Effectiveness of brief schema group therapy for borderline personality disorder symptoms: a randomized pilot study.

BACKGROUND AND OBJECTIVES: Schema group therapy is a potentially cost-effective treatment for borderline personality disorder (BPD). We piloted the feasibility and effectiveness of a 20-session schema group therapy without individual therapy among psychiatric BPD outpatients in a randomized pilot study registered as a clinical trial (ISRCTN76381242). METHODS: Altogether 42 psychiatric outpatients diagnosed with BPD were randomized 2:1 to a 20-session weekly schema group therapy plus treatment as usual (TAU) (n = 28) vs. a control group with TAU alone (n = 14). The primary outcome was decline of BPD symptoms in the short Borderline Symptom List (BSL-23) score. Secondary outcomes were decline in symptoms of anxiety, depression, alcohol use, and improvement in functioning and schema modes. Two external experts evaluated validity of the intervention based on videotaped sessions. RESULTS: Overall, 23 schema group therapy patients (82%) and 12 controls (86%) completed their treatment. Treatment validity good or very good. However, no significant differences emerged in the primary outcome mean BSL-23 decline (6.95 [SE 5.91] in group schema therapy vs. 12.55 [4.85] in TAU) or in any of the secondary outcome measures. LIMITATIONS: Despite randomization, the TAU subgroup had non-significantly higher baseline scores in most measures. Small sample size predisposing to type II errors; reliance on self-reported outcomes. CONCLUSIONS: Schema group therapy was feasible for psychiatric outpatients with BPD. However, in this small pilot study we did not find it more effective than TAU. Effectiveness of this short intervention remains open.

Linkage analysis of schizophrenia controlling for population substructure.

Etiological heterogeneity and complexity has hampered attempts to identify predisposing genes for schizophrenia. We sought to minimize the number of segregating genes involved by focusing on a population isolate with elevated disease prevalence. We exploited the well-established population history, and searched for disease susceptibility loci in families from two alternative founder lineages. We studied 28 schizophrenia pedigrees (123 nuclear families) from an outlying municipality on the eastern border of Finland. We divided the families based on their genealogy and defined two routes of immigration: southern and northern. We examined the kinship coefficients and allele frequency distributions within each group, and performed a linkage analysis based on 497 microsatellite markers across the genome. A high degree of historical relatedness was demonstrated by higher sharing of alleles than predicted by the relationships we identified within the previous four generations alone, as would be expected. Between the two subpopulations, allele frequencies were significantly different, consistent with their isolated genealogies. The southern families showed some evidence of linkage in a schizophrenia locus at 4q23 (Z = 3.3) near our previous finding with quantitative variation in verbal learning and memory [Paunio et al. (2004); Hum Mol Genet 13: 1693-1702], while the northern pedigrees gave most significant evidence on 10q21 (Z = 2.53). Joint analysis of families from both lineages suggested evidence of linkage only at 3p14 (Z = 3.18). Thus the detailed genealogical information led us to identification of distinct linkage signals for schizophrenia susceptibility loci between the three analyses we performed.

Incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes mellitus.

CONTEXT: Patients with schizophrenia have an increased risk of type 2 diabetes mellitus. However, very few studies have dealt with the association of type 1 diabetes and schizophrenia. Preliminary evidence points to a possible inverse association. OBJECTIVE: To investigate the incidence of schizophrenia in a nationwide cohort of patients with type 1 diabetes born in 1950 through 1959 in Finland. DESIGN: A cohort study of individuals born in 1950 through 1959 with a follow-up of 1969 through 1991. SETTING: Finland. PATIENTS: All individuals born in 1950 through 1959 with type 1 diabetes were identified through nationwide registers. The incidence of schizophrenia until 1992 among the total 1950-1959 cohort and in individuals with type 1 diabetes was calculated using information from 3 health care registers. MAIN OUTCOME MEASURE: Incidence of schizophrenia. RESULTS: The incidence of schizophrenia was 0.21 per 10 000 person-years in the group with type 1 diabetes and 0.56 per 10 000 person-years in the group without type 1 diabetes (P < .001). CONCLUSION: The incidence of schizophrenia is decreased in patients with type 1 diabetes.

Affective flattening and alogia associate with the familial form of schizophrenia.

Family history of schizophrenia has been associated with negative symptoms in the clinical picture. Our aim was to examine the signs and symptoms of schizophrenia in a genetically homogeneous isolate and a nationwide multiplex family sample, and to investigate the symptom dimensions and their association with the degree of familial loading for psychotic disorders and with consanguinity. For factor analysis of the Scales for the Assessment of Negative and Positive Symptoms, we included 290 patients with a DSM-IV diagnosis of schizophrenia: 63 multiplex family and 133 singleton patients from the isolate, and 94 nationwide multiplex family patients. The factor analysis yielded four factors. There was a significant difference between the multiplex and singleton patients, the former having more severe affective flattening and alogia. Further, the patients in isolate groups had fewer delusions and hallucinations compared with the whole country multiplex patients regardless of their familial loading for schizophrenia. This may be related to genetic homogeneity in the isolate. We conclude that patients with first-degree relatives with psychotic disorder have more severe negative symptoms.

Psychosis among "healthy" siblings of schizophrenia patients.

BACKGROUND: Schizophrenia aggregates in families and accurate diagnoses are essential for genetic studies of schizophrenia. In this study, we investigated whether siblings of patients with schizophrenia can be identified as free of any psychotic disorder using only register information. We also analyzed the emergence of psychotic disorders among siblings of patients with schizophrenia during seven to eleven years of follow-up. METHODS: A genetically homogenous population isolate in north-eastern Finland having 365 families with 446 patients with a diagnosis of schizophrenia was initially identified in 1991 using four nationwide registers. Between 1998 and 2002, 124 patients and 183 siblings in 110 families were contacted and interviewed using SCID-I, SCID-II and SANS. We also compared the frequency of mental disorders between siblings and a random population comparison group sample. RESULTS: Thirty (16%) siblings received a diagnosis of psychotic disorder in the interview. 14 siblings had had psychotic symptoms already before 1991, while 16 developed psychotic symptoms during the follow-up. Over half of the siblings (n = 99, 54%) had a lifetime diagnosis of any mental disorder in the interview. CONCLUSION: Register information cannot be used to exclude psychotic disorders among siblings of patients with schizophrenia. The high rate of emergence of new psychotic disorders among initially healthy siblings should be taken into account in genetic analysis.

Familial loading associates with impairment in visual span among healthy siblings of schizophrenia patients.

BACKGROUND: The effect of familial loading on neurocognitive deficits in relatives of schizophrenia patients has been detected in family and twin studies. The present study examined this effect among healthy siblings of schizophrenia patients in a Finnish isolate with high prevalence of schizophrenia. METHODS: We assessed performance in verbal and visual span tasks, in tests measuring intelligence, and in declarative verbal memory and learning tasks in 31 and 67 healthy siblings from families with one schizophrenia patient, or with two or more patients, respectively. The differences between the groups were tested using linear mixed effects models. RESULTS: An effect of familial loading was detected in the backward visual span task, measuring immediate visual memory with requirements from the visual domain of working memory. In this task, the healthy siblings from multiply affected families performed worse than those from the singleton families. CONCLUSIONS: The finding that the multiplex vs. singleton differences were selective to the backward visual span task, strengthens the view that the visual domain of working memory may provide a valuable endophenotypic marker for genetic schizophrenia studies.

Clinical phenotype of schizophrenia in a Finnish isolate.

We identified all cases in Finland (population of 5 million) with a diagnosis of schizophrenia born between 1940 and 1969, using four national computerised registers with high reliability. A sample of 397 families was identified in a genetically homogeneous internal isolate (population of 18,000) in northeastern Finland with high prevalence for schizophrenia and an LOD score of 3.8 in chromosome 1. Our aim was to examine with Operational Criteria Checklist for Psychotic Illness (OCCPI) factor analysis the psychotic and affective signs and symptoms of schizophrenia in this genetically homogeneous population, and compare them with findings from individuals with schizophrenia from multiplex families from the whole country. After collecting all original case notes, we made DSM-IV consensus diagnoses and completed OCCPI ratings on a lifetime basis. For the factor analysis, we accepted 190 patients with a diagnosis of schizophrenia. In addition, 466 schizophrenia patients from 147 multiplex families from the whole country were included in the analysis. The OCCPI factor analysis resulted in four factors: "delusions and hallucinations" and "negative" factors, plus two affective ("manic" and "depressive") factors. We compared the pattern of symptoms among three patient groups: isolate patients who were the only affected individuals in their family, isolate patients who had affected family members, and patients from the whole country with affected family members. We found no clear differences among these groups. However, there were significant differences in the frequency of individual OCCPI items between the study groups. Findings in this schizophrenia OCCPI phenotype study suggest that the clinical picture of schizophrenia in a genetically isolated and homogeneous population closely resembles our nationwide findings in Finland.

Prevalence and diagnosis of schizophrenia based on register, case record and interview data in an isolated Finnish birth cohort born 1940-1969.

INTRODUCTION: Schizophrenia occurs worldwide but the prevalence varies markedly. In Finland, schizophrenia is most prevalent in the northeastern region. Our aims were to reassess the register-, case record- and interview-based lifetime prevalence in a genetically homogeneous birth cohort from an isolate population with earlier reported high prevalence of schizophrenia and a chromosome linkage to chromosome 1q. METHODS: We identified all patients with a diagnosis of schizophrenia [International Classification of Diseases (ICD)-8, ICD-9 or ICD-10 codes], born 1940-1969 in the isolate (n=282) and alive (n=237) in 1998 using the Hospital Discharge, Disability Pension and Free Medicine Registers. The corresponding birth cohort of 14,817 persons and 12,368 alive in 1998 was identified from the National Population Register. We validated 69% of the register diagnosis by making DSM-IV consensus diagnoses, and interviewed 131 (55%) of the 237 patients with SCID-I and SCID-II. RESULTS: The register-based lifetime prevalence was 1.5% for schizophrenia and 1.9% for schizophrenia spectrum psychotic disorders: in birth cohorts born 1945 to 1959, the latter prevalence was especially high (2.4%). Of those with a register diagnosis of schizophrenia spectrum psychotic disorder, 69% or 63% also received a record-based consensus diagnosis or SCID interview diagnosis of schizophrenia, and the prevalence was 0.9-1.3 and 0.7-1.2%, respectively, when we reassessed most of the register-based cases. The cumulative incidence of schizophrenia spectrum psychotic disorders in the total birth cohort was 1.9%. CONCLUSION: In this isolate, the register, DSM-IV consensus and SCID interview-based lifetime prevalence of schizophrenia was internationally high. For genetic research work, the register diagnosis should be reassessed using either structured interview or the best estimate consensus diagnosis.

Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects.

We have previously reported a linkage peak on 1q42 in a Finnish schizophrenia sample. In this study we genotyped 28 single nucleotide polymorphisms (SNPs) from 1q42 covering the three candidate genes TRAX, DISC1 and DISC2, using a study sample of 458 Finnish families ascertained for schizophrenia. Two-point and haplotype association analysis revealed a significant region of interest within the DISC1 gene. A common haplotype (HEP3) was observed to be significantly under-transmitted to affected individuals (P=0.0031). HEP3 represents a two SNP haplotype spanning from intron 1 to exon 2 of DISC1. This haplotype also displayed sex differences in transmission distortion, the under-transmission being significant only to affected females (P=0.00024). Three other regions of interest were observed in the TRAX and DISC genes. However, analysis of only those families with complete genotype information specifically highlights the HEP3 haplotype as a true observation. The finding of a common under-transmitted SNP haplotype might imply that this particular allele offers some protection from the development of schizophrenia. Analysis of component-traits of schizophrenia, derived from the Operational Criteria Checklist of Psychotic Illness (OCCPI), displayed association of HEP3 to features of the general phenotype of schizophrenia, including traits representing delusions, hallucinations and negative symptoms. This study provides further evidence for the hypothesis that the DISC1 gene is involved in the aetiology of schizophrenia, and implies a putative sex difference for the effect of the gene. Our findings would also encourage more detailed analyses of the effect of DISC1 on the component-traits of schizophrenia.