Delusional psychoses: genetic findings as a critical variable for the validation of diagnostic criteria

77 patients with delusional psychoses, regardless of their nosological attribution (except severe organicity), and their first-degree relatives were diagnosed with the Research Diagnostic Criteria (RDC) and the Vienna Research Criteria (VRC). The diagnostic procedure was performed blindly in the relatives. Both criteria were sufficiently capable of identifying a schizophrenic and affective subgroup of patients characterized by the appearance of homotypical secondary cases. Apart from a small RDC schizoaffective group differing in genetic pattern, there exists another large group of nonschizophrenic, nonaffective delusional disorders lacking a genetic link to the above-mentioned diagnoses. In respect to the development of the diagnostic criteria, the results of this study call for the formulation of a narrow definition of schizophrenia (as in the VRC) which is based on thought disorder and affective blunting with the exception of so-called productive symptomatology (delusions, hallucinations); separate criteria for schizoaffective disorders (as in RDC), and a broad and nonrestrictive definition for nonschizophrenic delusional disorders.     

Familial aggregation of delusional proneness in schizophrenia and bipolar pedigrees

OBJECTIVE: Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder. To identify a potential psychotic dimension common to families of both bipolar and schizophrenia probands, the authors tested if delusional proneness was observed among first-degree relatives of bipolar and schizophrenia probands. METHOD: The authors included 32 schizophrenia probands and 61 bipolar probands and their respective first-degree relatives (N=63 and N=59). They were all interviewed with the Diagnostic Interview for Genetic Studies, and delusional proneness was assessed with a self-report questionnaire, the Peters et al. Delusions Inventory. Schizophrenia and bipolar probands were subdivided into subgroups according to the intensity of delusional symptoms assessed by Peters et al. Delusions Inventory scores, and the authors compared delusional proneness in their respective first-degree relatives. RESULTS: Familial aggregation of delusional proneness was demonstrated, since Peters et al. Delusions Inventory scores were higher among nonschizophrenic first-degree relatives of schizophrenia probands with productive symptoms and among first-degree relatives of bipolar probands with psychotic features during their affective episodes. The authors also found an intrafamilial correlation of delusional proneness scores in nonaffected siblings of schizophrenia and bipolar probands. CONCLUSIONS: Delusional proneness appears to be an inherited predisposition common to both schizophrenia and bipolar disorder. In the future, this dimension might be valuable when used as a quantitative phenotype in linkage and association studies.     

精神分裂症和情感障碍混合家系的遗传调查

目的 探讨精神分裂症和情感障碍混合家系的遗传效应。方法 采用严格的纳入标准,应用家族史法对55例混合家系的各级亲属2134人进行详细的调查记录。分三组进行分析。结果 (1)精神分裂症为先证者组,各级亲属精神分裂症的患病率为1.1％,与1993年全国七地区调查精神分裂症的群体患病率0.655％比较,P>0.05,统计学上无显著差异,一级亲属患病率为4.79％,各群体比较,P<0.05。各级亲属情感障碍的患病率为3.78％,与1992年全国七地区调查情感障碍的群体患病0.083％比较,P<0.05,统计学上有显著差异,一级亲属患病率为17.96％。(2)情感障碍为先证者组,各级亲属情感障碍患者率为1.234％,与群体比较,P<0.05,一级亲属患病为4.76％。各级亲属精神分裂症的患病率为3.67％,与群体比较,P<0.05,一级亲属患病率为12.24％。(3)混合组,各级亲属精神分裂症的患病率为2.27％,与群体比较,P<0.05,一级亲属患病率为9.44％。结论 混合家系中,血缘关系越近,亲属中精神分裂症和情感障碍的患病率越高;精神分裂症和情感障碍在遗传传递上可能具有交叉性。     

Position of affective symptomatology in the course of delusional psychoses

The present study investigates the frequency, gender distribution, mode of appearance, and prognostic value of affective symptoms in a group of 90 patients with paranoid disorders of various etiologies (with the exception of marked organicity) who underwent a follow-up control. It appears that affective symptoms manifest more frequently than the brunt of delusional and hallucinatory ones, whereby the pronounced differences in gender (preponderance of females) that appear in acute states disappear in the course of the illnesses. Altogether, the frequency of affective symptoms diminishes just as that of delusions and hallucinations. Paranoic syndromes (simple delusional syndrome with a logically organized structure corresponding to the classical concept of paranoia) are characterized by a particularly frequent occurrence of dysphoric (irritable) mood, systematic and unsystematic paraphrenias by a depressive mood. Delusion subsided in all three delusional entities in about 50% of the cases; however, defect develops in unsystematic paraphrenias more often to a statistically highly significant degree than in the other two forms. Despite the expected low stability of affective symptoms over longer periods of time, the presence of affective syndromes has a high prognostic value, even in a population characterized primarily by the presence of a mood-incongruent delusion. The results of this investigation suggest that Jaspers' hierarchical principle, still important for many diagnostic systems, according to which the presence of delusions and hallucinations is considered to be pathognomonic for schizophrenia and takes priority over any affective ones, be abandoned. The consequence this would have for the theoretical basis of the diagnosis of endogenous psychoses is that apart from affective syndromes only schizophrenic nuclear symptoms would form the basis of nosological diagnosis, and so-called productive symptoms (delusions and hallucinations) would be construed as a superstructure.     

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.     

Cycloid psychoses as atypical manic-depressive disorders. Results of a family study

BACKGROUND: Whereas a growing body of evidence suggests that cycloid psychoses have to be separated from schizophrenic psychoses, their relations to bipolar affective disorder are less clear. PATIENTS AND METHODS: In a controlled family study, we recruited 46 patients with cycloid psychosis (CP), 33 with manic-depressive illness (MDI), and 27 controls. Three hundred fifty-six of 389 living first-degree relatives were personally examined by experienced psychiatrists blinded to the diagnosis of the index proband. RESULTS: The relatives of CP patients showed significantly lower morbidity risk of functional psychoses than relatives of patients with MDI in Kaplan-Meier life table calculation. The morbidity risk for functional psychoses in relatives of patients with CP did not differ significantly from that in relatives of controls. CONCLUSION: These results suggest that CP are etiologically different from bipolar affective psychoses and cannot be integrated into the spectrum of bipolar affective disorders. The findings provide further evidence for a nosological independence of CP.     

Dysphoric mood in paranoid psychoses

Many authors have stressed the particular affective behavior in paranoid psychoses, mainly its dysphoric pattern. In 1983, Berner formulated the dysphoric axial syndrome as a third type of the endogenomorphous cyclothymic axial syndrome. In this paper two points are examined: (1) The interrelation between dysphoric and depressive and/or manic affective disorders in paranoid psychoses, cross-sectionally and longitudinally, in order to test the hypothesis of their independence, and (2) the relation of dysphoric mood disorders in paranoid psychoses to their course, again in comparison with other types of affective symptoms. The paper is based on an empirical study by Gabriel in 1978 on the phenomenology and the course of paranoid psychoses.     

Classification of functional psychoses and its implication for prognosis: comparison between ICD-10 and DSM-IV

BACKGROUND: The aim was to examine the agreement and differences between ICD-10 and DSM-IV in the classification of functional psychoses. Sampling and METHODS: In a sample of 218 first-hospitalised patients, ICD-10 diagnoses were compared with DSM-IV diagnoses. Functional psychoses of both diagnostic systems were classified into the four diagnostic groups schizophrenia, transient/episodic psychoses, delusional disorders and affective disorders. Based on information from a 15-year follow-up, it was examined which course is associated with each diagnostic group. RESULTS: Although in ICD-10 there was a higher frequency of schizophrenia and a lower one of affective disorders, a high agreement between ICD-10 and DSM-IV (kappa value of 0.82) was found. In both diagnostic systems, transient/episodic psychoses and affective disorders were mainly associated with a non-chronic course and schizophrenia was mainly associated with a chronic one. Nevertheless, several patients with transient/episodic psychoses showed a chronic course (ICD-10: 10%, DSM-IV: 15%) and more than one third of patients with schizophrenia a non-chronic one (ICD-10: 40%, DSM-IV: 33%). CONCLUSIONS: In the cross-sectional assessment, there is a high diagnostic agreement between ICD-10 and DSM-IV. With respect to the long-term course, the delimitation of transient/episodic psychoses from schizophrenia was neither completely achieved by ICD-10 nor by DSM-IV.     

Delusional disorders. I. Comparative long-term outcome

ABSTRACT— Of 301 first-admitted patients with delusional psychoses, 94 met DSM-III criteria of schizophrenia (S), 53 paranoid disorder (PD), 47 schizophreniform disorder (SFD), 35 schizoaffective disorder (SAD), 54 major affective disorder (AD), and 18 other disorders (OD). Retterstol selected the patients and personally interviewed them after 5–18 years, and later the author interviewed them after 22–39 (mean 30) years. At last follow-up good functioning was noticed in 42%, moderate symptoms in 22%, severe defect in 20%, and very severe defect in 16%; 40% were still delusional. On average S patients did poorest, and OD patients slightly better. AD patients had superior outcome, while PD, SFD and SAD patients showed an intermediate position, but a little closer to AD than to S. However, heterogeneous course and outcome was noticed in all diagnostic groups.     

Genetic associations between delusional disorder and paranoid schizophrenia: A novel etiologic approach.

OBJECTIVES: Genetic associations between delusional disorder and paranoid schizophrenia are not well understood, although involvement of biological factors has been suspected. We investigated the incidence of human leukocyte antigen (HLA) class I alleles in patients with delusional disorder and paranoid schizophrenia, first, to explore a possible immunogenetic etiology of these paranoid disorders and, second, to determine whether they share similar etiologic mechanisms. METHOD: We employed a nested case-control study design. Psychiatric reference data were available for 38,500 patients attending a hospital-based psychiatric outpatient department between 1998 and 2005. We enrolled 100 patients with delusional disorder and 50 patients with paranoid schizophrenia as the subject cases, using DSM-IV criteria. We considered equivalent numbers of healthy volunteers matched for age and ethnic background as control subjects. All subjects came from an India-born Bengali population. We applied the polymerase chain reaction-based molecular typing method to all patients and healthy subjects. RESULTS: The HLA-A*03 gene is significantly associated with delusional disorder as well as with paranoid schizophrenia. This HLA gene alone or in linkage disequilibrium with other HLA genes or other closely linked non-HLA genes may influence susceptibility to delusional disorder and paranoid schizophrenia. CONCLUSIONS: The study reveals important associations between HLA genes and paranoid disorders. Delusional disorder and paranoid schizophrenia may share similar etiologic mechanisms. This preliminary observation may help our understanding of the genetic basis of these paranoid disorders.     

Deficits in gain of smooth pursuit eye movements in schizophrenia and affective disorder patients and their unaffected relatives

OBJECTIVE: Disturbance of smooth pursuit eye movements has been discussed as marking a putative endophenotype closely associated with the genetic basis of schizophrenia. Previous studies are not conclusive in regard to the specificity of this marker. Therefore, oculomotor pursuit was evaluated in unaffected family members of index probands diagnosed as having either schizophrenia or affective disorders. METHOD: A series of eye tracking tasks were performed by 54 patients with schizophrenia or schizoaffective disorder, 46 patients with an affective disorder, 43 unaffected first-degree relatives of the schizophrenia patients, 36 unaffected first-degree relatives of the affective disorder patients, and 84 healthy comparison subjects. The gain, which relates the velocity of the eye movement to the velocity of the target, was determined to index the intactness of the oculomotor pursuit system. RESULTS: Mean pursuit gain was significantly lower in the schizophrenia and affective disorder patients than in the healthy comparison subjects. Moreover, the relatives of both the schizophrenia and affective disorder patients showed significant gain deficits of about one-half the size of those observed in the patients. CONCLUSIONS: Gain deficits are present in psychotic patients and in their unaffected biological relatives. This finding supports a genetic origin of eye tracking disturbances in major psychotic disorders. There is no evidence for diagnostic or familial specificity. The weak sensitivity of the marker suggests that it refers to a nonnecessary genetic factor in schizophrenic and affective disorders.     

The role of gender in identifying subtypes of schizophrenia: a latent class analytic approach

Past literature suggests that schizophrenic men and women may be at different risks for developing different subtypes of schizophrenia. This hypothesis was tested using data from the well-known retrospective cohort family studies, the Iowa 500 and the Iowa non-500. The sample consisted of 171 male and 161 female DSM-III schizophrenic patients and 713 of their first-degree relatives. First, bivariate tests for gender differences were conducted regarding family morbidity, age of onset, premorbid history, season of birth, and expression of deficit and affective symptoms. Restricted maximum likelihood latent class analysis was then used to test whether there was a subgroup of schizophrenic men who were more likely to have a low familial risk for schizophrenia or schizophrenia spectrum disorders, deficit symptoms, poor premorbid history, and birth in the winter months, suggesting possible early environmental insults, compared to schizophrenic women. Results showed that although men were more likely to meet these criteria, women also met them, thus suggesting gender differences in the prevalence of the subtype. Schizophrenic women were more likely to express a form of the illness characterized by dysphoria, persecutory delusions, and a higher family morbidity risk for schizophrenia than schizophrenic men. Results for spectrum disorders among relatives were equivocal with regard to gender.     

The concepts of axis syndromes 1965-1983

The first purpose of the paper is to sketch the development of the concept of axial syndromes, starting with the generation of the hypotheses in Berner's monograph on 'The paranoiac syndrome' published in 1965 and leading to the last formulation of the Viennese Research Criteria in 1983. The second purpose is to draw the attention on a series of empirical studies which have been undertaken in order to evaluate the classificatory validity of the concept, studies dealing with the long-term course of paranoid psychoses (both in a retrospective and a prospective design) and secondary cases of different diagnostic classes in the families of the same patients (first-degree relatives).     

A controlled family study of chronic psychoses. Schizophrenia and schizoaffective disorder

Two hundred thirty-seven relatives of 48 patients with chronic psychosis, diagnosed as either schizophrenia or schizoaffective disorder, along with 380 relatives of psychiatrically normal controls, were studied using systematic diagnostic interviews, information from relatives, and review of medical records where appropriate. A variety of nonbipolar psychotic disorders was found in the relatives of the patients. Comparing relatives of patients with schizophrenia with relatives of patients with schizoaffective disorder, there was no tendency for schizoaffective diagnosis or acute psychoses to aggregate separately from schizophrenia. Increased incidence of bipolar disorder was found in relatives of patients with schizoaffective disorder but not in relatives of patients with schizophrenia. Incidence of major affective disorder (bipolar and unipolar) was increased in relatives of probands with both types of psychoses. If we subdivide the ill probands according to whether or not they had a history of substance abuse, relatives of probands with substance abuse had greater frequency of affective disorder and substance abuse, but there were not significant differences in the number of relatives with nonbipolar psychoses.     

Recurrence risk for the relatives of delusional depressed patients

The recurrence risks for major depression among the relatives of patients with delusional depression have been calculated using a computer program. The risk tables have been based on the data from the 454 first-degree relatives of 77 probands with delusional depression, the 503 first-degree relatives of 76 non-delusional probands and the 980 first-degree relatives of 153 controls. The results showed that: the familial aggregation of the delusional depression seem to follow the multifactorial pattern of inheritance (segregation analysis), the heritability of the delusional depression was found to be 62, the recurrence risk varies from 0.5% to 36.2% for the various relatives and tables for recurrence risks are provided.     

What is the psychiatric significance of bilateral basal ganglia mineralization?

One percent (143) of patients who underwent cranial computed tomography at the Central Institute of Mental Health during the last 10 years had bilateral basal ganglia mineralization (BGM). The relationship of this finding to the psychiatric disorders in the group was evaluated by statistical comparison with a group of patients without BGM (control group). The odds ratios for affective disorders and for organic brain syndromes with affective or paranoid symptoms showed a mild, but statistically significant, increase in patients with BGM. There was no evidence of an increased proportion of dementia, schizophrenia, or alcoholism in those with BGM. Those with BGM had a higher mean age and significantly more cortical atrophy and ventricular enlargement than did patients without. These confounding variables contributed to clinical differences between the BGM and the control groups.     

Classification of chronic psychoses including delusional disorders and schizophrenias

A classification of chronic psychoses including nonparanoid schizophrenia, paranoid schizophrenia, paranoid state and paranoia (delusional disorder) is presented. This classification is dependent on a systematic increase in number of symptoms with each group. In particular, delusional disorder is examined with regard to family history. It is clear from the data which are presented that delusional disorder is more likely to be associated with a family history of such traits as suspiciousness, jealousy, secretiveness, and the presence of paranoid behavior or delusions. There is evidence that such familial traits are not seen in schizophrenia, only in delusional disorder.     

Hypochondriacal delusions in paranoid psychoses. Course and outcome compared with other types of delusions

From a large series of patients with delusional psychoses, first-time admitted to the Psychiatric Department, University of Oslo, hypochondriacal delusions were coded as the main delusion in 15 patients (0.4% of all admissions). These patients have been personally followed up by one of the authors (N.R.) after 5-18 years, and by the other author (S.O.) after 23-39 years (mean 30 years). The results are presented, also according to the newer diagnostic systems (DSM-III, DSM-III-R), and the course and outcome of hypochondriacal delusions are compared with those of other types of delusions. Course and outcome are mainly dependent on the diagnostic category, not the type of delusion. It is also demonstrated that the course and outcome in major affective disorders are more favourable than in paranoid disorders, with the latter being significantly different from schizophrenia.     

The prevalence of psychiatric morbidity among adults living in institutions

This paper presents prevalence data from the 1994 OPCS survey of psychiatric morbidity among adults permanently resident in institutions catering for people with mental health problems in Great Britain. It describes briefly the survey methods used, and how diagnoses of psychiatric morbidity were derived. Its main aim is to show the prevalence of psychiatric morbidity in different types of institutional settings. Residents were eligible for the survey if they were aged 16 to 64 at the date of sampling and were permanently resident at the establishment. Residents were defined as permanently resident if they had been living in the sampled establishment for six months or more, or had no other permanent address, or were likely to stay in the establishment for the foreseeable future. In 1994, about 33,200 adults aged 16 to 64 were permanently resident in accommodation for people with mental health problems. About a third of residents were in NHS hospitals, while about two-thirds were in residential care facilities. About two-thirds of adults interviewed suffered from schizophrenia, delusional and schizoaffective disorders. About 8% suffered from neurotic disorders and 8% suffered from affective psychoses (mainly bipolar affective disorder). The prevalence of schizophrenia, delusional, and schizoaffective disorders was higher in hospitals than in residential care, while the prevalence of neurotic and related disorders was higher in residential accommodation. The prevalence of schizophrenia, delusional, and schizoaffective disorders was higher in NHS psychiatric hospitals and general hospital units than in private hospitals, clinics or nursing homes.