PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of schbulOxford JournalsContact UsMy BasketMy AccountSchizophrenia BulletinAbout this JournalContact this JournalSubscriptionsCurrent IssueArchiveSearch
 
Schizophr Bull. Jul 2010; 36(4): 788–799.
Published online Dec 18, 2008. doi:  10.1093/schbul/sbn167
PMCID: PMC2894588
Periods of Recovery in Deficit Syndrome Schizophrenia: A 20-Year Multi–follow-up Longitudinal Study
Gregory P. Strauss,13 Martin Harrow,2 Linda S. Grossman,2 and Cherise Rosen2
2Department of Psychiatry, University of Illinois Medical Center, Chicago, IL
3Maryland Psychiatric Research Center, University of Maryland School of Medicine, PO Box 21247, Baltimore, MD 21228
1To whom correspondence should be addressed; tel: +1-410-402-7879, fax: +1-410-402-6023, e-mail: gstrauss/at/mprc.umaryland.edu.
Periods of recovery were examined in patients with and without deficit syndrome schizophrenia. Fifty-six patients with schizophrenia were studied, 39 of whom were divided into deficit and nondeficit syndrome schizophrenia subtypes using a proxy method. We also studied 39 nonpsychotic depressive comparison patients. Patients were evaluated as part of the Chicago Follow-up Study, which prospectively examined patients at regular intervals over a 20-year period. Using standardized instruments, patients were evaluated for the deficit syndrome, global recovery, rehospitalization, social dysfunction, occupational disability, and symptom presentation. Recovery was examined at 6 time points measured at 2-, 4.5-, 7.5-, 10-, 15-, and 20-year postindex hospitalization. Cumulatively, over the 20-year period, 13% of patients classified as meeting criteria for the deficit syndrome showed 1 or more 1-year periods of global recovery, in comparison to 63% of nondeficit schizophrenia patients and 77% of depressed patient controls. Results indicate that the deficit syndrome represents a persistently impaired subsample of schizophrenia patients, with continuous social, occupational, and symptom impairment. In contrast, nondeficit syndrome schizophrenia patients showed at least some periods of remission or recovery, with the likelihood of these periods increasing as they became older. Findings provide further support for the validity of the deficit syndrome concept and suggest that deficit status is characterized by a more persistently impaired course of illness and particularly poor long-term prognosis.
Keywords: schizophrenia, deficit syndrome, negative symptoms, recovery, course, outcome
Negative symptoms have received a great deal of attention over the past several decades because they have been found to be associated with deficits in functional outcome, poor treatment response, and biological correlates that differ from other symptoms of schizophrenia.1 A factor complicating research in this area is that negative symptoms can be caused by a number of factors that result in varied manifestations of illness. In an attempt to address this issue, Carpenter et al2 proposed that negative symptoms could be viewed in relation to whether they are persistent vs transient, as well whether they are primary and idiopathic to the illness or secondary to factors other than the disease process (eg, medication effects, depression, and anxiety). Patients who display multiple negative symptoms that are considered to be both primary and enduring (>1 year) meet criteria for the deficit syndrome—a putative subtype within the broader diagnosis of schizophrenia.1,2 Support for this classification comes from numerous studies showing that the deficit and nondeficit forms of schizophrenia differ on several key domains, such as biological correlates, risk factors, and etiology (see Kirkpatrick1 for review). The deficit syndrome has also been found to be particularly resistant to current pharmacological and psychosocial treatments, which may at least in part be due to a symptom presentation and course of illness that differs from nondeficit schizophrenia patients.35
To date, few studies have examined the longitudinal course of the deficit syndrome. In the Chestnut Lodge study, Fenton et al6 examined the natural history of illness, symptom progression, and longitudinal course in a large sample of deficit and nondeficit patients. Results indicated that negative symptoms were readily present in deficit syndrome patients at disease onset and that these symptoms progressed in severity over the first 5 years of illness. At first admission, deficit syndrome patients were also found to be less psychotic than nondeficit patients, and psychotic symptom severity remained constant when reassessed at index admission 7.5 years later. However, disorganized symptoms showed a more variable pattern, where the severity of thought disorder and bizarre behavior was roughly equivalent to nondeficit patients at first admission but increased in severity for the deficit syndrome patients alone upon reevaluation 7.5 years later. These differences suggest that deficit syndrome patients may have a tendency to become increasingly disorganized over time; however, the linkage between negative and disorganized symptoms remains unclear. Differences were also noted between deficit and nondeficit patients with regard to long-term outcome, where deficit syndrome patients were found to have poorer social functioning, greater work disability, and poorer global clinical outcome than nondeficit patients when assessed 19-year postadmission. Additionally, 78% of deficit patients in the Chestnut Lodge sample showed a continuous course of illness with no remissions in comparison to only 28% of the nondeficit patients. Thus, the Chestnut Lodge findings suggest that within the diagnosis of schizophrenia, those patients who meet criteria for the deficit syndrome display a persistently impaired course of illness and particularly poor long-term outcome that is characterized by an increasing severity of negative and disorganized symptoms.
Similar findings have been reported by other studies examining the longitudinal course of the deficit syndrome using shorter follow-up periods. In the Suffolk County Mental Health Project,7 which examined the course of symptom progression and outcome in first admission patients, deficit syndrome patients also displayed a worsening of negative symptoms when evaluated 2-year postindex. Poorer psychosocial functioning and greater global impairment was also found for deficit relative to nondeficit patients, and deficit patients were rated as having lower scores on measures of psychosis, both at admission and at 2-year follow-up—a finding that has been replicated in other longitudinal studies.8,9 Studies examining the stability of deficit syndrome categorization, both through the gold standard Schedule for the Deficit Syndrome (SDS)10 and proxy case identification methods, have also found deficit diagnosis and negative symptom severity to be highly stable and that the severity of deficit syndrome symptoms may increase over time.8,9 Thus, patients who are identified as having the deficit syndrome relatively early in the course of the disorder continue to meet deficit syndrome criteria when reevaluated up to 5 years later; however, it is unclear whether the stability of deficit/nondeficit categorization and negative symptom severity continues indefinitely when patients are assessed at much longer follow-ups.
Nonetheless, in longitudinal studies investigating persistently impaired schizophrenia patients, the deficit syndrome appears to be associated with a particularly poor long-term outcome, a worsening of negative symptoms over time, and possibly an increasing severity of disorganized symptoms over time.69 These findings on the deficit syndrome are seemingly in contrast to more recent studies, indicating that at least some schizophrenia patients show improvement in symptoms and global functioning throughout the course of the disorder.1114 Studies by our group and others have suggested that good outcome and recovery are possible in schizophrenia and even provided evidence that over 40% of patients with schizophrenia show 1 or more periods of global recovery throughout the course of the disorder.15 In the past decade, the issue of functional outcome and recovery has become increasingly important in schizophrenia. As such, the President’s New Freedom Commission on Mental Health has called for a transformation of the mental health system to a more consumer- and family-driven, recovery-focused system. At present, it is not clear as to which characteristics predict which patients with schizophrenia do and do not have potential for periods of recovery. Given that deficit syndrome patients have been reported to display significant social, occupational, and symptom impairments and that these clinical domains are included in most operational definitions of recovery,1622 the deficit/nondeficit distinction may represent an ideal place to begin exploring major characteristics that predict recovery in patients with schizophrenia.
Although it seems plausible to expect that deficit syndrome patients would display fewer periods of recovery given their propensity for poor outcome and persistent symptoms, this is a matter that has yet to be empirically tested. Unfortunately, only limited predictions can be made regarding whether deficit patients would be at reduced likelihood of recovery given that most previous longitudinal studies of the deficit syndrome have used a retrospective design and generally included an overrepresentation of persistently impaired schizophrenia patients. Prospective longitudinal assessments following patients at multiple follow-ups at the same point in their course of illness would provide a more comprehensive examination of the course of functional outcome and symptom progression in deficit syndrome patients and could provide a highly inclusive examination of characteristics predicting recovery. In the current study, we examined symptom progression, functional outcome, and recovery in a sample of schizophrenia and nonpsychotic depressed comparison patients taken from the Harrow Chicago Follow-up Study. Analysis of this data set allows for a prospective multi–follow-up investigation of a group of relatively higher functioning schizophrenia patients (eg, over 40% had some college education—see “Methods” section) who were initially assessed early in the course of their disorder and then reassessed over 6 successive follow-up evaluations conducted over a 20-year period. We hypothesized that (1) deficit syndrome patients would show poorer social functioning, greater work disability, and a higher number of rehospitalizations in comparison to nondeficit patients and that these impairments would be stable over the course of the disorder, (2) deficit syndrome patients would show less severe psychotic and disorganized symptoms than nondeficit patients early in the course of the disorder; however, deficit patients would become increasingly disorganized with time, while nondeficit patients in contrast would show a reduction in symptom severity in later years, (3) deficit patients would show a greater severity of negative symptoms than nondeficit patients, and the severity of negative symptoms would remain constant or even increase for deficit patients over the 20-year period, and (4) deficit syndrome patients would display fewer periods of recovery than nondeficit patients at each of the 6 follow-ups over the 20-year period.
Participants
A sample of 95 patients, including 56 patients with schizophrenia and 39 nonpsychotic unipolar depressive comparison patients, were selected from the Harrow Chicago Follow-up Study (At the 20-year follow-up, 254 total combined schizophrenia and other patients were assessed, including 59 patients with schizophrenia. Of these 59 schizophrenia patients, 56 were included in analyses (95%) and 3 were excluded due to missing data [page 7].), a prospective multi–follow-up research program studying potential recovery, outcome, and course in patients with schizophrenia and mood disorders.15,22 The categorization of subjects into deficit and nondeficit categories reduced the sample of 56 schizophrenia patients to 39 subjects used in deficit-nondeficit comparisons. The initially young sample of patients recruited from private and public hospitals was assessed relatively early in the course of the disorder, at index hospitalization, and then reassessed prospectively over 6 successive follow-up evaluations conducted over a 20-year period. To get early young patients with no or only 1 hospital admission, patients under the age of 32 were recruited from inpatient and outpatient hospital settings, with a mean age of approximately 23 years. Evaluations were conducted at a mean of 2-, 4.5-, 7.5-, 10-, 15-, and 20-year postindex hospitalization. All patients were assessed at a minimum of 4 of the 6 follow-up periods. Patients were not sampled if complete data were not available. Thus, patients eliminated from the total sample cannot be compared with those included because they did not have complete data. The average patient had less than 1 follow-up period with missing data points. The mean number of missing follow-up periods per patient group was deficit = 0.78, range = 0–2; nondeficit = 0.54, range = 0–2; and depressed = 0.69, range = 0–2. The number of missing data points at each follow-up was consistent (ie, no significant differences) between deficit and nondeficit groups and between schizophrenia and depressive patients. Treatment data for schizophrenia patients at the 15- and 20-year follow-ups included percentage of patients on antipsychotics (15 year = 62%; 20 year = 56%); percentage of patients on other psychiatric medications but not antipsychotics (15 year = 5%; 20 year = 12%); percentage of patients in some form of treatment but not on medication (15 year = 8%; 20 year = 6%); and the percentage of patients not receiving any form of treatment (15 year = 26%; 20 year = 26%). The majority of the schizophrenia patients who were not on antipsychotic medications had dropped out of treatment.
Diagnostic and Statistical Manual for Mental Disorders, Third Edition diagnoses were based on 2 structured research interviews2325 conducted at index hospitalization. Interrater reliability for schizophrenia diagnosis was high (κ = 0.88). Interviewers performing follow-up evaluations were not informed of diagnosis or the results of previous follow-up evaluations. Informed written consent was obtained at index hospitalization and at each follow-up, and the research was approved by an Institutional Review Board.
Comparisons of demographic characteristics between schizophrenia and depressed patients at the time of hospital admission indicated no significant differences in age (schizopherenia [SZ]: mean [M] = 23.1, SD = 3.8; non-psychotic depression [DEP]: M = 23.86, SD = 4.6; F = 0.97, P = .33), parental socioeconomic class (based partly on education and occupational functioning of the patient’s parents26) (SZ: M = 3.22, SD = 1.5; DEP: M = 3.09, SD = 1.35; F = 0.23, P = .63), marital status (SZ: 82.1% never married; DEP: 68.4% never married; χ2 = 3.15, P = .21), or race (SZ: 62.5% Caucasian; DEP: 73.7% Caucasian; χ2 = 1.63, P = .14). However, group differences were found for sex (SZ: 64.3% male; DEP: 40.4% male; χ2 = 6.49, P < .01) and education (SZ: M = 12.41, SD = 1.92; DEP: M = 13.80, SD = 1.83; F = 15.2, P < .001), where schizophrenia patients were less educated and predominantly male, while depressed patients were more highly educated and predominantly female. Forty-one percent of schizophrenia patients had some college education, suggesting that the cohort is a relatively higher functioning sample of schizophrenia patients. The overall patient group was a relatively young sample, with over 50% having no previous hospitalizations and approximately 75% with 1 or no previous hospitalizations. Slightly over half of the schizophrenia patients went on to experience frequent psychotic activity.22
Deficit Syndrome Schizophrenia Classification
A total of 56 schizophrenia patients were divided into deficit and nondeficit syndrome schizophrenia subtypes using a proxy method. This proxy method was based closely after proxy tools developed in other studies that have used previously established data sets where it was not possible to use the SDS interview.10 Previous studies have developed case identification tools by examining the clinical content of assessments administered and selecting subscales that covered content necessary for the deficit syndrome diagnosis (ie, presence of 6 negative symptoms, which are both primary disease processes and stable over a period of 1 year). These proxy, case identification tools have approximated major prognostic features of the SDS, namely restricted affect and diminished emotional range, using data from the Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), Schedule for the Assessment of Negative Symptoms, or a combination of measures. Proxy tools were derived from a priori considerations and designed to approximate criteria for the deficit syndrome as identified using the SDS (ie, the enduring presence of 6 negative symptoms that are considered primary manifestations of the illness). Based upon tools such as the BPRS and PANSS, 2 of these 6 features can be approximated: restricted affect and diminished emotional range. Restricted affect on the SDS is roughly equivalent to the BPRS/PANSS blunted affect items, and diminished emotional range on the SDS overlaps considerably with the absence of emotional experience as measured by the BPRS/PANSS anxiety, guilt feelings, depressive mood, and hostility items. Thus, the proxy method allows for an identification of cases with the unique features of the deficit syndrome and a means of ruling out secondary negative symptoms and, therefore, offers a means of reducing heterogeneity related to primary and secondary negative symptoms. Such tools have been validated across numerous studies, and case identification properties have been found to be stable over time.9,27
The proxy method developed here was derived from 3 primary measures used in the Chicago Follow-up Study: Schedule for Affective Disorders and Schizophrenia (SADS),28 Katz Adjustment Scale (KATZ),29 and the Behavior Rating Scale (BRS) of the Psychiatric Assessment Interview.30 The proxy case identification tool was defined as the sum of standardized (z score) SADS anger, guilt, anxiety, and depression items, subtracted from the BRS-restricted affect score, which was calculated by adding the Blank Expressionless Face (B02) and Reduced Changes in Inflection of Voice (C02) items (ie, proxy = [BRS B01 + BRS C02] − [SADS guilt + SADS anxiety + SADS depression + SADS anger). Thus, similar to the BPRS method developed by Kirkpatrick et al,9 the case identification method used here has 2 parts: blunted affect and diminished emotional range. Using this method, higher scores reflect greater severity of deficit syndrome symptoms. In cases where SADS data used to index diminished emotional range was missing, values were replaced by KATZ anxiety, guilt, anger, and depression items. KATZ and SADS diminished emotional range summary score items were positively correlated (r = .69, P < .001).
A large number of studies have utilized proxy tools to identify deficit and nondeficit patients and found that these tools are capable of identifying a group of schizophrenia patients who display unique characteristics, thereby supporting the utility and validity of these procedures (eg, Subotnik et al,31,32 Cohen and Docherty,33 Cohen et al,34 and Messias and Kirkpatrick35). More recent studies have adopted a modified proxy procedure used to identify groups of deficit and nondeficit patients that more closely resemble patients identified using the SDS interview. In light of prevalence estimates showing that the deficit syndrome is found in approximately 20%–25% of outpatient schizophrenia samples, many studies using a proxy case identification tool have adopted the New Proxy for the Deficit Syndrome method developed by Kirkpatrick et al36 and identified the upper 25% of schizophrenia patients as representing the deficit syndrome. This procedure also eliminates the middle quartile of patients, which consist of a highly mixed group of deficit and nondeficit patients, and the inclusion of the bottom 2 quartiles, who represent a relatively pure group that display clinical and demographic characteristics consistent with nondeficit patients identified using the SDS. Following these procedures established by Kirkpatrick et al,36 we divided our schizophrenia sample in this manner to obtain a more homogeneous group of deficit and nondeficit patients. Of the 56 total schizophrenia patients, those patients with the highest 25% of proxy scores (n = 14) were considered deficit, the lowest 45% were nondeficit (n = 25), and the middle 30% (n = 17) were excluded. Thus, categorization resulted in the identification of 14 deficit and 25 nondeficit patients.
Follow-up Assessments
At each follow-up, ratings of psychosis, thought disorder/disorganization, and negative symptoms were obtained. Psychotic activity was assessed using total delusion and hallucination scores from the SADS. Hallucination and delusions scores ranged from 1 to 3 (1 = absent, 2 = weak or equivocal, and 3 = definitely present) and reflect psychotic activity during the month prior to evaluation. Negative symptoms were rated from the BRS, which was completed at the end of each clinical interview. Negative symptoms assessed by the interview included flat affect, poverty of speech, and psychomotor retardation/poverty. Intraclass correlations between raters were .96 for the poverty of speech scale, .86 for the flat affect scale, and .85 for the psychomotor retardation/poverty scale. Patients were also administered the Harrow Functioning interview,15,23 a semistructured clinical interview designed to assess global functioning and adjustment, symptoms, work and social functioning, family adjustment, and rehospitalization. Thought disorder/disorganization was assessed using a comprehensive index scored from a battery of 3 tests: the Gorham Proverbs Test,37 the Goldstein Scheerer Object Sorting Test,38 and the Comprehension subtest from the Wechsler Adult Intelligence Scale (WAIS).39 The concept of disorganized thought encompasses and is scored on the 3 tests based on qualities associated with disorganized thinking, such as loose associations, illogical thinking, incoherent speech, and bizarre or strange expressions. The scoring system is described in a detailed manual40 and has been used in a number of reported studies.4143
Global functioning was assessed using the Levenstein-Klein-Pollack (LKP)44 scale and the Strauss-Carpenter Scales (S-CS).45 Functional outcome was assessed using the 8-point LKP scale, which has been used previously by our group and others to assess global functioning and adjustment.44 Global outcome scores assessed by the LKP are based on the domains of work and social adjustment, level of self-support, life disruptions, symptoms, relapse, and rehospitalization. A global outcome score is obtained by combining ratings from these individual domains. LKP global outcome scores were highly correlated with total scores on the Global Assessment Scale (43) r = .85 (P < .0001), which is almost identical to the Global Assessment of Functioning score. Interrater reliability was high (r =. 92) for the 8-point LKP scale. Using the 8-point LKP scores, patient outcome was divided into 3 levels of functioning: (1) good global outcome, remission, or recovery during the follow-up year (LKP score of 1 or 2) indicating adequate or near-adequate functioning in all areas, (2) moderate impairment, indicating difficulties in some but not all areas of adjustment during the follow-up year (LKP scores of 3–6), and (3) poor outcome during the last year, indicating uniformly poor functioning, or poor functioning in almost all areas, including poor psychosocial functioning and severe symptoms (LKP scores of 7 and 8). To measure psychosocial and instrumental work functioning, we used the S-CS. The 5-point rating scales used for each subscale (scores range from 0 to 4) have consistently demonstrated high interrater reliability.
Operational Definition of Recovery
Although recovery is seen as an important topic, no single operational definition of recovery currently prevails. As such, a variety of procedures are being used by different investigators. However, the majority of procedures used to define recovery identify several instrumental factors, including the absence of major symptoms, adequate instrumental work functioning, and adequate psychosocial functioning.1622 The operational definition of recovery employed here has been used by our group in a series of other reported studies15,46,47 and is defined as: (1) the absence of major symptoms throughout the follow-up year (absence of psychotic activity and absence of negative symptoms), (2) adequate psychosocial functioning, including instrumental (or paid) work half-time or more during the follow-up year (a score of “2” or greater on the 5-point [0–4] S-CS for work adjustment), and the absence of a very poor social activity level (a score of 2 or greater on the 5-point Strauss-Carpenter Social Activity Scale), and (3) no psychiatric rehospitalizations during the follow-up year. Using this operational definition, meeting criteria for recovery at 1 follow-up does not automatically guarantee that a patient will meet criteria at later follow-ups. Rather, at each follow-up, recovery is likely to be influenced by a number of factors, such as the natural course of schizophrenia and treatment regiment. Thus, the index of recovery implemented in the current study provides data on (a) the percentage of patients meeting criteria for recovery at each follow-up year and (b) the cumulative percentage of schizophrenia patients who, over the 20 years, ever show a period of 1 or more years of recovery.
Data Analysis
Chi-square analyses were used in tests of categorical differences, which included our measures of recovery at individual follow-ups and 1 or more follow-up periods of recovery. One-way ANOVAs were used in analyses of continuous variables, such as our measures of symptom severity and outcome. Repeated-measures ANOVA was used to assess changes in symptom severity and functional outcome over time.
Validity of Deficit Syndrome Classification
Deficit and nondeficit groups were compared on demographic and clinical variables at the time of classification (ie, 4.5-year follow-up) to ensure validity of the deficit/nondeficit categorization (see table 1). Deficit and nondeficit patients did not differ on age, education, social class, race, or WAIS information subtest scaled scores. Deficit syndrome patients displayed significantly more severe negative symptoms and did not significantly differ from nondeficit patients on positive symptoms or thought disorder/disorganization, although deficit patients showed a trend toward having less severe positive symptoms and disorganization at the time of deficit syndrome classification. Additionally, both deficit and nondeficit patients had a higher proportion of male than female subjects and a higher frequency of never having been married than having been married at index. These clinical and demographic characteristics suggest that the deficit syndrome group identified is highly consistent with the original deficit syndrome conceptualization.1,2
Table 1.
Table 1.
Demographic and Clinical Data for Schizophrenia Patients at the Time of Deficit Syndrome Classification
Temporal Stability of the Deficit Syndrome
Deficit syndrome diagnosis was calculated separately at the 2-, 4.5-, 7.5-, 10- , 15-, and 20-year follow-ups to determine stability of the deficit-nondeficit syndrome classification. Results indicated that of the patients classified as deficit at the 4.5-year follow-up, 67% were also classified as being deficit at the 2-year, 71% at the 7.5-year, 70% at the 10-year, 67% at the 15-year, and 75% at the 20-year follow-up. These stability estimates, over a considerably longer time frame, are generally consistent with data reported by other studies using the proxy case identification method.8,9 Here, we have used the percentage of patients at each follow-up as a measure of stability; however, we acknowledge that other analyses, such as survival analysis, might provide additional information on the stability of individual patients.
Medication Pattern of Deficit and Nondeficit Syndrome Patients
A somewhat higher proportion of deficit patients were prescribed antipsychotic medications at each follow-up (eg, 15-year follow-up deficit = 70% on antipsychotics; nondeficit = 48% on antipsychotics; P = .26; 20-year follow-up deficit = 78% on antipsychotics; nondeficit = 48% on antipsychotics; P = .31); however, the differences were not significant (P > .10 at all follow-ups), and both groups showed a fluctuating pattern regarding the percentage of patients prescribed antipsychotics over the 20-year period. Very few deficit and nondeficit patients were prescribed antidepressants, and there were no significant differences with regard to the percentage of deficit and nondeficit patients prescribed antidepressant medications at any of the 6 follow-ups.
Diagnostic Differences in Symptom Severity at 6 Follow-ups Over 20 Years
Using flat affect scores as a dependent variable, results of a 2 (diagnostic group) × 6 (follow-up) repeated-measures ANOVA indicated a significant between-subjects effect of diagnosis, F1,30 = 26.7, P < .001 (η2 = .43), a nonsignificant within-subjects effect of time course, and a nonsignificant diagnosis × time course interaction. One-way ANOVA indicated that deficit syndrome patients exhibited significantly more flat affect than nondeficit patients at the 2- (F = 2.15, P < .05), 4.5- (F = 13.1, P < .001), 7.5- (F = 2.08, P < .05), and 15-year follow-ups (F = 2.53, P < .05).
For each of the variables of delusions, hallucinations, and disorganization, there were no significant differences for the main effects of diagnosis and time or the diagnosis × time interaction. Although differences did not reach statistical significance, the deficit patients showed a trend toward becoming slightly (although not significantly) more disorganized with time, while the severity of disorganization decreased at later follow-up periods among nondeficit patients.
Diagnostic Differences in Global Outcome at 6 Follow-ups Over 20 Years
Table 2 presents mean scores on global outcome for the 3 diagnostic groups at each of 6 follow-ups across a 20-year period. Using global LKP scores as a dependent variable, results of a 3 (diagnostic group) × 6 (follow-up) repeated-measures ANOVA indicated a significant between-subjects effect of diagnosis, F2,58 = 13.2, P < .001 (η2 = .38), as well as a significant within-subjects effect of time course, F5,58 = 2.31, P < .05 (η2 = .05). The diagnosis × time course interaction was nonsignificant. As can be seen in table 2, results indicate that at each of the 6 follow-ups spanning the 20-year period, deficit syndrome patients displayed poorer global outcome than nondeficit patients, who in turn had poorer global outcome than patients with depression.
Table 2.
Table 2.
Global Outcome for Patient Groups Across 6 Follow-up Intervals Spanning a 20-Year Period
Table 3 presents mean scores in employment, social functioning, and rehospitalizations for deficit, nondeficit, and depressed patients across the 6 follow-ups. Using Strauss-Carpenter Employment scores to assess work disability, the results of a 3 (diagnostic group) × 6 (follow-up) repeated-measures ANOVA indicated a significant between-subjects effect of diagnosis, F2,58 = 13.2, P < .001 (η2 = .38), nonsignificant within-subjects effect of time, and a significant time course × diagnosis interaction, F10,58 = 1.80, P < .05 (η2 = .08). One-way ANOVAs at each follow-up followed by post hoc Newman-Keuls tests indicated that schizophrenia patients displayed significantly greater work disability than depressed patients at each follow-up (P < .05), and deficit syndrome patients displayed greater occupational disability than nondeficit patients at all 6 follow-ups (P < .05). The magnitude of difference between deficit and nondeficit patients increased throughout the course of the disorder, with the greatest differences at the 15- and 20-year follow-ups.
Table 3.
Table 3.
Differences in Major Individual Areas of Functioning Across Diagnostic Groups
For both the Strauss-Carpenter Social Functioning and Rehospitalization scales, there were no significant differences for the main effects of diagnosis or time or for the diagnosis × time interaction. However, the between-subjects effect of diagnosis approached significance for rehospitalization, F2,58 = 2.83, P = .07 (η2 = .12). Although rehospitalization differences were not statistically significant, the pattern of means displayed among patient groups proved meaningful. Perhaps surprisingly, deficit syndrome patients showed fewer rehospitalizations than nondeficit patients at 5 of 6 follow-ups; however, these differences did not reach statistical significance (see table 3). Additionally, deficit syndrome patients had significantly fewer total hospitalizations across the course of illness than nondeficit patients (see table 1).
Diagnostic Differences in Periods of Global Recovery
Figure 1 presents the percentage of patients showing recovery for a year or longer across each of the 6 follow-ups. Chi-square analyses conducted at each of the 6 follow-ups indicated statistically significant differences in the rate of recovery among groups at the 2- (χ2 = 8.1, df = 2, P < .02), 4.5- (χ2 = 7.9, df = 2, P < .02), 7.5- (χ2 = 8.6, df = 2, P < .02), 10- (χ2 = 13.8, df = 2, P < .001), 15- (χ2 = 11.2, df = 2, P < .01), and 20-year (χ2 = 9.7, df = 2, P < .01) follow-ups. Differences between deficit and nondeficit syndrome schizophrenia patients were significant at the 10- (χ2 = 3.4, df = 1, P < .05), 15- (χ2 = 4.9, df = 1, P < .03), and 20-year (χ2 = 5.9, df = 1, P < .02) follow-ups. As can be seen in figure 1, results indicate that a smaller percentage of deficit syndrome patients than nondeficit patients or depressed patients were in recovery at each of the 6 follow-ups. Additionally, as can be seen in the figure, nondeficit patients are much more likely to recover later in the course of illness, with few patients meeting criteria for recovery prior to the 10-year follow-up; whereas deficit syndrome patients show low potential for a period of recovery early in their course and they show an even lower potential for a period of recovery later in their course. The lack of increased recovery over time in depressed patients can likely be attributed to these patients having relatively good outcome to begin with and that it would be hard for them to significantly improve over that baseline level.
Fig. 1.
Fig. 1.
Percentage of Patients in Recovery at each Follow-up Year.
Percentage of Patients Ever in Recovery Across 6 Follow-ups Over the 20-Year Period
The cumulative percentage of patients showing 1 or more periods of recovery over the 20-year period was also examined. Results indicate that significantly fewer nondeficit patients displayed at least 1 period of recovery over the 20 years in comparison to deficit patients, indicating that very few deficit patients show a period of recovery over the course of their disorder (χ2 = 9.7, df = 1, P < .01). Additionally, nonpsychotic depressed patients were significantly more likely to show at least 1 period of recovery than were schizophrenia patients, supporting numerous other reports indicating that the diagnosis of schizophrenia itself is associated with poorer outcome than nonpsychotic diagnoses (χ2 = 21.99, df = 2, P < .001) (see figure 2).
Fig. 2.
Fig. 2.
Percentage of Patients Ever in Recovery.
Diagnostic Differences in the Total Number of Follow-up Periods in Recovery
The mean total number of recovery periods experienced by deficit, nondeficit, and depressed patients over the 20-year period was also examined. Results indicate that depressed patients (M = 3.53, SD = 2.12) experience significantly more periods of recovery than schizophrenia patients (M = 1.08, SD = 1.70) (F = 27.9, P < .001). Within the schizophrenia groups, deficit syndrome patients experienced significantly fewer total periods of recovery than nondeficit patients, F1,36 = 15.65, P < .001. Deficit syndrome patients on average were unlikely to experience even 1 period of recovery over 6 evaluations spanning the 20-year period (M = 0.29), whereas nondeficit patients (M = 1.54) were found to be in recovery in approximately 1.5 of the 6 total follow-up periods.
To date, few studies have examined the course of psychopathology and long-term outcome in patients meeting criteria for deficit syndrome schizophrenia. Most longitudinal studies of the deficit syndrome have used a retrospective design and included an overrepresentation of persistently impaired, relatively older schizophrenia patients. To our knowledge, the current study is the first prospective multi–follow-up study examining clinical course and long-term outcome in the deficit syndrome and provides the longest spanning longitudinal data, with evaluations collected over a 20-year period. Additionally, our multi–follow-up research design has the advantage of identifying a relatively young, higher functioning sample of patients early in the course of illness and comparing them at the same points throughout the progression of the disorder. Using a longitudinal design permitted the presentation of data on several major areas that are of importance to understanding the course of the deficit syndrome, including: (1) the progression of psychotic, disorganized, and negative symptoms, (2) global outcome, (3) work disability, social dysfunction, and rehospitalization, (4) temporal stability of the deficit syndrome concept, and (5) periods of symptomatic and functional recovery.
Temporal Stability of the Deficit Syndrome Concept
Our data suggest that the proxy case identification method employed to identify deficit syndrome patients relatively early in the course of the disorder was predictive of later deficit syndrome diagnosis. Specifically, results indicate that of the schizophrenia patients classified as deficit, 71% were classified as deficit at the 7.5-year, 70% at the 10-year, 67% at the 15-year, and 75% at the 20-year follow-up. Deficit syndrome classification made using the proxy method that incorporated blunted affect and diminished emotional experience therefore appears to have good temporal stability. These results are generally consistent with several other studies examining temporal stability in the deficit syndrome, which have found reclassification rates to be quite high,8,9 and provide further support for the use of case identification tools in studies using established data sets where use of the gold standard SDS10 interview is not possible. Findings also provide additional support for the deficit syndrome concept as a reliable means of reducing heterogeneity in schizophrenia.
Symptom Progression
The progression of psychotic, disorganized, and negative symptoms was examined in deficit and nondeficit patients at 6 follow-up intervals over the 20-year period. Results indicated that deficit and nondeficit patients did not significantly differ with regard to the severity of hallucinations, delusions, or disorganization at each of the 6 follow-ups. Deficit syndrome patients do show a slightly, although not significantly, lower severity of delusions, hallucinations, and disorganized symptoms at earlier follow-ups; however, nondeficit patients show a relative decrease in symptom severity starting at the 15- and 20-year follow-ups, making these differences diminish in later years. These findings are consistent with both cross-sectional and longitudinal studies reporting that deficit patients either do not significantly differ from nondeficit patients or display a slightly lower severity of delusions, hallucinations, and disorganized symptoms than nondeficit patients (eg, Kirkpatrick et al,1,9 Fenton et al,6 Amador et al,8 and Strauss et al48), as well as long-term longitudinal studies indicating that deficit patients show increased levels of thought disorder and bizarre behavior in later years.6 The reason for this progressive worsening of disorganized symptoms in deficit syndrome patients is unclear. However, it may be that disorganized symptoms share some overlap with deficit symptoms and fluctuate in a similar course.6
There was a tendency for the severity of negative symptoms to be greater in deficit than nondeficit patients at each of the 6 follow-ups. These differences reached statistical significance at the 4.5-, 7.5-, and 15-year follow-ups. Unlike previous longitudinal studies,1,6,8,9 we did not find that negative symptoms progressed in severity in deficit patients. Rather, negative symptoms showed a fluctuating course, which was a pattern that also occurred in nondeficit patients. Discrepant findings between this and other studies may reflect differences in specific negative symptoms examined, as well as differences in patient characteristics, such as the inclusion of a more heterogeneous patient sample with a mixture of acute and persistently impaired schizophrenia patients.
Functional Outcome
Results indicated that deficit syndrome patients displayed poorer functioning on a multiyear basis than nondeficit schizophrenia patients and nonpsychotic depressives when patient groups were compared on a measure of global outcome. Although deficit syndrome patients displayed consistently poorer global outcome at each of 6 follow-ups, differences between schizophrenia groups did not become significant until the 15- and 20-year follow-ups. Much like symptom data, the pattern of differences observed for global outcome in later years can largely be attributed to nondeficit patients showing significant improvement at the 15- and 20-year follow-ups. Deficit syndrome patients displayed extremely poor global functioning that did not waver throughout the course of illness. Thus, deficit status appears to be associated with particularly poor long-term outcome.
Individual subscales from the S-CS were examined to determine whether deficit and nondeficit patients differed in individual areas of functional outcome. Work disability proved to be the area of functioning that best separated deficit and nondeficit patients. With regard to employment, deficit patients showed a level of work disability that was continuously more impaired than nondeficit patients at all 6 follow-ups; however, differences were most significant later in the course of illness when nondeficit patients showed marked improvement in vocational functioning.
The course of social dysfunction was somewhat more variable for both deficit and nondeficit patients. Both schizophrenia groups showed less social activity and poorer social functioning than depressed patients at each follow-up over the 20-year period. However, contrary to what might be expected, our sample of deficit patients was not consistently more impaired than nondeficit patients. In fact, deficit patients only showed poorer social functioning than nondeficit patients at 3 of the 6 follow-ups, and these differences did not reach statistical significance. However, social impairments were generally consistent in deficit patients and showed only minimal fluctuation across evaluations. Nondeficit patients on the other hand displayed a more variable trajectory of social dysfunction, such that their level of social activity and impairment fluctuated considerably throughout the course of the study.
Surprisingly, deficit syndrome patients had significantly fewer total hospitalizations than nondeficit patients and spent less time in hospitals at each evaluation except for the 2-year follow-up. However, the number of rehospitalizations experienced by deficit patients decreased rather dramatically after the 2-year evaluation and remained consistently low over the next 5 evaluations. Reduced rate of rehospitalizations seen in deficit patients does not appear to be a function of less severe psychotic symptoms because these are only marginally lower than nondeficit patients at early follow-ups and because psychosis scores are roughly equivalent at later follow-ups. It is more likely that the lower rate of rehospitalizations seen in deficit patients is due to having reduced social interactions and, thus, fewer opportunities for engaging in behavior that would require hospitalizations. The finding of decreased hospitalizations in the deficit syndrome can in some sense be seen as encouraging; however, this decrease does occur in the continuous presence of moderately severe symptoms and functional impairment. One possible explanation for this decreased rate of rehospitalization may therefore be that deficit patients display a rising “threshold of hospitalization.” In other words, after the first few years following initial hospitalization, it may take a significant increase in psychosis or disruption in activities of daily living to result in rehospitalization for deficit syndrome patients. Given that deficit patients display remarkably stable levels of symptoms, as well as functional impairment, they may, thus, fail to fluctuate enough to deviate from their typical presentation in a manner that would promote hospitalization. Whether this hospitalization threshold increases over time because deficit patients themselves and others within their social environment become habituated to the unwavering course of symptoms and functional impairment that affect deficit patients, or whether this phenomenon is better explained by a loss of hope in hospitalization producing a cure for the problems experienced by deficit syndrome patients, is an important question for future research that needs to be addressed.
Periods of Recovery
When an operational definition of recovery was employed that incorporates symptom severity, work disability, and potential rehospitalization, it became clear that schizophrenia patients show fewer periods of recovery than other psychiatric patients (see also Harrow et al15 and Grossmann et al46). However, on the positive side, many individuals with schizophrenia are capable of experiencing 1 or more periods of recovery over the natural course of their illness. We have previously reported that slightly over 40% of schizophrenia patients display 1 or more periods of recovery over a 15-year longitudinal period15 and that these rates are even higher for patients who leave treatment for a sustained period when they are compared with those who are treated.47 Data reported here extend this body of literature by comparing recovery in deficit and nondeficit syndrome schizophrenia patients.
In comparison to nondeficit patients, deficit syndrome patients were found to show fewer periods of recovery than nondeficit patients at all 6 evaluations conducted over a 20-year period, with differences reaching statistical significance at 4 of the 6 follow-ups. To better understand whether nondeficit schizophrenia patients show good outcome in comparison to other patients with psychiatric illness or whether these differences are only significant in relation to deficit syndrome patients alone, we also conducted comparisons between nondeficit schizophrenia and nonpsychotic depressed patients. These comparisons showed that that even though the nondeficit schizophrenia patients achieved better outcome than deficit syndrome patients, nondeficit schizophrenia patients still showed poorer outcome than less psychiatrically severe depressed patients. Thus, although nondeficit patients show some potential for recovery among schizophrenia patients, this potential is still lower than other psychiatric patients.
The data indicate that deficit patients are highly unlikely to show even 1 period of recovery (only 13%), whereas nearly two-thirds of nondeficit syndrome schizophrenia patients (63%) were in recovery at least at some point throughout the course of illness. Data also indicate that nondeficit patients are much more likely to recover later in the course of illness, with very few patients meeting criteria for recovery prior to the 10-year follow-up, whereas deficit syndrome patients show low potential for a period of recovery early in their course and they show an even lower potential for a period of recovery later in their course. It is important to note that these differences in recovery between deficit and nondeficit patients cannot be accounted for by a number of person-related factors (eg, sex, socioeconomic status, medication, and psychosis) that could influence recovery. Thus, there appears to be considerable hope for nondeficit syndrome schizophrenia patients who display potential for at least 1 or more periods of recovery; however, deficit syndrome patients seem to experience a particularly persistently impaired course of illness and are at greater risk for a very poor long-term prognosis.
To summarize, results do not paint an optimistic picture for deficit syndrome patients, indicating that they are more likely to experience a course of illness that is persistently impaired and have poorer long-term outcome than nondeficit patients. Specifically, when a group of schizophrenia patients with the deficit syndrome were compared with a demographically and clinically comparable group of nondeficit schizophrenia patients and nonpsychotic depressed controls, results indicated that deficit syndrome patients can be characterized as follows: (1) deficit patients evidence a persistently impaired course of psychotic and negative symptoms that remains moderate in severity throughout the course of illness, (2) there is a nonsignificant trend for deficit patients to become increasingly disorganized over time, (3) poor global outcome is evident early in the course of illness for deficit patients and more of them remain consistently impaired over time, (4) work disability is severe in deficit patients, who show limited capacity for vocational success, (5) rehospitalization rates are somewhat reduced in deficit syndrome patients, and (6) global recovery is seldom achieved among deficit patients and becomes even less likely later in the course of illness. Importantly, these results cannot simply be attributed to the deficit patients simply being more symptomatic than nondeficit patien1 but rather suggest that the unique features of the deficit syndrome are associated with poor outcome. The current results are limited by the relatively small sample of patients comprising deficit and nondeficit groups. Further studies are also needed to determine whether findings reported here changed at much longer follow-up periods. Nonetheless, these findings provide further validation of the deficit syndrome concept and additional support for the utility of the deficit vs nondeficit classification as a means of reducing heterogeneity in schizophrenia.
Funding
National Institute of Mental Health United States Public Health Service Grants (MH-26341 and MH-068688 to M.H.).
1. Kirkpatrick B, Buchanan RW, Ross DE, Carpenter WT., Jr A separate disease within the syndrome of schizophrenia. Arch Gen Psychiatry. 2001;58:165–171. [PubMed]
2. Carpenter WT, Heinrichs DW, Wagman AM. Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry. 1988;145:578–583. [PubMed]
3. Breier A, Buchanan RW, Kirkpatrick B, et al. Effect of clozapine on positive and negative symptoms in outpatients with schizophrenia. Am J Psychiatry. 1994;151:20–26. [PubMed]
4. Buchanan RW, Breier A, Kirkpatrick B, Ball P, Carpenter WT., Jr Positive and negative symptom response to clozapine in schizophrenic patients with and without the deficit syndrome. Am J Psychiatry. 1998;155:751–760. [PubMed]
5. Liberman RP, Mintz J, Zarate R. Comparison of efficacy of social skills training for deficit and nondeficit negative symptoms in schizophrenia. Am J Psychiatry. 1997;151:424–425. [PubMed]
6. Fenton WS, McGlashan TH, Victor BJ. Antecedents, symptom progression, and long-term outcome of the deficit syndrome in schizophrenia. Am J Psychiatry. 1994;151:351–356. [PubMed]
7. Kirkpatrick B, Ram R, Bromet E. The deficit syndrome in the Suffolk County Mental Health Project. Schizophr Res. 1996;22:119–126. [PubMed]
8. Amador XF, Kirkpatrick B, Buchanan RW, Carpenter WT, Jr, Marcinko L, Yale SA. Stability of the diagnosis of deficit syndrome in schizophrenia. Am J Psychiatry. 1999;156:637–639. [PubMed]
9. Kirkpatrick B, Buchanan RW, Breier A, Carpenter WT., Jr Case identification and stability of the deficit syndrome of schizophrenia. Psychiatry Res. 1993;47:47–56. [PubMed]
10. Kirkpatrick B, Buchanan RW, McKenney PD, Alphs LD, Carpenter WT., Jr The Schedule for the Deficit Syndrome: an instrument for research in schizophrenia. Psychiatry Res. 1989;30:119–123. [PubMed]
11. Liberman R, Kopelowicz A, Ventura J, Gutkind D. Operational criteria and factors related to recovery from schizophrenia. Int Rev Psychiatry. 2002;14:256–272.
12. Liberman R. Future directions for research studies and clinical work on recovery from schizophrenia: questions with some answers. Int Rev Psychiatry. 2002;14:337–342.
13. Russinova Z, Wewiorski N, Lyass A, Rogers E, Massaro J. Correlates of vocational recovery for persons with schizophrenia. Int Rev Psychiatry. 2002;14:303–311.
14. Spaniol L, Wewiorski N, Gagne C, Anthony W. The process of recovery from schizophrenia. Int Rev Psychiatry. 2002;14:327–336.
15. Harrow M, Grossman LS, Jobe TH, Herbener ES. Do patients with schizophrenia ever show periods of recovery? A 15-year multi-follow-up-study. Schizophr Bull. 2005;31:723–734. [PubMed]
16. Liberman R, Kopelowicz A. Recovery from schizophrenia: a challenge for the 21st century. Int Rev Psychiatry. 2002;14:245–255.
17. Robinson D, Woerner M, McMeniman M, Mendelowitz A, Bilder R. Symptomatic and functional recovery from a first episode of schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161:473–479. [PubMed]
18. Whitehorn D, Brown J, Richard J, Rui Q, Kopala L. Multiple dimensions of recovery in early psychosis. Int Rev Psychiatry. 2002;14:273–283.
19. Corrigan PW, Giffort D, Rashid F, Leary M, Okeke I. Recovery as a psychological construct. Community Ment Health J. 1999;35:231–239. [PubMed]
20. Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry. 1991;48:851–855. [PubMed]
21. Noordsy D, Torrey W, Mueser K, Mead S, O'Keefe C, Fox L. Recovery from severe mental illness: an intrapersonal and functional outcome definition. Int Rev Psychiatry. 2002;14:318–326.
22. Harrow M, Jobe TH. How frequent is chronic multiyear delusional activity and recovery in schizophrenia: a 20-year multi-followup. Schizophr Bull. 2008; Advance Access published on July 9, 2008. 10.1093/schbul/sbn074. [PMC free article] [PubMed]
23. Harrow M, Sands J, Silverstein M, Goldberg J. Course and outcome for schizophrenia vs other psychotic patients: a longitudinal study. Schizophr Bull. 1997;23:287–303. [PubMed]
24. Endicott J, Spitzer R. A diagnostic interview. Arch Gen Psychiatry. 1978;35:837–844. [PubMed]
25. Grinker R, Harrow M. Clinical Research in Schizophrenia: A Multidimensional Approach. Springfield, IL: Charles C. Thomas; 1987.
26. Hollingshead A, Redlich F. Social Class and Mental Illness. New York, NY: John Wiley and Sons; 1958.
27. Goetz RR, Corcoran C, Yale S. Validity of a ‘proxy’ for the deficit syndrome derived from the positive and negative syndrome scale (PANSS) Schizophr Res. 2007;93:169–177. [PubMed]
28. Endicott J, Spitzer RL. A diagnostic interview: the schedule for affective disorders and schizophrenia. Arch Gen Psychiatry. 1978;35:837–844. [PubMed]
29. Katz M, Lyerly S. Methods for measuring adjustment and social behavior in the community: I. Rationale, description, discriminative validity, and scale development. Psychol Rep. 1963;13:503–535.
30. Carpenter WT, Sacks MH, Strauss JS, Bartko JJ, Rayner J. Evaluating signs and symptoms: comparison of structured interview and clinical approaches. Br J Psychiatry. 1976;128:136–138. [PubMed]
31. Subotnik KL, Nuechterlein KH, Ventura J. MMPI discriminators of deficit vs. non-deficit recent-onset schizophrenia patients. Psychiatry Res. 2000;93:111–123. [PubMed]
32. Subotnik KL, Nuechterlein KH, Ventura J, Green MF, Hwang SS. Prediction of the deficit syndrome from initial deficit symptoms in the early course of schizophrenia. Psychiatry Res. 1998;80:53–59. [PubMed]
33. Cohen AS, Docherty NM. Deficit versus negative syndrome in schizophrenia: prediction of attentional impairment. Schizophr Bull. 2004;30:827–835. [PubMed]
34. Cohen AS, Docherty NM, Nienow T, Dinzeo T. Self-reported stress and the deficit syndrome of schizophrenia. Psychiatry. 2003;66:308–316. [PubMed]
35. Messias ED, Kirkpatrick B. Summer birth and deficit schizophrenia in the epidemiological catchment area study. J Nerv Ment Dis. 2001;189:608–612. [PubMed]
36. Kirkpatrick B, Amador XF, Flaum M. The deficit syndrome in the DSM-IV field trial: I. Alcohol and other drug abuse. Schizophr Res. 1996;20:69–77. [PubMed]
37. Gorham D. Proverbs test for clinical and experimental use. Psychol Rep. Monograph suppl 1. 1956:1–12.
38. Goldstein K, Scheerer M. Abstract and concrete behavior: an experimental study with special tests. In: Dashell JF, editor. Psychological Monographs. 1941; Vol 53 No. 2 (whole No. 239), S1–S151.
39. Wechsler D. Wechsler Adult Intelligence Scale Manual. New York, NY: Psychological Corporation; 1955.
40. Harrow M, Quinlan D. Disordered Thinking and Schizophrenic Psychopathology. New York, NY: Gardner Press; 1985.
41. Sponheim S, Surerus-Johnson C, Leskela J, Dieperink M. Proverb interpretation in schizophrenia: the significance of symptomatology and cognitive processes. Schizophr Res. 2003;65:117–123. [PubMed]
42. Harrow M, Grossman L, Silverstein M, Melter HY, Kettering RL, et al. A longitudinal study of thought disorder in manic patients. Arch Gen Psychiatry. 1986;43:781–785. [PubMed]
43. Holinger D, Shenton M, Wible C, et al. Superior temporal gyrus volume abnormalities and thought-disorder in left-handed schizophrenic men. Am J Psychiatry. 1999;156:1730–1735. [PMC free article] [PubMed]
44. Levenstein S, Klein D, Pollack M. Follow-up study of formerly hospitalized voluntary psychiatric patients: the first two years. Am J Psychiatry. 1966;122:1102–1109. [PubMed]
45. Strauss J, Carpenter W. The prediction of outcome in schizophrenia: I. Characteristics of outcome. Arch Gen Psychiatry. 1972;27:739–746. [PubMed]
46. Grossman LS, Harrow M, Rosen C, Faull R, Strauss GP. Sex differences in schizophrenia and other psychotic disorders: a 20-year longitudinal study of psychosis and recovery. Compr Psychiatry. 2008;49:523–529. [PMC free article] [PubMed]
47. Harrow M, Jobe TH. Factors involved in outcome and recovery in schizophrenia patients not on antipsychotic medications: a 15-year multifollow-up study. J Nerv Ment Dis. 2007;5:406–414. [PubMed]
48. Strauss GP, Allen DN, Duke LA, Ross SA, Schwartz J. Automatic affective processing impairments in patients with deficit syndrome schizophrenia. Schizophr Res. 2008;102:76–87. [PubMed]
Articles from Schizophrenia Bulletin are provided here courtesy of
Oxford University Press