Psychotic symptoms in Alzheimer disease: evidence for subtypes.

OBJECTIVE: Psychotic symptoms in Alzheimer disease (AD) identify a phenotype with distinct neurobiology and genetic architecture. The authors investigated whether AD with psychosis is homogeneous or is a composite of subtypes. METHODS: Authors performed factor and cluster analyses of the psychotic-symptom items of the CERAD Behavioral Rating Scale in 188 probable and possible AD subjects who have displayed at least one psychotic symptom. RESULTS: Exploratory factor analysis resulted in a one-factor solution that comprised misidentification delusions, auditory and visual hallucinations, and the misidentification of people. Persecutory delusions were also frequently present and were independent of the misidentification/hallucination factor. Cluster analysis yielded similar results. CONCLUSION: Misidentification/hallucinations and persecutory delusions may identify two subtypes of psychosis in AD. Longitudinal study is needed to determine whether these proposed subtypes remain stable and independent over time or merge into a single group over the course of illness.     

Stability of psychotic symptomatology (delusions,hallucinations), affective syndromes,and schizophrenic symptoms (thought disorder,incongruent affect) over episodes in remitting psychoses

Summary A study was made on 140 schizophrenics, 40 schizoaffectives, 59 unipolar depressives, and 30 bipolar affective disorder patients in order to determine the quality of psychopathology over multiple episodes. The schizoaffectives were the most likely to have multiple episodes. Among the schizophrenics, there were few episodes that lacked psychotic symptoms, but almost half of the episodes for the schizoaffectives were asscociated with an absence of psychotic symptoms. Three-quarters of the patients with unipolar depression and bipolar illness showed no psychotic symptoms either congruent or noncongruent. There was a striking finding that all diagnoses were associated with a decrease in psychotic symptoms over time. These psychotic symptoms (delusions and hallucinations) became particularly more scarce among the schizoaffectives, unipolars, and bipolars. There was a 50% to 67% decrease of episodes with psychotic symptoms as more episodes occurred. For schizophrenia and schizoaffective disorder the first ten episodes were very similar to each other for affective syndromes, formal thought disorder and/or incongruent affect, and delusions and hallucinations. It was not until much time had passed that the symptom pictures changed.     

Psychosis in a pediatric mood and anxiety disorders clinic: phenomenology and correlates

OBJECTIVES: To examine the demographics and phenomenology of psychosis in a sample of children and adolescents referred to a mood and anxiety disorders clinic. METHOD: Patients (N = 2,031) were assessed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present Episode version and classified as definite, probable, or nonpsychotic. Clinical and demographic characteristics of the groups were compared,and symptoms of psychosis were analyzed using factor analysis. RESULTS: Definite psychotic symptoms were seen in approximately 90 (4.5%) patients: 80% of these reported hallucinations (mainly auditory), 22% delusions, and 3.3% thought disorder. Of the patients with definite psychotic symptoms, 24% had bipolar disorder, 41% had major depression, 21% had subsyndromal depression, and 14% had schizophrenia spectrum disorders (schizophrenia and schizoaffective disorders). Factor analysis of the definite psychotic symptoms yielded 4 factors: hallucinations, thought disorder, delusions, and manic thought disorder. Psychotic patients had a higher frequency of comorbid disorders and suicidal ideation than nonpsychotic patients. CONCLUSIONS: Outpatient youngsters with mood disorders frequently present with psychotic symptoms, in particular auditory hallucinations. These patients commonly have comorbid psychiatric disorders and suicidal ideation.     

Predicting medication-free treatment response in acute psychosis: cross-validation from the Finnish Need-Adapted Project

This study tested predictors of 2-year antipsychotic-free response from the Soteria study (older, better social functioning, fewer cardinal symptoms) using data from the Finnish Acute Psychosis Integrated treatment study. The quasi-experimental study compared need-adapted family-oriented psychosocial intervention within a 3-week antipsychotic-free trial to psychosocial intervention plus antipsychotic medications. Forty-six percent of experimental completers (37% of intent-to-treat subjects) were successfully treated without antipsychotic medications for the entire 2-year study. The DSM-III-R diagnoses of schizophrenia and schizophreniform disorder and Soteria-suggested predictors were not related to antipsychotic-free response. Different variables within the same domains of good prognosis and fewer schizophrenia symptoms predicted antipsychotic-free response or nonresponse with 74% accuracy. The 6-month duration of symptom criterion distinguishing schizophrenia from schizophreniform disorder does not separate medication-free treatment responders from those requiring medications. Prognosis appears related to antipsychotic-free response and may be helpful in distinguishing schizophrenia from schizophreniform disorder in early episodes.     

Delusions and suicidality

OBJECTIVE: Delusions have been considered a risk factor for suicidal behavior. To determine whether specific delusion types are related to suicidal behaviors, the authors compared the clinical characteristics of patients with mood disorders and schizophrenia who did and did not have a history of suicide attempts. METHOD: After admission for inpatient or outpatient psychiatric treatment, 429 patients (ages 14-72 years; 47.1% male; and 73.0% Caucasian) were assessed with a structured clinical interview that generated axis I and II diagnoses. In addition, their psychiatric symptoms, history of suicide attempts, and overall functioning were rated. RESULTS: Data for three diagnostic subgroups (223 patients with major depression, 150 with schizophrenia, and 56 with bipolar disorder) were analyzed separately. Multivariate analyses did not find evidence of a relationship between delusions and history of suicidal ideation or suicide attempts in any of the diagnostic groups. CONCLUSIONS: This study did not find evidence that the presence of delusions distinguished persons with or without a history of suicide attempt.     

Schizophrenie und Wahn im höheren und hohen Lebensalter Epidemiologie und ätiologische Hypothesen

Knowledge of the similarities and differences between early- and late-onset schizophrenia and between late-onset schizophrenia and paranoid disorder of old age and very old age is fragmentary. We compared diagnosis, subtypes, syndromes and symptoms between first-episode schizophrenia (ICD-9: 295) and paranoid disorder (ICD-9: 297, 298.3/4.) over the life cycle in a population-based (N = 232) and a clinical first-admission sample (N = 1109). Apart from different age patterns of the sexes only two symptom groups were significantly different between early- and late-onset illness: paranoid and systematic delusions showed a linear increase, symptoms of disorganisation a linear decrease over the life cycle. Clearly different between early- and late-onset illness were the neurobiological and psychological risk factors, suggesting that both neurodevelopmental and neurodegenerative disorder causes psychopathology typical of schizophrenia. Late- (40 to 60) and very-late-onset (over 60) cases of both groups of illness showed the same symptom profiles, merely the number of symptoms being higher in the group diagnosed with schizophrenia. Age was the only factor significantly contributing to a clinico-diagnostic differentiation of schizophrenia from paranoid disorder beyond age 40.     

Neurological signs and the heterogeneity of schizophrenia

OBJECTIVE: More than 20 studies of schizophrenia have found a three-factor model of symptom complexes or syndromes consisting of hallucinations/delusions, disorganization of thought and behavior, and negative symptoms. Several lines of evidence suggest that these syndromes relate to neurobiological differences. We examined the relationship of these three syndromes to neurological signs. METHOD: The relationships among the subscales of the Neurological Evaluation Scale and hallucinations/delusions, disorganization, and the deficit syndrome were examined in 83 clinically stable outpatients with schizophrenia. Patients with the deficit syndrome have enduring, idiopathic (or primary) negative symptoms. RESULTS: Each of the three syndromes had a distinctive pattern of relationships to neurological signs. Disorganization was significantly related to the total score on the Neurological Evaluation Scale, to sensory integration, and to the sequencing of complex motor acts. The deficit syndrome was significantly related to sensory integration only. Neither hallucinations/delusions nor a continuous measure of negative symptoms derived from the Brief Psychiatric Rating Scale (that measured both primary and secondary negative symptoms, as well as enduring and transient symptoms) was related to any of the Neurological Evaluation Scale subscales or total score. Drug treatment was not related to neurological impairment. CONCLUSIONS: The results further support the neurobiological significance of the three clinical syndromes of schizophrenia. Ratings on a scale measuring negative symptoms appear to be less sensitive to neurobiological correlates than is the categorization of the presence or absence of the deficit syndrome.     

Positive and negative symptoms in affected sib pairs with schizophrenia: implications for genetic studies in an African Xhosa sample

Careful phenotyping and the identification of subtypes of schizophrenia can contribute significantly to the success of genetic studies in schizophrenia. The phenomenology of schizophrenia in affected sib pairs has been well-described in Caucasian populations, however a paucity of data exists for African populations. This study therefore investigated symptom dimensions in a sizeable group of affected Xhosa sib pairs as a means of evaluating the role of shared familial factors in the psychosis of schizophrenia. Five hundred and thirteen participants were interviewed with the Diagnostic Interview for Genetic Studies (DIGS), which included the Schedules for the Assessment of Negative and Positive symptoms (SANS/SAPS). One hundred and four sib pairs were then extracted (N = 208) for analysis of concordance for lifetime psychotic symptoms and an exploratory factor analysis of the SANS/SAPS. Concordance analysis of life-time symptoms indicated a significant concordance for olfactory hallucinations, persecutory delusions, jealousy, somatic, reference and control delusions as well as thought insertion and withdrawal. The factor analysis of the global scores of the SAPS and SANS revealed a five factor best-fit model and accounted for 92.5% of variance. The factors included a negative symptom factor, a positive symptom factor, a positive thought disorder and a bizarre behaviour component. The core symptomatology of schizophrenia in this sib pair sample was similar to that reported in Caucasian populations with the exception of higher rates of auditory hallucinations and delusions of persecution. In summary therefore; although the factor analysis only supported the concept of the universality of psychotic symptoms in schizophrenia, the concordance analysis of these symptoms did reveal hallucinations as well as delusions of control as possible candidates relevant for future research into genotype-phenotype relationships.     

Do maternal psychotic symptoms predict offspring's psychotic disorder? Findings from the Helsinki High-Risk Study

The Helsinki High-Risk (HR) Study is a follow-up study of 179 offspring born to mothers with DSM-IV-TR diagnoses of schizophrenia, schizoaffective disorder, other schizophrenia spectrum disorders, and affective psychoses. Mothers comprised all female patients born between 1916 and 1948 who had been treated with hospital diagnoses of schizophrenia, schizophreniform, or schizoaffective psychoses in any mental hospital in the city of Helsinki up to 1974, and who had given birth in Helsinki between 1960 and 1964. In this report we conducted a principal factor analysis of maternal symptoms using 12 items of the Major Symptoms of Schizophrenia Scale (MSSS), the global ratings of anhedonia-asociality and avolition-apathy from the Scale for the Assessment of Negative Symptoms (SANS), and the global rating of bizarre behavior from the Scale for the Assessment of Positive symptoms (SAPS), and examined whether the factor scores predicted the offspring's morbidity from psychotic disorders. We found a four-factor solution (negative, positive, catatonic, and affective symptom factors). High maternal positive symptom factor score significantly predicted decreased morbidity from schizophrenia among offspring (P=0.0098). Our result suggests that maternal positive symptoms are less harmful to the child than other maternal psychotic symptoms, and supports the view that positive symptoms are non-specific symptoms of psychosis rather than core features of schizophrenia.     

Relationship of psychotic symptom clusters in schizophrenia to neuroleptic treatment and growth hormone response to apomorphine

The authors propose an alternative model for relating clinically rated psychotic symptoms to biological measures in schizophrenic patients. They suggest that clinical presentation in schizophrenic patients comprises at least four distinct psychotic symptom clusters and that at most one or two of the symptom clusters are closely associated with central dopamine (DA) activity as measured by growth hormone (GH) response to apomorphine. Factor and cluster analytic techniques both identified the same four psychotic symptom clusters, three of which were similar to the major subtypes of schizophrenia: paranoid delusions (paranoid type), thought disorder (disorganized type), and catatonia (catatonic type). The fourth psychotic symptom cluster was auditory hallucinations, a prominent clinical feature of schizophrenia. The authors compared clinical symptom cluster scores to apomorphine-induced GH response by creating a new data set containing the output of the factor analysis of each patient's symptoms and GH response, and performing regression modeling of the patient's symptom cluster scores on GH response. Patients with elevated thought disorder cluster scores also had elevated GH responses to apomorphine, suggesting an association between thought disorder and central DA receptor supersensitivity. A fixed-dose neuroleptic trial showed that thought disorder and auditory hallucinations respond rapidly to treatment with a DA receptor blocker (haloperidol), while no significant effect on other symptom cluster scores occurred during the initial 2 weeks of treatment. These data suggest that two of the identified symptom clusters, thought disorder and auditory hallucinations, may be preferentially associated with central DA hyperactivity.     

Bizarre delusions and DSM-IV schizophrenia

The present study investigated whether schizophrenia patients with and without DSM-IV bizarre delusions, categorized as bizarre delusions of Schneiderian first rank symptoms (SBD) and as non-Schneiderian bizarre delusions (non-SBD), differed on demographic or clinical features, in view of the weight given to bizarre delusions in the diagnosis of schizophrenia. One hundred and twenty-nine in-patients with schizophrenia were assessed systematically for both types of bizarre delusions on the five domains of psychopathology of the Positive and Negative Syndrome Scale (PANSS; delusions/hallucinations, thought disorder/disorganization, excitement, negative symptoms and depressive symptoms) and for extrapyramidal side-effects. Inter-rater reliabilities for SBD and non-SBD were assessed and were exceptionally high (kappa value 0.85 and 0.92, respectively). Neither SBD nor non-SBD were associated with any demographic or non-PANSS clinical characteristics tested. However, the presence of non-SBD was significantly associated with more severe psychopathology in all five domains of the PANSS, whereas the presence of SBD was significantly associated with more severe psychopathology in three domains only: delusions/hallucinations, thought disorder/disorganization and depressive symptoms. However, patients with only SBD did not differ from patients with only non-SBD on any demographic or clinical variables, including five psychopathological domains. These findings suggest that, despite showing more severe symptoms, patients with DSM-IV bizarre delusions do not constitute a clinically distinguishable subgroup.     

Dimensions of schizophrenic positive symptoms: an exploratory factor analysis investigation

Current psychopathology classifies schizophrenic positive symptoms into four groups: delusions, hallucinations, formal thought disorder, and catatonic symptoms. The present study explores the factor structure of different positive symptoms to refine this classification. The 35 positive symptoms of 429 psychiatric patients, consecutively admitted to any of 95 mental hospitals, with diagnosis of the ICD-10 F20 schizophrenia, were studied. After excluding those items with a base rate of 10% or less, factor analysis yielded six factors. The first factor was loaded by most of Schneider’s first-rank symptoms and two specific auditory hallucinations; the second by all the catatonic symptoms and incoherence; the third by bodily delusions/hallucinations; the fourth by delusions of persecution and reference; the fifth by grandiose and religious delusions; and the sixth by visual and miscellaneous hallucinations. The finding that schizophrenic positive symptoms may have more than four dimensions suggests the need for reclassification of schizophrenic symptoms and for reconsideration of evidence-based diagnostic criteria for the disorder. Received: 26 January 1996 / Accepted: 12 December 1998     

Basic symptoms and their contribution to the differential typology of acute schizophrenic and schizoaffective disorders

One hundred and fifty male inpatients - 128 patients with DSM-IV schizophrenia and 22 patients with DSM-IV schizoaffective disorder - were investigated, over the course of their acute psychosis, on whether there were differences in the extent of basic symptoms (measured by the Bonn Scale for the Assessment of Basic Symptoms) according to their diagnostic subtype. Another aim was to find out if the diagnostic subtypes could be discriminated by means of basic symptoms and if clusters gained from basic symptoms were in accordance with the diagnostic subtypes. Differences in basic symptoms were found between the subtypes, but a clear discrimination of diagnostic subtypes by means of basic symptoms could not be achieved. There was indication that patients with prominent delusions or auditory hallucinations reported more basic symptoms than patients with exclusively prominent disorganization.     

Clinical features of illness in siblings with schizophrenia or schizoaffective disorder

Evidence implicating genetic or prenatal-perinatal environmental causes in the familial aggregation of schizophrenia led us to study 53 sets of siblings, two or more of whom had chronic psychosis, either schizophrenia or schizoaffective disorder. We looked for similarities in clinical features and concordance of diagnosis within sibships to test for shared familial causes. Clinical variables, including diagnosis, specific symptoms, age at onset, and nongenetic perinatal factors, were studied. Auditory hallucinations, paranoid delusions, thought disorder, negative symptoms, and poor premorbid social adjustment did not significantly correlate in siblings. Concordance was found for schizoaffective disorder and history of major depressive episodes, suggesting that schizophrenia with a depressive component and Research Diagnostic Criteria schizoaffective illness may represent a specific etiologic subtype(s) of the illness, whereas the other noted symptoms may represent the variable expression of the disorder. Age at onset and at first hospitalization were significantly correlated, consistent with genetic or other familial factors on time of onset. Birth complications were significantly more frequent among the schizophrenic compared with non-psychotic siblings, had a familial component, and tended to be associated with an earlier age at onset. Thus, nongenetic perinatal factors may increase the risk for schizophrenia in a familial form of the illness and contribute to the correlation of ages at onset in siblings.     

The psychosis of schizophrenia: prevalence, response to atypical antipsychotics, and prediction of outcome.

BACKGROUND: Psychosis is a defining feature of schizophrenia consisting of formal thought disorder, delusions, and hallucinations. Although psychosis is present in the majority of patients with schizophrenia, the prevalence, responsiveness to atypical antipsychotic drug therapy, and prediction of outcome of individual psychotic symptoms in a population of well-diagnosed patients with schizophrenia have not been conclusively established. METHODS: This paper examined the prevalence, responsiveness to the atypical antipsychotic olanzapine, and relationship to outcome of individual psychotic symptoms using data from a previously reported large multicenter, double-blind clinical trial of olanzapine (mean daily dose at endpoint = 13.6 +/- 6.9 mg/day). RESULTS: The most frequently reported psychotic symptoms at baseline were delusions (65%), conceptual disorganization (50%), and hallucinations (52%), and the majority of patients (68%) experienced from one to three symptoms. Additionally, with olanzapine treatment there were significant improvements (p < .001) in baseline to endpoint Positive and Negative Symptom Scale (PANSS) psychotic item scores, with the largest effect sizes observed for hallucinatory behavior, unusual thought content, suspiciousness/persecution, and delusions. During the acute phase of the trial, quality of life was correlated significantly with baseline conceptual disorganization (p = .038) and unusual thought content (p = .023), and time spent in the hospital was correlated with unusual thought content (p = .005). CONCLUSIONS: The implications of these for the clinical management of schizophrenia are discussed.     

Domains of psychopathology: an approach to the reduction of heterogeneity in schizophrenia

The manifest clinical heterogeneity of schizophrenia, combined with the failure, to date, to demonstrate the existence of a unitary disease process, has led to the conceptualization of schizophrenia as a pathophysiologically heterogeneous disorder. Various approaches have been developed to define homogeneous subgroups of schizophrenic patients. An alternative approach to the use of multiple criteria for defining putative disease entities is the use of specific sign and symptom complexes, or domains of psychopathology, for reducing heterogeneity. There is now considerable evidence supporting the separation of schizophrenic symptoms into three domains: hallucinations and delusions, thought disorder, and deficit symptoms. The conceptual evolution and validating evidence for this approach are reviewed, and an illustration of how the domains of psychopathology are applied in schizophrenia research is presented.     

'Schizoaffective disorder': dead or alive?

Schizoaffective disorder, traditionally classified under schizophrenia, recently tends to be subsumed under affective disorder. This article reports a study of 35 sib pairs, where each six was independently diagnosed as having schizophrenia (SC), affective disorder (AD), or schizoaffective disorder (SA). The observed numbers of same-diagnosis pairs (ADAD, SASA, SCSC) were compared with the numbers expected if the three disorders are genetically independent. The results showed a significant deficiency only in the observed number of SASA pairs, which suggests that schizophrenia and affective disorder are genetically distinct whereas schizoaffective disorder is not. To test whether schizoaffective disorder is a variant of affective disorder or schizophrenia, the observed number of ADSA and SASC pairs were compared against the expected numbers. No significant differences were found, which suggests that schizoaffective disorder is genetically heterogeneous, with at least two subtypes, one a variant of affective disorder, the other a variant of schizophrenia.