Are communication deviance and expressed emotion related to family history of psychiatric disorders in schizophrenia?

Studies have reported that certain measures of intrafamilial transactions are associated with an increased risk both for the initial onset of schizophrenia and for its recurrence following the initial episode of disorder. Two of the most studied of these are communication deviance (CD), a measure of subclinical thought disorder expressed in speech, and expressed emotion (EE), defined as notable attitudes of criticism and/or emotional overinvolvement manifested in a semistructured interview. A previous study (Goldstein et al. 1992) examined whether these two measures were associated with the presence of a diagnosable psychiatric disorder in the biological parents of recent-onset schizophrenia patients. In general, they were not. The present study went one step further. It examined whether these same measures were correlated with family history of schizophrenia or affective disorder in the biological parents and siblings of these same parents. High EE was not associated with a greater family history of schizophrenia spectrum disorders among the parent's parents and siblings but was unexpectedly found to be inversely associated with familial affective disorders. In contrast, CD was associated with a family history of schizophrenia spectrum disorders among the parent's parents and siblings. The findings are consistent with the possibility that CD may be an indicator of a genetic vulnerability factor for schizophrenia.     

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。     

A comparative study on schizophrenia diagnosed by ICD-9 and DSM-III: course, family history and stability of diagnosis

Data from the Taipei Center of the International Pilot Study of Schizophrenia were reanalyzed using the ICD-9 and DSM-III diagnoses at 7-year follow-up. Patients diagnosed as schizophrenic according to DSM-III were shown to be a more homogeneous group in terms of their clinical manifestations, social functions and family psychiatric history than those defined as schizophrenic by ICD-9. The discordant cases of ICD-9 schizophrenia and DSM-III affective disorders were found to be different from the concordant schizophrenic group, but similar to the concordant group of affective disorders diagnosed by ICD-9 and DSM-III. Thirty-five per cent of mood-incongruent psychotic major depressive disorders defined by DSM-III at initial evaluation were diagnosed as schizophrenia at 7-year follow-up.     

Phenomenologic relationship of eating disorders to major affective disorder

We administered the National Institute of Mental Health Diagnostic Interview Schedule to 41 patients with a lifetime history of anorexia nervosa (25 with and 16 without bulimia) and to 49 patients with bulimia alone. Results showed that 77% of the patients with eating disorders had a lifetime diagnosis of DSM-III major affective disorder, a rate significantly higher than that found in comparison groups composed of the first-degree relatives of probands with schizophrenia and bipolar disorder. High lifetime rates of anxiety disorders, substance use disorders, and kleptomania were also observed. By contrast, few cases of personality disorders and no cases of schizophrenia were found. These findings combine with the results of studies of family history, long-term outcome, response to biological tests, and treatment response to suggest that anorexia nervosa and bulimia may be closely related to major affective disorder.     

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.     

Are some genetic risk factors common to schizophrenia, bipolar disorder and depression? evidence fromDISC1, GRIK4 andNRG1

Depression is common in patients with schizophrenia and it is well established from family studies that rates of depression are increased among relatives of probands with schizophrenia, making it likely that the phenotypes described under the categories of affective and non-affective psychoses share some genetic risk factors. Family linkage studies have identified several chromosomal regions likely to contain risk genes for schizophrenia and bipolar disorder, suggesting common susceptibility loci. Candidate gene association studies have provided further evidence to suggest that some genes including two of the most studied candidates, Disrupted in Schizophrenia 1 (DISC1) and Neuregulin 1 (NRG1) may be involved in both types of psychosis. We have recently identified another strong candidate for a role in both schizophrenia and affective disorders, GRIK4 a glutamate receptor mapped to chromosome 11q23 [Glutamate Receptor, Ionotropic, Kainate, type 4]. This gene is disrupted by a translocation breakpoint in a patient with schizophrenia, and case control studies show significant association of GRIK4 with both schizophrenia and bipolar disorder. Identifying genes implicated in the psychoses may eventually provide the basis for classification based on biology rather than symptoms, and suggest novel treatment strategies for these complex brain disorders.     

The heritability of schizophrenia and schizoaffective disorder. A family study

Ninety-one consecutively admitted patients with schizophrenia (n = 21), schizoaffective depression (n = 43), or psychotic depression (n = 27) entered a blind family study along with 36 never-ill controls. Though schizophrenia spectrum disorders clustered within families, they were not significantly more prevalent in the families of schizophrenic probands. In contrast, morbid risks for affective disorder clearly separated the families of psychotically depressed probands from the families of both schizophrenics and controls. Family study data for schizoaffective probands indicated links to both affective disorder and schizophrenia and suggested, as well, that a small number of patients with schizoaffective disorder may carry a genetic liability to both conditions.     

Adult outcome of social function in adolescent-onset schizophrenia and affective psychosis

OBJECTIVE: To examine and compare the adult outcome in a representative sample of hospitalized adolescent-onset psychoses including occupational and social aspects. METHOD: A total of 81 patients with a first episode of early-onset psychosis (before age 19 years) presenting to the University Hospital of Lund, Sweden, between 1982 and 1993 were followed up an average of 10.5 years (range 5.1-18.2) after admission. Initial diagnosis was assessed from records and consisted of DSM-IV schizophrenia (n = 32), schizoaffective disorder (n = 7), bipolar disorder (n = 25), and major depressive disorder with psychotic features (n = 17). All could be traced and assigned a major outcome group. RESULTS: Early-onset schizophrenia spectrum disorder suffered a chronic course with a poor outcome in 79% of the cases, while early-onset affective psychosis in 74% showed a good or intermediate outcome. The poor outcome (26%) in the affective group was connected to mental retardation in 7% and to progression to a schizoaffective disorder in 12%. A particularly severe outcome was seen for schizophrenia spectrum patients with a family history of nonaffective psychosis. CONCLUSIONS: Early-onset schizophrenia spectrum disorder showed a severe course while affective psychoses had a much more benign functional outcome.     

Affective disturbance in eating disorders

Thirty-three bulimic and 14 restrictive anorexics were compared on DSM-III diagnoses of affective and anxiety disorders, observer-rated and self-rated measures of depression and anxiety, and family history. A subgroup of 18 eating disorder subjects was administered the dexamethasone suppression test. The same 18 subjects were compared to 13 subjects with affective disorder on the Schedule for Affective Disorders and Schizophrenia. It was found that a large group with bulimia and restrictive anorexia nervosa was subject to a depressive disorder. Thirty-eight percent of the sample fulfilled criteria for a major depressive episode. The dysphoric experience seemed as intense in the bulimic and restricter group. There was a high incidence of dexamethasone nonsuppression (55%), which was found to be related to various measures of depression. Bulimics and restricters differed in their family history of affective disorder. While 61% of bulimics had a positive history of depression, this was found in only 23% of restricters (p less than .03).     

Diagnostic stability in adolescent onset psychotic disorders

The purpose was to examine the long-term stability of a diagnosis of psychotic disorder in adolescence and to focus on diagnostic change over time. A total of 88 patients with a first episode of early onset psychosis (before 19 years) were followed up an average of 10.5 years (range 5.1-18.2) after admission. This report includes the 68 patients who could be traced and interviewed with the Positive and Negative Symptom Scale and lifetime Structured Clinical Interview for DSM-IV diagnosis. An initial diagnostic split between schizophrenia spectrum and affective disorder had a good (> 80 %) Positive Predictive Validity and Sensitivity. The main diagnostic shift was an influx to schizophrenia spectrum disorder (n = 6). These patients resembled the stable affective group (n = 27) in premorbid and prodromal aspects but changed over time to resemble the poor outcome of the stable schizophrenia spectrum group (n = 28) albeit with fewer negative symptoms and a better social function. Family history of nonaffective psychosis in first or second degree relatives was often found in the "change to schizophrenia group". A diagnosis in adolescence of schizophrenia spectrum or affective psychotic disorder is usually stable over time. A subgroup of non-schizophrenia patients go on to develop a schizophrenia spectrum disorder.     

Understanding schizoaffective disorder: from psychobiology to psychosocial functioning

Psychobiologic evidence and psychosocial functioning in patients with schizoaffective disorder suggest that the disease may be a distinct disorder, a variant of schizophrenia or affective disorders, the comorbidity of schizophrenia and a mood disorder, or an intermediate disorder on a spectrum that ranges from schizophrenia to mood disorders. These data, although inconclusive, contribute to clinicians' understanding of the etiology of the disorder. Further research may lead to an increased understanding of the disorder, improved treatment, and, ultimately, better outcomes.     

The dichotomy of schizophrenia and affective disorders in extended pedigrees

The paper reports the first controlled family study investigating not only 1st but also 2nd and 3rd degree relatives of patients with schizophrenia by direct diagnostic interviews. Regardless of their degree of relationship, all biological relatives of the patients were found to be at an elevated risk of schizophrenia (5.0% in 1st, 3.1% in 2nd, 1.5% in 3rd degree relatives compared to 0.8% among controls). Schizoaffective and affective disorders have also been found to be more common in the three groups of relatives but without a monotone decline of prevalence rates across the groups. Other psychiatric disorders were not found to be at an elevated risk in relatives of patients compared to controls. Thus, our findings support the hypothesis that psychotic, as well as affective disorders, aggregate in families of individuals with schizophrenia.However, in our study, the risk of schizophrenia and the risk of affective disorders correlated. Particularly, the magnitude of the risk of schizophrenia among relatives of probands with schizophrenia varied with the occurrence of affective disorders in relatives. In relatives, the risk of schizophrenia was maximal in absence of a family history of affective disorder. This constellation holds true even if only families of index cases without any affective syndrome during lifetime are considered.     

Clinical characteristics of bipolar I patients according to their family history of affective disorders

BACKGROUND: The familial nature of bipolar disorder has been well described and multiple genes are probably involved in most or all cases. Each gene contributes equally to a bipolar phenotype and it may contribute to clinical characteristics. However, the genetic transmission of bipolar disorder remained undetermined up to now, partly due to clinical and genetically heterogeneity. In Tunisia, genetic study will profit from specific interests and advantages: the high rates of consanguinity, the existence of large families, and the relative geographical stability of the population. OBJECTIVE: The aim of this study was to compare clinical characteristics of familial and nonfamilial bipolar I disorder. METHOD: One hundred and thirty subjects met DSM-IV criteria for a bipolar I disorder; they were recruited and divided into groups according to their family history of affective disorders. Group 1 with a familial history group, comporting bipolar I patients with a family history of affective disorders in first and second degree relatives (n = 76; 52 males and 24 females, mean age = 37.2 +/- 10.7 years) was compared to group 2 (nonfamilial history group), comporting bipolar I patients without a family history of affective disorders (n = 54; 29 males and 25 females, mean age = 38.1 +/- 10.9 years). Available information was obtained from a structured clinical interview, collateral history, and medical records. The family investigation permitted completion of genealogies over three generations. The comparison of the two groups was based on the clinical characteristics (age at onset, numbers of affective episodes, nature and severity of the last affective episode,...). RESULTS: There were no significant differences between the two groups concerning demographic and social features, with the exception of professional activity. Indeed 30.2% of patients with a family history of affective disorders were unemployed versus 12.9% of patients without a family history of affective disorders (p = 0.02). Bipolar I patients with a family history of affective disorders were characterised by an early age at onset of the first episode (before 20 years) (48.7 versus 24.0%; p = 0.004), a high frequency of affective episodes (8.1 +/- 3.6 versus 6.0 +/- 3.5; p = 0.002) and had been more often hospitalised than patients without a family history of affective disorders (5.7 +/- 3.0 versus 4.7 +/- 3.0; p = 0.06). No significant differences were found concerning the nature of the first affective episode in bipolar I patients with or without a family history of affective disorders. Eleven women had developed their first affective episode during the puerperal period; eight of whom had a family history of affective disorders (p = 0.07). The last affective episode was significantly more severe (94.8 versus 77.8%; p = 0.003) and more often associated with psychotic features (55.3 versus 35.2%; p = 0.02) in patients with a family history of affective disorders. After multiple regression, the high frequency of affective episodes and the severity of last episode were more related with a family history of affective disorders. CONCLUSION: The results of our study provide evidence of familiality for some clinical characteristics which can be useful as phenotypic measures in future molecular genetic studies.     

Kleptomania: a report of 20 cases

OBJECTIVE: The authors' objective was to provide phenomenologic, family history, and treatment response data on a group of rigorously diagnosed patients with kleptomania. METHOD: Twenty consecutive inpatients and outpatients met DSM-III-R criteria for current kleptomania or a past history of kleptomania. These patients were given structured diagnostic interviews, and their family histories of psychiatric disorders were assessed blindly. The patients' responses to psychosocial and biological treatments were also assessed. RESULTS: All of the kleptomanic patients had lifetime diagnoses of major mood disorders, 16 had lifetime diagnoses of anxiety disorders, and 12 had lifetime diagnoses of eating disorders. A high morbid risk of major mood disorders (0.31) was found in their first-degree relatives. Ten of 18 patients receiving thymoleptic medications reported reduction or remission of their stealing behavior. CONCLUSIONS: Kleptomania may be related to major mood disorder and perhaps may represent another form of "affective spectrum disorder."     

Family history study of major psychiatric disorders and syndromes

The family history of major psychiatric disorders was examined among relatives of 193 in-patients fulfilling the Research Diagnostic Criteria (RDC) for Schizophrenia, Unspecified Functional Psychoses, Schizoaffective Disorder, Manic Disorder or Major Depressive Disorder. The morbid risk (MR) for schizophrenia was greater among the relatives of probands with non-affective psychoses whereas the MR for mania was greater among the relatives of probands with affective bipolar disorder. When major psychiatric syndromes were examined, only manic syndrome showed familial aggregation.     

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

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

Boundaries of schizophrenia.

The frontiers of schizophrenia are being increasingly challenged from several directions. In addition to ongoing debate as to divisions between schizophrenia and disorders of the schizophrenic spectrum, including schizotypal personality disorder and schizophreniform disorder, it has been suggested that obsessive-compulsive disorder might overlap phenomenologically with schizophrenia. There has been a long debate around the relationship of schizophrenia to affective disorders, particularly bipolar and schizoaffective disorder. The evidence suggests that although schizotypal personality and schizophreniform disorders are not homogeneous syndromes, they are related to or represent milder forms of schizophrenia. Obsessive-compulsive disorder seems to involve pathology in many of the same regions as observed in some patients with schizophrenia, which may account for the significant incidence of obsessive-compulsive symptoms in a subset of patients with schizophrenia. Despite similarities between schizophrenia and bipolar disorder, significant differences extend across suggested causes, phenomenology, and pathophysiology. These findings support the current conceptualization that the two disorders represent distinct disorders, probably with heterogeneous causes, rather than the ends of a spectrum of symptoms comprising a single syndrome. Schizoaffective disorder likely is made up of patients from the schizophrenic and bipolar cluster of illnesses. The long-standing debate as to the boundaries of schizophrenia is ultimately must await the eventual further elaboration of the underlying causes of schizophrenia and other psychotic disorders.     

Mobility limitations in persons with psychotic disorder: findings from a population-based survey

BACKGROUND: There are few reports on mobility limitations in persons with psychotic disorder although restrictions in mobility may aggravate the general functional limitations of these patients. Our aim was to investigate mobility limitations among subjects with psychotic disorder in a general population-based sample. METHODS: A nationally representative sample of 6,927 persons aged 30 and older self-reported mobility limitations in an interview and was examined in performance tests. Diagnostic assessment of DSM-IV psychotic disorders combined SCID interview and case note data. Lifetime-ever diagnoses of psychotic disorder were classified into schizophrenia, other nonaffective psychotic disorders and affective psychoses. RESULTS: Self-reported mobility limitations were highly prevalent in persons with schizophrenia and other nonaffective psychosis, but not in the affective psychosis group. After adjusting for age and sex, persons with schizophrenia and other nonaffective psychoses but not affective psychoses had significantly increased odds of having both self-reported and test-based mobility limitations as well as weak muscle strength. Schizophrenia remained an independent predictor of mobility limitations even after controlling for lifestyle-related factors and chronic medical conditions. Among persons with nonaffective psychoses, higher levels of negative symptoms predicted mobility limitations. CONCLUSION: Self-reported mobility limitations are prevalent already at a young age in persons with schizophrenia and other nonaffective psychotic disorders, and among older persons with these disorders both self-reported limitations and measured performance tests show lower capacity in mobility. Difficulties in mobility are associated with negative symptoms. Mental health care professionals should pay attention to mobility limitations in persons with psychotic disorder.     

Outcome after 40 years in DSM-III schizophreniform disorder

In an earlier report, we described the course of the index episode and the family history of patients with schizophreniform disorder, schizophrenia, or affective disorder. Those data indicated that DSM-III schizophreniform disorder defined a heterogeneous group that bore a closer relationship to schizophrenia than to affective disorder. The present report extends the study of these same patients to a 40-year field follow-up. As the earlier short-term and family history findings predicted, marital, occupational, mental, and residential status ratings for the schizophreniform group assumed intermediate positions between those for patients with affective disorder and those for schizophrenics but fell closer to the latter. Contrary to the short-term outcome findings, the present data show no relationship between illness duration at index admission and outcome status ratings after 40 years.     

Genetic models of schizophrenia and bipolar disorder

Abstract Schizophrenia and affective disorder have been considered to be nosologically and etiologically distinct disorders. This postulate is challenged by progress in new biological research. Both disorders are strongly influenced by genetic factors; thus genetic research is a main contributor to this discussion. We review current evidence of the genetic relationship between schizophrenia and affective disorders, mainly bipolar disorder (the various genetic research methods have been particularly applied to bipolar disorder). Recent family and twin studies reveal a growing consistency in demonstrating cosegregation between both disorders which is difficult to detect with certainty given the low base rates. Systematic molecular genetic search for specific genes impacting on either disorder has now identified one gene which is apparently involved in both disorders (G72/G30); other candidate genes reveal some evidence to present as susceptibility genes with very modest effects for each of both disorders, although not consistently so (e. g., COMT, BDNF). There is room for speculation about other common susceptibility genes, given the overlap between candidate regions for schizophrenia and those for bipolar disorder emerging from linkage studies.