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With the introduction of a clear definition of symptomatic remission from the Remission in Schizophrenia Working Group (RSWG), studies have sought to characterize cognitive functioning in remitted and non-remitted schizophrenia patients. However, most investigations of cognition and remission are cross-sectional or have studied samples of chronically ill patients. Therefore, the aim of this study was to compare cognitive performance between remitted and non-remitted first-episode psychosis (FEP) patients longitudinally. Seventy patients were categorized as remitted (n=17) or non-remitted (n=53) using the full RSWG criteria after being treated for approximately 15months, during which cognition was evaluated twice. Since our previous investigations in FEP have isolated verbal memory as a potential cognitive marker of symptomatic remission, analyses were limited to verbal, visual and working memory. We have found that non-remitted patients had a significantly worse verbal memory performance than remitted patients after 3months (F(1,68)=6.47, p=0.006) and 15months of treatment (F(1,68)=19.49, p<0.001). Visual memory was also significantly lower in non-remitted patients compared to those in remission but only at initial assessment (F(1,68)=8.21, p=0.003) while working memory performance was similar at both time points. Our findings suggest that verbal memory may be a specific and stable marker of clinical remission in FEP patients. This cognitive domain can easily be evaluated at treatment intake in the hope of identifying early on patients who are less likely to remit., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Although persistent negative symptoms (PNS) are known to contribute significantly to poor functional outcome, they remain poorly understood. We examined the heuristic value of various PNS definitions and their respective prevalence in patients with first episode psychosis (FEP). We also contrasted those definitions to the Proxy for the Deficit Syndrome (PDS) to identify deficit syndrome (DS) in the same FEP cohort., Methods: One hundred and fifty-eight FEP patients were separated into PNS and non-PNS groups based on ratings from the Scale for Assessment of Negative Symptoms (SANS). PNS was defined in the following ways: 1) having a score of 3 or greater on at least 1 global subscale of the SANS (PNS&#95;1); 2) having a score of 3 or more on at least 2 global subscales of the SANS (PNS&#95;2); and 3) having a score of 3 or more on a combination of specific SANS subscales and items (PNS&#95;H). For all three definitions, symptoms had to be present for a minimum of six consecutive months. Negative symptoms were measured upon entry to the program and subsequently at 1,2,3,6,9 and 12 months. Functional outcome was quantified at first assessment and month 12., Results: PNS prevalence: PNS&#95;1 (27%); PNS&#95;2 (13.2%); PNS&#95;H (13.2%). The prevalence of DS was found to be 3% when applying the PDS. Regardless of the definition being applied, when compared to non-PNS, patients in the PNS group were shown to have significantly worse functioning at month 12. All three PNS definitions showed similar associations with functional outcome at month 12., Conclusion: Persistent negative symptoms are present in about 27% of FEP patients with both affective and non-affective psychosis. Although there has previously been doubt as to whether PNS represents a separate subdomain of negative symptoms, the current study suggests that PNS may be more applicable to FEP when compared to DS. Although all three PNS definitions were comparable in predicting functional outcome, we suggest that the PNS definition employed is dependent on the clinical or research objective at hand.

Objective: In psychotic disorders, impairments in cognition have been associated with both clinical and functional outcome, while deficits in social cognition have been associated with functional outcome. As an extension to a recent report on neurocognition and short-term clinical outcome in first-episode psychosis (FEP), the current study explored whether social cognitive deficits could also identify poor short-term clinical outcome among FEP patients., Methods: We defined the social-cognition domain based on the scores from the Hinting Task and the Four Factor Tests of Social Intelligence. Data were collected in 45 FEP patients and 26 healthy controls. The patients were divided into good- and poor-outcome groups based on clinical data at six months following initiation of treatment. Social cognition was compared among 27 poor-outcome, 18 good-outcome, and 26 healthy-control participants., Results: Outcome groups significantly differed in the social cognition domain (z-scores: poor outcome=-2.0 [SD=1.4]; good outcome=-1.0 [SD=1.0]; p=0.005), with both groups scoring significantly lower than the control group (p<0.003). Moreover, outcome groups differed significantly only on the Cartoon Predictions subtest (z-scores: poor outcome=-2.7 [SD=2.7]; good outcome=-0.7 [SD=1.8]; p=0.001) among the five subtests used., Conclusions: Overall, social cognition appears to be compromised in all FEP patients compared to healthy controls. More interestingly, significant differences in social cognitive impairments exist between good and poor short-term clinical outcome groups, with the largest effect found in the Cartoon Predictions subtest.

Alterations of the fornix in chronic patients with psychosis are well established, but its integrity in the early stage of schizophrenia remains unknown. Thirty-two patients experiencing first-episode schizophrenia (FES) and 25 matched controls completed a DTI scan. DTI-tractography was used to estimate fractional anisotropy (FA) in bilateral fornices. The analysis showed significant overall FA reductions in the fornix in FES patients relative to controls. No significant correlations were found between FA values and clinical and sociodemographic data in FES patients. These findings revealed slight alterations along the fornix in early stage of schizophrenia., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Context: Memory is one of the cognitive functions most affected in schizophrenia, with deficits observed from the first episode of psychosis (FEP). Previous studies have indicated that some memory processes may be more affected than others., Objective: To examine the neural correlates of 3 specific memory processes in FEP by means of functional magnetic resonance imaging (fMRI)., Design: Case-control study., Setting: Prevention and Early Intervention Program for Psychoses of the Douglas Hospital and Montreal Neurological Institute, McGill University. Subjects Twenty-six patients with FEP and 20 healthy controls., Main Outcome Measures: Behavioral performance and regional brain activity measured during memory encoding by fMRI. Our fMRI design included 3 within-subject contrasts (associative vs item-oriented encoding, encoding of arbitrary vs semantically related image pairs, and successful vs unsuccessful memory encoding) that were then used for group conjunctions and between-group analyses., Results: Patients with FEP showed normal activation of several brain regions, including the prefrontal cortex, hippocampus, and parahippocampal cortex, during successful memory encoding and associative encoding. In contrast, the hippocampus and surrounding medial temporal areas showed reduced activity during the encoding of arbitrary pairs. This selective dysfunction reflected by abnormal brain activation during encoding was accompanied by a greater deficit for subsequent recognition of arbitrary pairs relative to the semantically related pairs., Conclusions: This study demonstrated that, in the same group of patients with FEP, the hippocampus could show either normal or abnormal modulation of activation depending on the specific cognitive process that was examined. The normal modulation of hippocampal activation observed during successful memory encoding in FEP argues against a general inability to recruit this region. Instead, the dysfunction was specifically linked to semantic relatedness. This selective deficit seems to affect memory performance in FEP and denotes an important representational problem that may confer greater vulnerability to psychotic disorders and would thus be interesting to examine in high-risk populations.

Objectives: Shorter duration of untreated psychosis (DUP) is often correlated with a poorer response to treatment. In this paper we test the hypothesis that the importance of DUP is moderated by early premorbid adjustment., Method: Three year prospective data were collected for 154 first episode patients. DUP, premorbid adjustment and symptoms were assessed at time of presentation for treatment and symptoms were reassessed after three years of treatment., Results: DUP was correlated with level of symptoms at three years only for patients with better premorbid adjustment in childhood and early adolescence., Conclusions: These results suggest that DUP may have more of an impact on treatment response for those with a less pernicious, more reversible form of illness.

Background: Social cognition is a complex phenomenon involving several distinct processes. Numerous studies have shown that individuals with schizophrenia are largely impaired on this domain of cognition. However, most have focused on a single aspect of social cognition, namely "theory of mind" and/or included patients with long standing illness., Objective: The main objective of the present study was to identify social cognition deficits in first episode of schizophrenia spectrum psychosis using a case control design and a comprehensive assessment that allowed the exploration of several dimensions of this phenomenon., Subjects: 36 patients with a first episode of psychosis and 25 healthy controls participated in this study., Material: Measures of social cognition included the Hinting Task and the Four Factor Test of Social Intelligence., Results: Significant group differences were found on both tasks, but the Four Factor Test of Social Intelligence revealed a stronger group effect and the effects observed remained significant once IQ was covaried. Social cognition did not show any correlations with level of symptoms., Conclusion: Social cognition deficits are present during the first episode of psychosis. These impairments do not seem to be a consequence of group differences in overall intellectual functioning and are likely to be state-independent.

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

The frequency of various early signs of illness was examined in 96 first-episode patients suffering from schizophrenia, schizoaffective, or schizophreniform disorder. A factor analysis of these early signs was performed, and each of the five dimensions identified was examined for its relation to symptoms of psychosis at presentation and after 1 year of treatment. The results suggested five primary dimensions of early signs: emotional dysphoria and odd perceptual and cognitive content, impaired functioning, changes related to psychobiological or vegetative functioning, suspiciousness accompanied by difficulties in concentration, and irritability/aggression. Impaired functioning in the prepsychosis period was associated with higher negative symptoms at presentation for treatment, and higher levels of psychobiological changes were associated with lower positive symptoms of psychosis after a year of treatment. The latter findings may indicate that patients with more profound indications of affective disturbance or stress have a better prognosis.

N-acetylaspartate (NAA) has been associated with neuronal integrity and function, and choline-containing compounds have been linked to neuronal membrane integrity. This study examined the influence of the duration of untreated psychosis, duration of prodromal symptoms and total length of untreated illness on these markers of neuronal loss or damage. In vivo 1H magnetic resonance spectroscopy data were acquired from 1.5-cc volumes in the left anterior cingulate and left thalamus of 19 never-treated first episode schizophrenic subjects using STEAM20 at 4.0 Tesla. Duration of untreated psychosis, prodrome and total length of untreated illness were correlated with levels of NAA and choline. No significant correlation was observed between NAA and duration of untreated psychosis and untreated illness in both regions examined. Thalamic NAA negatively correlated with duration of prodromal symptoms. A positive correlation between choline and duration of untreated psychosis was identified in both regions studied. Delays in treatment of psychotic symptoms of schizophrenia were not associated with a reduction in markers of neuronal integrity or function in contrast to longer prodromal periods, which were associated with lower NAA. Neuronal damage, potentially detectable via lower NAA, may be occurring before the onset of psychosis. Increased choline is associated with longer duration of untreated psychosis and could indicate that psychosis-related membrane alterations precede the appearance of NAA reductions observed by studies of chronic schizophrenia.

Patients with schizophrenia who show persistent negative symptoms are an important subgroup, but they are difficult to identify early in the course of illness. The objective of this study was to examine characteristics that discriminate between first-episode psychosis (FEP) patients in whom primary negative symptoms did or did not persist after 1 year of treatment. Patients with a DSM-IV diagnosis of FEP whose primary negative symptoms did (N = 36) or did not (N = 35) persist at 1 year were contrasted on their baseline and 1-year characteristics. Results showed that patients with persistent primary negative symptoms (N = 36) had a significantly longer duration of untreated psychosis (p < .005), worse premorbid adjustment during early (p < .001) and late adolescence (p < .01), and a higher level of affective flattening (p < .01) at initial presentation compared with patients with transitory primary negative symptoms. The former group also showed significantly lower remission rates at 1 year (p < .001). Multiple regression analysis confirmed the independent contribution of duration of untreated psychosis, premorbid adjustment, and affective flattening at baseline to the patients' likelihood of developing persistent negative symptoms. It may therefore be possible to distinguish a subgroup of FEP patients whose primary negative symptoms are likely to persist on the basis of characteristics shown at initial presentation for treatment.

Vulnerability-stress models suggest that training in specific stress management techniques should yield benefits to those suffering from schizophrenia and related disorders. In this paper, we describe an evaluation of the impact of adding a stress management program to other medical and psychosocial interventions for such patients. Outcomes were compared for 121 patients randomly assigned to receive either a 12-week stress management program with follow-up sessions or participation in a social activities group. The two treatment conditions did not differ in levels of symptoms, perceived stress or life skills immediately after completion of treatment or at 1-year follow-up. Patients who received the stress management program did have fewer hospital admissions in the year following treatment. This effect of stress management was most apparent for those who showed high levels of attendance for treatment sessions. It was concluded that training in stress management may provide patients with skills for coping with acute stressors and reduce the likelihood of subsequent acute exacerbation of symptoms with need for hospitalization.

This paper describes the cognitive functioning of a community cohort of individuals presenting with a first episode of a schizophrenia spectrum psychosis. Data were obtained for 107 patients (mean age 25 years) following stabilization of acute psychotic symptoms, mostly with the use of novel antipsychotics, on measures of intellectual, memory, attentional and executive functioning using a standardized battery of cognitive measures, including WAIS III and WMS III. While patients generally performed in the average range across the majority of measures, deficits (Z-scores >1.0 S.D.) were observed on measures of speed of information processing (PASAT, WAIS III) and executive functions (Stroop Test and Trails B), with the greatest deficits observed on tests of processing speed (PASAT). Discrepancy scores between the NART and the WAIS suggest subtle but statistically significant declines in full scale and performance IQ following onset of psychosis. Differences in cognitive functioning between diagnostic groups were not supported. Comparison of the highest and lowest functioning patients with respect to the cognitive measures also did not support any demographic or clinical differences between these two subgroups. Our results suggest a relatively benign cognitive profile in first-episode schizophrenia spectrum psychosis, regardless of diagnosis, when most potential incidence cases in the community are included. The most severe deficits reported were on measures of speeded information processing, and level of performance did not distinguish between patients demographically or clinically.

Objective: It has been hypothesized that patients with a diagnosis of schizophrenia who have a positive family history for schizophrenia will show greater reactivity of their symptoms to increasing levels of stress or negative affect than will patients without such a family history. In the past this hypothesis has only been tested through manipulations of negative affect in laboratory settings. In this paper we test this hypothesis using longitudinal clinical data., Method: Data were derived from an earlier longitudinal study using monthly assessments of daily stressors (Hassles Scale) and symptom measures (the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms). We compared longitudinal stress to symptom relations in 12 patients with schizophrenia for whom a positive family history of schizophrenia could be identified with 12 matched schizophrenic patients without any known family history of psychiatric illness., Results: There was evidence that patients with a family history of schizophrenia demonstrated a stronger relation between stress and total score on the Scale for the Assessment of Positive Symptoms. This difference appears to have primarily reflected a greater reactivity to stress of reality distortion symptoms in the positive family history group. The two groups did not differ in apparent reactivity to stress of the disorganization and psychomotor poverty dimensions of symptomatology., Conclusions: The results of this study provide support from a naturalistic, longitudinal clinical study for the hypothesis that reactivity to stress of some symptoms of schizophrenia may vary as a function of family history of the disorder.

Objective: A secondary analysis of our data to investigate if sex influences the specificity of the relationship between each of the 3 clinical syndromes (i.e., reality distortion, disorganization and psychomotor poverty) in schizophrenia and the neurocognitive functions that are thought to represent regional brain functions., Patients and Design: Fifty-seven male and 30 female patients with a DSM-III-R diagnosis of schizophrenia were rated on the Scale for Assessment of Negative Symptoms and the Scale for Assessment of Positive Symptoms to derive scores for psychomotor poverty, disorganization, and reality distortion syndromes. All subjects completed a battery of neuropsychological tests purported to assess functioning of left temporal, right temporal, left basal frontal, right basal frontal, and dorsolateral prefrontal cortex., Results: Correlation coefficients between syndrome scores and neuropsychological measures showed only word fluency (left frontal functioning) to have a statistically significant association with psychomotor poverty in women (p < 0.01). This relation was specific to psychomotor poverty syndrome. No relations between neurocognitive measures and symptoms were seen in men., Conclusions: The lack of specific relations between symptom dimensions in schizophrenia may be influenced by the fact that the neuronal circuitry associated with particular symptom dimensions may differ in men and women.

Objective: It has been suggested that level of cognitive functioning as assessed by formal neurocognitive tests may be as important as, or even more important than, symptoms in predicting level of community functioning for patients with schizophrenia. The results of past prospective studies, when carefully examined, do not consistently support this hypothesis. In the current study, the authors used symptom and neurocognitive data to predict subsequent level of functioning in the community., Method: Neurocognitive and symptom data collected as part of an earlier study were used to predict the community functioning of 50 patients with a diagnosis of schizophrenia. Using the Life Skills Profile, staff of a community mental health program assessed community functioning while blind to the earlier symptom ratings and neurocognitive performance., Results: Symptoms were more predictive of community functioning than were neurocognitive measures. Disorganization symptoms were generally more predictive of community functioning than was either psychomotor poverty or reality distortion., Conclusions: The results of this study and of previous longitudinal studies suggest the importance of using symptom levels after optimal treatment, rather than symptoms during acute episodes, as predictors of community functioning. They also indicate the need to evaluate the effects of treatment on disorganization as a separable dimension of symptoms.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

Background: In the past it has been postulated that dysphoric emotions may be related to positive and/or negative symptoms in schizophrenia. The results of several recent studies have suggested that composite dysphoria indices are more strongly related to positive than negative symptoms. In the current study we use part correlation techniques to examine the possible unique contributions of two aspects of dysphoria--depression and anxiety--to three syndromes of symptoms (reality distortion, disorganization and psychomotor poverty) within schizophrenia., Methods: Data were obtained from 60 patients with a DSM-III-R diagnosis of schizophrenia. Symptoms of schizophrenia were assessed using the SAPS and SANS and dysphoria was assessed using both self-report (BDI and BAI) and observer ratings (HRSD and HARS). Assessment of schizophrenia symptoms and ratings of depression and anxiety were completed by different observers. In addition, drug induced extrapyramidal side effects were rated., Results: Part correlations showed that unique aspects of anxiety (particularly physiological arousal) were correlated with reality distortion while unique aspects of depression (including psychomotor slowing and loss of social interest) were related to psychomotor poverty. At least part of the latter relationship may be due to extrapyramidal side effects of neuroleptic medication., Conclusions: Although there is considerable overlap between anxiety and depression, it appears that the unique arousing or activating aspects of anxiety are related to the experience of reality distortion symptoms in schizophrenia and the unique slowing and withdrawal aspects of depression are particularly related to psychomotor poverty. Possible reasons for these relationships are discussed.

Background: Frith et al (1995) and others have hypothesised that disruptions in the connection between left frontal and temporal areas of the brain are a central deficit in schizophrenia. In this paper we examine whether such connectivity as assessed by EEG coherence is related to level of symptoms in patients with schizophrenia., Method: For 73 patients with schizophrenia, assessment of the EEG coherence between frontal and temporal regions were carried out under conditions of activation by a mathematical task, and between frontal and occipital regions when performing a visuo-spatial task. We then examined the relationship between these coherence measures and the reality distortion, disorganisation and psychomotor poverty dimensions of symptomatology., Results: Only left frontal-temporal connectivity was found to have a significant negative relationship to symptomatology. This relationship was, however, specific to reality distortion rather than to symptoms of disorganisation or psychomotor poverty, and may be more characteristic of males than females., Conclusions: Disruption of frontal-temporal connectivity appears to have a specific relationship to reality distortion symptoms in schizophrenia.

Background: On the basis of Liddle's three-syndrome model of schizophrenia, it was predicted that: (1) symptoms of psychomotor poverty would be particularly correlated with impaired performance on neuropsychological tests likely to reflect functioning of the dorsolateral prefrontal cortex; (2) disorganisation would be particularly correlated with impaired performance on tests sensitive to medio-basal prefrontal functioning; and (3) reality distortion would be particularly correlated with measures sensitive to temporal lobe functioning., Method: The above hypotheses were tested on 87 subjects with a confirmed diagnosis of schizophrenia. Patients' symptoms were scored for each of the three syndromes. Patients completed six neuropsychological tests designed to measure impairment in specific areas of the brain., Results: There was no support for the first two hypotheses. There was, however, evidence of a specific relationship between reality distortion and neuropsychological performance usually considered to be related to left temporal lobe functioning., Conclusions: Although not directly supporting the first two hypotheses; the results are, in general, consistent with there being different cortical-subcortical circuits associated with each of psychomotor poverty and disorganisation. Temporal lobe functioning appears to have particular significance for the reality distortion syndrome.

Objective: To review the data and discuss clinical recommendations for treating negative symptoms of schizophrenia. Negative symptoms (e.g., poverty of thought, affective blunting) have been regarded as part of schizophrenia since Kraepelin's early descriptions, although they remain a subject of controversy. For example, it is unclear if negative symptoms are distinct from other psychiatric symptoms such as depression, or are in actuality depression within schizophrenia. Recent evidence suggests that negative symptoms are independent of depression., Method: Factor analytic studies have suggested that a negative factor (loss of affect, volition, poverty of thinking) may be distinguished from other components and is separable from a depression factor. Experimental use of vignettes have also been useful in the assessment of negative symptoms. A second controversial area is whether or not the presence or absence of affect is the fundamental issue separating schizophrenia from other psychoses., Results: A continuum of psychosis has been hypothesized, with unipolar psychotic depression at one pole and schizophrenia with defect state at the other. Within this proposed continuum, negative symptoms are associated only with schizophrenia without affect and with defect state schizophrenia. As such, variation in affect could be a primary determinant of the type of psychosis., Conclusion: It appears that negative symptoms are a distinct aspect of schizophrenia and may aid in our understanding of psychotic disorders.

Background: There has been evidence that psychopathology in schizophrenia consists of three separable syndromes: reality distortion, disorganisation, and psychomotor poverty. The objective of this study was to explore the relationship between planning and execution of movement and each of the syndromes in schizophrenia., Method: Twenty-one right handed DSM-III-R schizophrenic patients performed a total of 80 trials of a motor movement task, varying distance of movement x size of the target x hand. Times taken to plan the movement (RT) and to carry it out (MT) were examined for their relationship with contemporaneous as well as lifetime profiles of the three syndromes in schizophrenia., Results: Significant correlations are reported between RT and current as well as lifetime measures of disorganisation syndrome. Somewhat weaker correlations are reported between RT and psychomotor poverty, but only for the right-handed tasks. Partial correlations suggest that the influence of neuroleptic medication explains all but one of the correlations between psychomotor poverty and RT, but does not account for the relationship between disorganisation and RT. No other relationship emerged between any of the movement and symptom measures., Conclusions: These findings indicate that dysfunction in movement planning is related primarily to concurrent disorganisation, as well as to the prominence of disorganisation over the patient's history.

In examining the heterogeneity of symptomatology in schizophrenia, several theoretical models have been advanced. These models are useful in understanding the psychopathology of the disease, as well as possibly guiding treatment and determining prognosis. This paper discusses the two-syndrome and three-syndrome models for the primary symptoms of schizophrenia and their relationship to other symptoms often encountered. In addition, their significance and relevance for treatment are explored.

It is often stated that there are identifiable prodromal symptoms of psychosis in patients suffering from schizophrenia. In this article, we review the evidence for the existence of such prodromal symptoms. Computerized and direct searches of the psychiatric literature were conducted to identify relevant reports. The methods and findings of the studies were then examined for their relevance to several issues concerning prodromal symptoms. We found that very few studies have directly assessed the relationship between putative prodromal symptoms and the exacerbation of psychosis. The research that has been reported suggests that prodromal symptoms have only modest power as predictors of relapse. It appears that while some individual schizophrenia patients may show reasonably consistent patterns of prodromal symptoms, such symptoms are probably of limited general value in predicting psychosis. Two particular issues that warrant further investigation are individual differences in patterns of prodromal symptoms and the extent to which such symptoms actually precede changes in level of psychosis.

There has been very little research on the ability of a measure of daily stressors such as the Hassles Scale to predict symptomatology in schizophrenia. We examined this issue in a group of 55 outpatients with a DSM-III-R diagnosis of schizophrenia. The patients were assessed on a monthly basis for a minimum of 12 months. The Hassles Scale was used to assess daily stressors and the indices of symptomatology included the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, the Beck Depression Inventory, the Self-Evaluation Questionnaire, and the General Health Questionnaire. Longitudinal data on the relationship between Hassles score and symptomatology were analyzed for each patient. Statistically significant correlations of symptoms with stressors for the previous month were found in a greater number of patients than would be expected by chance. There was some reduction in the number of significant correlations when the possible role of prior symptomatology was statistically controlled for.

This paper describes a prospective study of the relationship between non-psychotic prodromal symptoms and psychotic symptoms in 55 schizophrenic (DSM-III-R) out-patients. Once a month, a number of non-psychotic symptoms generally regarded as prodromal symptoms in schizophrenia were assessed, as well as psychotic symptoms, with standardised self-administered instruments and rating scales for a minimum of 12 months (range 12-29). The data were analysed for each patient using a longitudinal correlational design with a 1-month lag between the prodromal and psychotic symptoms over the total period. Results showed that in less than one-fifth of subjects did any of the prodromal symptoms, individually or in combination, show a significantly positive correlation with the subsequent level of psychotic symptoms. Such relationships were significant in an even smaller proportion of subjects when the confounding effect of concurrent psychotic symptoms on prodromal symptoms was partialled out. High levels of prodromal symptoms appeared to have adequate specificity but low sensitivity in their power to predict high levels of subsequent psychotic symptoms. There were no differences in age, gender, medication levels, and the number of previous admissions between the subjects who did or did not show a relationship between putative prodromal symptoms and psychotic symptoms.

Monthly assessments of depression, anxiety, and positive and negative symptoms of schizophrenia were performed on 52 schizophrenic patients over periods ranging from 12 to 29 months. Data were analyzed to assess the extent to which symptoms of dysphoria (anxiety and depression) were more strongly related to negative or positive symptoms of schizophrenia. Consistent with past research using comparisons across subjects, the current longitudinal data show that there is a more consistent relationship between dysphoria and positive rather than negative symptoms.

Fifty-nine DSM-III-R schizophrenic outpatients were assessed for positive and negative symptoms using Andreasen's Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). Reevaluation of these patients 12 months later revealed a moderate degree of stability for both SAPS and SANS total scores and most of their subscales. Only the subscale scores for apathy and bizarre behaviour failed to show a significant correlation in stability in 12 months. The results are discussed in the context of the reported literature.

One hundred and fifty-five DSM-IIIR schizophrenic patients were assessed for positive and negative symptoms using Andreasen's Scale for Assessment of Positive Symptoms (SAPS) and the Scale for Assessment of Negative Symptoms (SANS). Interrelationships of individual positive and negative symptoms were examined using a factor analysis. Results of the factor analysis are consistent with Liddle's proposition that there are three syndromes underlying symptomatology in schizophrenia: disorganization; psychomotor poverty and reality distortion.

Empirical research concerning the relationship between life event stressors and schizophrenia is critically reviewed. In accordance with the view that patients suffering from schizophrenia are vulnerable to stress, there is evidence of a relationship between stressors and variation in severity of symptoms over time. There is less indication that schizophrenic patients have had higher levels of stressors than the general population or than patients suffering from other psychiatric disorders. These findings are consistent with vulnerability-stress models of the development of schizophrenia.

Research on the relationship between stress and schizophrenia is fraught with conceptual and methodological problems. These problems include issues related to the nature and measurement of stress, the likelihood of reciprocal influences between stress and symptoms, and the adequate assessment of symptoms. Several recommendations are made regarding future research in this area. These include using multiple and broadly based measures of different types of stressors and symptoms, greater use of truly prospective research designs, and the evaluation of the effects of interventions specifically designed to reduce stress in patients who suffer from schizophrenia.

The relationships between depression, anxiety and positive and negative symptoms of schizophrenia were examined in a study of 95 schizophrenic patients who were receiving out-patient care. Various measures of depression and anxiety showed a pattern of interrelationships which suggested that they were measuring a general state of dysphoria rather than separate dimensions of anxiety and depression. Dysphoria was found to be more reliably related to level of positive symptomatology than to negative symptoms.

The relationship of major life events and daily stressors to subjective stress was investigated in outpatients suffering from schizophrenia. Daily stressors or hassles were found to be more predictive of subjective stress than were major life events. These findings were not influenced by whether a cross sectional or prospective analysis was used. The implications for future research on stress and schizophrenia are discussed.

The relationship of the Five Minute Speech Sample (FMSS) to the Camberwell Family Interview and its coding system were evaluated. The Camberwell Family Interview and the FMSS were administered to twenty-three relatives of patients diagnosed with schizophrenia. Overall, the results supported the utility of the FMSS and its coding system as a brief screening device for measuring expressed emotion.

The relationship of the Camberwell Family Interview (CFI) with two self-report scales purported to measure levels of expressed emotion was assessed. Fifteen schizophrenic patients and 22 of their relatives completed the Level of Expressed Emotion Scale (LEE) and the Influential Relationships Questionnaire (IRQ). The relatives of patients also participated in Camberwell Family Interviews (CFI). Results supported the value of the self-report measures in evaluating the affective environment of patients with schizophrenia.