Relationship of schizotypal personality disorder to schizophrenia: genetics

The adoptive, family, and twin studies show that schizotypal personality features are found among the relatives of schizophrenics. However, it has not been shown that there is a higher risk of schizophrenia among the relatives of schizotypals. An explanation may be that the current DSM-III criteria of schizotypal personality disorder do not adequately define schizotypals genetically related to schizophrenia. While some of the cases that meet DSM-III criteria are within the schizophrenia spectrum, others are unrelated to schizophrenia. There is reason to believe that schizotypals characterized by distant relationship to others, suspiciousness, eccentricity, peculiar communication, and dysfunctional school and work performance are within the schizophrenic sphere, while individuals with psychotic-like symptoms phenomenologically similar to schizophrenia and diagnosed as schizotypal personality disorders in DSM-III represent decompensation of other personality disorders.     

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.     

Frontal release signs among patients with schizophrenia, their first-degree biological relatives, and non-psychiatric controls

BACKGROUND: Frontal release signs (FRS) are a subset of neurological soft signs that are overrepresented among patients with schizophrenia and their unaffected relatives and may be correlated with neuropsychological functioning and chronicity of illness. This study sought to explore FRS and their associations with verbal memory and symptoms of schizophrenia in an African American sample of patients, and FRS and their associations with verbal memory and schizotypal features among first-degree relatives and non-psychiatric controls. METHOD: FRS, verbal memory, schizophrenia symptoms (in patients), and schizotypal features (in relatives and controls) were assessed in 63 patients with schizophrenia and related disorders, 33 of their unaffected first-degree relatives, and 51 controls. RESULTS: Patients and their relatives displayed greater FRS than controls. Among relatives and controls, greater FRS were related to greater self-reported disorganized and interpersonal features of schizotypal personality disorder. FRS were not associated with patients' schizophrenia symptoms in the expected direction. In the entire sample, greater FRS were associated with poorer verbal working memory. CONCLUSIONS: Because they are easy to assess, may be correlated with neuropsychological functioning, and appear to covary with level of genetic diathesis for schizophrenia, the study of FRS may shed light on the neurodevelopmental processes that underlie schizophrenia.     

An independent analysis of the Danish Adoption Study of Schizophrenia. VI. The relationship between psychiatric disorders as defined by DSM-III in the relatives and adoptees

In this report, modified DSM-III criteria were applied to all the available interviews with adoptees from the greater Copenhagen sample of the Danish Adoption Study of Schizophrenia. In the adoptees, reasonable agreement was found between our DSM-III diagnoses and the original diagnoses using global DSM-II-based criteria by Kety et al for their categories of chronic and acute, but not borderline, schizophrenia. Comparing DSM-III-based diagnoses in adoptees and relatives, schizophrenia, schizotypal personality disorder, and paranoid personality disorder were all significantly more common in the biologic relatives of schizophrenic v screened control adoptees. These three diagnoses, which together form a tentative "schizophrenia spectrum," were also significantly concentrated in the biologic relatives of adoptees with schizoaffective disorder, mainly schizophrenic subtype, and schizotypal personality disorder, but not in biologic relatives of adoptees with schizophreniform disorder or atypical psychosis.     

The schizotypal personality disorder: historical origins and current status

BACKGROUND: The schizotypal personality disorder is a recent psychiatric nosological concept developed by Spitzer at the end of the 1970s, based on the analysis of the characteristics of relatives of schizophrenic subjects included in the adoption studies carried out in the same decade by Kety, Wender and Rosenthal. HISTORICAL ASPECTS: However, this entity is based on older observations, at the beginning of the past century, showing common behavioural characteristics in relatives of schizophrenics. Its status within our current nosography remains dubious, sometimes classified among personality disorders, sometimes in the schizophrenia spectrum disorders. It is interesting to present the origins of this concept that stem from two complementary approaches: a family approach and a clinical approach of sporadic cases and then to redefine the framework within which the diagnostic approach was based and its continuity, up until our current classifications, the DSM and CIM. CURRENT STATUS: The historical origins cannot summarize the disorder and it appears important to redefine the multidimensional characteristics of the schizotypal personality disorder, generally a three-factor model. Indeed, dimensional models of psychosis are becoming established as conceptually and clinically useful. Recent studies on the dimensionality of psychosis show an evolution of the schizotypal concept, initially defined as being part of the schizophrenia spectrum and which now appears to be more broadly linked to a concept of unitary psychosis, including the bipolar disorder. CONCLUSION: Dimensions of psychosis seem to be associated with different familial aggregation and risk of psychosis, suggesting that they are underlined by different physiopathological processes. Hence, the dimensional approach can help to disentangle the genetic heterogeneity of the disease.     

Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits

OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD: Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS: The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.     

Sensory gating deficits assessed by the P50 event-related potential in subjects with schizotypal personality disorder

OBJECTIVE: The schizophrenia spectrum includes individuals with schizophrenia, their relatives, and individuals with schizotypal personality disorder. Subjects in the schizophrenia spectrum have disorders of attention, cognition, and information processing. Attention and information processing can be assessed by testing suppression of the P50 event-related potential; the amplitude of the P50 wave is measured in response to each of two auditory clicks. In normal subjects, the P50 wave following the second click is suppressed, or "gated." Schizophrenic patients and their relatives show less suppression of the second P50 wave. Deficits in P50 suppression have high heritability and show linkage to the alpha-7 subunit of the nicotinic cholinergic receptor gene in families with schizophrenia, suggesting that deficits in P50 suppression are trait markers for gating abnormalities in schizophrenia spectrum subjects. Although schizotypal subjects have been shown to have deficits in sensorimotor gating as measured by prepulse inhibition, to the authors' knowledge P50 sensory gating in schizotypal personality disorder has yet to be reported. METHOD: P50 suppression in 26 subjects with schizotypal personality disorder and 23 normal subjects was assessed through auditory conditioning and testing. RESULTS: The subjects with schizotypal personality had significantly less P50 suppression than did the normal subjects. CONCLUSIONS: Subjects with schizotypal personality disorder may have trait-linked sensory gating deficits similar to those in patients with schizophrenia and their relatives. Because these subjects may manifest sensory gating deficits without overt psychotic symptoms, it is likely that these deficits represent a core cognitive dysfunction of the schizophrenia spectrum.     

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.     

Increased morbid risk for schizophrenia-related disorders in relatives of schizotypal personality disordered patients

To evaluate whether probands from a clinical sample diagnosed as having DSM-III schizotypal and/or paranoid personality disorder have a familial relationship to the schizophrenia-related disorders, the morbid risk for schizophrenia-related disorders and other psychiatric disorders were evaluated in the first-degree relatives of patients with schizotypal and/or paranoid personality disorder and compared with the corresponding risk for these disorders in the first-degree relatives of patients with other non-schizophrenia-related personality disorders. The morbid risk for all schizophrenia-related disorders, and specifically for schizophrenia-related personality disorders, was significantly greater among the relatives of the probands with schizotypal and/or paranoid personality disorder than among the relatives of probands with other personality disorder. The morbid risk for other psychiatric disorders did not differ significantly between the first-degree relatives of the schizotypal/paranoid personality disorder and the other personality disorder control proband samples. These results suggest a specific familial association between schizophrenia-related disorders, particularly schizophrenia-related personality disorders, and clinically diagnosed schizotypal patients.     

Temperament and character dimensions of the relatives of schizophrenia patients and controls: the relationship between schizotypal features and personality.

PURPOSE: Previous findings indicated that schizophrenia patients might have a different personality structure from the general population on several dimensions of temperament and character. Some authors proposed that HA might be a marker of underlying genetic vulnerability to schizophrenia. Studies on high-risk subjects and first degree relatives of patients is essential to test the value of a measure as a marker of genetic vulnerability to a disease. Few studies tested the biopsychosocial model of personality on unaffected relatives of schizophrenia. SUBJECTS AND METHODS: We compared the Temperament and Character (TCI) profiles of 94 first degree relatives of schizophrenia and 75 controls. We also investigated the relationship between schizotypy and TCI dimensions in the study sample. RESULTS: The harm avoidance scores of the relatives of schizophrenia patients with schizotypal features were significantly higher. Self transcendence scores were also significantly higher among relatives with schizotypal features. In contrast, the relatives of the patients with schizophrenia who did not have schizotypal features had higher SD and C scores than the control group. DISCUSSION AND CONCLUSION: This finding is consistent with the previous findings which suggested harm avoidance as a vulnerability indicator of schizophrenia. Some character features like self transcendence might be also associated with schizotypal features.     

Eye tracking impairment in clinically identified patients with schizotypal personality disorder

Eye tracking accuracy, which has been found to be impaired in schizophrenic patients and their relatives, was assessed in 26 patients with schizotypal personality disorder, 17 control subjects with other non-schizophrenia-related personality disorders, 29 normal control subjects, and 44 schizophrenic patients. Both schizotypal and schizophrenic patients, but not control subjects with other personality disorders, demonstrated significantly more impaired tracking than the normal control subjects. These results suggest that patients with clinically defined schizotypal personality disorder may be biologically related to schizophrenic patients as part of a spectrum of schizophrenia-related disorders.     

Three-factor model of schizotypal personality: invariance across culture, gender, religious affiliation, family adversity, and psychopathology

Whilst the syndrome approach to schizotypy has recently demonstrated differential correlates of a three-factor model of schizotypal personality, variations in the nature of these factors question a basic assumption of this approach. This study tested competing models of the factor structure of schizotypal personality using the Schizotypal Personality Questionnaire (SPQ) in a sample of 1,201 Mauritians. Factor invariance across gender, ethnicity, family adversity, and religion and across a psychopathologically select group was also assessed. Results suggest that a three-factor model, Cognitive-Perceptual Deficits, Interpersonal Deficits, and Disorganization, underlies individual differences across widely varying groups. Other competing three-factor schizotypal personality models did not fit the data better. It is argued that the three-factor Disorganized model is a well-replicated model of DSM schizotypal personality in community samples but possibly not in some clinical samples.     

A family study of schizophrenic and normal control probands: implications for the spectrum concept of schizophrenia

Morbidity risks for mental illness were determined in 750 first-degree relatives of chronic schizophrenic and normal control probands. Psychiatric disorders that were more frequent in relatives of schizophrenic probands than in relatives of normal control probands were chronic schizophrenia (5.8% versus 0.6%), schizotypal personality disorder (definite, 14.6% versus 2.1%; probable, 12.1% versus 6.5%), and paranoid personality disorder (7.3% versus 2.3%). The data suggest that schizotypal and paranoid personality disorders are genetically related to schizophrenia. The implications for schizophrenia research are discussed.     

"Schizotaxia": clinical implications and new directions for research

We sought to show that (1) schizotaxia (Meehl's term for the predisposition to schizophrenia) is a clinically consequential condition, and (2) distinguishing it from schizotypal personality disorder may be useful from both clinical and scientific perspectives. We review the features of schizotaxia that may be relevant in clinical settings and discuss their implications for the diagnosis, psychosocial functioning, family intervention and treatment of people in schizophrenia families. Our review indicates that prior work finds some of the nonpsychotic and nonschizotypal relatives of schizophrenia patients to have a psychiatric syndrome characterized by negative symptoms, neuropsychological impairment, and psychosocial dysfunction. Following Meehl, we call this constellation of clinical and neurobiological features schizotaxia. The studies we review suggest it may be worthwhile to consider schizotaxia as a separate diagnostic class. Doing so would alert clinicians to a neurobehavioral syndrome not adequately covered by current diagnostic criteria and would motivate researchers to develop diagnostic and therapeutic approaches aimed at helping schizotaxic individuals and, perhaps, preventing the onset of schizophrenia.     

Schizotypal personality traits in nonpsychotic relatives are associated with positive symptoms in psychotic probands

There remains disagreement over whether increased risk of schizotypal personality disorder (SPD) is confined to the relatives of patients with a diagnosis of schizophrenia or whether it is a more general characteristic of the relatives of all psychotic patients. To examine the relationship between schizotypal dimensions in relatives and psychopathological syndromes in patients with functional psychoses, factor analysis was carried out on (1) ratings from Present State Examination (PSE) interviews with 172 consecutively admitted patients with psychosis (52% of them with schizophrenia), and (2) ratings on items from three schizotypal scales concerning 263 of their nonpsychotic first degree relatives. The factors derived from the patients' PSE interviews were correlated with the schizotypal factors and the nine DSM-IV criteria for SPD concerning the relatives and subjected to a canonical correlation analysis. In this study, no differences were observed concerning the distribution of schizotypal factors or DSM-IV schizotypal features in the relatives of patients with different psychotic diagnoses. However, a syndrome characterized by delusions, hallucinations, and thought interference (positive symptoms) in patients was correlated with high scores on the three schizotypy scales and with positive and negative schizotypal features in relatives.     

Amphetamine, psychosis, and cognition in the schizophrenia spectrum

We previously reported that subjects with a schizophrenia spectrum personality disorder (ie, an odd cluster personality disorder), of which the prototype is schizotypal personality disorder, show cognitive impairment in circumscribed areas (working memory) compared with healthy control subjects, and that amphetamine administration improves working memory in subjects with schizotypal personality disorder. In this larger series, we wanted to determine whether amphetamine treatment ameliorates working memory impairment using three groups: subjects with a schizophrenia spectrum personality disorder (ie, schizotypal, paranoid, or schizoid personality disorder), other (subjects with nonschizophrenia spectrum) personality disorder, and healthy volunteers. We hypothesized that amphetamine treatment would improve cognitive function in domains in which subjects with schizophrenia spectrum personality disorder show impairment compared with healthy volunteers and the other personality disorder group. Overall, amphetamine treatment did not improve performance in any task compared with placebo, and there was no group by drug interaction in the total sample. However, when the sample was restricted to the subjects who showed impairment at baseline, amphetamine treatment improved visuospatial working memory. In the total patient sample, amphetamine treatment reduced negative symptoms, whereas positive symptoms remained unchanged. Amphetamine treatment improves working memory in those subjects with cognitive impairment at baseline, most of whom meet criteria for a schizophrenia spectrum disorder.     

Do schizotypal symptoms mediate the relationship between genetic risk for schizophrenia and impaired neuropsychological performance in co-twins of schizophrenic patients?

BACKGROUND: Neurocognitive deficits and symptoms of schizotypal personality disorder are both elevated in the first-degree relatives of schizophrenic patients, but their relationship to each other and their potential common genetic source remain unclear. METHODS: Fifty unaffected co-twins of schizophrenic patients and 123 control twins were assessed with a neuropsychological battery and structured clinical interviews. RESULTS: Working memory was influenced by genetic risk for schizophrenia but not schizotypal symptoms. Nearly all other domains were influenced by schizotypy symptoms but only in the co-twins of schizophrenic patients. Schizotypy symptoms in the absence of a family history did not seem to be related to impaired neurocognitive functioning. CONCLUSIONS: Schizotypy symptoms in those with genetic risk for schizophrenia are associated with increased risk for cognitive deficits. Some neurocognitive deficits might covary with subpsychotic symptoms due to a shared genetic factor. Community-ascertained schizotypal individuals might not be appropriate for modeling underlying genetic risk for schizophrenia.     

Diagnostic approaches to schizotypal personality disorder: a historical perspective

The goal of this article is to provide a historical perspective on the DSM-III concept of schizotypal personality disorder. It is argued that two major traditions have influenced our conceptualization of this diagnostic entity. The first or familial approach emphasizes the characteristic traits found in the deviant but nonpsychotic relatives of schizophrenics. The second or clinical approach focuses on patients who appear to demonstrate the fundamental symptoms of schizophrenia without psychotic symptoms or severe personality deterioration. A review of these two traditions concludes that while similar in some regards, they also differ in important ways in their views on the characteristics of the true "schizotype." The impact of these two traditions is then traced through the Danish Adoption Studies of Kety et al. to the development of the DSM-III criteria for schizotypal personality by Spitzer, Endicott, and Gibbon. Finally, the article reviews recent studies on the validity of specific criteria for schizotypal personality disorder (SPD) and reassesses the conceptual issue about the nature of the relationship of SPD to schizophrenia on the one hand and to other personality disorders on the other.     

The pathophysiology of schizophrenia disorders: perspectives from the spectrum

OBJECTIVE: This overview focuses on neurobiological abnormalities found in subjects with schizotypal personality disorder, the prototype of the schizophrenia spectrum disorders, and chronic schizophrenia in the context of common vulnerabilities shared by schizotypal personality disorder and schizophrenia, as well as the factors that protect against the severe cognitive/social deficits and frank psychosis of chronic schizophrenia. A pathophysiological model of the relationship between schizotypal personality disorder and schizophrenia was developed based on this data. METHOD: The authors provide a selective review of major findings regarding the pathophysiology of schizotypal personality disorder and integrate these results in conjunction with preclinical studies into a model of the pathophysiology of the spectrum. RESULTS: People with schizotypal personality disorder share phenomenological, genetic, and cognitive abnormalities with people with chronic schizophrenia. While temporal volume reductions appear to be common to both groups, there may be preservation of frontal lobe volume in schizotypal personality disorder compared to schizophrenia. Findings to date regarding striatal volume, metabolic rate, and dopamine release in subjects with schizotypal personality disorder compared to subjects with chronic schizophrenia are consistent with hypotheses of reduced striatal dopaminergic activity in schizotypal personality disorder compared to schizophrenia. CONCLUSIONS: Genetic or environmental factors that promote greater frontal capacity and reduced striatal dopaminergic reactivity might contribute to sparing people with schizotypal personality disorder from the psychosis and severe social and cognitive deterioration of chronic schizophrenia. Further research is required to test these hypotheses more definitively.     

New perspectives on schizotypal personality disorder

Schizotypal personality disorder is the prototype of the schizophrenia-related personality disorders and has been demonstrated to have phenomenologic, biologic, treatment, and outcome characteristics similar to those of schizophrenic patients. These studies suggest that patients with schizotypal personality disorder, like schizophrenic patients, show cognitive impairment, but the impairment is more focal and involves primarily working memory, verbal learning, and sustained attention rather than generalized intellectual deficits. Schizotypal patients, like schizophrenic patients show reductions in temporal lobe volume, but seem to be spared the frontal volume reductions found in some studies of schizophrenic patients and in our laboratory. Better frontal “buffering” may prevent the more severe cognitive and social deterioration associated with schizophrenia. Furthermore, schizotypal patients appear to show less susceptibility to psychotic symptoms, in part perhaps because of better buffered subcortical dopaminergic activity as suggested by recent data from a SPECT/amphetamine paradigm, glucose metabolic study, and structural studies of basal ganglia. These findings are discussed in terms of a model of schizotypal personality disorder where schizotypal patients have better capacity for compensatory buffering in lateral and subcortical brain regions, protecting them from the more severe symptoms of chronic schizophrenia.