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.     

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.     

An integration of schizophrenia with schizotypy: identification of schizotaxia and implications for research on treatment and prevention

The liability to schizophrenia (schizotaxia) is associated with deficits in a variety of domains, including negative symptoms and neuropsychological deficits, even in the absence of psychosis or pre-psychotic prodromal symptoms. Conceptually, this view of schizotaxia is similar to negative schizotypy (i.e., schizotypal personality disorder minus the positive symptoms). It is broader than DSM-IV schizotypal personality disorder (SPD), however, in that more relatives of patients with schizophrenia show core symptoms of schizotaxia than meet the diagnostic criteria for SPD. Three lines of evidence support the validity of schizotaxia. First, evidence of concurrent validation was obtained by showing that schizotaxic subjects were more impaired than non-schizotaxic subjects on a variety of independent clinical scales. Second, schizotaxic subjects showed higher levels of negative symptoms on the Structured Interview for Schizotypy than non-schizotaxic subjects, but did not differ on positive symptoms. Third, subjects who met predetermined criteria for schizotaxia (i.e., negative symptoms and neuropsychological deficits) showed positive effects following treatment with low doses of risperidone (0.25-2.0 mg). Thus, clinical deficits in schizotaxia may be identifiable, and to a significant extent, reversible. Implications for the conception of schizotypy and the prevention of schizophrenia will be discussed.     

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.     

Motor dysfunction in schizotypal personality disorder.

Past research has revealed that schizophrenia is associated with voluntary movement abnormalities, as well as higher rates of involuntary movements. On instrumental motor tasks, patients manifest reduced motor stability, excessive force and more contralateral motor overflow (movement in the non-responding hand). In the present study, an instrumental motor task (manual response forced-choice task) was administered to a group of adults with schizotypal personality disorder (SPD) in order to determine whether they show motor deficits similar to those observed in schizophrenia. As predicted, the schizotypal subjects were excessive and more variable in motor force, compared to healthy controls and other personality-disordered subjects. Additionally, the force and variability of the motor responses were positively correlated with ratings of both positive and negative SPD symptoms. Finally, motor overflow and negative symptoms were associated with higher salivary cortisol levels. The pattern of findings is consistent with previous reports linking motor abnormalities and heightened cortisol with schizotypal personality disorder.     

Early stage vision in schizophrenia and schizotypal personality disorder

Previous studies of visual perception have reported deficits in contrast sensitivity and dot motion discrimination in schizophrenia. We tested whether these deficits also appear in schizotypal personality disorder (SPD). SPD appears to be genetically and symptomatically related to schizophrenia, but without the marked psychosocial impairment associated with psychotic disorders. The present study investigated contrast sensitivity for moving and static gratings, form discrimination and dot motion discrimination in 24 patients with schizophrenia or schizoaffective disorder (SZ), 16 individuals with SPD, and 40 control subjects. SZ, but not SPD subjects, showed impairments on tests of contrast sensitivity for static and moving gratings, form discrimination in noise, and dot motion discrimination. Visual performance did not differ between medicated SZ patients and patients withdrawn from medication. These results confirm early stage visual deficits in schizophrenia regardless of medication status. SPD subjects, in contrast, show intact early stage visual processing despite the presence of marked schizotypal symptoms.     

Dopamine regulation in schizotypal personality disorder and psychosis

It has recently been proposed that reduced stimulation of prefrontal cortex DI receptors secondary to hypoactivity of mesocortical dopamine (DA) projections may explain the cognitive impairments experienced by patients with schizophrenia and the schizophrenia spectrum. Findings from studies done during the past two decades suggest that schizotypal personality disorder (SPD), the prototypic disorder of the schizophrenia spectrum, is associated with cognitive deficits and social deterioration that are qualitatively similar, although less severe, to those observed in schizophrenia. It generally is acknowledged that the psychotic symptoms of schizophrenia are associated with hyperactivity of mesolimbic DA projections resulting in excessive stimulation of striatal D2 receptors. In contrast with schizophrenia, dopaminergic interventions improved cognitive function in SPD without worsening psychotic-like symptoms, raising the possibility that patients with SPD are protected against increases in subcortical dopaminergic activity associated with psychosis. However, mounting evidence suggests that alterations in other neurotransmitter systems (eg, glutamate, γ-aminobutyric acid, opioid, serotonergic) may be involved in the pathophysiology of schizophrenia. This over view focuses on common DA-related neurobiological vulnerabilities shared by schizophrenia and the schizophrenia spectrum, in addition to factors that protect SPD from the overt psychotic symptoms and more severe social and cognitive deficits experienced by patients with chronic schizophrenia.     

Schizotypal personality disorder in individuals with and without schizophrenic relatives: similarities and contrasts in neurocognitive and clinical functioning.

Schizophrenia-spectrum disorders may reflect the genotype for schizophrenia. One such disorder, Schizotypal Personality Disorder (SPD), was examined as a function of family history of schizophrenia. Clinical profiles and neurocognitive functioning were evaluated in 25 schizotypal subjects (10 SPD with schizophrenic relatives and 15 SPD without schizophrenic relatives), and in 24 normal controls. The primary finding is that vigilance performance was similarly impaired in both SPD groups. An additional neurocognitive impairment, comprehension of grammatical constructions, was observed only in the SPD group with schizophrenic relatives. Of interest, the clinical profiles of the two SPD groups did not differ significantly. These results suggest that schizotypal personality disorder is associated with a continuum of neurocognitive vulnerability that increases as a function of family history of schizophrenia.     

Auditory steady state response in the schizophrenia, first-degree relatives, and schizotypal personality disorder

The power and phase synchronization of the auditory steady state response (ASSR) at 40 Hz stimulation is usually reduced in schizophrenia (SZ). The sensitivity of the 40 Hz ASSR to schizophrenia spectrum phenotypes, such as schizotypal personality disorder (SPD), or to familial risk has been less well characterized. We compared the ASSR of patients with SZ, persons with schizotypal personality disorder, first degree relatives of patients with SZ, and healthy control participants. ASSRs were obtained to 20, 30, 40 and 50 Hz click trains, and assessed using measures of power (mean trial power or MTP) and phase consistency (phase locking factor or PLF). The MTP to 40 Hz stimulation was reduced in relatives, and there was a trend for MTP reduction in SZ. The 40 Hz ASSR was not reduced in SPD participants. PLF did not differ among groups. These data suggest the 40 Hz ASSR is sensitive to familial risk factors associated with schizophrenia.     

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.     

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.     

Clinical characteristics of schizotypal-related obsessive-compulsive disorder

In this study we compared 15 patients with DSM-IV obsessive-compulsive disorder (OCD) and schizotypal personality disorder (SPD) and 31 non-SPD OCD patients. OCD-SPD patients had poorer insight, more negative symptoms, lower functioning, more antipsychotic augmentation and more first-degree relatives with schizophrenia-spectrum disorders. A distinct clinical phenotype of OCD associated with SPD should be considered when investigating etiopathogenetic mechanisms.     

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.     

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.     

Schizotypal symptoms in the relatives of schizophrenia patients: an empirical analysis of the factor structure

This study examined the nature of schizotypal symptoms in the relatives of schizophrenia patients and investigated phenomenological differences in symptomatology manifested by a familial sample and a clinical sample of personality disorder patients. Confirmatory factor analyses were used to test models of DSM-III-R schizotypal symptoms in the first degree relatives (n = 172) of schizophrenia patients. A multisample analysis was conducted to determine whether the same model adequately described the schizotypal symptoms rated in the relatives of schizophrenia patients and in clinically selected personality disorder patients. The results indicated that a three-factor model consisting of cognitive/perceptual, interpersonal, and disorganization factors yielded the best fit to the data from the relatives of schizophrenia patients, but that this model did not adequately describe both the relatives of schizophrenia patients and personality disorder patients. These findings indicate that the structure of schizotypal symptoms in the relatives of schizophrenia patients is similar to the three-factor model of schizophrenia symptoms often reported, but not the same as the structure of schizotypal symptoms in clinically selected personality disorder patients.     

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest.     

A family study of nailfold plexus visibility in psychotic disorders.

It has been proposed that the nailfold subpapillary plexus visibility score (PVS) may be a marker of susceptibility to schizophrenia. To further investigate this hypothesis, we evaluated plexus visibility in a sample of 61 chronic schizophrenics, a large sample of first-episode psychotic patients and their first-degree relatives (50 with schizophrenia, and 51 of their relatives; 29 with schizophreniform disorder, 30 of their relatives; 32 with major depression with psychotic features, 35 of their relatives; 33 with a bipolar disorder with psychotic features, 32 of their relatives), and 169 normal control subjects. Group comparisons demonstrated that (1) the probands with chronic schizophrenia, first episode schizophrenia, and schizophreniform disorder did not differ from one another on PVS; (2) these subjects combined had higher PVS ratings than the other two proband groups and normal subjects combined (who did not differ); and (3) none of the relative groups significantly differed from either one another or the normal subjects. On the other hand, relatives of schizophrenia spectrum probands with high PVS (greater than or equal to 10.0) had higher PVS ratings than the relatives of such probands with low PVS. Patterns of familial correlations suggested that PVS was moderately heritable (0.40). There was no evidence that nonadditive genetic variation influenced the trait.     

Psychotic features in chronic posttraumatic stress disorder and schizophrenia: comparative severity

Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms, and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-IV criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic schizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms.     

Latent class analysis of DSM-IV schizotypal personality disorder criteria in psychiatric patients

The aim of the study was to evaluate the latent structure of DSM-IV schizotypal personality disorder (SPD) diagnostic criteria. The sample consisted of 564 consecutively admitted inpatients and outpatients. Exploratory latent class analysis identified a four-class model as the best fitting model for DSM-IV SPD criteria. The first of the SPD latent classes was mainly characterized by odd thinking, inappropriate affect, and interpersonal features; the second class by cognitive/perceptual difficulties; the third class by paranoid features; and the fourth class by absence of SPD features. The conditional probability pattern of the fourclass solution could be safely replicated across confounder strata. Unlike previous findings, oddness, aloofness, and social withdrawal, rather than positive symptoms, best characterized SPD even in clinical samples.     

Personality disorder in the families of depressed, schizophrenic, and never-ill probands

In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never-ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders.