Visual-spatial processing and dimensions of schizophrenia: a preliminary study on 62 schizophrenic subjects.

The aim of the study was to explore the relationships between the performance in figure-ground segregation and the clinical dimensions in schizophrenia. Sixty-two schizophrenic subjects filled out the embedded figures test (EFT) and the schizophrenic symptomatology was rated using the brief psychiatric rating scale (BPRS). The BPRS items were grouped into four categories: positive, negative, general and disorganization. The results showed in male schizophrenics negative and significant correlations between EFT scores and negative or disorganization subscales. Taken into account that in schizotypic subjects EFT scores was negatively correlated with negative dimension of schizotypy we suggested that those relationship could constitute a trait of the disease.     

Neurobiological measures of schizotypal personality disorder: defining an inhibitory endophenotype?

OBJECTIVE: Subjects with schizotypal personality disorder demonstrate deficits in inhibition when assessed on prepulse inhibition, P50 suppression, and antisaccade paradigms. This study determined if distinct subgroups of subjects with schizotypal personality disorder could be identified on the basis of performance on these measures and whether endophenotypes could be defined for future genetic study by using measures of inhibitory function. METHOD: Prepulse inhibition, P50 suppression, and antisaccade paradigms were assessed in 21 subjects with schizotypal personality disorder. RESULTS: Seven subjects with schizotypal personality disorder had deficits on each paradigm; seven had no deficits on any paradigm. P50 and antisaccade deficits were present in five of the same subjects and significantly correlated. CONCLUSIONS: These results suggest that P50 and antisaccade performance reflects a common endophenotype and that prepulse inhibition identifies a separate endophenotype reflecting different neurobiological substrate(s) in subjects with schizotypal personality disorder. This pattern may generalize to schizophrenia spectrum disorder patients.     

Confirming schizotypic personality configurations in hypothetically psychosis-prone university students

The personality features of hypothetically psychosis-prone (or schizotypic) subjects were examined. Schizotypic (n = 32) and control (n = 44) subjects were identified within a pool of 726 randomly ascertained nonclinical university students who had completed the Perceptual Aberration Scale (PAS) during a large-scale screening study. Approximately 4-6 months after the initial screening, the schizotypic and control subjects completed the Minnesota Multiphasic Personality Inventory (MMPI). Schizotypic subjects as a group displayed an average MMPI profile consistent with schizotypic personality features, whereas the control subjects did not. Moreover, multivariate profile analysis revealed that the schizotypic group MMPI profile differed significantly in shape from the control group profile. Finally, schizophrenia-related MMPI high-point codes were five times as prevalent among the PAS-identified schizotypic subjects as among the controls. The results suggest that the PAS identifies individuals who show schizotypic personality MMPI configurations and may carry a latent vulnerability for schizophrenia or, more broadly, psychosis.     

Self-reported schizotypy and bipolar disorder: demonstration of a lack of specificity of the Kings Schizotypy Questionnaire

Previous studies have demonstrated that schizophrenia patients score highly on self-reported measures of schizotypy such as the Kings Schizotypy Questionnaire (KSQ), but relatively little is known about the specificity of these self-reported features to schizophrenia. We aimed to explore the specificity of schizotypal features to schizophrenia by measuring their prevalence in subjects with bipolar disorder. The Kings Schizotypy Questionnaire (KSQ) was administered to participants (n=92) in a sibling-pair genetic linkage study of bipolar disorder. Scores were compared with those of participants in a similarly designed, concurrent family study of schizophrenia (n=135) and psychiatrically well controls (n=263). The bipolar group had significantly more schizotypal features than controls but significantly less than schizophrenia patients. Whether a bipolar subject had experienced positive psychosis had no effect on his/her schizotypy score. We conclude that elevated self-reported schizotypy as measured by the KSQ is not specific to schizophrenia, and may be associated with functional psychosis in general.     

Anomalous self-experiences are strongly associated with negative symptoms in a clinical high-risk for psychosis sample

ObjectiveAnomalous self-experiences (ASE) are considered as central features of the schizophrenia spectrum disorders and prodromal schizophrenia. We investigated total and single-item prevalence of these phenomena in a clinical high-risk (CHR) for psychosis sample, and associations with conventional psychosis-risk symptoms, present and childhood global/psychosocial functioning, and childhood trauma.MethodsThe sample (n = 38) included 31 CHR, according to ultra-high risk or cognitive basic symptoms (COGDIS) criteria, and seven with non-progressive attenuated positive symptoms. Psychopathological evaluations included the Examination of Anomalous Self-Experience (EASE), Structured Clinical Interview for Prodromal Syndromes (SIPS), Schizophrenia Proneness Instrument – Adult (SPI-A) (only the COGDIS-criteria), a diagnostic interview (SCID-I), Global Assessment of Functioning – Split version (S-GAF), Premorbid Adjustment Scale (PAS) and Childhood Trauma Questionnaire (CTQ).ResultsThe mean total EASE score was in line with reports from other CHR samples, and was particularly enhanced in schizotypal personality disorder and in subjects fulfilling COGDIS-criteria. The four most frequent EASE-items were present in two-thirds or more of the participants. EASE total was significantly associated with negative and disorganization symptoms. A multiple regression analysis revealed that the level of negative symptoms explained most of the variance in EASE total.ConclusionsThese results corroborates other findings that anomalous self-experiences are frequent and important features in CHR conditions and in the schizophrenia spectrum. The strong associations with negative symptoms and cognitive disturbances (COGDIS) should be investigated in longitudinal studies to address causality, psychopathological pathways and schizophrenia spectrum specificity. The weaker correlation between EASE total and positive symptoms may partly be related to a restricted range of positive symptoms.     

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.     

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.     

Schizotypal traits in adolescents: Links to family history of psychosis and psychological distress

ObjectiveStudies in the general population report that unusual subjective experiences are relatively common. Such experiences have been conceptualized either as extreme personality traits or as vulnerability markers for psychosis, and often grouped under the expression “schizotypal experiences”. This study investigates the heterogeneity of schizotypal traits using factor and latent class analysis.MethodsOne thousand and thirty-two adolescents were recruited for this study. Schizotypal experiences were assessed with the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE); psychological distress was assessed with the General Health Questionnaire (GHQ). Confirmatory Factorial Analysis (CFA) and Latent Class Analysis (LCA) were performed on the O-LIFE and on the association with the GHQ and demographic variables.ResultsCFA replicated the original 4-factor structure of the O-LIFE. Three latent classes (LC) of schizotypal features were identified: participants in LC1 (26% of the total sample) showed minimal level of item endorsement; LC2 accounted for 52% of the sample and showed overall higher item endorsement compared to LC1, especially for disorganization and positive signs of schizotypy, but not for negative affective items. LC3 (22%) showed an overall higher level of item endorsement across schizotypal dimensions, and positive association with psychological distress and family history of psychosis.DiscussionDifferent latent class of schizotypal features can be empirically defined in adolescent community samples. The most extreme class is defined not only by a profile of higher positive replies to the items, but also by anhedonia, high psychological distress, and family history of psychosis. These findings can inform prevention research in schizophrenia.     

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.     

Psychosis prediction: 12-month follow up of a high-risk ("prodromal") group

Intervention in the prodromal phase of schizophrenia and related psychoses may result in attenuation, delay or even prevention of the onset of psychosis in some individuals. However, a "prodrome" is difficult to recognise prospectively because of its nonspecific symptoms.This study set out to recruit and follow up subjects at high risk of transition to psychosis with the aim of examining the predictive power for psychosis onset of certain mental state and illness variables.Symptomatic individuals with either a family history of psychotic disorder, schizotypal personality disorder, subthreshold psychotic symptoms or brief transient psychotic symptoms were assessed and followed up monthly for 12 months or until psychosis onset.Twenty of 49 subjects (40.8%) developed a psychotic disorder within 12 months. Some highly significant predictors of psychosis were found: long duration of prodromal symptoms, poor functioning at intake, low-grade psychotic symptoms, depression and disorganization. Combining some predictive variables yielded a strategy for psychosis prediction with good sensitivity (86%), specificity (91%) positive predictive value (80%) and negative predictive value (94%) within 6 months.This study illustrates that it is possible to recruit and follow up individuals at ultra high risk of developing psychosis within a relatively brief follow-up period. Despite low numbers some highly significant predictors of psychosis were found. The findings support the development of more specific preventive strategies targeting the prodromal phase for some individuals at ultra high risk of schizophrenia.     

Prospective memory deficits in subjects with schizophrenia spectrum disorders: a comparison study with schizophrenic subjects, psychometrically defined schizotypal subjects, and healthy controls

Memory impairment is one of the core deficits in schizophrenia. This study explored the memory profiles of schizophrenic and psychometrically defined schizotypal subjects. The study participants included 15 patients with schizophrenia, 41 schizotypal subjects, and 20 healthy controls. All of the participants completed verbal and visual memory, working memory, and prospective memory tasks. The results showed that patients with schizophrenia were impaired in all aspects of memory function, whereas the schizotypal subjects tended to show moderate to large impairment effect sizes in prospective memory. It is suggested that prospective memory be considered a potential endophenotype of schizophrenia.     

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.     

Frequency of normative word associations in the speech of individuals at familial high-risk for schizophrenia

The intrusion of associations into speech in schizophrenia disrupts coherence and comprehensibility, a feature of formal thought disorder referred to as loosened associations. We have previously proposed that loosened associations may result from hyperactivity in semantic association networks, leading to an increased frequency of associated words appearing in speech. Using Computed Associations in Sequential Text (CAST) software to quantify the frequency of such associations in speech, we have reported more frequent normative associations in language samples from patients with schizophrenia and in individuals with schizotypal characteristics. The present study further examined this deviance in schizophrenia by studying normative associations in those who share genes with an individual with schizophrenia, (i.e. first-degree relatives of probands with schizophrenia; HR) but who do not have an illness. Familial high-risk participants (n=22), and controls (n=24) provided verbal responses to cards from the Thematic Apperception Test. CAST analysis revealed that HR used more associated words in their speech compared to controls. Furthermore, the frequency of normative word associations was positively correlated with dimensional and total scores of schizotypy derived from ratings of the structured interview for schizotypy, which confirms past research showing a relationship between schizotypy and hyperassociations. Our results suggest that some language disturbances in schizophrenia likely arise from an underlying psychopathological mechanism, hyperactivity of semantic associations.     

Neurological soft signs and schizotypal dimensions in unaffected siblings of patients with schizophrenia

The objectives were to determine the neurological soft signs (NSS) scores in unaffected siblings of patients with schizophrenia compared with healthy controls and to examine their relationships with schizotypal dimensions. Participants comprised 31 unaffected siblings of patients with schizophrenia and 60 healthy controls matched according to age, gender and school level who were assessed by the Schizotypal Personality Questionnaire (SPQ) and the Krebs et al. NSS Scale. Higher NSS total scores and sub-scores were found in the unaffected siblings compared with the controls. The SPQ total score was significantly higher in unaffected siblings compared with control subjects. The NSS total score was positively correlated with the SPQ total score and the SPQ disorganization sub-score in unaffected siblings of patients with schizophrenia. Additionally, in unaffected siblings, motor coordination and integration abnormalities were positively correlated with the SPQ total score and the cognitive-perceptual sub-score. Motor integration abnormalities were also correlated with the SPQ disorganization sub-score. These results reveal that NSS, especially motor signs, are associated with some schizotypal dimensions in siblings of patients with schizophrenia, suggesting the value of using both assessments to study high risk populations.     

Learned Irrelevance and Associative Learning Is Attenuated in Individuals at Risk for Psychosis but not in Asymptomatic First-Degree Relatives of Schizophrenia Patients: Translational State Markers of Psychosis?

Learned irrelevance (LIrr) refers to a form of selective learning that develops as a result of prior noncorrelated exposures of the predicted and predictor stimuli. In learning situations that depend on the associative link between the predicted and predictor stimuli, LIrr is expressed as a retardation of learning. It represents a form of modulation of learning by selective attention. Given the relevance of selective attention impairment to both positive and cognitive schizophrenia symptoms, the question remains whether LIrr impairment represents a state (relating to symptom manifestation) or trait (relating to schizophrenia endophenotypes) marker of human psychosis. We examined this by evaluating the expression of LIrr in an associative learning paradigm in (1) asymptomatic first-degree relatives of schizophrenia patients (SZ-relatives) and in (2) individuals exhibiting prodromal signs of psychosis (“ultrahigh risk” [UHR] patients) in each case relative to demographically matched healthy control subjects. There was no evidence for aberrant LIrr in SZ-relatives, but LIrr as well as associative learning were attenuated in UHR patients. It is concluded that LIrr deficiency in conjunction with a learning impairment might be a useful state marker predictive of psychotic state but a relatively weak link to a potential schizophrenia endophenotype.     

Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia.

OBJECTIVE: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms. METHOD: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task. RESULTS: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms. CONCLUSIONS: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.     

Elevated levels of schizotypal features in parents of patients with a family history of schizophrenia spectrum disorders

There is some evidence that schizotypal traits are related to a genetic or familial liability to develop schizophrenia. However, it is unclear whether the number of schizotypal traits is elevated in parents of schizophrenia patients compared with controls. This study used the Schizotypal Personality Questionnaire to investigate the difference in number of schizotypal traits between both parents of 36 patients with schizophrenia (n = 72 persons) and 26 healthy married control couples (n = 52 persons). Parents of patients had a lower score on the positive dimension of schizotypy than healthy controls. There was no difference on the negative or disorganization dimension between groups. The difference on the positive dimension might have been caused by a difference in response style between parents of patients and controls due to the fact that parents are more familiar with schizophrenia than controls. Of interest, parents with a family history of schizophrenia spectrum disorders had more positive and negative schizotypal traits than parents without a family history of schizophrenia spectrum disorders. Because these two groups of parents differ in only genetic risk, not familiarity with schizophrenia, results suggest that the negative and positive dimension of schizotypy are related to a familial or genetic vulnerability to schizophrenia.     

Orbitofrontal sulcogyral pattern and olfactory sulcus depth in the schizophrenia spectrum

Morphological changes in the orbitofrontal cortex (OFC), such as an altered sulcogyral pattern of the ‘H-shaped’ orbital sulcus and a shallow olfactory sulcus, have been demonstrated in schizophrenia, possibly reflecting deviations in early neurodevelopment. However, it remains unclear whether patients with schizotypal features exhibit similar OFC changes. This magnetic resonance imaging study examined the OFC sulcogyral pattern (Types I, II, III, and IV) and olfactory sulcus morphology in 102 patients with schizophrenia, 47 patients with schizotypal disorder, and 84 healthy controls. The OFC sulcogyral pattern distribution between the groups was significantly different on the right hemisphere, with the schizophrenia patients showing a decrease in Type I (vs controls and schizotypal patients) and an increase in Type III (vs controls) expression. However, the schizotypal patients and controls did not differ in the OFC pattern. There were significant group differences in the olfactory sulcus depth bilaterally (schizophrenia patients < schizotypal patients < controls). Our findings suggest that schizotypal disorder, a milder form of schizophrenia spectrum disorders, partly shares the OFC changes (i.e., altered depth of the olfactory sulcus) with schizophrenia, possibly reflecting a common disease vulnerability. However, altered distribution of the OFC pattern specific to schizophrenia may at least partly reflect neurodevelopmental pathology related to a greater susceptibility to overt psychosis.