How the study of schizotypy helps to advance How the study of schizotypy helps to advance our understanding of schizophrenia: our understanding of schizophrenia:

The SRF Webinar The SRF Webinar (July 6, 2015)(July 6, 2015)

Mark F. Lenzenweger, PhDMark F. Lenzenweger, PhDDepartment of PsychologyDepartment of Psychology

State University of New York at BinghamtonState University of New York at Binghamton

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Department of PsychiatryDepartment of Psychiatry

Weill Cornell Medical CollegeWeill Cornell Medical College

Copyright © 2015 by Mark F. Lenzenweger

Goals of the Webinar• Introduce the schizotypy concept to an audience

consisting of technical and non-technical interested parties, including consumers

• Define the concept and illustrate its potential utility, with some historical review

• Seek connections with other schizophrenia research domains through our discussants (prodromal schizophrenia studies; genetics; neurocognition)

• Point out misconceptions or misunderstandings

What can the study of schizotypy offer to schizophrenia research? A unifying investigative framework

Lenzenweger (2006)r

• Clinical schizophrenia is but one psychotic expression of schizophrenia-liability (another is delusional disorder)

• Unexpressed liability has been confirmed (e.g., Gottesman & Bertelsen, 1989) and can be transmitted “quietly”

• Schizophrenia liability expressions are likely variable (ranging from psychosis to schizotypic clinical features through subtle laboratory assessed abnormalities) [endophenotypes]

• Genetics research (GWAS) has found relatively few genes of schizophrenia relevance despite a heritability > .80.

• Prodromal cases “convert” to schizophrenia less than 36% of the time; leaving the other 64% to be explained.

Pulling together threads in the panorama of schizophrenia liability

Terminology

• Schizotypy: a latent personality organization that harbors the liability for schizophrenia

• Schizotype: one who possesses schizotypy as a personality organization

• Schizotypic pathology: Observable psychopathology deriving from schizotypy (ranging from psychosis through SRPD features)

Case 4: Claire, a 27 year old married woman, works as a code writer for a large software company in a Northern California city. Claire tends to dress in an unusual manner, tending to wear clothing that often seems far too heavy for the warm climate in which she lives. Throughout childhood she had only one friend, who she continues to talk to on the phone on a weekly basis. She has no other close friends to speak of beyond her husband. In college, she pursued a double major in German literature and computer science. She met the man she would later marry in a college computer science class. He told her that he was drawn to her because she was “quirky” and “eccentric.” Claire has described an “unusual ability to sense what will happen in the world,” something akin to a “sixth-sense” and she maintains it goes beyond simply intuition. She also feels that she can influence events with her mind, for example she thinks that she can make a red light turn green (though she denies that she really “believes” she can do so). She collects small figurines and amulets that she feels help her to “find her way through the world.” Claire’s co-workers do not know her very well, but they find her “pleasant enough, although sort of flaky.” When speaking to most people she appears ill at ease (anxiety) and seems relieved when the conversation ends. She shows emotional reciprocity, but it is strained. On occasion she grimaces or giggles in response to some aspect of her contribution to a conversation that other people in the conversation regard as odd or “weird.” Her face, otherwise, displays little in the way of emotion.

Possible features of non-psychotic schizotypic psychopathology

• Being a loner and lacking close friends outside of the immediate family

• Incorrect interpretation of events, including feeling that external events have personal meaning

• Peculiar, eccentric or unusual thinking, beliefs or behavior

• Dressing in peculiar ways

• Belief in special powers, such as telepathy

• Perceptual alterations, in some cases bodily illusions or body-image distortions, including phantom pains or other distortions in the sense of touch (exteroception, proprioception)

• Persistent and excessive social anxiety (e.g., the ‘carrot grater’ experience)

• Peculiar style of speech, such as loose or vague patterns of speaking or rambling oddly and endlessly during conversations

• Suspicious or paranoid ideas, hypersensitivity, and constant doubts about the loyalty and fidelity of others (“Why did the government change the $20 bill appearance?”)

• Flat emotions, or limited or inappropriate emotional responses

Do not confuse with Asperger’s Syndrome Adapted from Mayo Clinic

Two vantage points on the schizotypy construct

• Schizotypy as the underlying liability for schizophrenia, schizophrenia-related psychopathology, and schizophrenia endophenotypes

• Schizotypy as a normal personality dimension

Two vantage points on the schizotypy construct

• Schizotypy as the underlying liability for schizophrenia, schizophrenia-related psychopathology, and schizophrenia endophenotypes

• Schizotypy as a normal personality dimension

Normal Personality?: agentic extraversion, affiliative extraversion, anxiety, fear, nonaffective constraint

Early Observations from Masters of Schizotypic Phenomenology

• “... in the families attacked there comes under observation with relative frequency besides dementia praecox a series of other anomalies, especially manic-depressive insanity and eccentric personalities [italics added]. ... the latter are probably for the most part to be regarded as “latent schizophrenias” and therefore essentially the same as the principal malady” (Kraepelin, 1919/1971).

 • “There is also a latent schizophrenia, and I am convinced that this

is the most frequent form, although admittedly these people hardly ever come for treatment ...In this form we see in nuce all the symptoms and all combinations of symptoms which are present in the manifest types of the disease” (Bleuler, 1911/1950).

Kraepelin Bleuler Rado

Meehl Gottesman

Meehl & Gottesman

Interest in schizotypy from differing methodological vantage points

Paul H. Hoch

David Rosenthal

Seymour S. Kety

Rado, S. (1960)

Major papers: 1962, 1989, 1990; Checklist for schizotypic signs (1964)

Paul E. Meehl, PhD(1920-2003)

Meehl, P.E. (1962)

Schizotypy

Liability for Schizophrenia

Schizotypy is a latent construct invisible to the naked, unaided eye

Plane of observation

Schizotypy and schizotypy indicators:

Don’t confuse the latent construct with the measured indicator of the construct

STY, PAR, SZD, AVD

PD Features

Psychometric indexes

(Endo-phenotypes)

Laboratory measures

(Endo-phenotypes)

Indicators are not isomorphic with the latent construct.

Schizophrenia

and related psychoses

SZ gene(s) Schizotypy

SL? SL? S?

PGP?

PGP?

Social Learning Influences

Stressors and polygenetic potentiators

Personality organization

Latent level (unobservable)

Schizotypicdisorders

Endophenotypes

Schizophrenia

Schizotaxia

“2nd hit”

Schizotypes

Manifest level(observable)

CNS

The BrainDNA

Not visible to “naked” eyeCandidates: sustained attention, eye

tracking,working memory, motor function, thought disorder (secondary cognitive

slippage), psychometrics

S?

Epigenetic Factors?

Schizophreniarelated

psychoses

Prodrome ?

Plane of observation

(Synaptic slippage due to hypokrisia)

Optional

Copyright © 2010 M.F. Lenzenweger

Schizotypy

Liability for Schizophrenia

Schizotypy is a latent construct invisible to the naked, unaided eye

Plane of observation

Schizotypy and schizotypy indicators:

Don’t confuse the latent construct with the measured indicator of the construct

STY, PAR, SZD, AVD

PD Features

Psychometric indexes

(Endo-phenotypes)

Laboratory measures

(Endo-phenotypes)

Indicators are not isomorphic with the latent construct.

Schizophrenia

and related psychoses

Recognizing Schizotypy Indications

• Clinical schizophrenia, schizophreniform illness, delusional disorder are recognizable. (psychotic illnesses are reasonably discernible by experienced clinicians)

• How do we recognize schizotypy indications? (non-psychotic variants)

• Personality disorder symptoms are assessed using existing technologies (e.g., IPDE).

• Specialized psychological inventories

Approaches to Defining the Presence of Schizotypy

• Genetic

• Laboratory

• Clinical

• Expectancies for illness based on parental affection status

• Deviance on quantitative indexes (endophenotypes)

• Clinically visible dysfunction / signs / symptoms

• Traditional Genetic High-Risk Studies

• Psychometric High-Risk Studies

• A. Sub-syndromal or “prodromal” quasi-psychotic individuals

B. SRPDs

Approaches to Defining the Presence of Schizotypy

• Genetic

• Laboratory

• Clinical

• Expectancies for illness based on parental affection status

• Deviance on quantitative indexes

(endophenotypes)

• Clinically visible dysfunction / signs / symptoms

• Traditional Genetic High-Risk Studies

• Psychometric High-Risk Studies

• A. Sub-syndromal or “prodromal” quasi-psychotic individuals

B. SRPDs

What is an endophenotype?

• Gottesman and Shields (1972) advanced the argument that endophenotypes should be considered internal phenotypes that might someday be detectable in families of schizophrenics “…either biological or behavioral (psychometric pattern), which will not only discriminate schizophrenics from other psychotics, but will also be found in all identical co-twins of schizophrenics whether concordant or discordant” (1972, p. 336).

A Research IllustrationA Research Illustration: : Consider the features associated with Consider the features associated with

individuals who display elevations on a individuals who display elevations on a well-known schizotypy endophenotypewell-known schizotypy endophenotype.

The Perceptual Aberration ScaleThe Perceptual Aberration Scale

(Chapman, Chapman, & Raulin, 1978)

PAS: Sample Items• Occasionally I have felt as though my body did not exist

(T)• I have never felt that my arms and legs have momentarily

grown in size (F)• Sometimes people whom I know well begin to look like

strangers (T)• Ordinarily colors seem much too bright for me (without

taking drugs) (T)• It has seemed at times as if my body was melting into my

surroundings (T)

PAS as Endophenotype• Associated with schizophrenia and non-psychotic

schizotypic symptoms• State factors do not explain associations• Reliability (internal consistency)• Reliability (test-retest)• Heritable • Higher in biological relatives where schizophrenia is

present in the family• Associated with many other criteria of validity

High PAS Schizotypic persons display:• Increased rate of familial schizophrenia• Sustained attention deficits• Spatial working memory deficits• Smooth pursuit eye movement deficits• MMPI schizophrenia-related deviance• Executive functioning deficits (WCST)• Antisaccade performance patterns• Subtle thought disorder • Schizotypic clinical PD features• Social cognition deficits

Not explained by anxiety or depression

What we know about schizotypic perceptual aberrations and

molecular genetic findings?

• PAS is clearly heritable (Miller & Chapman, 1993; MacDonald et al., 2001)

• Neuregulin 1• ZNF804A variations (zinc finger protein)

• Val158Met COMT (val/val) [catechol–O-methyl transferase]

• Perhaps more in light of 108 schizophrenia-related loci (Nature, 2014)

What is the underlying nature of the schizotypy construct?

• Psychopathologists often ask: “Does schizotypy have a qualitative or discontinuous nature (on/off) or is it perfectly quantitative or dimensional (graded) in nature?”

• Statistical evidence to date favors evidence for a relatively strong discontinuity, which could reflect a type difference or a strong threshold effect (e.g., presence of the deleterious amount and/or combination of genetic influences)

• Think of a liquid turning into a solid (water/ice)

Misunderstandings regarding dimensionality

• Measuring a phenomenon in a dimensional manner at the surface level does not ensure dimensionality at the latent level;

• Factor analysis does not provide evidence of dimensionality;

• Finding sub-threshold features of schizophrenia in non-psychotic people does not mean the liability for schizophrenia is dimensional;

• Histograms do not confirm dimensionality at latent level

Schizotypic persons display:• Increased rate of familial schizophrenia• Sustained attention deficits• Spatial working memory deficits• Smooth pursuit eye movement deficits• MMPI schizophrenia-related deviance• Executive functioning deficits (WCST)• Antisaccade performance patterns• Subtle thought disorder • Schizotypic clinical features• Social cognition deficits

Not explained by anxiety or depression

What happens to schizotypic persons over time?

• The information available on this topic is somewhat limited.

• Longitudinal studies of 10 years or greater duration suggest that some schizotypic persons go on to develop psychosis (schizophrenia related)

• Lenzenweger 17 year follow-up study: (At follow-up: psychosis, SRPD features, schizotypal features, impaired social adjustment, more treatment, and so on.)

Rational Hierarchical Expanded Schizophrenia Phenotype

• Level I: Schizophrenia, Schizophreniform

• Level II: I + Delusional Disorder, Psychosis NOS (mainly schiz), or Schizoaffective (mainly schiz)

• Level III: I + II + Schizotypal PD or Paranoid PD

• Level IV: I + II + III + Schizoid PD or Avoidant PD

A rational and empirically supported expanded phenotype

Level I

Level II

Level III

Level IV

Thank you for Thank you for your kind your kind attention!attention!