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.     

The familial aggregation of psychotic symptoms in bipolar disorder pedigrees

OBJECTIVE: Symptomatic overlap between affective disorders and schizophrenia has long been noted. More recently, family and linkage studies have provided some evidence for overlapping genetic susceptibility between bipolar disorder and schizophrenia. If shared genes are responsible for the psychotic manifestations of both disorders, these genes may result in clustering of psychotic symptoms in some bipolar disorder pedigrees. The authors tested this hypothesis in families ascertained for a genetic study of bipolar disorder. METHOD: Rates of psychotic symptoms-defined as hallucinations or delusions-during affective episodes were compared in families of 47 psychotic and 18 nonpsychotic probands with bipolar I disorder. The analysis included 202 first-degree relatives with major affective disorder. RESULTS: Significantly more families of psychotic probands than families of nonpsychotic probands (64% versus 28%) contained at least one relative who had affective disorder with psychotic symptoms. Significantly more affectively ill relatives of psychotic probands than of nonpsychotic probands (34% versus 11%) had psychotic symptoms. An analysis of clustering of psychotic subjects across all families revealed significant familial aggregation. Clustering of psychosis was also apparent when only bipolar I disorder was considered the affected phenotype. CONCLUSIONS: Psychotic bipolar disorder may delineate a subtype of value for genetic and biological investigations. Families with this subtype should be used to search for linkage in chromosomal regions 10p12-13, 13q32, 18p11.2, and 22q11-13, where susceptibility genes common to bipolar disorder and schizophrenia may reside. Putative schizophrenia-associated biological markers, such as abnormal evoked response, oculomotor, and neuroimaging measures, could similarly be explored in such families.     

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.     

Elevated rates of schizophrenia in a familial sample with mental illness and intellectual disability

Background It is unknown whether intellectual disability (ID) is more familially related to psychotic mood disorders or schizophrenia. L. S. Penrose's large sample of families with two or more members admitted to psychiatric hospitals provided a unique opportunity to investigate the familial relationship between mild ID, schizophrenia and psychotic affective disorders. Method There were 183 affected relative pairs comprising probands with mild ID (95 male, 88 female) and their first or second degree relatives with schizophrenia or psychotic affective disorder. Results There were nearly twice as many relatives with a diagnosis of schizophrenia (n = 121) as relatives with affective disorders (n = 62) among the intellectually impaired probands. This excess of schizophrenia was statistically significant, even after accounting for the increased risk of hospitalization for schizophrenia (P = 0.005), and was fairly constant across the different relative types. First‐degree relatives with either mental illness were more likely to be parents (n = 77) than siblings (n = 51) or children (n = 3), but there was no excess of mother–son pairs. Conclusions These results suggest a stronger familial relationship of ID with schizophrenia than psychotic affective disorder, and lend some support to the neurodevelopmental hypothesis of schizophrenia.     

Cognitive endophenotypes of psychosis within dimension and diagnosis

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.     

The group of schizoaffective and related psychoses: IV. A family study

There is increasing evidence that numerous affective symptoms are present during every stage of schizophrenia, often persisting throughout the patient's schizophrenic life.This study has shown that sick first-degree relatives have manifested a very similar clinical picture, course and outcome as the probands.Since the course of illness in both probands and relatives was chronic psychotic and deteriorating, it was characteristic of schizophrenia and not of affective disorder.Neither the presence of numerous affective symptoms, nor the family study indicated the presence of schizoaffective psychosis as a diagnostic entity.We suggest, therefore, that the term “undiagnosed” rather than schizoaffective psychosis be used when encountering acute cases of psychotic and affective symptoms.The methodological shortcomings of this study were discussed.     

Schizoaffective disorder and affective disorders with mood-incongruent psychotic features: keep separate or combine? Evidence from a family study.

OBJECTIVE: This study investigated whether the distinction between schizoaffective disorder and affective disorders with mood-incongruent psychotic features as described in DSM-III-R is reflected by aggregation of schizophrenia in the families of probands with the former disorder and aggregation of affective disorders mainly among the relatives of probands with the latter type of disorders. METHOD: The probands were 118 inpatients with definite lifetime diagnoses of DSM-III-R schizoaffective disorder or a major mood disorder with incongruent psychotic features according to structured clinical interviews. Diagnostic information on 475 of the probands' first-degree relatives was gathered through direct interviews (with 80% of the living first-degree relatives) or the family history approach. The rates of affective and psychotic disorders among these relatives were then compared with those among the relatives of a comparison group of 109 interviewed individuals from the general population who were matched on sociodemographic factors to the inpatient probands. RESULTS: With regard to the familial aggregation of schizophrenia, the DSM-III-R distinction emerged as valid. However, the risk of unipolar affective disorders was enhanced in the families of all of the subgroups of patients studied. The unipolar/bipolar distinction in both DSM-III-R diagnostic groups was reflected by distinct patterns of bipolar disorders in the relatives. CONCLUSIONS: The results partly support the DSM-III-R dichotomy of schizoaffective disorder and affective disorders with mood-incongruent psychotic features. Although the differences between these two diagnostic groups were significant, the magnitude of the differences remained relatively modest.     

Personality disorder in the families of depressed, schizophrenic, and never-ill probands

In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never-ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders.     

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.     

Investigating the association between neurocognition and psychosis in bipolar disorder: further evidence for the overlap with schizophrenia

Objectives: In schizophrenia, a distinction is made between psychosis with developmental and cognitive impairment on the one hand and psychosis without developmental impairment and positive symptoms on the other. In this study, we investigated whether this model can be extended to bipolar disorder by testing the hypothesis that neurocognitive functioning is inversely related to positive psychotic symptoms in bipolar disorder. Methods: Neurocognitive functioning and psychopathology were assessed in (i) 76 patients with bipolar disorder, (ii) 39 of their healthy first‐degree relatives, and (iii) 61 healthy controls. Cognitive performance of bipolar patients and their first‐degree relatives was investigated, taking into account the possible moderating effect of the level of expression of psychosis in patients and relatives. Results: Bipolar patients showed impaired cognitive performance on multiple cognitive domains, whereas performance of their relatives was comparable to that of controls. A history of psychotic symptoms in patients was suggestive of less likelihood of cognitive alterations in relatives, and the presence of subclinical psychotic symptoms within the group of relatives predicted better cognitive performance. Conclusions: The finding of similar psychosis‐cognition associations in bipolar disorder as implied by the two pathways leading to nonaffective psychotic disorders suggests that this model might be extended to the continuum spanning affective and nonaffective psychosis. This is in line with the idea of a partially overlapping vulnerability to bipolar disorder and schizophrenia and provides an explanation for the apparent differences in cognitive alterations in those at risk for the two disorders.     

A family study of DSM-III-R schizoaffective disorder, depressive type, compared with schizophrenia and psychotic and nonpsychotic major depression

OBJECTIVE: To assess the validity of DSM-III-R schizoaffective disorder, the authors explored the morbid risks for schizophrenia and major affective disorders in the first-degree relatives of patients with schizoaffective disorder and relevant other diagnoses. METHOD: In addition to patients with DSM-III-R schizoaffective disorder, depressive type (N = 21), the probands included patients with mood-incongruent psychotic depression (N = 22), mood-congruent psychotic depression (N = 19), nonpsychotic depression (N = 27), or schizophrenia (N = 28) and normal subjects (N = 18). The patients were consecutively recruited from the outpatient facilities of a university psychiatry department; the normal subjects were students and nurses. All probands were directly interviewed, with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version (SADS-L), by a psychiatrist blind to information about relatives. Consenting relatives were directly interviewed, with the SADS-L, by two psychiatrists blind to the probands' diagnoses. The direct interview was supplemented--or replaced, when an interview was not possible (24%)--by family history data from all available sources. Morbid risks in relatives were calculated according to the Weinberg method. RESULTS: The relatives of the schizoaffective patients had almost the same risk for schizophrenia as the relatives of the schizophrenic patients. In the relatives of the patients mood-incongruent psychotic depression, the morbid risk for major affective disorders was about one-half that of the relatives of the patients with mood-congruent psychotic depression and one-third that of the relatives of the patients with nonpsychotic depression, but these differences did not reach statistical significance. CONCLUSIONS: These results suggest that DSM-III-R schizoaffective disorder is close to schizophrenia and largely corresponds to mainly schizophrenic schizoaffective disorder in the Research Diagnostic Criteria, whereas DSM-III-R mood-incongruent psychotic depression is probably quite heterogeneous and should be studied further.     

Familial rates of affective disorder. A report from the National Institute of Mental Health Collaborative Study

We examined familial rates of affective disorder and related illness in a cohort of 955 probands studied at five centers in the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression: Boston, Chicago, Iowa City, New York, and St. Louis. Six hundred sixteen of these probands were entered into a family study, and 3423 of their first-degree relatives were evaluated. The probands were divided into five diagnostic groups: schizoaffective-bipolar (n = 37), schizoaffective-depressed (n = 18), bipolar I (n = 151), bipolar II (n = 76), and unipolar (n = 330). The relatives of bipolar I probands had a higher rate of bipolar I illness than the relatives of unipolar probands, but the relatives of unipolar probands did not have a higher rate of unipolar illness than the relatives of bipolar I probands. The relatives of probands with schizoaffective disorder, depressed subtype, had a higher rate of schizophrenia than the relatives of schizoaffective-bipolar probands, suggesting that bipolar schizoaffective disorder may be closer to pure affective disorder while schizoaffective depression may be closer to schizophrenia. An increase in bipolar II illness was also observed in the relatives of bipolar II probands. Overall, these data support the widely accepted distinction between bipolar and unipolar affective disorders.     

Psychiatric morbidity in the relatives of patients with DSM-III schizophreniform disorder: comparisons with the relatives of schizophrenic and bipolar disorder patients

Risks for psychiatric disorders (RDC) among first degree relatives of DSM-III schizophreniform, bipolar, and schizophrenic probands obtained from an epidemiologic sample using family history methods were examined. The relatives of the schizophreniform probands differed from the relatives of the schizophrenic and bipolar probands. The relatives of schizophreniform probands had significantly higher rates of affective illnesses (with the exception of bipolar illness) than the relatives of schizophrenic probands, and they had a significantly higher rate of psychotic affective disorders than the relatives of the bipolar probands.     

Are schizophrenia and affective disorder related? A selective literature review.

OBJECTIVE: Although most modern investigators accept the Kraepelinian view that schizophrenia and affective disorder are biologically distinct, others have suggested the psychoses are on a continuum of liability. This article is a selective review of evidence for the continuum model. METHOD: The author focuses on family, twin, and adoption data that do not support the Kraepelinian view of psychosis. Evidence characterized to a lesser extent includes the frequency of intermediate forms of illness (i.e., schizoaffective disorder), the inability to separate psychoses by classical symptoms into well-defined clusters, and the inability of laboratory measures to clearly define psychotic subgroups. RESULTS: The data demonstrate that schizophrenia and affective disorder do co-occur in some families. Whether this co-occurrence reflects true overlap is unclear, and significant pathophysiological heterogeneity may underlie clinical continuity. In some recent studies the inclusion of nonmelancholic depressions in the affective illness category may have masked overlap. CONCLUSIONS: The author suggests that the Kraepelinian view of psychoses may need modification. Future research should focus on factors that may reveal overlap between schizophrenia and affective disorder: severity of schizophrenia and affective disorder in probands, severity of depression in relatives, the effect of the unipolar-bipolar disorder relationship on the co-occurrence of affective disorder and schizophrenia, and the relationship of nongenetic factors that might alter the clinical expression of a shared genotype. Also, investigators should not presume a dichotomy or continuum but should examine pure and mixed pedigrees and look for state- and trait-related endophenotypes, the convergence of which would provide the basis for focused molecular genetic study.     

A DSM-III family study of the nonschizophrenic psychotic disorders

The authors conducted a blind DSM-III family study based on probands diagnosed from long-term follow-up information as having schizophreniform disorder, schizoaffective disorder, or psychotic affective illness. The pattern of psychopathology in relatives of schizophreniform probands closely resembled that found previously in relatives of schizophrenic probands. Relatives of schizoaffective probands had an excess risk for schizophrenia, other psychoses, and bipolar illness. The pattern of illness found in relatives of the probands meeting Research Diagnostic Criteria for mainly schizophrenic schizoaffective disorder appeared indistinguishable from that of relatives of schizophrenic probands. Relatives of probands with psychotic affective disorder had an excess risk for schizophrenia and for unipolar and bipolar affective disorder.     

An MRI study of the superior temporal subregions in first-episode patients with various psychotic disorders

Morphologic abnormalities of the superior temporal gyrus (STG) have been reported in schizophrenia, but have not been extensively studied in other psychotic disorders such as affective psychosis. In the present study, magnetic resonance imaging was used to examine the volumes of the STG and its subregions [planum polare (PP), Heschl gyrus (HG), planum temporale (PT), rostral STG, and caudal STG] in 162 first-episode patients with various psychotic disorders [46 schizophrenia (31 schizophrenia and 15 schizoaffective disorder), 57 schizophreniform disorder, 34 affective psychosis, and 25 other psychoses] and 62 age- and sex-matched healthy controls. The first-episode schizophrenia patients had significantly less gray matter in HG, PT, and caudal STG bilaterally compared with all other groups, but there was no difference between the controls and affective psychosis, schizophreniform disorder, or other psychoses for any STG subregion. The STG white matter volume did not differ between groups. Our findings indicate that morphologic abnormalities of the STG gray matter are specific to schizophrenia among various psychotic disorders, implicating its role in the underlying pathophysiology of schizophrenia.     

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.     

A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Survey of cases of familial mental illness. L. S. Penrose, July 1945.

An investigation was made of all known cases of mental illness where more than one member of the family entered one of the Ontario Mental Hospitals. The materials is fairly complete for a period of 18 years. Analysis of the resulting data, on pairs of relatives, gave rise to the following conclusions of particular interest. (i) Schizophrenia, affective psychosis, senile psychosis, Huntington's chorea and mental defect are shown to be conditions which remain significantly true to type when mental disease occurs in different members of a family. As a rider to this, however, it is found that schizophrenia and affective psychosis are not very distinct entities and groups of closely related familial cases frequently include both diagnoses. (ii) Schizophrenia is a rare diagnosis in the fathers of patients and occurs in only 8.7% of fathers, as opposed to the 30.7% in the whole sample of relatives: it is not so rare in mothers (24.5%). (iii) The most frequent type of relationship in pairs of patients is sister and sister: next in frequency is the type brother and brother, then brother and sister. Mother and son, mother and daughter, father and daughter and then father and sone come next in order. Less frequent are uncle and nephew or uncle and niece and, again less frequent, aunt and nephew or niece; grandparents and grandchildren were rarely found. (iv) Fathers, diagnosed schizophrenic or first admitted below the age of 35, have more psychotic sons than psychotic daughters, but the reverse is true for mothers in the same categories. (v) Fathers diagnosed as having affective illness or first admitted at the age of 35 or over have more psychotic daughters than psychotic sons, but the reverse is true for mothers in the same categories. (vi) Male subjects with either schizophrenic or affective diagnosis and in early- or late-onset age groups, have more psychotic brothers than psychotic sisters. Similarly, female subjects have more psychotic sisters than psychotic brothers. (vii) Each main diagnosis group has its characteristic first admission age. (viii) The first admission age is earlier in males than in females for schizophrenics, and later in males than in females for affective disorders. (ix) Study of first admission ages in families indicates that parents and, particularly, grandparents are much older than children and, particularly, grandchildren at first admission. This effect is not attributed to progressive degeneration. (x) Male subjects show a significantly wider scatter of first admission ages than do female subjects.(ABSTRACT TRUNCATED AT 400 WORDS)