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.     

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.     

Linkage analysis of candidate regions using a composite neurocognitive phenotype correlated with schizophrenia

As schizophrenia is genetically and clinically heterogeneous, systematic investigations are required to determine whether ICD-10 or DSM-IV categorical diagnoses identify a phenotype suitable and sufficient for genetic research, or whether correlated phenotypes incorporating neurocognitive performance and personality traits provide a phenotypic characterisation that accounts better for the underlying variation. We utilised a grade of membership (GoM) model (a mathematical typology developed for studies of complex biological systems) to integrate multiple cognitive and personality measurements into a limited number of composite graded traits (latent pure types) in a sample of 61 nuclear families comprising 80 subjects with ICD-10/DSM-IV schizophrenia or schizophrenia spectrum disorders and 138 nonpsychotic first-degree relatives. GoM probability scores, computed for all subjects, allowed individuals to be partly assigned to more than one pure type. Two distinct and contrasting neurocognitive phenotypes, one familial, associated with paranoid schizophrenia, and one sporadic, associated with nonparanoid schizophrenia, accounted for 74% of the affected subjects. Combining clinical diagnosis with GoM scores to stratify the entire sample into liability classes, and using variance component analysis (SOLAR), in addition to parametric and nonparametric multipoint linkage analysis, we explored candidate regions on chromosomes 6, 10 and 22. The results indicated suggestive linkage for the familial neurocognitive phenotype (multipoint MLS 2.6 under a low-penetrance model and MLS>3.0 under a high-penetrance model) to a 14 cM area on chromosome 6, including the entire HLA region. Results for chromosomes 10 and 22 were negative. The findings suggest that the familial neurocognitive phenotype may be a pleiotropic expression of genes underlying the susceptibility to paranoid schizophrenia. We conclude that use of composite neurocognitive and personality trait measurements as correlated phenotypes supplementing clinical diagnosis can help stratify the liability to schizophrenia across all members of families prior to linkage, allow the search for susceptibility genes to focus selectively on subsets of families at high genetic risk, and augment considerably the power of genetic analysis.     

The impact of gender and age at onset on the familial aggregation of schizophrenia

Summary Some recent family studies have shown that the familial risk for schizophrenia is higher in female than in male schizophrenics. It is debated whether the risks for the other disorders, such as schizotypal personality disorder or affective disorders in families of schizophrenics are similarly influenced by the proband's gender. Also, the reason for the effect of proband's gender on the recurrence risk for schizophrenia has not been clarified. This family study (159 probands, 589 first degree relatives) confirms that schizophrenia, but also schizophrenia spectrum disorders were more frequent in families of female compared with male schizophrenics. Neither age at onset in probands nor the interaction between gender and age at onset in probands had a relevant impact on the risk figures in relatives. Affective disorders occurred in families independently of the probands' gender. Aetiological heterogeneity or ascertainment bias may account for the modifying effect of proband's gender in schizophrenia.     

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.     

Offspring of parents with schizophrenia: mental disorders during childhood and adolescence

Although offspring of parents with schizophrenia are at risk for schizophrenic illness as adults, little is known about their pattern of symptoms as children and adolescents. Lifetime Axis I and II DSM-III-R diagnoses were made for 116 young people (ages 12-22). Forty-one subjects had a parent with schizophrenia, 39 had a parent with a nonschizophrenic mental disorder, and 36 had parents with no mental illness. Schizophrenia spectrum disorders occurred at higher rates among young people with a parent with schizophrenia (17.1%) than in other young people (5.3%), even after controlling for mental disorder in the nonproband parent. Schizophrenia and schizotypal personality disorder occurred exclusively in offspring of parents with schizophrenia. Offspring of parents with schizophrenia were also at increased risk for avoidant personality disorder but not paranoid personality disorder. Although lifetime anxiety disorders were common in all young people regardless of parent diagnosis, current anxiety disorders were more prevalent for the adolescent offspring of parents with schizophrenia. These data strongly suggest familial vulnerability to schizophrenia spectrum disorder that is observable before adulthood, particularly for males.     

Affective and impulsive personality disorder traits in the relatives of patients with borderline personality disorder

OBJECTIVE: This study tested the hypothesis that the risk for affective and impulsive personality disorder traits commonly found in patients with borderline personality disorder would be greater in the first-degree relatives of probands with borderline personality disorder than in two comparison groups. METHOD: Blind family history interviews were conducted with family informants to assess the extent to which first-degree relatives of 29 probands with borderline personality disorder, 22 probands with other personality disorders who met three or fewer of the criteria for borderline personality disorder, and 43 probands with schizophrenia fulfilled operationalized criteria for the two kinds of personality disorder traits and for other diagnostic categories. The crude proportions of adult relatives with each diagnosis, as well as the age-adjusted morbid risks, were assessed in the three groups of relatives. RESULTS: The risks for affective and impulsive personality disorder traits were independently greater in the 129 relatives of the borderline probands than in the 105 relatives of the probands with other personality disorders and the 218 relatives of the schizophrenic probands. There was no similarly greater risk for any other psychiatric disorder assessed, including major affective disorder. In addition, the relatives of borderline probands with current or past major depressive disorder showed a greater risk for major affective disorders than the relatives of never-depressed probands with other personality disorders but not the relatives of never-depressed borderline probands. CONCLUSIONS: These results suggest familial transmission of the hallmark borderline-related personality characteristics and raise the possibility that these familial traits may be partially independent.     

Genetic heterogeneity in schizophrenia II: conditional analyses of affected schizophrenia sibling pairs provide evidence for an interaction between markers on chromosome 8p and 14q

Information from multiple genome scans and collaborative efforts suggests that schizophrenia is a heterogeneous, complex disorder with polygenic and environmental antecedents. In a previous paper we demonstrated that stratification of families on the basis of co-segregating phenotypes (psychotic affective disorders (PAD) and schizophrenia spectrum personality disorders (SSPD) in first-degree relatives of schizophrenic probands increased linkage evidence in the chromosome 8p21 region (D8S1771) among families with co-segregating SSPD. We have now applied a method of conditional analysis of sib-pairs affected with schizophrenia, examining shared alleles identical-by-descent (IBD) at multiple loci. The method yields enhanced evidence for linkage to the chromosome 8p21 region conditioned upon increased allele sharing at a chromosome 14 region. The method produces a more refined estimate of the putative disease locus on chromosome 8p21, narrowing the region from 18 cM (95% confidence interval) in our previous genome scan, to approximately 9.6 cM. We have also shown that the affected siblings sharing two alleles IBD at the chromosome 8p21 region and one allele IBD at the chromosome 14 region differ significantly in clinical symptoms from non-sharing affected siblings. Thus the analysis of allele sharing at a putative schizophrenia susceptibility locus conditioned on allele sharing at other loci provides another important method for dealing with heterogeneity.     

Validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands

This study examined the validity of the family history method for diagnosing schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders in first-degree relatives of schizophrenia probands. This is the first large-scale study that examined the validity of the family history method for diagnosing DSM-III-R personality disorders. The best estimate DSM-III-R diagnoses of 264 first-degree relatives of 117 adult-onset schizophrenia probands based on direct structured diagnostic interviews, family history interview, and medical records were compared to Family History Research Diagnostic Criteria (FH-RDC) diagnoses based on the NIMH Relative Psychiatric History Interview and to family history Structured Clinical Interview for DSM-III-R: Personality Disorders (SCID-II) diagnoses based on the SCID-II adapted to a third person format. Diagnoses of relatives were made blind to proband diagnostic status. The median sensitivity for schizophrenia and the related psychoses was 29% (range 0-50%), the median specificity 99% (range 98-100%), and the median positive predictive value (PPV) 67% (range 20-80%). The median sensitivity for the personality diagnoses was 25% (range 14-71%), the median specificity 100% (range 99-100%), and the median PPV 100% (range 67-100%). The family history method has low sensitivity but has excellent specificity and PPV for schizophrenia, schizophrenia-related psychoses, and schizophrenia-spectrum personality disorders. The kappa coefficient for the family history method was moderately good for the psychoses (0.598) and for paranoid and schizotypal personality disorder (0.576). Using the family history method, the validity of making schizophrenia-related personality disorder diagnoses was comparable to that of making psychotic disorder diagnoses.     

Genetic boundaries of the schizophrenia spectrum: evidence from the Finnish Adoptive Family Study of Schizophrenia

OBJECTIVE: Identification of the genetically related disorders in the putative schizophrenia spectrum is an unresolved problem. Data from the Finnish Adoptive Family Study of Schizophrenia, which was designed to disentangle genetic and environmental factors influencing risk for schizophrenia, were used to examine clinical phenotypes of schizophrenia spectrum disorders in adopted-away offspring of mothers with schizophrenia spectrum disorders. METHOD: Subjects were 190 adoptees at broadly defined genetic high risk who had biological mothers with schizophrenia spectrum disorders, including a subgroup of 137 adoptees at narrowly defined high risk whose mothers had DSM-III-R schizophrenia. These high-risk groups, followed to a median age of 44 years, were compared diagnostically with 192 low-risk adoptees whose biological mothers had either a non-schizophrenia-spectrum diagnosis or no lifetime psychiatric diagnosis. RESULTS: In adoptees whose mothers had schizophrenia, the mean lifetime, age-corrected morbid risk for narrowly defined schizophrenia was 5.34% (SE=1.97%), compared to 1.74% (SE=1.00%) for low-risk adoptees, a marginally nonsignificant difference. In adoptees whose mothers had schizophrenia spectrum disorders, the mean age-corrected morbid risk for a schizophrenia spectrum disorder was 22.46% (SE=3.56%), compared with 4.36% (SE=1.51%) for low-risk adoptees, a significant difference. Within the comprehensive array of schizophrenia spectrum disorders, schizotypal personality disorder was found significantly more often in high-risk than in low-risk adoptees. The frequency of the group of nonschizophrenic nonaffective psychoses collectively differentiated high-risk and low-risk adoptees, but the frequencies of the separate disorders within this category did not. The two groups were not differentiated by the prevalence of paranoid personality disorder and of affective disorders with psychotic features. CONCLUSIONS: In adopted-away offspring of mothers with schizophrenia spectrum disorders, the genetic liability for schizophrenia-related illness (with the rearing contributions of the biological mothers disentangled) is broadly dispersed. Genetically oriented studies of schizophrenia-related disorders and studies of genotype-environment interaction should consider not only narrowly defined, typical schizophrenia but also schizotypal and schizoid personality disorders and nonschizophrenic nonaffective psychoses.     

A longitudinal study of schizophrenia- and affective spectrum disorders in individuals diagnosed with a developmental language disorder as children

The prevalence and types of schizophrenia- and affective spectrum disorders were studied in 469 individuals with a developmental language disorder (DLD), assessed in the same clinic during a period of 10 years, and 2,345 controls from the general population. All participants were screened through the nationwide Danish Psychiatric Central Register (DPCR). The mean length of follow-up was 34.7 years, and the mean age at follow-up 35.8 years. The results show an excess of schizophrenia spectrum disorders (F20-F29) within participants with DLD when compared with controls from the overall population (6.4% vs. 1.8%; P < 0.0001). For schizophrenia (F20.x) the respective figures were 3.8% versus 1.1%; P = 0.0001. The variable degree of expressive language disorder was significantly associated with a schizophrenia spectrum disorder diagnosis in the DPCR. There was no significant increase in affective spectrum disorders (F30-F39) in the DLD case group (3.4% vs. 2.0%; P = 0.05). Our results provide additional support to the notion that DLD is a marker of increased vulnerability to the development of schizophrenia spectrum disorders.     

Saccadic eye movement abnormalities in relatives of patients with schizophrenia

Recent studies note abnormalities in saccadic eye movements of relatives of patients with schizophrenia. The current study examined which aspects of the saccadic system are affected, whether these saccadic abnormalities are associated with schizophrenia spectrum personality symptoms (SSP), and whether such an association is dependent on a family history of schizophrenia. Furthermore, the study examined what proportion of relatives have the saccadic abnormality(ies). Fifty-five first-degree relatives with no DSM-III-R Axis I diagnosis participated in the study. Twenty-one of these relatives experienced SSP symptoms and 34 had no Axis II diagnosis. Sixty-two subjects with no Axis I diagnosis were recruited from the community. Twenty-five experienced SSP symptoms and 37 had no Axis II diagnosis. Prosaccades (saccades toward the target) and antisaccades (saccades made in the opposite direction of the target jump) were examined. Relatives, particularly those with SSP, had difficulties with the antisaccade task as suggested by higher error rates and longer antisaccade latency. Prosaccades were not different in relatives compared to the community subjects, although the effects of field were different in the two groups on some measures. The antisaccade latency was 'abnormal' in only a small proportion (1.6%) of community subjects compared to 14.9% of all relatives (35.3% of SSP relatives and 3.3% of non-SSP relatives). Relatives of patients with schizophrenia have deficits in aspects of the saccadic system involved in generating internally driven saccades and inhibition of unwanted saccades. These deficits implicate frontal ocular motor neuronal circuitry involving frontal cortical and basal ganglia areas. These deficits are associated with SSP symptoms, but not in the absence of a blood relationship to schizophrenia. The relatively high prevalence rate of the abnormality in at-risk subjects may have relevance for use of these measures in linkage analysis.     

Relationship between positive and negative symptoms of schizophrenia and schizotypal symptoms in nonpsychotic relatives.

BACKGROUND: Continuous rather than categorical measures of psychopathology may provide greater statistical power to detect susceptibility loci for schizophrenia. However, it has not been established that the dimensions of schizophrenic symptomatology and personality traits in nonpsychotic individuals share etiological factors. We therefore sought to clarify the relationship between positive and negative symptoms of schizophrenic probands and dimensions of schizotypy in their first-degree relatives. METHODS: In the Roscommon Family Study, we examined the ability of positive and negative symptoms in probands to predict 7 factors of schizotypy in nonpsychotic relatives using regression analysis. These consisted of positive, negative, and avoidant symptoms; odd speech; suspicious behavior; social dysfunction; and symptoms of borderline personality disorder. We examined 3 proband groups: schizophrenia (n = 127); schizophrenia, simple schizophrenia, and schizoaffective disorder (n = 178); and all nonaffective psychoses (n = 216), and their nonpsychotic relatives (n = 309, 477, and 584, respectively). RESULTS: Positive symptoms in all nonaffective psychoses probands predicted positive schizotypy (beta = 0.1972, P =.0004), social dysfunction (beta = 0.0719, P =.0489), and borderline personality disorder symptoms (beta = 0.1327, P =.0084) in relatives, while negative symptoms predicted negative schizotypy (beta = 0.2069, P =.0002), odd speech (beta = 0.2592, P =.0001), suspicious behavior (beta = 0.2749, P =.0001), and social dysfunction (beta =.2398, P =.0002). Proband negative symptoms and borderline personality disorder symptoms in relatives in the schizophrenia, simple schizophrenia, and schizoaffective disorder group were inversely related (beta = -0.1185, P =.05). CONCLUSIONS: Positive and negative symptoms in schizophrenia predict corresponding schizotypal symptoms in relatives. This provides evidence that these schizophrenic symptom factors (1) are etiologically distinct from each other and (2) occur on an etiological continuum with their personality-based counterparts.     

Significant correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy

Prior family and adoption studies have suggested a genetic relationship between schizophrenia and schizotypy. However, this has never been verified using linkage methods. We therefore attempted to test for a correlation in linkage signals from genome-wide scans of schizophrenia and schizotypy. The Irish study of high-density schizophrenia families comprises 270 families with at least two members with schizophrenia or poor-outcome schizoaffective disorder (n=637). Non-psychotic relatives were assessed using the structured interview for schizotypy (n=746). A 10-cM multipoint, non-parametric, autosomal genome-wide scan of schizophrenia was performed in Merlin. A scan of a quantitative trait comprising ratings of DSM-III-R criteria for schizotypal personality disorder in non-psychotic relatives was also performed. Schizotypy logarithm of the odds (LOD) scores were regressed onto schizophrenia LOD scores at all loci, with adjustment for spatial autocorrelation. To assess empirical significance, this was also carried out using 1000 null scans of schizotypy. The number of jointly linked loci in the real data was compared to distribution of jointly linked loci in the null scans. No markers were suggestively linked to schizotypy based on strict Lander-Kruglyak criteria. Schizotypy LODs predicted schizophrenia LODs above chance expectation genome wide (empirical P=0.04). Two and four loci yielded nonparametric LOD (NPLs) >1.0 and >0.75, respectively, for both schizophrenia and schizotypy (genome-wide empirical P=0.04 and 0.02, respectively). These results suggest that at least a subset of schizophrenia susceptibility genes also affects schizotypy in non-psychotic relatives. Power may therefore be increased in molecular genetic studies of schizophrenia if they incorporate measures of schizotypy in non-psychotic relatives.     

Familial aggregation of schizophrenia and schizophrenia spectrum disorders. Evaluation of conflicting results

In this issue, Coryell and Zimmerman report no significant increase in the risk of schizophrenia or "schizophrenia spectrum" personality disorders in relatives of schizophrenics vs never-ill controls. This article attempts to evaluate critically and interpret their findings. Given the modest number of relatives studied, their negative findings regarding schizophrenia could easily be the result of sampling variation. Relatives were assessed using a general personality disorder instrument, and over two thirds were interviewed by telephone; this method may have a low sensitivity to detect key features of the schizophrenia spectrum such as inadequate rapport and suspiciousness. True population differences may, however, exist in the pattern of familial aggregation for schizophrenia and related disorders. The convincing demonstration of this would be of considerable interest and should lead to a constructive search for the source of the interpopulation differences.     

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.     

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.     

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.     

Schizophreniform disorder,delusional disorder and psychotic disorder not otherwise specified: clinical features,outcome and familial psychopathology

The relationship between DSM-III-R schizophreniform disorder, delusional disorder (DD) and psychotic disorder not otherwise specified (PD-NOS) and schizophrenia and affective illness (AI) remains uncertain. We explore this question in the Roscommon Family Study by examining symptoms, outcome and patterns of psychopathology in relatives. Probands were selected from a population-based case registry in the west of Ireland with an ICD-9 diagnosis of schizophrenia or AI. Personal interviews were conducted with 88% of traceable, living probands, a mean of 16 years after onset, and 86% of traceable, living first-degree relatives. Best-estimate diagnoses were made at follow-up. Schizophreniform disorder, DD and PD-NOS constituted 6.4%, 2.8% and 7.5%, respectively, of all probands with a registry diagnosis of schizophrenia. Probands with schizophreniform disorder had prominent positive psychotic symptoms, negligible negative symptoms and a good outcome, comparable to that seen in AI probands. Their relatives had an excess risk of schizophrenia spectrum illness but not AI. Probands with DD had prominent delusions but no other psychotic symptoms, few negative symptoms, fair to good outcome and an increased risk in relatives for alcoholism. Probands with PD-NOS had both moderate positive and negative psychotic symptoms, a poor to fair outcome and a substantially elevated risk in relatives of schizophrenia and schizophrenia spectrum disorders but not AI. These results suggest that i) DSM-III-R criteria for schizophreniform disorder define a good outcome disorder with prominent positive psychotic symptoms that probably has a familial relationship to schizophrenia, but not AI; ii) DD is a rare, monosymptomatic psychosis that may have a modest etiologic relationship with alcoholism, but probably not with schizophrenia or AI and iii) PD-NOS is probably heterogeneous but, of these 3 disorders, most closely resembles schizophrenia with respect to symptoms, outcome and familial psychopathology. These results should be seen as tentative given the small number of probands and relatives evaluated.     

Increase in harm avoidance by genetic loading of schizophrenia

BackgroundSchizophrenia is highly familial neuropsychiatric disorder with heritability estimated at 60% to 90%. Even unaffected first-degree relatives of schizophrenia manifested some neuropsychologic abnormalities, neurologic soft sign, and morphologic anomalies. Because personality traits are under genetic influence and considerable heritability, we intended to evaluate temperament and character of first-degree relatives of schizophrenia and the influence of schizophrenia genetic loading on their temperament and character.MethodsTemperament and Character Inventory was completed by 97 first-degree relatives of schizophrenia or schizoaffective disorder, 48 schizophrenic probands (44 patients with schizophrenia and 4 patients with schizoaffective disorder), and 106 control subjects. Within first-degree relatives, parents who have additional probands with schizophrenia spectrum disorder in their ascendant or collateral pedigree and siblings who have offspring with schizophrenia spectrum disorder were defined as presumed carriers (n = 20). Group differences in Temperament and Character Inventory scores were compared using a mixed-model analysis of variance with family as a random effect and age as a covariate.ResultsHarm avoidance (HA) scores increased in the order of control subjects, the first-degree relatives, and probands. Among the relatives, presumed carriers, but not presumed noncarriers, had higher HA compared with control subjects. In addition, probands showed significantly low reward dependence, low self-directedness, and low cooperativeness scores compared with the first-degree relatives and control subjects. Probands had also higher self-transcendence scores than the first-degree relatives and had lower persistence scores than control subjects.ConclusionsOur findings that HA increases in proportion to the genetic loading of schizophrenia suggest that it may be a potential endophenotype of schizophrenia.