associations were found between negative dimension schizotypy and striatocortical rsFC. We also found positive correlations between schizotypy total scores and lateralization index of right dorsal caudate and right rostral putamen. In conclusion, the present study extends previous evidence of altered striatocortical rsFC in the schizophrenia spectrum. The observed associations resemble in part the alterations observed in psychotic patients and their relatives, providing support for dimensionality from schizotypal personality to the clinical disorder. Hum Brain Mapp 39:288–299, 2018. © 2017 Wiley Periodicals, Inc.     

Schizotypal traits impact upon executive working memory and aspects of IQ

Previous inconsistent findings concerning a link between working memory dysfunction and negative aspects of non-clinical schizotypy have been interpreted to cast doubt on the continuity model of ‘negative psychosis-proneness’. This study employed the Letter-Number-Sequencing (LNS) task and the Trail-Making Test to assess more demanding, executive working memory. A secondary concern was to rule out possible mediating effects of familial schizophrenia. It was hypothesised that executive working memory impairment would be associated primarily with negative rather than positive schizotypy even in the absence of familial schizophrenia. Matrix reasoning controlled for IQ. In 87 university-student participants with no known family history of schizophrenia, lower LNS scores were associated with higher levels of negative and positive schizotypy traits. Counter to expectations, matrix reasoning scores were also associated with schizotypy, primarily the cognitive/perceptual traits. Results were similar when participants with a known family history of schizophrenia (10) were included (N = 97). Findings support the view that impairment of executive working memory (indexed by LNS) is a reliable cognitive marker for negative (and perhaps also positive) schizophrenia vulnerability, independent of familial schizophrenia, and provide the first indication that some facets of IQ (e.g. inductive reasoning) might also be compromised in non-clinical schizotypy.     

Higher prefrontal cortical thickness in high schizotypal personality trait

A model of schizophrenia-spectrum disorders hypothesized that schizotypy shares biomarkers with schizophrenia but due to protective factors such as a greater prefrontal cortex those individuals have a reduced vulnerability to schizophrenia. In contrast to previous studies exploring volumetric brain correlates of schizotypy focussing on clinical samples or relying on between-group comparisons we measured cortical thickness and correlated it with the expression of schizotypal personality traits in a mentally healthy sample. We acquired high-resolution MRI scans from 34 subjects and used FreeSurfer to model the grey-white and pial surfaces for each individual cortex in order to compute the distance between these surfaces to obtain a measure of cortical thickness. Differences in cortical thickness were correlated with positive and negative factors of schizotypy as assessed by means of the schizotypal personality questionnaire. We found a significant positive correlation between right dorso-lateral prefrontal cortex (DLPFC) and right dorsal premotor cortex/frontal eye fields (dPMC/FEF) and the total schizotypy score, between right DLPFC and the positive factor, and between right temporo-parietal junction and the negative factor of schizotypy. The volume of thalamus was negatively correlated with schizotypy. A significant negative correlation between thalamus volume and dPMC/FEF cortical thickness was observed. One may speculate that this finding is in line with the hypothesis of a compensatory role of greater prefrontal cortex in schizotypy in healthy populations.     

Schizotypal dimensions: continuity between schizophrenia and bipolar disorders

BACKGROUND: Family studies have suggested that schizophrenia and bipolar disorders share some susceptibility factors. Schizotypal personality disorder (SPD) may be an intermediate phenotype common both to schizophrenia and bipolar disorders. We explored the familiality of schizotypal dimensions by comparing the magnitude of schizotypal dimensions between schizophrenic and bipolar relatives. We also looked for intra-familial resemblance for these dimensions, and for an increased familial risk of schizophrenia and/or bipolar disorders associated with a particular schizotypal dimension. METHODS: We used the Schizotypal Personality Questionnaire (SPQ) to study the three schizotypal dimensions (disorganization, negative and positive) in a sample of unaffected first-degree relatives of schizophrenic (N=85), psychotic bipolar (N=63) and bipolar (N=32) probands. Differences between groups were tested using a two-tailed t-test or ANOVA for continuous variables and a chi-squared test for discrete variables. We used the intraclass correlation method to study the intra-familial correlation. Linear mixed models were used to measure the familial risk. RESULTS: The disorganization dimension appears to be common to relatives of both schizophrenia and psychotic bipolar disorders, but not in the relatives of non-psychotic bipolar probands. This dimension also increases the familial risk of these two disorders. The negative dimension shows intra-familial resemblance (R=0.29), we failed to observe the expected familiality for the disorganized dimension. CONCLUSIONS: The shared nature of the disorganization dimension shown by a similar familial risk for schizophrenia and psychotic bipolar disorders suggests that same genetic background may underlie psychotic disorders. Although, negative dimension is familial, it is not associated for an increased familial risk for both disorders.     

Childhood schizotypy and positive symptoms in schizophrenic patients predict schizotypy in relatives

BACKGROUND: Schizotypy is one phenotypic expression of the familial-genetic liability to schizophrenia, but its precise relationship to frank psychotic symptoms remains unclear. We, therefore, set out to examine the relationships between (a) premorbid personality in schizophrenic patients, (b) the psychopathology they showed, and (c) schizotypal traits in their relatives. METHOD: Ninety consecutively admitted schizophrenic patients were interviewed with the Present State Examination (PSE). Their mothers were interviewed concerning their childhood personality and social adjustment, and 121 of their well relatives were evaluated with three different schizotypal scales. Factor analyses were carried out on (a) the nine main psychotic symptoms from the patients' PSE interview, and on (b) the schizotypal features derived from the scales completed by the first-degree relatives. Correlation coefficients were calculated between premorbid personality traits, and factor scores in probands and in relatives. RESULTS: No relationship was found between childhood schizoid-schizotypal personality traits and any particular dimension of psychopathology in patients. The positive syndrome in patients was correlated with higher scores for relatives on the three schizotypy scales, but did not predict any specific pattern of schizotypy in the relatives. Premorbid schizoid-schizotypal traits were also correlated with schizotypy in the relatives. CONCLUSIONS: Schizotypy in relatives has a familial relationship with schizoid-schizotypal traits in the childhood, and with positive symptoms during the illness, of schizophrenic patients.     

Handedness and schizotypy in non-psychotic relatives of patients with schizophrenia

Existing studies have found the relationship between handedness and schizotypy to be inconsistent, and had limited generalisability since only highly homogeneous groups have been investigated. This study aimed to examine the relation between handedness and the four schizotypal factors identified from a previous confirmatory factor analysis in a population of high familial loading for schizophrenia. Study participants consisted of non-psychotic first-degree relatives (850 parents and 334 siblings) of sib-pairs who were co-affected with schizophrenia. All participants were interviewed with the Diagnostic Interview for Genetic Studies, which contains a section of the modified Structured Interview for Schizotypy, and the Annett handedness questionnaire. Both categorical and continuous indicators for handedness were examined. Non-right-handed siblings of schizophrenia patients displayed more positive schizotypal features than their right-handed counterparts when the two-way Annett's handedness classification was adopted. No association was found when handedness was treated as continuous. The relationship between handedness and schizotypy was insignificant for parents probably due to the strong social pressure against left-handedness. We concluded that categorical non-right-handedness was associated with positive schizotypy in non-psychotic siblings of schizophrenia patients. The results indicate that an atypical cerebral lateralisation underlying non-right-handedness may be also a contributing factor to positive schizotypy.     

Handedness and schizotypy in non-psychotic relatives of patients with schizophrenia

Existing studies have found the relationship between handedness and schizotypy to be inconsistent, and had limited generalisability since only highly homogeneous groups have been investigated. This study aimed to examine the relation between handedness and the four schizotypal factors identified from a previous confirmatory factor analysis in a population of high familial loading for schizophrenia. Study participants consisted of non-psychotic first-degree relatives (850 parents and 334 siblings) of sib-pairs who were co-affected with schizophrenia. All participants were interviewed with the Diagnostic Interview for Genetic Studies, which contains a section of the modified Structured Interview for Schizotypy, and the Annett handedness questionnaire. Both categorical and continuous indicators for handedness were examined. Non-right-handed siblings of schizophrenia patients displayed more positive schizotypal features than their right-handed counterparts when the two-way Annett's handedness classification was adopted. No association was found when handedness was treated as continuous. The relationship between handedness and schizotypy was insignificant for parents probably due to the strong social pressure against left-handedness. We concluded that categorical non-right-handedness was associated with positive schizotypy in non-psychotic siblings of schizophrenia patients. The results indicate that an atypical cerebral lateralisation underlying non-right-handedness may be also a contributing factor to positive schizotypy.     

Overlap of autistic and schizotypal traits in adolescents with Autism Spectrum Disorders

This study addresses the unraveling of the relationship between autism spectrum and schizophrenia spectrum traits in a population of adolescents with Autism Spectrum Disorders (ASD). Recent studies comparing isolated symptoms of both spectrum disorders as well as diagnostic criteria for each (DSM-IV-TR) suggest resemblances in the clinical phenotype. A group of 27 adolescents with ASD (11 to 18 years) and 30 typically developing adolescents, matched for age and gender, participated in this study. Within the ASD group 11 adolescents satisfied DSM-IV-TR criteria for schizotypal personality disorders. Autistic and schizotypal traits were identified by means of well validated questionnaires (Autism Questionnaire, AQ and Schizotypal Personality Questionnaire-Revised, SPQ). Significantly more schizotypal traits in adolescents with ASD were found than in typically developing controls. Besides high levels of negative symptoms, adolescents with ASD also displayed high levels of positive and disorganized symptoms. There appeared to be a relationship between the mean level of autistic symptoms and schizotypal traits, as well as specific associations between autistic symptoms and negative, disorganized and positive schizotypal symptoms within individuals. Schizotypal symptomatology in all sub dimensions that are reflected by the SPQ scores, was most prominently associated with attention switching problems of the autism symptoms from the AQ. These findings indicate that patients diagnosed with an ASD show schizophrenia spectrum traits in adolescence. Although other studies have provided empirical support for this overlap in diagnostic criteria between both spectrum disorders, the present findings add to the literature that behavioral overlap is not limited to negative schizotypal symptoms, but extends to disorganized and positive symptoms as well.     

The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study

Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate in the relatives of schizophrenic patients, supporting the view that both are likely to reflect genetic contributions to liability to schizophrenia. Within the relatives of schizophrenic patients, however, the interrelationships between these potential indicators of liability to schizophrenia are not well known. Using data from the UCLA Family Study, we examine the interrelationships between personality disorder symptoms and neurocognitive functioning in nonpsychotic first-degree relatives of schizophrenic patients. Factor analyses indicate that several dimensions of schizotypy can be identified. A neurocognitive dysfunction dimension includes loadings from measures of sequential visual conceptual tracking, rapid perceptual encoding and search, and focused, sustained attention as well as the rating of odd and eccentric behavior from schizotypal personality disorder. Other aspects of schizotypal personality disorder form separate positive schizotypy and negative schizotypy dimensions. These analyses support the view that schizotypy is multidimensional in relatives of schizophrenic patients and indicate that neurocognitive deficits in perception and attention are associated with particular schizotypal personality features.     

精神分裂症患者一级亲属人格特征的研究

目的 探讨精神分裂症患者一级亲属的人格特征.方法 采用分裂型人格问卷(SPQ)及三维人格问卷(TPQ)评定181例精神分裂症患者一级亲属(高危组)、321名正常对照个体(对照组)的人格特征.结果 高危组sPQ阴性分裂型人格维度评分[(9.80±7.05)分]高于对照组[(8.42±5.87)分],差异有统计学意义(P＜0.05).高危组在TPQ寻求新奇维度评分[(15.60±5.62)分]、奖赏依赖维度评分[(17.41 ±1.13)分]与对照组[(14.20±2.83)分,(18.22±3.26)分]的差异均有统计学意义(P均＜0.01).高危组的阴性分裂型人格维度分数与寻求新奇维度、奖赏依赖维度分数显著相关(r=0.17和-0.23).结论 精神分裂症患者一级亲属具有阴性分裂型维度、寻求新奇维度、奖赏依赖维度的人格特征.     

The kings schizotypy questionnaire as a quantitative measure of schizophrenia liability

We used a new self-report measure, the Kings Schizotypy Questionnaire (KSQ; Williams, M. The psychometric assessment of schizotypal personality. PhD thesis. Institute of Psychiatry, University of London, 1993), to investigate schizotypy as a quantitative measure of familial liability to schizophrenia. The KSQ was administered to 135 DSM-IV schizophrenia probands, 153 of their healthy first-degree relatives, and 267 control subjects. We found that the questionnaire clearly differentiated schizophrenic from non-schizophrenic individuals, but failed to differentiate the relatives from controls. Possible reasons for this include defensive responding among relatives, self-selection bias among relatives, differences in data collection methods, and the possibility that positive aspects of schizotypy may not be closely related to familial liability to schizophrenia.     

Self-reported schizotypy and bipolar disorder: demonstration of a lack of specificity of the Kings Schizotypy Questionnaire

Previous studies have demonstrated that schizophrenia patients score highly on self-reported measures of schizotypy such as the Kings Schizotypy Questionnaire (KSQ), but relatively little is known about the specificity of these self-reported features to schizophrenia. We aimed to explore the specificity of schizotypal features to schizophrenia by measuring their prevalence in subjects with bipolar disorder. The Kings Schizotypy Questionnaire (KSQ) was administered to participants (n=92) in a sibling-pair genetic linkage study of bipolar disorder. Scores were compared with those of participants in a similarly designed, concurrent family study of schizophrenia (n=135) and psychiatrically well controls (n=263). The bipolar group had significantly more schizotypal features than controls but significantly less than schizophrenia patients. Whether a bipolar subject had experienced positive psychosis had no effect on his/her schizotypy score. We conclude that elevated self-reported schizotypy as measured by the KSQ is not specific to schizophrenia, and may be associated with functional psychosis in general.     

WCST performance and schizotypal features in the first-degree relatives of patients with schizophrenia.

Since the findings concerning the Wisconsin Card Sorting Test (WCST) performance of healthy first-degree relatives of patients with schizophrenia are equivocal, it still remains unclear whether the WCST may serve as a neuropsychological indicator of vulnerability to schizophrenia. The aim of this study was to evaluate whether the first-degree relatives' schizotypal features could account for these discrepancies. The subjects were 24 schizophrenic probands, 49 of their first-degree relatives and 41 normal controls. The computerized version of the WCST was used and schizotypy features were assessed using four of Chapman's scales. The patient group performed worse on the WCST and had higher scores of schizotypy than the control group. The relatives group did not significantly differ from the control, neither on the WCST performance nor on the scores of schizotypy. However, the subgroup of relatives and the subgroup of patients with high scores on the negative dimension of schizotypy showed a worse performance on the WCST than the subgroups with low scores. There were no differences on the WCST performance between the subgroups with high vs. low scores on the positive dimension of schizotypy. Thus, discrepancies across studies could be explained by a confounding factor represented by the negative dimension of schizotypy.     

Familial association of schizotypal traits with psychotic and affective disorders

The criteria for schizotypal personality disorder were developed on the basis of traits observed in biologic relatives of schizophrenic and borderline schizophrenic probands from the Danish adoption studies. In this review, the relationship between schizotypal personality disorder and the schizophrenic spectrum, affective disorders, and psychotic disorders is explored. A dimension of psychosis may overlap with the schizophrenia spectrum to yield chronic schizophrenia, with the affective disorders spectrum to yield psychotic affective disorder, or by itself lead to other psychotic disorders. Schizotypal personality disorder in this model is posited to represent schizophrenia spectrum disorder that does not overlap with psychosis, whereas nonpsychotic affective disorders represent the affective disorders that do not overlap with psychosis. Delusional disorder represents another psychotic disorder that is not specifically related to either schizophrenia or the affective disorders. Evidence suggests that the schizotypal personality disorder criteria, particularly those emphasizing the negative symptoms or deficit-like symptoms of this disorder, specifically identify a unique relationship to the schizophrenia spectrum.     

Multiple dimensions of schizotypy in first degree biological relatives of schizophrenia patients

Considerable research has been devoted to identifying individuals predisposed to schizophrenia, with much of the effort devoted to identifying the personality characteristics of the biological relatives of schizophrenia patients. Although resource-consuming interviews have yielded promising results, investigators have long sought self-report measures that index genetic risk for schizophrenia. The Schizotypal Personality Questionnaire (SPQ) is a self-report measure that assesses the nine features of DSM-defined schizotypy. The SPQ, modified to include validity scales, was administered to 135 nonpsychotic first degree relatives of schizophrenia patients and 112 healthy controls. Principal components analysis (PCA) yielded three factors that correlated highly with previously reported factors (social-interpersonal, cognitive-perceptual, and disorganization). Social-interpersonal deficits were found to best differentiate relatives from controls. Contrary to the hypothesis that schizophrenia relatives are more defensive in responding to schizotypy questionnaires, relatives were significantly less defensive than controls. The results demonstrate that a multidimensional paper-and-pencil measure can characterize schizotypal features in schizophrenia relatives, which will be useful for the further delineation of the heritable schizophrenia spectrum phenotype.     

Associations between schizotypy and cerebral laterality

Atypical lateralization for language has been found in schizophrenia, suggesting that language and thought disorders on the schizophrenia spectrum may be due to left hemispheric dysfunction. However, research with those with non-clinical schizotypy has been inconsistent, with some studies finding reduced or reversed language laterality (particularly with positive schizotypal traits), and others finding typical left hemispheric specialization. The aim of the current study was to use both a behavioural (dual reading-finger tapping) task and an functional magnetic resonance imaging lexical decision task to investigate language laterality in a university sample of high- and low-schizotypal adults. Findings revealed no evidence for atypical lateralization in our sample for both overall schizotypy (measured by the Oxford-Liverpool Inventory of Feelings and Experiences) and positive schizotypy (measured by the Unusual Experiences subscale) groups. Our findings provide further evidence that non-clinical schizotypy is not associated with atypical language laterality.     

Frontal and occipital perfusion changes in dissociative identity disorder

There is some evidence that emotional reactivity to daily life stress is related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the emotional distress is elevated in schizophrenia patients with positive compared to negative family history. The aim of the study was to test the hypothesis that a persistent higher level of emotional distress in schizophrenia subjects is associated with a positive family history of schizophrenia. This study used the Talbieh Brief Distress Inventory (TBDI), the Positive and Negative Syndrome Scale (PANSS; including dysphoric mood, positive and negative subscales), Montgomery-Asberg Depression Rating Scale (MADRS), and the Distress Scale for Adverse Symptoms (DSAS) to investigate the difference in the magnitude of emotional distress scores between schizophrenia subjects with and without a positive family history of schizophrenia over time. Data were recorded for 69 multiplex family and 79 singleton patients at admission and about 16 months thereafter. No between-group differences were obtained in PANSS and DSAS scores. With regard to the TBDI: (a) both group of patients had no significant differences in emotional distress scores at admission; (b) patients with negative family history reported improvement in distress severity and depression severity (MADRS) 16 months after admission, while those with positive family history experienced persistent elevated emotional distress, mainly, on obsessiveness, and depression subscales; and (c) both groups of patients are characterized by elevated emotional distress at follow-up examination compared to healthy subjects. Thus, it appears that there is a strong association between positive family history and persistent elevated emotional distress. Because patients with positive and negative family history are likely to differ in genetic risk, our results suggest that long-term elevated levels of emotional distress may be related to a familial (environmental)/genetic vulnerability to schizophrenia.