Schizotypy: An Organizing Framework for Schizophrenia Research

ABSTRACT— Schizophrenia is the most devastating form of psychopathology known to humankind, and it has been slow to yield clues to its origins. Meehl's (1962, 1990) model detailed the nature of the latent liability for schizophrenia known as schizotypy and provided a major organizing function for research on schizophrenia. The schizotypy model integrates genetic and environmental contributions to liability as well as accounting for a range of clinical outcomes, all deriving from a genuine liability for the illness. Schizotypy, as a latent personality organization that harbors the liability for schizophrenia, provides a framework for detecting fundamental features of liability to schizophrenia prior to the onset of clinical illness. The schizotypy model is reviewed, the strategic benefits of it are discussed, and methods for detecting schizotypy are presented. A focus on perceptual aberrations—a schizotypic feature—in individuals unaffected by schizophrenia has yielded valuable clues to preclinical disturbances in neurocognitive processes, risk for schizophrenia among biological relatives, and genomic substrates, all of which are of interest to schizophrenia researchers.     

Resolving the latent structure of schizophrenia endophenotypes using expectation-maximization-based finite mixture modeling

Prior research has focused on the latent structure of endophenotypic markers of schizophrenia liability, or schizotypy. The work supports the existence of 2 relatively distinct latent classes and derives largely from the taxometric analysis of psychometric values. The present study used finite mixture modeling as a technique for discerning latent structure and the laboratory-measured endophenotypes of sustained attention deficits and eye-tracking dysfunction as endophenotype indexes. In a large adult community sample (N=311), finite mixture analysis of the sustained attention index d' and 2 eye-tracking indexes (gain and catch-up saccade rate) revealed evidence for 2 latent components. A putative schizotypy class accounted for 27% of the sample. A supplementary maximum covariance taxometric analysis yielded highly consistent results. Subjects in the schizotypy component displayed higher rates of schizotypal personality features and an increased rate of treated schizophrenia in their 1st-degree biological relatives compared with subjects in the other component. Implications of these results are examined in light of major theories of schizophrenia liability, and methodological advantages of finite mixture modeling for psychopathology research, with particular emphasis on genomic issues, are discussed.     

内表型方法在精神疾病研究中的应用

精神疾病在很大程度上受到遗传的影响,而对疾病的遗传学研究却没有得到一致的结论,内表型正是在这一背景下提出。内表型是可以通过生化测试或显微镜检查发现的内在的表现型,即内表型不是很明显的、外在的而是微观的、内在的,内表型比疾病的外在表现更接近疾病的生物学基础,更少受到外在因素的影响,因而通过内表型来研究疾病的遗传基因有着显著的优势。现有的精神疾病诊断和分类标准都是以临床症状和行为描述为基础的,缺少生物学基础,基于内表型的分析对建立疾病的诊断和分类的生物学基础是非常重要的。内表型可以是神经生理的,生物化学的,神经解剖的,认知的,神经心理学的测量。作为内表型需要满足与疾病共同存在,可遗传,状态独立,在家庭中和疾病共分离,在病人未发病亲属中比一般人群的比率要高等标准。该文在介绍了内表型的概念,说明了内表型的原理,优点与用处,以及作为内表型需要满足的标准之后,进而以几种常见的精神疾病（多动症、精神分裂症、抑郁症）为例说明了目前认知内表型研究的进展,其中反应抑制和工作记忆可以作为多动症的内表型,注意、言语记忆和工作记忆可以作为精神分裂症和抑郁症的内表型,文章回顾了它们作为内表型所满足的标准的相关文献。最后对内表型的研究做出了展望     

The "prodromal" patient: both symptomatic and at-risk

This article discusses conceptual issues relevant to the prospective diagnosis of the schizophrenic prodrome. Recent efforts to diagnose these patients with operational criteria based on current symptoms are reviewed. Symptomatic patients so identified appear to be treatment-seeking and to have mild cognitive impairments. In addition to being currently symptomatic, these patients are imminently at risk for progression of illness and development of schizophrenia. Data from three international centers suggest that this risk is approximately 40% over the next year of follow-up if untreated. The implications of the reviewed data for the appropriateness of the term "prodromal" and for treatment/prevention research for these patients are discussed.     

I. Genotype-environment interaction in the schizophrenia spectrum: genetic liability and global family ratings in the Finnish Adoption Study

In the Finnish Adoption Study, a national sample of adoptees with high versus low genetic liability for schizophrenia spectrum disorders was indexed by DSM-III-R diagnoses of their biological, adopting-away mothers. The rearing-family environments of the adoptees were independently evaluated from global ratings of directly observed adoptive family relationships. The interaction of high genetic liability and dysfunction of the rearing families predicted highly significantly to schizophrenia spectrum disorder of the adoptees at 21-year follow-up. Either low genetic liability or healthy rearing protected against a spectrum outcomes for the adoptees. Initial adoptive parent diagnosis, as a proxy for rearing family dysfunction, predicted to adoptee outcome only as a trend.     

Research on the clinical usefulness of the Rorschach: 1. The diagnosis of schizophrenia

Research on the use of the Rorschach in the diagnosis of schizophrenia is reviewed. The analysis of this research (from that done by Rorschach to the most recent) indicates that schizophrenics do not respond in any unique fashion to any particular determinant or any particular card. The research also indicates that the computation of percentages and ratios, no matter how complex, does not facilitate the identification of a schizophrenic process. What the research does demonstrate is that schizophrenia, in its overt as well as latent and borderline forms, is detectable on the Rorschach through an analysis of the patient's thinking. The thinking of the schizophrenic reveals highly personal, illogical, and bizarre associations to the blots. This analysis of thinking is not accomplished through assessment of the formal properties of the blots, e.g., the analysis of response to color, movement, shading, the color-to-movement ratio, or form level (low form level proves to be a function of psychoticism, not schizophrenia, per se) but more in terms of the phenomenology of the responses.     

Exploring the latent structure of the Perceptual Aberration, Magical Ideation, and Physical Anhedonia Scales in a German sample.

The schizotypy model proposed by Meehl (1990) assumes a discontinuous distribution of schizophrenia liability. The "schizogene" is thought to determine if one is at risk for psychosis (i.e., whether one is a member of the taxon or its complement, which are considered to be the two latent classes). Using a German non-student sample (n = 809) we wanted to (1) replicate the results of prior research pertaining to the latent structure and base rate of schizotypy assessed by the Perceptual Aberration Scale (PER; Chapman, Chapman, & Raulin, 1978), and (2) investigate whether the same holds true for two other prominent psychometric indices, the Magical Ideation Scale (MI; Eckblad & Chapman, 1983) and the Physical Anhedonia Scale (PhA; Chapman et al., 1976), if one uses the same kind of analysis--the MAXCOV-HITMAX analysis based on subsets of items (Meehl, 1973). Pertaining to PER and PhA, our results are in accordance with prior research showing a latent class structure and a base rate of about 12% for schizotypy. However, for MI, there was no evidence of a taxonic structure. Possible reasons for MI's negative results are discussed as well as the role of the concept "anhedonia."     

Schizophrenia and impulsive aggression: A heuristic inquiry with forensic and clinical implications

Assessment of a violent act committed by an offender with schizophrenia typically focuses on whether the act was due to distortions in thought or perception, i.e., delusions or hallucination. An important but less appreciated feature is the impulsivity of the act, which can have forensic and therapeutic implications. Here a modification of Barratt's classification of aggressive behavior is presented that includes premeditated (instrumental), medical (secondary), impulsive (expressive), and compulsive (instrumental and expressive) aggression. Violence due to a mental condition such as schizophrenia is considered medical, but even aggression motivated by delusions or hallucinations can also be characterized as impulsive, premeditated, or compulsive. Although research on aggression and schizophrenia is limited with regard to the impulsivity–premeditation dimension and difficult to compare, current evidence suggests this to be an important consideration in the assessment of aggression in individuals with schizophrenia, important both forensically and therapeutically. Future research on the impulsive–premeditated quality of aggressive acts by offenders with schizophrenia—research wherein aggressive behavior is defined, situational context is clarified, and diagnostic criteria are explicitly followed—should further refine our understanding of the nature of aggressive acts associated with schizophrenia. Findings from such research will undoubtedly inform assessment, treatment, and forensic relevance of schizophrenia-related physical aggression. Copyright © 2008 John Wiley & Sons, Ltd.     

Clinician race, situational attributions, and diagnoses of mood versus schizophrenia disorders

This research examined clinicians' consideration of situational factors in diagnostic decisions of mood vs. schizophrenia disorders among psychiatric inpatients from a low-income, African American community. Clinicians completed questionnaires describing their diagnostic decisions. Responses reflecting the usage of situational information were investigated. African American clinicians used situational information more than non-African American clinicians. However, this increased attention to situational information was not uniquely associated with a particular diagnostic decision for African American clinicians. In contrast, consideration of situational attributions by non-African American clinicians did increase the probability of a mood diagnosis. Logistic regression analyses suggested differential application of a diagnostic standard among African American and non-African American clinicians. Implications for enhancing the cultural sensitivity of diagnosis practices are discussed.     

Psychometric schizotypy and motor performance

Motor abnormalities have long been a focus in discussions of schizophrenia. The present study used a newly developed line drawing task to examine fine motor performance and psychometrically assessed schizotypy in a large, randomly ascertained sample of young adults (N = 120) with no history of psychosis. Poor motor performance on the line drawing task, indexed by root-mean-square error (RMS), was significantly related to 4 separate psychometric measures of schizotypy in the overall sample. The psychometric schizotypy-RMS association remained significant for 2 of the schizotypy measures even when the effects of intellectual functioning, mental state factors, and sustained attention were statistically controlled in a regression analysis. The status of the line drawing index as a schizophrenia liability measure is discussed.     

Somatosensory processing and schizophrenia liability: proprioception, exteroceptive sensitivity, and graphesthesia performance in the biological relatives of schizophrenia patients

In the present study, the authors examined somatosensory processing in 30 biological relatives of persons with schizophrenia (hereafter called "schizophrenia relatives"), 30 biological relatives of persons with bipolar affective disorder (psychiatric family control subjects), and 30 healthy control subjects with no family history of psychopathology. All 3 groups completed a weight discrimination task, a 2-point discrimination task, and a complex cognitive somatosensory task (i.e., graphesthesia). The schizophrenia relatives performed significantly worse on all 3 somatosensory tasks compared with both the healthy control subjects and the bipolar relatives. The healthy control subjects and psychiatric family control subjects showed no significant differences on any of the somatosensory tasks. Within the weight discrimination and 2-point discrimination tasks, schizophrenia relatives showed group differences on the d' index, the measure of sensitivity, whereas all 3 groups did not differ on lnbeta, the measure of response bias, suggesting a genuine difference in weight and touch sensitivity. The d' value of the weight discrimination task was significantly associated with both the cognitive-perceptual factor and negative symptom factor of the clinical questionnaire (e.g., Schizotypal Personality Questionnaire; SPQ), whereas the 2-point discrimination d' value and graphesthesia scores were significantly associated only with the cognitive-perceptual factor of the SPQ. Implications for the possible relation between somatosensory task performance and schizophrenia liability are discussed.     

Confirming the latent structure and base rate of schizotypy: a taxometric analysis.

Meehl's (1962, 1990) model of schizotypy and the development of schizophrenia implies that the structure of liability for schizophrenia is dichotomous and that a "schizogene" determines membership in a latent class, or taxon (Meehl & Golden, 1982). The authors sought to determine the latent structure and base rate of schizotypy. They applied Meehl's (1973; Meehl & Golden, 1982) MAXCOV-HITMAX taxometric analytic procedures to a subset of items from the Perceptual Aberration Scale (PAS; Chapman, Chapman, & Raulin, 1978), a prominent psychometric index of schizotypy, derived from a randomly ascertained nonclinical university sample (N = 1,093). The results, in accordance with Meehl's conjectures, strongly suggest that schizotypy, as assessed by the PAS, is taxonic at the latent level with a general population taxon base rate of approximately .10.     

Assessing ADHD across settings: contributions of behavioral assessment to categorical decision making

Adapted methods of behavioral assessment to assess home and school functioning in a way that maps directly to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., [DSM-IV]; American Psychiatric Association, 1994). The study was conducted in a school-based sample with 5- to 12-year-old children referred to a school intervention team. A multigate set of procedures was used to assign children to one of 3 groups: attention deficit hyperactivity disorder (ADHD), inattentive group; ADHD, combined group; and a non-ADHD control group. The ADHD Rating Scale-IV was used to assess parent and teacher ratings of ADHD symptoms as delineated in DSM-IV. The findings suggest that the use of a fixed cutoff point (i.e., 6 or more symptoms), which is employed in the DSM-IV, is often not the best strategy for making diagnostic decisions. The optimal approach depends on whether diagnostic information is being provided by the parent or teacher and whether the purpose of assessment is to conduct a screening or a diagnostic evaluation. Also, the results indicate that a strategy that aggregates symptoms in the order in which they are accurate in predicting a diagnosis of ADHD is a more effective strategy than the approach used in DSM-IV, which aggregates any combination of a specific number of items. Implications for using methods of behavioral assessment to make diagnostic decisions using DSM-IV criteria are discussed.     

Using latent class growth analysis to form trajectories of premorbid adjustment in schizophrenia

Premorbid adjustment varies widely among individuals with schizophrenia and has been shown to bear significantly on prodrome and onset characteristics, and on cognition, symptoms, and functioning after onset. The current analysis focused on the Premorbid Adjustment Scale, a retrospective measure assessing social and academic function at several time points from early childhood to illness onset. In an effort to explore discrete developmental subtypes, we applied latent class growth analysis to data from the Premorbid Adjustment Scale in our sample of individuals with schizophrenia (N = 208), finding three latent trajectory classes. The first of these classes showed consistently adequate-to-good social and academic functioning before onset; the second showed initially good function and deterioration with time until onset; the third showed poor functioning in childhood that deteriorated further during the years up to diagnosis. The classes differed significantly in terms of age of onset, processing speed, and functioning after onset. There were no significant differences in symptomatology. Our findings illustrate a potentially powerful methodological approach to the problem of heterogeneity in schizophrenia research, and add weight to the notion that aspects of premorbid history may be useful for subtyping schizophrenia patients. The potential implications of this subtyping strategy, including those pertaining to potential genetics studies, are discussed.     

The Discriminative Validity of the Whitaker Index of Schizophrenic Thinking

An attempt was made to assess the discriminative validity of the WIST with a sample of psychiatric inpatients. Through the use of a standardized structured interview and a diagnostic system for schizophrenia based on the use of discriminant function analysis with nonpathognomic symptom combinations, a reliable and valid system was used to establish the criterion diagnosis. Approximately 63% of patients reliably diagnosed as schizophrenic were detected via the WIST while only 14% of nonschizophrenic patients scored in the schizophrenic range on the WIST. The assets and liabilities of using the WIST to diagnose schizophrenia are discussed.     

The discriminative validity of the Whitaker Index of Schizophrenic Thinking

An attempt was made to assess the discriminative validity of the WIST with a sample of psychiatric inpatients. Through the use of a standardized structured interview and a diagnostic system for schizophrenia based on the use of discriminant function analysis with nonpathognomic symptom combinations, a reliable and valid system was used to establish the criterion diagnosis. Approximately 63% of patients reliably diagnosed as schizophrenic were detected via the WIST while only 14% of nonschizophrenic patients scored in the schizophrenic range on the WIST. The assets and liabilities of using the WIST to diagnose schizophrenia are discussed.     

Development of social functioning in preschizophrenia children and adolescents: a systematic review

Schizophrenia is associated with severe deficits in social functioning. Similar deficits may be present prior to psychosis onset, in childhood and adolescence. If so, then prepsychosis social deficits could provide clues to the development of pathological processes in preschizophrenia children and could potentially improve early identification of the disorder and suggest targets for intervention. Evidence is reviewed from birth cohort, case- control, and familial high-risk studies within distinct periods of development to clarify the nature, timing, and specificity of social deficits in preschizophrenia children and adolescents. The results indicate that poor social functioning does differentiate preschizophrenia children and adolescents from their peers and can be a sensitive and potentially specific predictor of schizophrenia, not just psychopathology in general. Furthermore, age (but not sex) appears to be an important moderator of the strength and specificity of the association between particular social deficits (e.g., externalizing, internalizing) and later schizophrenia. Results are discussed in the context of current developmental theories of timing and pathophysiology of schizophrenia involving hypothalamic- pituitary-adrenal dysregulation. Implications for the early identification and treatment of preschizophrenia individuals are also considered.     

Smooth pursuit eye movement and schizotypy in the community

Deficits in smooth pursuit eye movements are well documented in schizophrenia and schizotypic psychopathology. The status of eye tracking dysfunction (ETD) as an endophenotype for schizophrenia liability is relatively robust. However, the relation of ETD to schizophrenia-related deviance in the general population has not been confirmed. This study examined smooth pursuit eye tracking and schizotypal personality features in the general population. Smooth pursuit eye movement and schizotypal features were measured in 300 adult community subjects. The sample included both sexes, subjects with a wide age and educational range, and subjects with no prior history of psychosis. Primary outcome measures were peak gain (eye velocity/target velocity), catch-up saccade rate, and schizotypal feature scores. Total schizotypal features were significantly associated with decreased peak gain and were associated at the trend level with increased catch-up saccade rate. These associations were essentially unchanged after controlling for age, sex, and intellectual level effects. These data confirm a hypothesized association between schizotypal features and poorer eye tracking performance (principally, peak gain) in the general population as well as support the conceptualization of ETD as an endophenotype for schizophrenia liability.     

A developmental-contextual perspective on youth covictimization by community violence

Witnessing violence within the community-covictimization-has been recognized as a threat to the optimal development of youth. Following a discussion of methodological issues that plague covictimization research, the literature on covictimization is reviewed, beginning with findings on its prevalence. Correlates of covictimization are then examined within the Shakoor and Chalmers framework, comprising emotional, cognitive, and behavioral domains. Recent lines of research investigating interactions among these three domains are also explored. Further, a developmental-contextual approach toward studying covictimization is outlined and, from this perspective, the relationship of covictimization to social cognition, health-related behaviors, parenting, and social support is discussed. Finally, recommendations for further research are presented.