Schizophrenia and schizophrenia-spectrum personality disorders in the first-degree relatives of children with schizophrenia: the UCLA family study

BACKGROUND: This study tested the hypothesis that childhood-onset schizophrenia (COS) is a variant of adult-onset schizophrenia (AOS) by determining if first-degree relatives of COS probands have an increased risk for schizophrenia and schizotypal and paranoid personality disorders. METHODS: Relatives of COS probands (n = 148) were compared with relatives of attention-deficit/hyperactivity disorder (ADHD) (n = 368) and community control (n = 206) probands. Age-appropriate structured diagnostic interviews were used to assign DSM-III-R diagnoses to probands and their relatives. Family psychiatric history was elicited from multiple informants. Diagnoses of relatives were made blind to information about probands' diagnoses. Final consensus diagnoses, which integrated family history, direct interview information, and medical records, are reported in this article. RESULTS: There was an increased lifetime morbid risk for schizophrenia (4.95% +/- 2.16%) and schizotypal personality disorder (4.20% +/- 2.06%) in the parents of COS probands compared with parents of ADHD (0.45% +/- 0.45%, 0.91% +/- 0.63%) and community control (0%) probands. The parents of COS probands diagnosed as having schizophrenia had an early age of first onset of schizophrenia. Risk for avoidant personality disorder (9.41% +/- 3.17%) was increased in the parents of COS probands compared with parents of community controls (1.67% +/- 1.17%). CONCLUSIONS: The psychiatric disorders that do and do not aggregate in the parents of COS probands are remarkably similar to the disorders that do and do not aggregate in the parents of adults with schizophrenia in modern family studies. These findings provide compelling support for the hypothesis of etiological continuity between COS and AOS.     

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.     

Neurocognitive functioning and schizophrenia spectrum disorders can be independent expressions of familial liability for schizophrenia in community control children: the UCLA family study

This study provided a further test of the hypothesis that certain neuromotor, language and verbal memory dysfunctions reflect genetic predisposition to schizophrenia, by examining the effects of family loading for schizophrenia (FLS) in normal controls without personal histories of schizophrenia or attention deficit hyperactivity disorder. In a case control design, 11 community controls (CC) with FLS were compared to 47 CC without FLS on tests of expressive and receptive language, visual motor coordination, full scale intelligence and verbal memory. In this study, FLS primarily reflects the incidence of schizophrenia spectrum diagnoses in the second-degree relatives of CC probands. CC probands with FLS had significantly poorer general intelligence, expressive and receptive vocabulary abilities, visual motor coordination and slower motor speed than CC probands without FLS. The variance in neurocognitive functioning associated with FLS is not due to the presence of any psychiatric disorders in CC probands, nor the presence of schizophrenia spectrum disorders in their parents. The relation between FLS and neurocognitive and neuromotor functioning in CC probands was moderated by the parent's cognitive functioning. The results of the present study indicate that familial liability to schizophrenia can be transmitted across two generations, independent of the presence of schizophrenia spectrum disorders in either the parent or proband, and account for significant variance in proband neurocognitive and neuromotor functioning.These findings suggest the neurocognitive and neuromotor functioning and schizophrenia spectrum disorders can be relatively independent expressions of familial liability to schizophrenia.     

Caregiver burden in recent-onset schizophrenia and spectrum disorders: the influence of symptoms and personality traits

Earlier studies that used two symptom dimensions indicate that the caregiver burden for patients with schizophrenia is significantly determined by their negative symptoms. The purpose of this study is to examine the relationship between symptom severity in recent-onset schizophrenia and caregiver burden in a more differentiated way (i.e., five-symptom dimensions). Based on previous research, which shows that patients' personality traits influence the course of schizophrenia, we theorize that personality traits could also influence caregiver burden. So far, this hypothesis has never been studied. Therefore, the second purpose of this study is to examine whether patients' personality traits would contribute to caregiver burden. The results of this study showed that the disorganization symptom component was the predicting variable of the subscales supervision, tension, urging, distress, and the overall amount of caregiver burden in a linear regression analysis. Personality traits of patients played no substantial role in caregiver burden. These findings suggest that psychoeducational programs should address the severity of disorganization symptoms to reduce caregiver burden in the early phase of schizophrenia.     

Considering DSM-5: personality diagnostics in patients with schizophrenia spectrum disorders

The aims of this study were to examine the prevalence of personality disorders (PD) in patients with schizophrenia spectrum disorders (SSD), to examine the interaction of axis-I and axis-II symptoms to provide an estimate on the confounding potential of SSD psychopathology in the establishment of DSM-IV PD diagnoses, and to discuss implications concerning the proposed changes in DSM-5. Patients with SSD, aged 18 to 65 years, and being at least partially remitted (PANSS total score < 75) were included. PD was examined categorically and dimensionally using the SCID-II screening questionnaire and interview, and SSD psychopathology was rated using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Forty-five patients (31 with schizophrenia) were included in the current study. Mean age was 37.2 years, and the median duration of illness was 9.5 years. Mean PANSS total score was 42.5. The cumulative prevalence of PD in our collective was 20%, with obsessive-compulsive, antisocial, and borderline PD being the most frequent. There were no cases of cluster A PD diagnoses. In the dimensional analysis, numerous correlations of small to medium effect size emerged between maladaptive personality traits and SSD psychopathology. PD is present in a clinically relevant subgroup of SSD patients and has to be recognized in SSD treatment. Currently, it remains unclear to what extent correlations between personality traits and SSD symptoms can be explained by content overlap or co-variation of SSD psychopathology and PD traits. SSD psychopathology may bias PD diagnostics and lead to a higher percentage of categorical PD diagnoses, especially considering the proposed changes in DSM-5.     

Increased prevalence of schizophrenia spectrum disorders in relatives of neuroleptic-nonresponsive schizophrenic patients

OBJECTIVE: It is suggested that schizophrenic patients who respond to neuroleptic medication and those who do not might differ with respect to their pathogenesis. In particular, it has been proposed that genetic factors may contribute to treatment response and/or outcome. In order to test this hypothesis, we compared the pattern of familial aggregation of schizophrenia related disorders in schizophrenic patients who are either responders (R) or nonresponders (NR) to typical neuroleptics. METHOD: R (n=36) or NR (n=35) patients to typical neuroleptics and healthy controls (n=63) were recruited. At least one key informant relative of each proband was interviewed blind as to the status of the proband using the Family Interview for Genetic Studies. Morbid risk for schizophrenia and cluster A personality disorders and family loading score for schizophrenia were examined in first- and second-degree relatives of these probands. RESULTS: First-degree relatives of NR patients were at a significantly higher risk for schizophrenia (MR=8.84), compared, respectively, to relatives of controls (MR=1.52) or relatives of R patients (MR=2.45). The same pattern was observed in second-degree relatives. Family loading score for schizophrenia in first- and second-degree relatives was significantly higher in NR compared to R patients. CONCLUSIONS: Schizophrenic patients who do not respond to typical neuroleptics may suffer from a more familial form of schizophrenia compared to patients who are responders.     

The structure of schizotypy: relationships between neurocognitive and personality disorder features in relatives of schizophrenic patients in the UCLA Family Study

Schizotypal personality features and certain neurocognitive deficits have been shown to aggregate in the relatives of schizophrenic patients, supporting the view that both are likely to reflect genetic contributions to liability to schizophrenia. Within the relatives of schizophrenic patients, however, the interrelationships between these potential indicators of liability to schizophrenia are not well known. Using data from the UCLA Family Study, we examine the interrelationships between personality disorder symptoms and neurocognitive functioning in nonpsychotic first-degree relatives of schizophrenic patients. Factor analyses indicate that several dimensions of schizotypy can be identified. A neurocognitive dysfunction dimension includes loadings from measures of sequential visual conceptual tracking, rapid perceptual encoding and search, and focused, sustained attention as well as the rating of odd and eccentric behavior from schizotypal personality disorder. Other aspects of schizotypal personality disorder form separate positive schizotypy and negative schizotypy dimensions. These analyses support the view that schizotypy is multidimensional in relatives of schizophrenic patients and indicate that neurocognitive deficits in perception and attention are associated with particular schizotypal personality features.     

Association between white matter fiber integrity and subclinical psychotic symptoms in schizophrenia patients and unaffected relatives

The authors examined whether multiple childhood indicators of neurodevelopmental instability known to relate to schizophrenia-spectrum disorders could predict later schizophrenia-spectrum outcomes. A standardized battery of neurological and intellectual assessments was administered to a sample of 265 Danish children in 1972, when participants were 10-13 years old. Parent psychiatric diagnoses were also obtained in order to evaluate the predictive strength of neurodevelopmental factors in combination with genetic risk. Adult diagnostic information was available for 244 members of the sample. Participants were grouped into three categories indicating level of genetic risk: children with a parent with schizophrenia (n=94); children with a parent with a non-psychotic mental health diagnosis (n=84); and children with a parent with no records of psychiatric hospitalization (n=66). Variables measured included minor physical anomalies (MPAs), coordination, ocular alignment, laterality, and IQ. Adult diagnoses were assessed through psychiatric interviews in 1992, as well as through a scan of the national psychiatric registry through 2007. Through a combination of multiple childhood predictors, the model correctly classified 73% (24 of 33) of the participants who eventually developed a schizophrenia-spectrum outcome in adulthood. Results suggest that, with replication, multivariate premorbid prediction could potentially be a useful complementary approach to identifying individuals at risk for developing a schizophrenia-spectrum disorder. Genetic risk, MPAs, and other markers of neurodevelopmental instability may be useful for comprehensive prediction models.     

Neuropsychological performance and spectrum personality traits in the relatives of patients with schizophrenia and affective psychosis

Neuropsychological deficits are found in both schizophrenic patients and their relatives, and some studies have shown similar, but less severe, deficits in affective psychotic patients and their relatives. We set out to establish: (a) whether schizophrenia spectrum personality traits are more common in the relatives of schizophrenic patients than, in the relatives of affective psychotic patients; and (b) what the relation is between spectrum personality traits and neuropsychological deficits in these relatives. Relatives were interviewed using the International Personality Disorder Examination (IPDE), and also completed the National Adult Reading Test (NART), the Trail Making Test (TMT; Parts A and B) and Thurstone's Verbal Fluency Test (TVFT). Spectrum personality traits were equally common in 129 relatives of schizophrenic patients and 106 relatives of affective psychotic patients, but the performance of the former group was inferior to that of the latter on the NART and the TVFT. Relatives with high paranoid traits had lower NART scores than relatives without such personality traits; similarly, those with high schizoid traits took longer to complete the TMT, part B, than those without such traits; and relatives with high schizotypal traits generated significantly fewer words on the TVFT than those without such traits. We conclude that relatives of schizophrenic and affective psychotic patients share a propensity to schizophrenia spectrum traits, but relatives of the former have poorer neuropsychological performance. Furthermore, there exists an association between neuropsychological deficits and spectrum traits in both groups of relatives; in particular those with high paranoid traits have lower IQ scores than their less paranoid counterparts.     

Stress response symptoms in relatives of acutely admitted psychotic patients: A pilot study

Objective: The aim of this study is to identify specific stress response symptoms in relatives of acutely admitted psychotic patients, and to compare these responses with those of relatives of chronic inpatients. Method: Twenty-five relatives of acutely hospitalized, psychotic patients and 21 relatives of chronic inpatients were assessed within days of the acute patient's admission and 6 weeks later. The Impact Event Scale assessed intrusion and avoidance; items from the General Health Questionnaire (GHQ) and the Spielberger State Anxiety Inventory (STAI) assessed arousal. Results: At the first assessment, relatives of the acutely admitted psychotic patients reported higher intensity of intrusive symptoms, and more often a high arousal level compared to the relatives of chronic inpatients. Six weeks later, relatives of acutely admitted psychotic patients revealed both higher intensity and higher number of intrusive and avoidance symptoms, and higher level of arousal symptoms. Seven relatives of acutely admitted psychotic patients and no relatives of the chronic inpatients reported moderate to high level of intrusion, avoidance and arousal at both assessments. Conclusion: Relatives of acutely admitted psychotic patients revealed strong acute and persistent stress responses, similar to those described in subjects exposed to severe or life threatening illness. Even relatives of the chronic inpatients revealed stress-specific symptoms, but at a lower level. Specific stress response symptoms may impair the relatives' well-being, care-giving abilities, and their co-operation with the mental health system. Our results suggest that stress response symptoms in relatives should be given more attention.     

Schizoidia in schizophrenia spectrum and personality disorders: role of dissociation

Dissociation was one of the roots of the nosopoetic construct "schizophrenia", and a link seems to exist between psychotic and dissociative phenomena. We explored the relationship between dissociation and schizoidia as defined by the Dissociative Experiences Scale (DES) total score and the schizoidia subscale of the Munich Personality Test (MPT), respectively. The study comprised 43 outpatients diagnosed with schizophrenia spectrum disorders in remission, 47 outpatients with personality disorders and 42 non-patients. Besides the DES and the MPT, all participants also completed parts of the Symptom Checklist (SCL-90-R) and theTrauma Questionnaire (TQ). In the final multivariable logistic model, a set of five variables was identified as the strongest contributors to the occurrence of schizoida. The model included TQ broken home, MPT neuroticism, schizophrenia spectrum and personality disorder diagnoses, and SCL aggressivity; it did not include any dissociation variable. The purported relationship between dissociation and schizoidia could not be confirmed; the existence of schizophrenia-inherent dissociation appears questionable.     

Duration mismatch negativity in biological relatives of patients with schizophrenia spectrum disorders.

BACKGROUND: One of the most consistent findings in schizophrenia research over the past decade is a reduction in the amplitude of an auditory event-related brain potential known as mismatch negativity (MMN), which is generated whenever a deviant sound occurs in a background of repetitive auditory stimulation. The reduced amplitude of MMN in schizophrenia was first observed for deviant sounds that differ in duration relative to background standard sounds, and similar findings have been observed for sounds that are deviant in frequency. The aim of this study was to determine whether first-degree relatives of schizophrenia patients show a similar reduction in MMN amplitude to duration deviants. METHODS: We measured MMN to duration increments (deviants 100 msec vs. standards 50 msec) in 22 medicated patients with a diagnosis in the schizophrenia spectrum, 17 individuals who were first-degree unaffected relatives of patients, and 21 healthy control subjects. RESULTS: Mismatch negativity amplitude was reduced in patients and relatives compared with control subjects. There were no significant differences between patients and relatives. In contrast, the subsequent positive component, P3a, was larger in relatives compared with patients. CONCLUSIONS: These findings suggest that a reduced MMN amplitude may be an endophenotype marker of the predisposition to schizophrenia.     

Psychopathology and personality traits in psychotic patients and their first-degree relatives

Personality dimensions have been associated with symptoms dimensions in schizophrenic patients (SP). In this paper we study the relationships between symptoms of functional psychoses and personality dimensions in SP and their first-degree relatives (SR), in other psychotic patients (PP) and their first-degree relatives (PR), and in healthy controls in order to evaluate the possible clinical dimensionality of these disorders. Twenty-nine SP, 29 SR, 18 PP, 18 PR and 188 controls were assessed using the temperament and character inventory (TCI-R). Current symptoms were evaluated with positive and negative syndrome scale (PANSS) using the five-factor model described previously (positive [PF], negative [NF], disorganized [DF], excitement [EF] and anxiety/depression [ADF]). Our TCI-R results showed that patients had different personality dimensions from the control group, but in relatives, these scores were not different from controls. With regard to symptomatology, we highlight the relations observed between harm avoidance (HA) and PANSS NF, and between self-transcendence (ST) and PANSS PF. From a personality traits-genetic factors point of view, schizophrenia and other psychosis may be initially differentiated by temperamental traits such as HA. The so-called characterial traits like ST would be associated with the appearance of psychotic symptoms.     

Avoidant personality disorder is a separable schizophrenia-spectrum personality disorder even when controlling for the presence of paranoid and schizotypal personality disorders The UCLA family study

It is unresolved whether avoidant personality disorder (APD) is an independent schizophrenia (Sz)-spectrum personality disorder (PD). Some studies find APD and social anxiety symptoms (Sxs) to be separable dimensions of psychopathology in relatives (Rels) of schizophrenics while other studies find avoidant Sxs to be correlated with schizotypal and paranoid Sxs. Rates of APD among first-degree Rels of Sz probands, attention-deficit/hyperactivity disorder (ADHD) probands, and community control (CC) probands were examined. Further analyses examined rates when controlling for the presence of schizotypal (SPD) and paranoid (PPD) personality disorders, differences in APD Sxs between relative groups, and whether APD in Rels of Szs reflects a near miss for another Sz-spectrum PD. Three hundred sixty-two first-degree Rels of Sz probands, 201 relatives of ADHD probands, and 245 Rels of CC probands were interviewed for the presence of DSM-III-R Axis I and II disorders. Diagnoses, integrating family history, interview information, and medical records, were determined. APD occurred more frequently in Rels of Sz probands compared to CC probands (p<0.001) and also when controlling for SPD and PPD (p<0.005). Two Sxs of APD were most characteristic of the Rels of Sz probands: "avoids social or occupational activities..." and "exaggerates the potential difficulties..." 65% of the Rels of Sz probands who had diagnoses of APD were more than one criterion short of a DSM-III-R diagnosis of either SPD or PPD. This indicates that APD is a separate Sz-spectrum disorder, and not merely a sub-clinical form of SPD or PPD.     

Dimensional structure of psychotic symptoms: an item-level analysis of SAPS and SANS symptoms in psychotic disorders.

The factor structure of psychotic symptoms as assessed by means of the Scales for the Assessment of Positive and Negative Symptoms (SAPS and SANS) was examined in a sample of 660 psychotic inpatients. Analyses were conducted at item-level. Principal-component analysis (PCA) was used to extract factors, the OBLIMIN procedure to rotate factors, and the eigen value greater-than-one criterion to determine the number of factors. PCA resulted in 11 interpretable factors explaining 64% of the total variance: poverty of affect/speech, thought disorder/inappropriate affect, bizarre delusions, social dysfunction, other delusions, paranoid delusions, bizarre behavior, nonauditory hallucinations, auditory hallucinations, manic thought disorder, and attention. Many of the factors were significantly intercorrelated. A second-order PCA resulted in four second-order factors, the first three roughly corresponding to the well-known psychosis, disorganization and negative dimensions. It is concluded that the factor structure of psychotic symptoms is more complex than is generally acknowledged, and that the dimensions of psychosis, disorganization and negative represent second-order dimensions. The subscale composition of the SAPS and SANS was not supported.     

Associative stigma in family members of psychotic patients in Flanders: An exploratory study

AIM: To assess presence and severity of associative stigma in family members of psychotic patients and factors for higher associative stigma.METHODS: Standardized semi-structured interview of 150 family members of psychotic patients receiving full time treatment. This study on associative stigma in family members of psychotic patients was part of a larger research program on the burden of the family, using “Interview for the Burden of the Family” and the chapters stigma, treatment and attribution from the “Family interview Schedule”. The respondents were relatives, one per patient, either partner or parent. The patients had been diagnosed with schizophrenia or schizo-affective disorder. All contacts with patients and relatives were in Dutch. Relatives were deemed suitable to participate in this research if they saw the patient at least once a week. Recruitment took place in a standardized way: after obtaining the patient’s consent, the relatives were approached to participate. The results were analyzed using SPSS Version 18.0.RESULTS: The prevalence of associative stigma in this sample is 86%. Feelings of depression in the majority of family members are prominent. Twenty-one point three percent experienced guilt more or less frequent, while shame was less pronounced. Also, 18.6% of all respondents indicated that they tried to hide the illness of their family member for others regularly or more. Three six point seven percent really kept secret about it in certain circumstances and 29.3% made efforts to explain what the situation or psychiatric condition of their family member really is like. Factors with marked significance towards higher associative stigma are a worsened relationship between the patient and the family member, conduct problems to family members, the patients’ residence in a residential care setting, and hereditary attributional factors like genetic hereditability and character. The level of associative stigma has significantly been predicted by the burden of aggressive disruptions to family housemates of the psychotic patient.CONCLUSION: Family members of psychotic patients in Flanders experience higher associative stigma compared to previous international research. Disruptive behavior by the patient towards in-housing family members is the most accurate predictor of higher associative stigma.     

精神分裂症患者及其一级亲属性格特征的对照研究

目的探讨精神分裂症患者及其一级亲属的性格特征。方法选取住我院治疗处于缓解期的精神分裂症患者48例和一级亲属与正常组各79人，进行MMPI测查分析。结果精神分裂症患者及其一级亲属Hs、D、Hy、Pd、Pa、Pt、Sc量表分高于正常人，而患者和一级亲属间各量表分接近。结论精神分裂症患者及一级亲属具有明显的分裂性人格，两者的性格特征可能有着共同的遗传学基础。     

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.