9a
Mark F. Lenzenweger
The overview of Cluster A personality disorders, focused primarily on schizotypal personality disorder (SPD), by Kerns (this volume) is rich and robust. It provides an excellent survey of the wave tops from multiple research literatures bearing upon the SPD condition/construct, which is reflective of the American Psychiatric Association’s DSM-system definition of the condition from DSM-III through DSM-5. There is much to like about this review and it presents an opportunity to reflect on conceptual and methodological issues related to the schizotypy construct, schizotypic psychopathology, schizotypal personality disorder, and schizophrenia. I offer these reflections in the spirit of advancing the discourse in this area as well as to provide historical and empirical context. My reflections are offered in no particular order and I seek to be succinct.
Brief Background and Orienting Comments
It is important to explicate several relevant distinctions regarding the meaning of the term schizotypic. The terms schizotypal PD and paranoid PD (PPD) denote the personality disorders as defined by the DSM nomenclature. SPD and PPD are defined by sets of atheoretical descriptors (signs and symptoms) that serve as diagnostic criteria; DSM systems (from 1980 [DSM-III] to the present [DSM-5]) eschew any relationship to an explanatory framework or theory for these disorders. Moreover, given their relatively high degree of comorbidity, shared phenomenological features, and empirical relationship to clinical schizophrenia, SPD and PPD are often referred to as the “schizophrenia-related personality disorders” (SRPDs) and are viewed as falling within the realm of “schizophrenia spectrum disorders.” In contrast to the term SRPD, schizotypic can be used to describe a range of signs and symptoms that are the phenotypic manifestation of schizotypy, or a latent personality organization that derives from a liability for schizophrenia. The term schizotypic can also serve as a generic shorthand descriptor of attenuated “schizophrenia-like” phenomenology that is fundamentally nonpsychotic. The schizotypic – schizophrenia phenomenological similarities are compelling, for example, perceptual aberrations ≈ hallucinations; suspiciousness/paranoid ≈ delusions; odd speech ≈ thought disorder; odd behavior ≈ bizarre behavior; social isolation ≈ asociality/withdrawal; blunted emotions ≈ flattened affect; peculiar ideas ≈ bizarre beliefs; and diminished pleasure ≈ anhedonia. SPD and PPD can readily be conceived of as manifestations of schizotypy as well, but they are not isomorphic with the schizotypy construct (Figure 9.a.1). Schizotypic psychopathology serves as a generic term for this broader class of schizophrenia-related mental disturbance. A schizotype is a person displaying evidence of schizotypic psychopathology. DSM-defined schizoid personality disorder is not always considered an SRPD (albeit a Cluster A condition) in light of available evidence.
SPD and schizotypy represent rich and complex constructs. However, schizotypy and SPD are not fungible concepts, although the terms have been used interchangeably by some and this has unfortunately introduced some lack of conceptual clarity in the theoretical and empirical literature. Schizotypy implies a theoretical model that has considerable utility as an organizing framework for the study of schizophrenia (see Meehl, 1962, 1990; see also Lenzenweger, 2006, 2010), schizophrenia-related psychopathology (e.g., delusional disorder, psychosis-NOS, schizotypal and paranoid personality disorder), and putative schizophrenia endophenotypes, a view I have advocated for over 30 years (Lenzenweger, 1994, 1998, 2006, 2010, 2015, 2018; Lenzenweger & Loranger, 1989). The leverage provided by the schizotypy model, especially as advocated by Meehl (1962, 1990; Figure 9.a.1), for understanding schizophrenia and its pathogenesis has been shown to be appreciable and Kerns rightly promotes this substantive thrust implicitly. Moreover, the schizotypy model and associated empirical research have helped to adjust the phenotypic boundaries of schizophrenia phenotype in the DSM-5 (e.g., schizotypal pathology is now included with schizophrenia). Illuminating the nature of schizotypy may aid in unraveling the current puzzle of the very low conversion to schizophrenia rates seen in “prodromal” schizophrenia research. Finally, I have argued that the schizotypy framework may be useful in understanding configurations of genes relevant to schizophrenia variants (Lenzenweger, 2010, pp. 234–235), an idea that is beginning to gain traction (Arnedo et al., 2015). There is no doubt that incorporation of schizotypy indicators into genomic studies of schizophrenia will increase their statistical resolving power. The advantages of a cleaner unit of analysis (the schizotype) free from the effects of medication, institutionalization, and neurocognitive decline are axiomatic.
Figure 9.a.1
Developmental model relating the genetic diathesis for schizophrenia, schizotaxia, and schizotypy and implied levels of analysis (inspired by Meehl 1962, 1990, with modifications by Lenzenweger, 2010). Those factors to the left of the vertical broken line (i.e., plane of observation) are “latent” and therefore unobservable with the unaided naked eye, whereas those factors to the right of the plane of observation are manifest (or observable). A DNA based liability – primary synaptic slippage (embodied in Meehl’s hypothetical process denoted “hypokrisia”) – creates impaired CNS based neural circuitry (schizotaxia) that eventuates in a personality organization (schizotypy) that harbors the liability for schizophrenia. Meehl (1962, 1990) viewed the genetically-determined liability to be entirely taxonic in nature (i.e., present or absent). However, this liability could also be determined by a confluence of genetic factors, probably many in number and of small effect, that have summed to pass a critical threshold (perhaps as many as 108 loci contribute to this liability: Schizophrenia Working Group of the Psychiatrics Genomics Consortium, 2014). The “synaptic slippage” in this model is consistent with modern-day concepts as diminished synaptic connectivity, abnormal connectivity, cognitive dysmetria, and so on. Social learning (SL) schedules interact with schizotaxia to yield to yield schizotypy. Psychosocial stressors (S) and polygenic potentiators (PGP) interact with schizotypy to yield manifest outcomes across a range of clinical compensation. Various possible manifest developmental outcomes include schizophrenia (which may involve an optional “second hit,” e.g., in utero exposure to maternal influenza), schizotypic psychopathology (e.g., schizotypal and/or paranoid personality disorders), or schizophrenia-related psychoses (e.g., delusional disorder). So-called “prodromal features” (withdrawal, reduced ideational richness, disorganized communication) may precede the onset of some (but not all) cases of schizophrenia. Endophenotypes (e.g., sustained attention deficits, eye tracking dysfunction, working memory impairments, motor dysfunction, thought disorder (secondary cognitive slippage), and/or psychometric deviance (PAS); see Gottesman & Gould, 2003), which are invisible to the unaided, “naked” eye (but detectable with appropriate technologies), are found below the plane of observation. Epigenetic factors refer to non-mutational phenomena, such as DNA methylation and histone acetylation (modification), that alter the expression of the schizophrenia gene (or genes). For example, there is the possibility that a hypermethylation process may serve to downregulate genes of relevance to schizophrenia. All individuals represented across this range of manifest outcomes are considered “schizotypes,” which does not necessarily imply an ICD or DSM diagnosis. Finally, if there are genetically distinct variants of schizophrenia (Arnedo et al., 2014), then each variant could follow a distinct developmental pathway comparable to that shown here but with different causal factors playing different roles across the variants.
© 2010, 2015 M. F. Lenzenweger, and used with permission
Reflections and Substantive Considerations
Schizotypy and Schizotypal Personality Disorder Are Not Fungible Terms
Although mentioned above, this point bears repeating. The schizotypy construct is broad and richly embedded in a developmental psychopathology framework, whereas SPD (likely a manifestation of schizotypy) represents an atheoretically organized collection of signs and symptoms as per the DSM system. The two concepts are not interchangeable and Kerns has encouraged the field to be precise in our language here, a view with which I agree.
Multidimensionality and Schizotypic Indicators
There has been a flood of reports in recent years that speak to the “multidimensionality” of schizotypic indicators. My dear friend, now late, Professor Irving Gottesman once quipped to me, “multidimensionality is simply a term that means complexity we do not understand.” That schizotypic indicators exist in some variety (the “multi” part) has been known since the time of Kraepelin and Bleuler and was emphasized by Meehl and others. The “dimensionality” part of the expression is trickier. What this typically means is that the multivariate statistical procedure factor analysis provided some evidence for more than one factor or component underlying the observed covariation in an indicator data set (symptoms or psychometric values). One must, however, be alert to the fact that factor analytic procedures by their very nature always find dimensions – that is all that they can do. Whether or not the resolved components have a genuinely quantitative (dimensional) nature at a latent level is an entirely different scientific question and calls for other analytic procedures that can answer it (see Lenzenweger, 2010 for extended discussion). There is complexity to schizotypal signs and symptoms for sure, that such complexity can be reduced to a smaller number of factors is true, but, in my view, the interesting questions emerge at the latent structure level.
Prodromal Schizophrenia and the Low Conversion Rate Problem
Professor Kerns draws important attention to the very low conversion rate to psychosis seen in the various prodromal schizophrenia studies. The prodromal (sometimes called “clinical high-risk” or “ultra high-risk”) approach, a derivative of earlier genetic and psychometric high-risk methods, has found that most young people (60–70 percent) deemed to be en route to schizophrenia (or, more broadly, psychosis) do not develop the condition during critical follow-ups (Fusar-Poli et al., 2013). It is highly likely that many of these so-called prodromal cases are simply schizotypes that will remain potentially impaired, but not clinically psychotic, across the lifespan. However, they may validly harbor an increased liability for schizophrenia (see Figure 9.a.1). I would argue that researchers interested in Cluster A disorders as well as schizotypy begin to probe this group of non-converters among the prodromal samples with greater precision.
Schizotypy, SPD, and Normal Personality
Professor Kerns writes “One view is that it is a schizophrenia-spectrum disorder, meaning a disorder less severe than schizophrenia but genetically related to it … A second view is that it reflects variation of normal personality traits” (p. 199 in the previous chapter). Sando Rado, Paul E. Meehl, myself, and others have long viewed schizotypy and schizotypic psychopathology as intimately connected to the illness we know as schizophrenia (see Lenzenweger, 1998, 2010, 2018). There is an alternative view, properly attributed to Claridge (1997) and colleagues, which views schizotypy as a “collection of psychotic traits [that] constitute an essentially healthy dimension of personality, which in adaptive form contributes to psychological variations as creativity, non-threatening hallucinations, and rewarding spiritual and mystical beliefs and experiences” (Rawlings, Williams, Haslam, & Claridge, 2008, p. 1670, italics added). This is known as the benign schizotypy model wherein schizotypy is viewed as a normal range personality trait varying by degree along a continuum and can even yield what is termed “healthy psychosis” (see Lenzenweger, 2015).
Most psychopathologists subscribe to a model that views schizophrenia as an illness and schizotypic conditions as falling within a spectrum of phenotypic outcomes derivative of an underlying liability for schizophrenia. Can we meaningfully relate schizotypic features to measures of normal personality? Of course, one can do so. The meaning of such associations, however, is an entirely different matter. We must always bear in mind that correlation does not imply continuity. Thus, while one can find correlations between indicators of schizotypy or SPD and measures of normal personality, it does not follow that one is the continuous extension of the other. Gedankenexperiment: I would imagine that schizophrenia symptoms correlate with neuroticism and openness to experience, but would we conclude that schizophrenia is an extreme expression of neuroticism or openness? The complexities of fitting schizotypic personality features, as expressive of schizophrenia liability, into frameworks seeking to model normal personality has always seemed challenging to me (Lenzenweger & Depue, 2016).
Parsimony in Language
Professor Kerns superbly shows an acute awareness of different methods of assessment for SPD and schizotypy. Others in the field, however, have conflated method of assessment with the nature of the construct under consideration (e.g., SPD or schizotypy measures). I see no conceptual gain in introducing idiosyncratic concepts such as “psychometric schizotypy” or “self-report schizotypy” as one has seen in recent years. If a measurement device is construct valid for the intended construct, how does the method of assessment being included in the name of the construct advance substantive discourse? We do not speak of “structured-clinical interview depression,” “self-report panic disorder,” or “observer-rated borderline personality disorder.”
Hedonic Capacity in Schizotypy, SPD, and Schizophrenia
Space limitations preclude a careful dissection of this issue; however, I believe hedonic capacity in relation to SPD (thinking narrowly) or schizotypy (thinking more broadly) is ripe for substantive and empirical development. It may well be that the diminished hedonic capacity we see in schizotypes may be reflective of the aversive impact that the harbored schizophrenia liability exerts on the psychosocial development and experience of schizotypic persons. This suggests the interesting possibility that the diminished hedonic capacity (sometimes referred to as “anhedonia”) is more of a psychological effect or artifact than otherwise. The work of Strauss and colleagues is relevant here (Strauss & Cohen, 2018).
Genetic Influences on SPD Features
The most influential early evidence that established a link between schizotypic phenomenology and clinical schizophrenia came from the Danish Adoption Study of Schizophrenia (Kety, Rosenthal, Wender, & Schulsinger, 1968). Using a definition of “borderline schizophrenia” heavily influenced by the clinical tradition, Kety et al. (1968) found elevated rates of borderline or latent schizophrenia in the biological relatives of adoptees with schizophrenia (replicated in Kety et al., 1994). These early adoption-study results provided compelling evidence for a genetically transmitted component underlying manifest schizophrenia and the less severe schizophrenia-like disorders. The hypothesized continuity between the schizophrenia and schizotypic conditions was thus not merely phenomenological, but also genetically influenced.
Clearly, this focus on the genetic bridge to schizophrenia has been sustained through a rich descriptive tradition and supported by findings indicating that schizotypic pathology is related genetically to schizophrenia per se (see Kendler, 2015, for review). Indeed, recent evidence, in the form of genome-wide association studies (GWAS) for loci relevant to schizophrenia and schizotypic psychopathology dimensions, confirms shared genetic substrates for the two forms of psychopathology (Bigdeli et al., 2014; Fanous et al., 2007).
The genes/symptoms puzzle is a fascinating one and Kerns directs us to it effectively. Consider also that empirical data have shown, in twin studies, that genetic influences for schizophrenia are clearly connected to negative schizophrenia symptoms, perhaps less so for the positive symptoms (Dworkin & Lenzenweger, 1984). That said the clinical schizophrenia diagnostic phenotype, which features positive symptoms quite prominently with a far more diminished role for negative symptoms, is clearly highly heritable. Perceptual aberrations (a positive schizotypic feature) predict elevated morbid risk for treated schizophrenia in the biological first-degree relatives of non-psychotic individuals (Lenzenweger & Loranger, 1989) and perceptual aberrations are associated with variation in genetic loci of interesting in schizophrenia (e.g., catechol-O-methyltransferase (COMT); neuregulin-1) (see Lenzenweger, 2018). Thus, the positive/negative distinction in both schizophrenia and in schizotypic conditions (including SPD) will need to be probed more deeply to extract all available meaning, an area where newer molecular genetic tools will be helpful. Finally, in this context it is worth considering the proposed notion of “pseudoschizotypy” (a putative false schizotype due to absence of a genetic liability for schizophrenia), a concept that is interesting but difficult to assess absent a gold standard criterion of validity against which to evaluate presumed schizotypy cases. How might we proceed on this notion? How can it be made empirically useful?
Summary
The utility of studying non-psychotic phenotypic variants of schizophrenia liability continues to represent an important vector in schizophrenia research. The viability and utility of the SPD phenotype is unquestionable; an expanded view of schizotypy (beyond simply SPD) will likely lend greater power and precision to further study of the nature of schizophrenia spectrum going forward.
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