Regressing to Prior Response Preference After Set Switching Implicates Striatal Dysfunction Across Psychotic Disorders: Findings From the B-SNIP Study

Difficulty switching behavioral response sets is established in psychotic disorders. In rodent models, prefrontal lesions cause difficulty initially switching to new response sets (perseverative errors) while striatal lesions cause difficulty suppressing responses to previous choice preferences (regressive errors). Studies of psychotic disorders have not previously assessed these 2 error types. Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) participants included probands with schizophrenia (N = 212), psychotic bipolar (N = 192), and schizoaffective disorder (N = 131), their first-degree relatives (N = 267,226,165 respectively), and healthy controls (N = 258). Participants completed the Penn Conditional Exclusion Test (PCET) to assess cognitive set switching and the Brief Assessment of Cognition in Schizophrenia (BACS) to assess generalized neuropsychological dysfunction. All proband groups displayed elevated rates of perseverative and regressive errors compared to controls. After correcting for generalized cognitive deficits to identify specific deficits in set shifting and maintenance, there were no significant group differences for perseverative errors, while the increased rate of regressive errors remained significant. Level of regressive errors was similar across proband groups with minimal correlations with antipsychotic medication dose, clinical ratings, and demographic characteristics. Relatives of schizophrenia patients showed increased rates of regressive errors, but familiality of this trait was significant only in bipolar pedigrees. Regressive errors were partially independent of generalized cognitive deficits, suggesting a potentially informative and specific cognitive deficit across psychotic disorders. Preclinical data indicate that this deficit could be related to altered function in a neural system that may include the dorsal striatum or other elements of frontostriatal systems.Key words: psychosis, schizophrenia, psychotic bipolar, B-SNIP, executive function, striatum     

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h ² = 0.79, P = 3.97e−15) and AVP (h ² = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.Key words: oxytocin, vasopressin, schizophrenia, bipolar disorder, emotion recognition     

Biomarker Profiles in Psychosis Risk Groups Within Unaffected Relatives Based on Familiality and Age

Investigating biomarkers in unaffected relatives (UR) of individuals with psychotic disorders has already proven productive in research on psychosis neurobiology. However, there is considerable heterogeneity among UR based on features linked to psychosis vulnerability. Here, using the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) dataset, we examined cognitive and neurophysiologic biomarkers in first-degree UR of psychosis probands, stratified by 2 widely used risk factors: familiality status of the respective proband (the presence or absence of a first- or second-degree relative with a history of psychotic disorder) and age (within or older than the common age range for developing psychosis). We investigated biomarkers that best differentiate the above specific risk subgroups. Additionally, we examined the relationship of biomarkers with Polygenic Risk Scores for Schizophrenia (PRS_SCZ) in a subsample of Caucasian probands and healthy controls (HC). Our results demonstrate that the Brief Assessment of Cognition in Schizophrenia (BACS) score, antisaccade error (ASE) factor, and stop-signal task (SST) factor best differentiate UR (n = 169) from HC (n = 137) (P = .013). Biomarker profiles of UR of familial (n = 82) and non-familial (n = 83) probands were not significantly different. Furthermore, ASE and SST factors best differentiated younger UR (age ≤ 30) (n = 59) from older UR (n = 110) and HC from both age groups (age ≤ 30 years, n=49; age > 30 years, n = 88) (P < .001). In addition, BACS (r = −0.175, P = .006) and ASE factor (r = 0.188, P = .006) showed associations with PRS_SCZ. Taken together, our findings indicate that cognitive biomarkers—“top-down inhibition” impairments in particular—may be of critical importance as indicators of psychosis vulnerability.     

Generalized and Specific Neurocognitive Deficits in Psychotic Disorders: Utility for Evaluating Pharmacological Treatment Effects and as Intermediate Phenotypes for Gene Discovery

A growing body of research suggests that schizophrenia and bipolar disorder share overlapping clinical, neurobiological, and genetic features, raising important questions about the boundaries and distinctiveness of these 2 major psychiatric disorders. A generalized cognitive impairment has long been understood to be a core feature of schizophrenia. More recently, it has become apparent that cognitive impairment also occurs in bipolar disorder, particularly in those patients with a history of psychotic symptoms. Whether a generalized deficit exists across a spectrum of psychotic disorders is less clearly established. Additionally, in the context of a broad impairment, it remains a significant challenge to identify deficits in specific cognitive processes that may have distinct neurochemical or regional brain substrates and linkages to particular risk-associated genetic factors. In this article, we review the findings from neuropsychological studies across a spectrum that includes schizophrenia, schizoaffective and bipolar disorders, and conclude the available evidence strongly supports that a generalized deficit is present across psychotic disorders that differs in severity more so than form. We then consider the implications of generalized and specific deficits in psychosis for 2 areas of research—the evaluation of pharmacological treatments targeting cognitive deficits, and the investigation of cognitive intermediate phenotypes in family genetic studies. Examples from the literature that touch on the relevance of the generalized deficit in these contexts are provided, as well as consideration for the continued need to identify specific impairments that are separable from the generalized deficit in order to advance drug and gene discovery.Key words: schizophrenia, schizoaffective disorder, bipolar disorder, neuropsychology, cognition, endophenotype, treatment effects     

Hippocampal Volume Is Reduced in Schizophrenia and Schizoaffective Disorder But Not in Psychotic Bipolar I Disorder Demonstrated by Both Manual Tracing and Automated Parcellation (FreeSurfer)

This study examined hippocampal volume as a putative biomarker for psychotic illness in the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) psychosis sample, contrasting manual tracing and semiautomated (FreeSurfer) region-of-interest outcomes. The study sample (n = 596) included probands with schizophrenia (SZ, n = 71), schizoaffective disorder (SAD, n = 70), and psychotic bipolar I disorder (BDP, n = 86); their first-degree relatives (SZ-Rel, n = 74; SAD-Rel, n = 62; BDP-Rel, n = 88); and healthy controls (HC, n = 145). Hippocampal volumes were derived from 3Tesla T1-weighted MPRAGE images using manual tracing/3DSlicer3.6.3 and semiautomated parcellation/FreeSurfer5.1,64bit. Volumetric outcomes from both methodologies were contrasted in HC and probands and relatives across the 3 diagnoses, using mixed-effect regression models (SAS9.3 Proc MIXED); Pearson correlations between manual tracing and FreeSurfer outcomes were computed. SZ (P = .0007–.02) and SAD (P = .003–.14) had lower hippocampal volumes compared with HC, whereas BDP showed normal volumes bilaterally (P = .18–.55). All relative groups had hippocampal volumes not different from controls (P = .12–.97) and higher than those observed in probands (P = .003–.09), except for FreeSurfer measures in bipolar probands vs relatives (P = .64–.99). Outcomes from manual tracing and FreeSurfer showed direct, moderate to strong, correlations (r = .51–.73, P < .05). These findings from a large psychosis sample support decreased hippocampal volume as a putative biomarker for schizophrenia and schizoaffective disorder, but not for psychotic bipolar I disorder, and may reflect a cumulative effect of divergent primary disease processes and/or lifetime medication use. Manual tracing and semiautomated parcellation regional volumetric approaches may provide useful outcomes for defining measurable biomarkers underlying severe mental illness.Key words: schizophrenia, psychotic bipolar disorder, hippocampus, manual tracing, FreeSurfer     

Saccadic disinhibition in patients with acute and remitted schizophrenia and their first-degree biological relatives

OBJECTIVE: Performance on measures of saccadic inhibition and control was investigated in a large family study of schizophrenia to evaluate the utility of using antisaccade task performance as an endophenotypic marker of genetic liability for schizophrenia. METHOD: Ninety-five patients with acute schizophrenia and 116 of their first-degree biological relatives, 13 schizophrenia patients whose illness was in full remission, 35 patients with acute psychotic affective disorder, and 109 nonpsychiatric comparison subjects were administered antisaccade and prosaccade tasks. RESULTS: Both schizophrenia patient groups had a greater number of errors on the antisaccade task than did the first-degree relatives and the affective disorder group, which both had more errors than the comparison subjects. Among the first-degree relatives of the probands with acute schizophrenia, relatives of poor-performing patients performed worse on the antisaccade task than relatives of patients with good performance. Reflexive errors were not likely the result of interfering psychotic symptoms, medication, or medication side effects. Although the schizophrenia patients demonstrated other signs of saccadic abnormalities, these problems, which were not observed in their relatives even though they had high antisaccade error rates, seem unlikely to account for the higher antisaccade error rate of the schizophrenia patients. CONCLUSIONS: These findings suggest that saccadic disinhibition is strongly associated with the genetic liability for schizophrenia.     

Polygenic risk for type 2 diabetes mellitus among individuals with psychosis and their relatives

BackgroundAn elevated prevalence of Type 2 diabetes (T2D) has been observed in people with psychotic disorders and their relatives compared to the general population. It is not known whether this population also has increased genetic risk for T2D.MethodsSubjects included probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, their first-degree relatives without psychotic disorders, and healthy controls, who participated in the Bipolar Schizophrenia Network for Intermediate Phenotypes study. We constructed sets of polygenic risk scores for T2D (PGRS_T2D) and schizophrenia (PGRS_SCHIZ) using publicly available data from genome-wide association studies. We then explored the correlation of PGRS_T2D with psychiatric proband or relative status, and with self-reported diabetes. Caucasians and African–Americans were analyzed separately. We also evaluated correlations between PGRS_SCHIZ and diabetes mellitus among Caucasian probands and their relatives.ResultsIn Caucasians, PGRS_T2D was correlated with self-reported diabetes mellitus within probands, but was not correlated with proband or relative status in the whole sample. In African–Americans, a PGRS_T2D based on selected risk alleles for T2D in this population did not correlate with proband or relative status. PGRS_SCHIZ was not correlated with self-reported diabetes within Caucasian probands.ConclusionDifferences in polygenic risk for T2D do not explain the increased prevalence of diabetes mellitus observed in psychosis probands and their relatives.     

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.     

Obsessive-Compulsive Disorder,Psychosis, and Bipolarity: A Longitudinal Cohort and Multigenerational Family Study

Obsessive-compulsive disorder (OCD) often co-occurs with psychotic and bipolar disorders; this comorbidity complicates the clinical management of these conditions. In this population-based longitudinal and multigenerational family study, we examined the patterns of comorbidity, longitudinal risks, and shared familial risks between these disorders. Participants were individuals with a diagnosis of OCD (n = 19814), schizophrenia (n = 58336), bipolar disorder (n = 48180), and schizoaffective disorder (n = 14904) included in the Swedish Patient Register between January 1969 and December 2009; their first-, second-, and third-degree relatives; and population-matched (1:10 ratio) unaffected comparison individuals and their relatives. The Swedish Prescribed Drug Register was used to control for the potential effect of medication in the longitudinal analyses. Individuals with OCD had a 12-fold increased risk of having a comorbid diagnosis of schizophrenia and a 13-fold increased risk of bipolar disorder and schizoaffective disorder. Longitudinal analyses showed that individuals first diagnosed with OCD had an increased risk for later diagnosis of all other disorders, and vice versa. The risk of bipolar disorder was reduced, but not eliminated, when the use of selective serotonin reuptake inhibitors was adjusted for. OCD-unaffected first-, second-, and third-degree relatives of probands with OCD had a significantly increased risk for all 3 disorders; the magnitude of this risk decreased as the genetic distance increased. We conclude that OCD is etiologically related to both schizophrenia spectrum and bipolar disorders. The results have implications for current gene-searching efforts and for clinical practice.Key words: OCD, schizophrenia, schizoaffective disorder, bipolar disorder, genetic epidemiology     

Obsessive-compulsive and panic symptoms in patients with first-admission psychosis

OBJECTIVE: The occurrence, persistence and specificity of the association between comorbid obsessive-compulsive and panic symptoms and three psychotic disorders--schizophrenia/schizoaffective disorder, bipolar disorder with psychosis, and major depression with psychosis--were examined in a first-admission, epidemiologically defined group of patients with psychotic symptoms. METHOD: The Structured Clinical Interview for DSM-III-R obsessive-compulsive and panic modules were administered at baseline and 24-month follow-up to patients with schizophrenia/schizoaffective disorder (N=225), bipolar disorder with psychosis (N=138), and major depression with psychosis (N=87) participating in the Suffolk County (N.Y.) Mental Health Project. The rates of subsyndromal symptoms and disorder criteria met were compared across the three psychosis groups. Recognition and treatment of anxiety symptoms at initial discharge and impact of the baseline presence of anxiety symptoms on 24-month clinical status were also examined. RESULTS: Obsessive-compulsive and panic symptoms were present at baseline in 10%-20% of all three groups. There was no specific association between obsessive-compulsive symptoms and any specific psychosis diagnosis; however, women with major depression with psychosis had a significantly higher rate of panic symptoms than the other two groups, and schizophrenia/schizoaffective disorder patients with baseline panic symptoms were significantly more likely to exhibit positive symptoms of psychosis after 24 months. CONCLUSIONS: The authors found no specific association between obsessive-compulsive symptoms and diagnosis early in the illness course, but the finding of an association between panic symptoms and psychotic depression among female patients and between baseline panic and positive psychotic symptoms in schizophrenia/schizoaffective disorder patients at 24 months suggests the need for further study.     

Antisaccade task performance in patients at ultra high risk for developing psychosis

Patients with schizophrenia consistently perform worse than healthy controls on the antisaccade task in which the subject is required to inhibit a reflexive saccade to a suddenly appearing visual target and look in the opposite direction. To our knowledge there is no research yet showing how patients at ultra high risk (UHR) for developing psychosis perform on the antisaccade task. The aim of the present study was to investigate antisaccade task performance in UHR patients. Patients were eligible for the study when they met criteria for one or more of the following groups: Attenuated symptoms or brief limited intermitted psychotic symptoms or a first-degree family member with a psychotic disorder and reduced functioning or basic symptoms. In 35 UHR patients we assessed antisaccades, neuropsychological test performance and symptomatology. Antisaccade task results were compared with those obtained in 42 age- and intelligence-matched patients with recent-onset schizophrenia and 28 matched healthy controls. Antisaccade error rate was significantly higher in the UHR patients than in the controls. Schizophrenia patients performed worse than the UHR patients and the control subjects. We found a trend towards higher antisaccade error rate at baseline in the UHR patients who later made the transition to psychosis compared to the UHR patients who did not make the transition to psychosis. Poor spatial working memory function was related to increased antisaccade errors in the UHR group. Abnormal antisaccade task performance is also present in patients at UHR for developing psychosis. Subsequent research needs to clarify if increased antisaccade error rate is predictive of a psychotic episode. In UHR patients, poor antisaccade performance may reflect working memory dysfunction.     

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.     

Neurophysiological Evidence of Corollary Discharge Function During Vocalization in Psychotic Patients and Their Nonpsychotic First-Degree Relatives

Predictions about sensations resulting from motor acts are instantiated through neural mechanisms such as the corollary discharge. With each action, the corollary discharge provides an unconscious comparison between predicted and actual sensations resulting from the action; closer matches result in greater suppression of sensation. This mechanism is disrupted in schizophrenia (SZ) and may contribute to, or reflect a failure to, distinguish self- from externally generated experiences, a hallmark of psychosis. We asked whether disruption is specific to SZ or is seen in other psychotic illnesses and in first-degree relatives of psychotic patients. Corollary discharge function was assessed in SZ patients (n = 30), schizoaffective (SA) patients (n = 19), bipolar patients with a history of psychosis (BPP; n = 39), nonpsychotic relatives of SZ (n = 30), SA (n = 23), and BPP (n = 50) patients, and healthy controls (n = 43). The N1 component of the event-related potential, reflecting auditory cortical responses to sounds, was elicited by speech sound onset as subjects talked and later when they listened to a recording of those sounds. N1 was suppressed during talking compared to N1 during listening, consistent with the suppressive action of the corollary discharge mechanism. Suppression was significantly reduced in SZ and BPP patients, with a similar trend in the smaller SA group. Patient groups did not differ, and unaffected relatives did not differ from controls or probands. The failure to monitor sensations resulting from self-generated actions, implicating corollary discharge dysfunction, may be a common feature across affective and nonaffective psychosis. Data from unaffected family members do not indicate that this is a marker of psychosis risk.Key words: psychosis, corollary discharge, ERP, N1, first-degree relatives     

Contributions of genetic risk and fetal hypoxia to hippocampal volume in patients with schizophrenia or schizoaffective disorder,their unaffected siblings,and healthy unrelated volunteers

OBJECTIVE: The authors examined in an epidemiologic sample the contributions of genetic predisposition and history of fetal hypoxia to hippocampal volume in patients with psychosis. METHOD: High-resolution magnetic resonance imaging was used to measure hippocampal volumes in 72 psychotic probands (60 with schizophrenia and 12 with schizoaffective disorder, ascertained so as to be representative of all such probands in a Helsinki birth cohort), 58 nonpsychotic full siblings of the probands, and 53 demographically similar healthy comparison subjects with no family history of psychosis. RESULTS: Hippocampal volume differences occurred in a stepwise fashion with each increase in genetic load for schizophrenia. The probands had smaller hippocampal volumes than did their full siblings, who in turn had smaller hippocampal volumes than did the healthy comparison subjects. Among the probands, smaller hippocampal volumes were seen in those who experienced fetal hypoxia than in those who did not, a difference not noted within the other two groups. Finally, within the schizophrenic/schizoaffective disorder patients, smaller hippocampal volumes correlated positively with age at onset independent of duration of illness. CONCLUSIONS: These findings suggest that in patients with schizophrenia spectrum disorders, hippocampal volume is influenced in part by schizophrenia susceptibility genes and an interaction of these genes with fetal hypoxia. They further suggest that hippocampal volume in schizophrenia or schizoaffective disorder may be linked to time of disease onset.     

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.     

Antisaccade performance is related to genetic loading for schizophrenia

Disturbances of the oculomotor system are promising endophenotypes for schizophrenia. Increased error rates in the antisaccade task and prolonged antisaccade latencies have been found in patients with schizophrenia and their first degree relatives. We investigated oculomotor performance in 41 parents of schizophrenia patients and 22 controls with a prosaccade task and an antisaccade task. Parents were grouped into parents with a positive family history for schizophrenia (N = 9) and parents with a negative family history for schizophrenia (N = 32). An overlap-paradigm was applied; eye movements were recorded using infrared oculography. The combined group of parents made more antisaccade direction errors than controls (p = 0.005) and there was a linear increase in direction errors from controls via negative family history parents to positive family history parents (p = 0.008). Antisaccade latencies were prolonged in the combined parent group (p = 0.057) compared to controls and there was a linear increase in latency with genetic loading (p = 0.018). No group differences were found for prosaccade parameters. These results support the hypothesis that antisaccade impairment is associated with genetic loading for schizophrenia.     

Early onset psychotic disorders: Diagnostic stability and clinical characteristics

Objectives: To examine the clinical features and diagnostic stability of early-onset psychotic disorders. Methods: These data are from a two-year longitudinal prospective study of youth with psychotic disorders. Standardized diagnostic assessments are administered at baseline and at one and two-year's follow-up. Results: Fifty-one subjects have been recruited to date; 18 with schizophrenia, 14 with bipolar disorder, 7 with schizoaffective disorder, 1 with an organic psychosis, and 11 subjects whose symptoms where either questionable and/or did not meet diagnostic criteria for another disorder (classified as psychosis nos). Thirty-nine subjects were reassessed at year one, twenty-four at year two. Three subjects have been lost to follow-up. The study diagnosis was the same as the first onset diagnosis (prior to entering the study) in 50 % of subjects. Over the two-year period of the study, the diagnosis remained unchanged in over 90 % of subjects. Subjects with schizophrenia had higher ratings of premorbid impairment, including social withdrawal and dysfunctional peer relationships, than those with bipolar disorder. At the one-year follow-up, subjects with schizophrenia and schizoaffective disorder had significantly higher rates of delusions, bizarre behavior, and negative symptoms than those with bipolar disorder. Subjects with bipolar disorder tended to have cyclical courses, whereas those with schizophrenia and schizoaffective disorder were often chronically impaired. Subjects with psychosis nos had higher rates of dissociative symptoms and histories of child maltreatment. Conclusions: Early-onset psychotic disorders can be reliably diagnosed using standardized assessments and are stable over a two-year period. Compared to bipolar disorder, schizophrenia is associated with a poorer premorbid history, and persistent positive and negative symptoms.     

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.     

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.     

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.