Ego-pathology and common symptom factors in schizophrenia

The phenomenological construct of ego-pathology in schizophrenia has been widely referred to in psychopathological textbooks but was systematically assessed in very few empirical studies. This study investigated the association between ego-pathology (Ego-Pathology Inventory) and common symptom factors (Positive and Negative Symptom Scale) in paranoid schizophrenia patients within 3 days after admission and after 2 weeks of treatment. The predictive value of ego-pathology for short-term treatment outcome was also assessed. A factor analysis of all subscale scores revealed a four-factor solution: positive symptoms, negative symptoms, and two distinct ego-pathology factors, i.e., general and identity. Although the ego-pathology subscale "activity" loaded on the positive symptom factor, the other four subscales formed the two ego-pathology factors with no high loadings on other factors. High scores on ego-demarcation at admission predicted poor treatment outcome after 2 weeks. The findings suggest that ego-pathology might be used to capture additional and clinically meaningful symptom dimensions in schizophrenia.     

Anhedonia in depression and schizophrenia: a reexamination.

The purpose of this study was to utilize factor analysis to help determine whether anhedonia is a symptom of both depression and schizophrenia. Measures of depression, positive and negative symptoms of schizophrenia, and anhedonia were administered to a group of schizophrenic patients (N = 54) and to a group of patients with major depressive disorder (N = 27). The correlation matrix among the various scales was subjected to an oblique exploratory factor analysis. Three factors were extracted, accounting for three quarters of the variance. The first measured depression, the second measured positive symptoms, and the third measured negative symptoms. Anhedonia loaded significantly on the first factor but not on the third, suggesting that it is a symptom of depression rather than schizophrenia. These results were corroborated by means of confirmatory factor analysis. We conclude that anhedonia is a symptom of depression and that it only appears to be a symptom of schizophrenia because it is a component of emotional blunting which is indeed a negative symptom of schizophrenia.     

首发精神分裂症患者症状群因子分析研究

目的　探讨首发精神分裂症患者治疗前存在的独立症状群及其治疗后的变化。方法　对首发精神分裂症患者 ,在治疗前后分别评定简明精神病评定量表、阴性症状评定量表、汉密尔顿抑郁量表和测查 7种认知功能 ,然后进行因子分析。结果　首发精神分裂症患者的认知症状、阴性症状、情感症状在治疗前、后完全独立 ,无明显变化 ;而阳性症状的独立性在治疗前、后则不稳定 ,因子负荷分别在执行功能、情感症状因子上。结论　在首发精神分裂症患者中情感症状、认知症状是独立存在的 ,与治疗干预、阴性症状及阳性症状关系不肯定 ,应重视对两者的评估和治疗。     

Basic symptoms and psychotic symptoms: Their relationships in the at risk mental states,first episode and multi-episode schizophrenia

In the field of the early psychosis two main approaches attempt to develop rating tools, one investigating the basic symptoms domain, and the other the attenuated psychotic symptoms. To explore the relationship between basic symptoms (BSs) and other symptom domains in different phases of the psychotic illness 32 at ultra-high risk (UHR), 49 first episode schizophrenia (FES), 42 multiple episode schizophrenia (MES), and 28 generalized anxiety disorder (GAD) patients were enrolled. Participants were assessed using the SIPS/SOPS and the FCQ scales. Analyses of covariance taking into account socio-demographic and clinical variables significantly different between groups were applied to compare FCQ and SOPS scores. Finally FCQ and SOPS principal component analysis was carried out in the schizophrenia spectrum group. SOPS scores were higher in the UHR, FES and MES groups compared to the GAD control group. Concordantly, FES and MES groups had a higher number of basic symptoms in comparison with the GAD group, whereas UHR did not differ from the control group. The largest number of correlations between BSs and psychotic symptoms was found in the GAD group. According to the principal component analysis (PCA) five factors were extracted, with the BSs loading on a unique factor. Our findings imply that the boundary between psychotic and non-psychotic conditions cannot be outlined on the basis of the presence/absence of basic and psychotic symptoms.     

Depressive factors and their relationships with other symptom domains in schizophrenia, schizoaffective disorder, and psychotic depression

Relationships among different symptom domains were investigated in patients with acute exacerbation of schizophrenia with depressive symptoms, psychotic depression, or schizoaffective disorder, depressive subtype. Scores for depression and depressive factors were correlated with positive, negative, and extrapyramidal symptoms within diagnostic categories. No between-group differences in the relationship of different symptom domains could be found, and no substantial relationship between depression and positive symptoms could be revealed in any diagnostic subgroup. Only the retardation factor of depression showed a significant overlap with negative symptoms; depressive core symptoms did not. Core symptoms of depression were independent from other symptoms in all investigated diagnostic groups. Depression seems to represent a heterogeneous symptom domain with unique relationships of components to positive and negative symptoms across nosological borders. A more differentiated assessment, analysis, and treatment of depressive symptoms is therefore recommended for patients with combined depressive and psychotic symptoms.     

Schizophrenia with prominent catatonic features ('catatonic schizophrenia'). II. Factor analysis of the catatonic syndrome

Previous factor analyses of catatonia have yielded conflicting results for several reasons including small and/or diagnostically heterogeneous samples and incomparability or lack of standardized assessment. This study examined the factor structure of catatonia in a large, diagnostically homogenous sample of patients with chronic schizophrenia using standardized rating instruments. A random sample of 225 Chinese inpatients diagnosed with schizophrenia according to DSM-IV criteria were selected from the long-stay wards of a psychiatric hospital. They were assessed with a battery of rating scales measuring psychopathology, extrapyramidal motor status, and level of functioning. Catatonia was rated using the Bush-Francis Catatonia Rating Scale. Factor analysis using principal component analysis and Varimax rotation with Kaiser normalization was performed. Four factors were identified with Eigenvalues of 3.27, 2.58, 2.28 and 1.88. The percentage of variance explained by each of the four factors was 15.9%, 12.0%, 11.8% and 10.2% respectively, and together they explained 49.9% of the total variance. Factor 1 loaded on "negative/withdrawn" phenomena, Factor 2 on "automatic" phenomena, Factor 3 on "repetitive/echo" phenomena and Factor 4 on "agitated/resistive" phenomena. In multivariate linear regression analysis negative symptoms and akinesia were associated with 'negative' catatonic symptoms, antipsychotic doses and atypical antipsychotics with 'automatic' symptoms, length of current admission, severity of psychopathology and younger age at onset with 'repetitive' symptoms and age, poor functioning and severity of psychopathology with 'agitated' catatonic symptom scores. The results support recent findings that four main factors underlie catatonic signs/symptoms in chronic schizophrenia.     

Nonspecific and attenuated negative symptoms in patients at clinical high-risk for schizophrenia

BACKGROUND: Retrospective studies have shown that nonspecific psychopathology and negative symptoms, including social isolation and academic dysfunction, tend to precede onset of psychosis. The present report describes the baseline psychopathology of subjects in the Hillside Recognition and Prevention (RAP) Program, and presents an operationalized classification algorithm for the prospective study of both positive and negative symptoms of clinical high-risk (CHR) for schizophrenia. METHODS: Eighty-two adolescent and young adult patients were characterized using semi-structured interviews of both a parent informant and the patient. The Scale of Prodromal Symptoms (SOPS) was utilized to derive a three-part classification scheme: CHR- subjects (n=20) were defined as having at least one attenuated negative symptom with no positive symptoms; CHR+ subjects (n=42) were defined as having one or more attenuated positive symptoms without psychosis; schizophrenia-like psychosis (SLP) subjects (n=20) were defined as having a psychotic symptom, but without meeting criterion A, B, or C of DSM-IV schizophrenia. RESULTS: Social isolation was the most common presenting symptom. The three RAP subgroups did not significantly differ in levels of attenuated negative and disorganized symptoms, despite the fact that these were not required for inclusion in the CHR+ and SLP groups. Common co-morbid diagnoses included major depression, attention deficit hyperactivity disorder, avoidant personality disorder, and Cluster A personality disorders. CONCLUSIONS: Negative symptoms and other nonspecific behavioral abnormalities represent clinically important phenomena in prodromal patients, and may provide insight into pathophysiologic mechanisms in schizophrenia and possible preventive interventions.     

Exploring depression in schizophrenia.

BACKGROUND: A consistent amount of empirical research suggests that depression, besides interfering with quality of life and social functioning, may influence other symptom dimensions in schizophrenia, thus constituting an important domain for treatment strategies, outcome, and prognosis. AIM: This study investigated the factorial structure of the Calgary depression scale for schizophrenia (CDSS) in a sample of schizophrenic patients and explored the relationships between such factors, major symptom dimensions and subjective experiences. METHODS: One hundred and sixty-one subjects were examined to assess the severity of schizophrenic symptoms (scored according to the five-dimensional model of Toomey et al. [28]), the distress due to the subjective experience of negative symptoms, and the degree of subjectively-felt cognitive-affective vulnerability (i.e. basic symptoms). RESULTS: Principal component analysis revealed CDSS to include three main factors, namely: "depression-hopelessness" (factor I), "guilty idea of reference-pathological guilt" (factor II) and "early wakening" (factor III). Whereas the last factor did not correlate with any of the other psychopathological domains, the first two factors revealed multiple correlations with both diagnostic symptoms and subjective experiences. CONCLUSIONS: The results confirm the threefold factorial structure of the CDSS previously reported by the authors of the scale and could shed further light on the psychopathological nature of the components of depression in schizophrenia. The specific correlation patterns with diagnostic and subjective psychopatholgy substantiate the clinical distinction between a general depression factor ("depression-hopelessness") and a cognitive-guilt factor ("guilty idea of reference-pathological guilt").     

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.     

PANSS factors and scores in schizophrenic and bipolar disorders during an index acute episode: a further analysis of the cognitive component

To investigate the factor structure of psychotic symptoms, we compared the clinical characteristics of manic patients with those of schizophrenic patients evaluated with positive and negative syndrome scale (PANSS). The clinical symptoms of 148 bipolar patients and 86 schizophrenic patients hospitalized for an index psychotic episode were assessed. Schizophrenic patients showed more positive and cognitive symptoms than bipolars. The factor analysis of the two PANSS scores showed a three-factor solution with 'positive', 'negative' and 'mixed' depressive-activated factors for bipolars and 'positive', 'negative' and 'depressive' factors for schizophrenics. In both groups, the 'cognitive cluster' loaded on the first 'positive' factor while the 'lack of insight' (LOI) has a different meaning in the two groups, more related to the positive symptoms in the bipolar patients and more related to the negative symptoms in the schizophrenic patients. This finding suggests that LOI could be a non-unitary phenomenon in psychoses and it should be further explored to better elucidate differences in symptom structures between schizophrenic and bipolar disorders.     

The assessment of "prodromal schizophrenia": unresolved issues and future directions

Because of the novelty of research with clinical high risk ("prodromal") patients, many unresolved issues exist concerning how the prodromal state is defined and measured. Data are presented from the Recognition and Prevention (RAP) program at the Zucker Hillside Hospital to address several outstanding questions. Baseline attenuated positive symptoms were rated in 42 putatively prodromal patients in the RAP program using the Scale of Prodromal Symptoms (SOPS). Followup data of 6 months or more were available on 34 of these subjects; 9 of these (26.5%) developed psychotic disorders. Patients who developed psychosis had significantly higher SOPS positive symptom scores at baseline than those who did not. Various thresholds, using both total SOPS positive symptom scores and highest single item score, significantly predicted transition to psychosis, which calls into question appropriate cutoffs for the distinction between health, prodromal status, and psychosis. The SOPS positive symptom "conceptual disorganization" was found to be significantly related to disorganized behavior but not to other positive symptoms or to psychotic outcome, suggesting the importance of examining dimensions of psychopathology. The dimensional quantification of prodromal symptom severity may be an important direction for future studies of the assessment of at-risk states.     

Duration of attenuated positive and negative symptoms in individuals at clinical high risk: Associations with risk of conversion to psychosis and functional outcome

Research in individuals at clinical high-risk (CHR) for psychosis has focused on subjects with no more than 12 months of present or worsened attenuated positive symptoms. However, the impact of long duration attenuated positive and/or negative prodromal symptoms on outcomes is unclear. Seventy-six CHR subjects with attenuated positive symptoms and at least moderate severity level negative symptoms rated on the Scale of Prodromal Symptoms (SOPS) were prospectively followed for a mean of 3.0 ± 1.6 years. Social and Role functioning was assessed with the Global Functioning: Social and Role scales. Correlations between attenuated positive and negative symptom duration and severity and conversion to psychosis and functional outcomes were analyzed. The average onset of SOPS rated negative symptoms (M = 53.24 months, SD = 48.90, median = 37.27) was approximately twelve months prior to the emergence of attenuated positive symptom (M = 40.15 months, SD = 40.33, median = 24.77, P < 0.05). More severe positive symptoms (P = 0.004), but not longer duration of positive (P = 0.412) or negative (P = 0.754) symptoms, predicted conversion to psychosis. Neither positive symptom duration (P = 0.181) nor severity (P = 0.469) predicted role or social functioning at study endpoint. Conversely, longer negative symptom duration predicted poor social functioning (P = 0.004). Overall, our findings suggest that the severity of attenuated positive symptoms at baseline may be more important than symptom duration for determining individuals at increased risk of developing psychosis. In contrast, long-standing negative symptoms may be associated with persistent social difficulties and therefore have an important position in the treatment of disability.     

Correlations Between Brain Structure and Symptom Dimensions of Psychosis in Schizophrenia,Schizoaffective, and Psychotic Bipolar I Disorders

Introduction:

Structural alterations may correlate with symptom severity in psychotic disorders, but the existing literature on this issue is heterogeneous. In addition, it is not known how cortical thickness and cortical surface area correlate with symptom dimensions of psychosis.

Methods:

Subjects included 455 individuals with schizophrenia, schizoaffective, or bipolar I disorders. Data were obtained as part of the Bipolar Schizophrenia Network for Intermediate Phenotypes study. Diagnosis was made through the Structured Clinical Interview for DSM-IV. Positive and negative symptom subscales were assessed using the Positive and Negative Syndrome Scale. Structural brain measurements were extracted from T1-weight structural MRIs using FreeSurfer v5.1 and were correlated with symptom subscales using partial correlations. Exploratory factor analysis was also used to identify factors among those regions correlating with symptom subscales.

Results:

The positive symptom subscale correlated inversely with gray matter volume (GMV) and cortical thickness in frontal and temporal regions, whereas the negative symptom subscale correlated inversely with right frontal cortical surface area. Among regions correlating with the positive subscale, factor analysis identified four factors, including a temporal cortical thickness factor and frontal GMV factor. Among regions correlating with the negative subscale, factor analysis identified a frontal GMV-cortical surface area factor. There was no significant diagnosis by structure interactions with symptom severity.

Conclusions:

Structural measures correlate with positive and negative symptom severity in psychotic disorders. Cortical thickness demonstrated more associations with psychopathology than cortical surface area.Key words: positive, negative, cortical thickness, surface area, psychopathology, gray matter     

The structure of negative symptoms within schizophrenia: implications for assessment

This review examines the structural validity of negative symptoms focusing on 2 questions: (1) Do negative symptoms represent a domain separate from other symptoms in schizophrenia? and (2) Within negative symptoms, is there a structure that suggests multidimensionality? Results from exploratory and confirmatory factor analytic studies are examined to address these questions. Across studies and symptom instruments, negative symptoms appear to consistently emerge as a factor separate from other dimensions of the illness in schizophrenia. Whether 2-, 3-, or 5-factor models are identified, negative symptoms consistently load on a factor separate from positive symptoms, affective symptoms of depression or anxiety, and symptoms of disorganization. Focusing on negative symptoms themselves, factor analytic findings suggest that this construct is multidimensional with at least 2 factors (involving diminished expression and anhedonia-asociality). Although these factors were replicable, serious limitations were noted in this literature. Thus, 2- (or even 3- or 5-) factor models of negative symptoms should not be considered definitive, but rather all converge to support the general conclusion of the multidimensionality of negative symptoms. The later findings indicate the importance of employing assessments that provide adequate coverage of the broad domain of negative symptoms. Importantly, caution is noted in the interpretability of findings based on existing instruments, and implications for future assessment are discussed.     

Symptom dimensions in the course of childhood-onset schizophrenia

The symptom dimensions of childhood-onset schizophrenia (COS) are described by focussing on the clinical features of 44 patients at onset of illness during the first episode and at follow-up investigation 42 years after onset. All subjects were re-diagnosed according to DSM IV. The symptomatology was evaluated with the Positive and Negative Symptom Scale (PANSS) at onset and at follow-up. Two principal component factor analyses with varimax-rotation were applied to the complete items set of the PANSS. The frequencies of positive, negative, and global symptoms were compared longitudinally in an ANOVA-repeated measures design. The factor analysis revealed 5 orthogonal symptom dimensions (factors) at onset of psychosis: Cognition, social withdrawal, antisocial behaviour, excitement, and reality distortion. At follow-up a five-factor solution was found, too, but different dimensions emerged: a positive, negative, excitement, cognitive, and anxiety/depression component which fits to the 5-factor model of White et al. (1997). The first psychotic episode of EOS is accompanied with more unspecific symptoms such as social withdrawal and antisocial behavior. In the later stages of (COS) the structure of symptom dimensions changes to that known from adult-onset schizophrenia (AOS). The results indicate that COS and AOS are comparable nosological entities and that more than 3 dimensions are required to describe the relevant clinical symptom structure. Positive and global symptoms decreased significantly during the course of illness. The frequencies of negative symptoms did not change which demonstrates their disabling impact.     

Symptom dimensions in the course of childhood-onset schizophrenia

The symptom dimensions of childhood-onset schizophrenia (COS) are described by focussing on the clinical features of 44 patients at onset of illness during the first episode and at follow-up investigation 42 years after onset. All subjects were re-diagnosed according to DSM IV. The symptomatology was evaluated with the Positive and Negative Symptom Scale (PANSS) at onset and at follow-up. Two prinicpal component factor analyses with varimax-rotation were applied to the complete items set of the PANSS. The frequencies of positive, negative, and global symptoms were compared longitudinally in an ANOVA-repeated measures design. The factor analysis revealed 5 orthogonal symptom dimensions (factors) at onset of psychosis: Cognition, social withdrawal, antisocial behaviour, excitement, and reality distortion. At follow-up a five-factor solution was found, too, but different dimensions emerged: a positive, negative, excitement, cognitive, and anxiety/depression component which fits to the 5-factor model of White et al. (1997). The first psychotic episode of EOS is accompanied with more unspecific symptoms such as social withdrawal and antisocial behavior. In the later stages of (COS) the structure of symptom dimensions changes to that known from adult-onset schizophrenia (AOS). The results indicate that COS and AOS are comparable nosological entities and that more than 3 dimensions are required to describe the relevant clinical symptom structure. Positive and global symptoms decreased significantly during the course of illness. The frequencies of negative symptoms did not change which demonstrates their disabling impact.     

Symptom factors in early-onset psychotic disorders

OBJECTIVE: To examine the factor structure of symptom ratings in early-onset psychotic illnesses. METHOD: Subjects were drawn from a 2-year prospective study of early onset psychotic disorders. Principal components analysis with orthogonal (varimax) rotation was used to create factors from baseline ratings on the Schedule for Positive Symptoms, the Schedule for Negative Symptoms, and the Brief Psychiatric Rating Scale for Children. RESULTS: Youths with schizophrenia (n = 27), bipolar disorder (n = 22), and psychosis not otherwise specified (n = 20) were included. Four symptom factors were identified: negative symptoms, positive symptoms, behavioral problems, and dysphoria. Negative symptoms were predictive of the diagnosis of schizophrenia and treatment with antipsychotic medications. Neither behavior problems nor dysphoria were predictive of diagnosis. In subjects who completed follow-up assessments at year 1 (n = 49) and year 2 (n = 39), negative symptoms and behavioral problems predicted poorer functioning. CONCLUSIONS: The four factors are clinically relevant, with both treatment planning and prognostic implications. Negative symptoms best differentiated schizophrenia from the other disorders. Behavior problems and dysphoria were nonspecific problems that occurred in all three disorders, which likely leads to misdiagnosis in community settings.     

Factor versus cluster models of schizotypal traits. I: a comparison of unselected and highly schizotypal samples.

Factor analytic studies have long supported the division of schizophrenic symptoms into three relatively orthogonal factors: positive symptoms, negative symptoms, and disorders of relatedness/disorganization. Similarly, factor analyses of schizotypy often yield three factors: positive symptoms, negative symptoms, and social anxiety or disorganization. Recent cluster analyses, however, suggest that not all patients can be simply categorized according to these factors. Cluster analyses of schizotypal symptoms tend to result in clusters of individuals who are low in all factors, high in more than one factor, or high predominantly in one factor. The present study sought to compare factor and cluster models of schizotypal symptoms, as measured by the SPQ, PAS, and MIS, in unselected individuals and highly schizotypal individuals. Consistent with prior research, factor analysis of a large unselected undergraduate sample yielded three factors: "positive", "negative", and "disorganized." Factor analysis of schizotypal undergraduates produced the same three factors, plus a fourth designated "paranoid thinking." In contrast, cluster analysis of the unselected sample yielded four clusters ("low schizotypy", "average schizotypy", and "high schizotypy", plus "positive/disorganized"). Cluster analysis of the schizotypal subsample produced four clusters: "low schizotypy", "positive", "negative" and "high schizotypy."     

The timing of negative symptom exacerbations in relationship to positive symptom exacerbations in the early course of schizophrenia

Although positive and negative symptoms appear to represent independent symptom dimensions of psychopathology when evaluated cross-sectionally among individuals with schizophrenia, it is not known if exacerbations of symptoms on these two dimensions are independent. This prospective longitudinal study examined the temporal relationship between the positive and negative symptom exacerbations among 48 recent-onset schizophrenia or schizoaffective patients who received symptom ratings every 2 weeks on the Brief Psychiatric Rating Scale. Patients were followed for a period of at least 1 year and a mean of 3 years. To examine the temporal relationship between positive and negative symptoms, six time periods were defined in relation to psychotic exacerbation or relapse (e.g., prodromal, concurrent, post-psychotic) and used to compare the timing of positive and negative symptom exacerbations. A substantial proportion of patients had exacerbations of positive symptoms (77%) and negative (42%) symptoms. Negative symptom exacerbations occurred simultaneously with positive symptom exacerbations to a significantly greater extent than expected by chance, and occurred less frequently than expected by chance during the time period most temporally removed from positive symptom exacerbations. Results suggest that the timing of some negative symptom exacerbations is linked to that of positive symptom exacerbations during the early course of schizophrenia.