Associations Between Cognitive Function, Schizophrenic Symptoms, and Functional Outcome in Early-Onset Schizophrenia with and Without a Familial Burden of Psychosis

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Isr J Psychiatry Relat Sci - Vol. 52 - No 3 (2015) Associations Between Cognitive Function, Schizophrenic Symptoms, and Functional Outcome in Early-onset Schizophrenia With and Without a Familial Burden of Psychosis

Beata Hintze, PhD, 1 and Alina Borkowska, PhD2

1 Institute of Applied Psychology, Faculty of Applied Social Sciences, Maria Grzegorzewska Academy of Special Education, Warsaw, Poland. 2 Department of Clinical Neuropsychology, Nicolaus Copernicus University, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland

Conflict of interest – The authors declare no conflicts of interest. This study was sponsored by the Maria Grzegorzewska Academy ABSTRACT for Special Education through a statutory grant to the author BW 01/09-III. Objective: The purpose of the present study was to assess the relationship between various domains of cognitive functions, the intensity of psychopathological symptoms, INTRODUCTION and the general functional outcome in adolescents with Schizophrenia is considered a severe psychiatric neuro- early-onset schizophrenia. developmental disorder with numerous structural and Method: 33 adolescents with early-onset schizophrenia functional brain changes, mostly in the prefrontal cortex. (EOS) were investigated in their partial symptom These abnormalities result in cognitive disturbances, remission period. The control group consisted of 30 especially with regard to working memory and executive healthy adolescents. Schizophrenia was diagnosed on functions, and are considered to be the core and enduring the basis of ICD-10 criteria. Psychopathological symptoms deficits in schizophrenia (1, 2). It has been found that were assessed with the use of the PANSS (Positive and cognitive dysfunctions are associated with a poor general Negative Symptoms Scale) scale. General functioning functional outcome in patients with schizophrenia (3, 4). was evaluated with the use of the CGAS (Children’s Global Early-onset schizophrenia (EOS) is defined as schizo- Assessment Scale) scale. phrenia with an onset before 18 years of age. A comparison of the course of illness in EOS and AOS (adult-onset Results: Significant dysfunctions of various aspects schizophrenia) shows that early-onset schizophrenia is of working memory, executive functions, and verbal characterized by a higher rate of various developmental memory were found in the group of EOS adolescents, brain abnormalities and premorbid disturbances, a greater as compared to the control group. Working memory intensity of negative symptoms, worse performance in and executive function deficits were significantlymore neuropsychological tests, and poorer functional outcome, severe in patients with a greater intensity of negative also with regard to social skills (5-9). Furthermore, EOS schizophrenia symptoms. EOS patients with a familial patients exhibit numerous neurodevelopmental problems burden of psychosis presented greater cognitive deficits in childhood, especially psychomotor retardation (includ- than patients without such a burden. ing delayed walking), worse visuospatial coordination, Conclusions: These data suggest that visual working stereotyped movements, language and speech disorders, memory and verbal memory deficits with a higher including delayed speech, and inferior psychosocial intensity of negative and positive symptoms proved to abilities, such as social isolation and withdrawal. These be significant predictors of poor functioning. Limitations problems are usually associated with worse academic of the study are discussed. performance. Patients with early-onset schizophrenia, as compared to their healthy peers, perform lower on tests

Address for Correspondence: Beata Hintze, PhD, The Maria Grzegorzewska Academy of Special Education, ul. Szczesliwicka 40, 02-353 Warsaw, Poland. [email protected]

6 BEATA HINTZ AND ALINA BORKOWSKA measuring verbal, visual and working memory, atten- (1, 2, 6, 11). As to clinical symptoms, both positive and tion and concentration, conceptual thinking, as well as negative symptoms were described as more severe in visuospatial and visuomotor coordination. Their global EOS than in AOS patients (29). level of intelligence tends to be lower compared to healthy We hypothesize that cognitive deficits, especially individuals. Cognitive performance of EOS patients is in various modalities of working memory and verbal usually 2-3 standard deviations (SD) below the results of memory, together with a higher intensity of psycho- average healthy subjects (10-14). Current research using pathological symptoms, both positive and negative, the MATRICS test battery showed that adolescents with might be considered as significant predictors of poor schizophrenia spectrum disorders present significantly global functioning of EOS patients in the remission lower abilities in most cognitive domains, except social period. cognition tasks, in comparison with healthy controls. These differences are the greatest with regard to working memory as well as verbal and visual learning. Cognitive METHODS performance of patients ranges between 0.8 and 1.8 SD below the healthy population (15). However, studies PARTICIPANTS among patients with first-episode psychosis showed that PATIENT GROUP patients with EOS, as compared to adolescent patients The study examined 33 adolescent patients with early- with other (non-organic, non-affective) psychoses, may onset schizophrenia: 13 females and 20 males, aged have more global IQ deficits when examined directly 15-19 (mean 17.4 ± 1.2 SD). The inclusion criteria after the onset of illness (16). comprised a diagnosis of EOS (according to ICD-10 Moreover, the results of some studies indicate worse criteria) in at least a partial remission of the illness with cognitive functioning, especially with regard to visual- pharmacotherapy in outpatient clinics or rehabilitation motor coordination and attention in schizophrenic centers. Thirty-six percent of adolescents with schizo- patients with psychotic symptoms in first-degree rela- phrenia had a familial burden of psychosis, i.e., their tives as compared to patients without a family history first-degree relatives had been diagnosed with psychotic of psychosis (17). disorders. The exclusion criteria contained current or Many studies reported the relationship between cogni- past psychoactive substance abuse, a diagnosis of mental tive deficits and the intensity of negative symptoms to retardation according to ICD-10 criteria, pervasive be the most predictive variable of functional outcome, developmental disorders, and serious neurological or including social skills, school or work performance, and somatic disorders. independent living in adult-onset and chronic All patients were treated with second generation anti- schizophrenia (18-21). psychotics (olanzapine, risperidone, quetiapine, clo- In the case of EOS patients, the results are not as con- zapine) administered in a stable standard daily dosage. clusive. Some studies established an association between Sixteen patients were in monotherapy, and 17 received several cognitive deficits and worse general functional polytherapy (a combination of two atypical neuroleptics). outcome, including social and daily living skills (22-25). CONTROL GROUP Other research indicates that positive and/or only negative The control group consisted of 30 healthy adolescents symptoms as such are the crucial predictors of general whose age, sex and education (number of completed years functional outcome in EOS (9, 26-28). However, it is still of schooling) matched (one to one) the EOS patients. unclear which particular cognitive dysfunctions might There were 13 females and 17 males aged 15-19 (mean age serve as good predictors of global functioning in EOS. 17.0 ±1.3 SD). All the healthy adolescents were recruited Therefore, the aim of this study was to assess the relation- from schools in the same area where the patients from the ship between chosen parameters of selected cognitive experimental group lived. The exclusion criteria for the domains - working memory, executive functions, verbal control group were as follows: current or past psychoac- memory and learning, and the intensity of symptoms tive substance abuse, a diagnosis of mental retardation (both positive and negative) as well as global functional according to ICD-10 criteria, pervasive developmental outcome in patients with an early onset of schizophrenia. disorders, serious neurological or somatic disorders, and The above mentioned cognitive domains are regarded positive family history of psychiatric illnesses (psychiatric as the most important deficits in EOS as well as in AOS disorders in first-degree relatives).

7 COGNITION, SYMPTOMS AND FUNCTION IN EARLY SCHIZOPHRENIA

ETHICAL ISSUES the time of performance (in seconds) and the number The study complied with the ethical standards laid down of incorrect responses (35), according to the Polish in the 1964 Helsinki Declaration. The design of the study validated version (36). Rey’s Auditory Verbal Learning was approved by the Ethics Committee of the Academy Test (RAVLT) was used for the measurement of memory of Special Education in Warsaw. Participation in the abilities. The following parameters were assessed: general investigation was voluntary. All adolescents (patients and number of words recalled in five repetitions (immedi- control group members) and their parents or legal guard- ate memory) and the number of words recalled after a ians signed an informed consent. All individuals taking 20-minute delay period (delayed memory) (37), accord- part in the study were informed of their right to withdraw ing to the Polish validated version (38). their consent at any time, without consequences. Statistical calculations were performed with the use of STATISTICA 7 software. The Student’s t-test was used to PROCEDURE evaluate the differences in means between the two groups. The diagnosis of EOS and the evaluation of the intensity For comparisons between schizophrenic patients with and of psychopathological schizophrenia symptoms were without a familial burden of psychosis the Mann-Whitney carried out by psychiatrists before neuropsychological U test was used (because the data did not meet the para- testing. Psychosocial functioning and neuropsychological metric analysis criteria). The correlation coefficients were assessment of each subject was conducted by the authors computed using Pearson correlations between the results of during one individual session, with breaks when needed. neuropsychological tests, clinical data, and C-GAS scores. The patients were tested in an outpatient clinic or in a To establish the predictive capacity of the cognitive and rehabilitation center, while the controls were investigated clinical variables on the functioning domains, a regression at their schools or in the Academy of Special Education model was fitted using the forward stepwise method. Those in Warsaw. variables which showed a significant correlation with the C-GAS score were included as potential predictors. INSTRUMENTS Significance was set at p<0.05. The assessment of schizophrenic symptoms (positive, negative, and general psychopathology) was conducted with the Polish validated version (30) of the Positive and RESULTS Negative Symptoms Scale (PANSS) (31). Psychosocial functioning was evaluated with the Children’s Global SAMPLE CHARACTERISTICS Assessment Scale (CGAS) (32) translated into Polish The demographic and clinical characteristics of the sample with the author’s consent. are shown in Table 1. There were no significant differences For the evaluation of selected cognitive domains a in age and educational attainment (years of schooling) battery of neuropsychological tests was used. Executive functions and working memory were assessed with Table 1. Demographic and clinical characteristics of EOS patients and controls the Wisconsin Card Sorting Test (WCST) (the CV 4 EOS patients N=33 Controls N=30 test computer version by Heaton) (33). The following Demographic and parameters were taken into account: percentage of perse- clinical characteristics Mean (SD) Mean (SD) t-value Age 17.4 (± 1.2) 17.0 (±1.3) 1.06 verative and nonperseverative errors, percentage of total Education (years) 9.7 (± 0.9) 9.8 ( ±1.2) 0.30 (perseverative and nonperseverative) errors, percent- Age at onset (years) 15.3 (± 1.4) age of conceptual level responses, number of correctly Hospitalizations 2.5 (± 1.8) Length of illness (years) 2.0 (± 1.1) completed categories, and number of cards needed to PANSS dimensions complete the first category. The N-back test was used Positive 13.5 (± 4.4) Negative 24.5 (± 8.3) for the evaluation of visual working memory (Coppola General 39 (± 12.2) 1-back version). The measured parameters included the Total 77 (± 21.9) percentage of correct and incorrect responses and the C-GAS 58.1 (± 8.9) mean reaction time (34). The Trail Making Test was also Gender N % N % used – part A to assess psychomotor speed and part B Female 13 40 13 43 Male 20 60 17 57 to evaluate visuospatial working memory and the ability Familial burden of 12 36 0 0 to shift strategies. The analyzed parameters included psychosis

8 BEATA HINTZ AND ALINA BORKOWSKA

longer performance time in parts A Table 2. Results of neuropsychological tests in EOS patients and controls and B in TMT and more errors in part EOS patients Controls N=33 N=30 B. They also had significantly lower Neurocognitive tests Mean (SD) Mean (SD) t-test p -level results in RAVLT, both in immediate WCST and delayed recall, as compared to their % perseverative errors 11.93 ( ±6.31) 7.46 (±1.65) 3.76 p<.001 healthy peers. % nonperseverative errors 11.34 (±6.19) 7.13 (±2.72) 3.42 p<.01 % total errors 23.28 (± 10.70) 14.60 (±3.17) 4.26 p<.0001 EOS patients with a familial burden % conceptual level responses 71.18 (±15.37) 83.13 (±4.02) -4.12 p<.001 of psychosis had poorer results on some categories completed 5.59 ( ± 0.87) 6.00 (±0.00) -2.54 p<.01 neuropsychological tests as compared to trials to complete 1st category 15.31 (± 7.92) 12.00 (± 1.87) 2.23 p <.05 patients without such a burden (Table 3). N-back They achieved a lower percentage of cor- % number correct 77.81 (±24.65) 99.46 (± 1.73) -4.79 p<.0001 % number wrong 22.18 (±24.65) 0.53 (±1.73) 4.79 p<.0001 rect responses in the N-back test and had reaction time (msec) 662.45 (±361.41) 417 (±195.74) 3.30 p<.001 a longer performance time on the TMT B test, which indicates a greater level of TMT TMT A (sec) 35.90 (±11.82) 17.60 (±3.15) 8.21 p<.0001 set shifting and visual working memory TMT B (sec) 88.81 (±40.89) 41.58 (±13.03) 6.04 p<.0001 disturbances. No significant differences RAVLT between EOS patients with and without trials I-V 45.43 (±8.88) 56.66 (± 7.72) -5.22 p<.0001 a family burden were observed in the recall after 20 min 9.50 (±2.50) 13.03 (±1.92.) -6.13 p<.001 PANSS (severity of positive, negative and t Student test general symptoms) and CGAS scores. between adolescents suffering from schizophrenia and NEUROPSYCHOLOGICAL TESTS AND SYMPTOMS: their healthy peers. In the patient group, the majority of GLOBAL FUNCTIONING adolescents experienced the onset of schizophrenia at the No correlations between the performance on neuropsy- age of 14-17 (91%). Only three individuals (9%) had a chological tests and the intensity of positive symptoms very early onset of schizophrenia (VEOS) at 12-13 years of on the PANSS scale were found, as shown in Table 4. A age. Thirty-six percent of adolescents with schizophrenia greater intensity of negative symptoms correlated with had a familial burden of psychosis. Participants were a lower performance on the WCST (higher percentage receiving atypical antipsychotics. Twenty-one of them of perseverative errors) and in two parameters of the (63%) were able to return to regular school at the time N-back test, as well as a longer time required to perform of enrolment. Seven patients continued individualized the TMT B test. education (21%), while five (16 %) remained absent from Global functional impairment measured by the school on medical leave. CGAS scale was associated with worse results of neuropsychological tests. Patients with a greater impairment PERFORMANCE ON NEUROCOGNITIVE TESTS in CGAS (lower score) had a significantly higher per- Performance on neurocognitive tests is shown in Table centage of perseverative errors and a lower percentage 2. EOS adolescents performed significantly lower in all test parameters compared to Table 3. Neurocognitive test performance in EOS patients with and without healthy individuals. In the WCST, EOS familial burden of psychosis patients had a significantly higher per- EOS patients without EOS patients with familial burden familial burden centage of total perseverative and non- N=21 N=12 Z-adjusted perseverative errors, a lower percentage Neurocognitive tests Mean (SD) Mean (SD) p – level of conceptual level responses, a lower per- N-back % number correct 86.67 18.8 62.33 26.8 2.66 p<.01 centage of correctly completed categories, % number wrong 18.8 590.62 26.8 788.17 p<.01 -1.83 and needed more cards to complete the reaction time (msec.) 13.33 342.1 37.67 374.3 -2.66 p=.06* first category. TMT EOS patients had a significantly lower TMT A (sec) 34.63 73.33 38.33 115.91 -1.46 -2.61 TMT B (sec) 13.5 25.9 8.2 48.8 p=.14 p<.01 number of correct responses and a longer *tendency, Mann-Whitney U test reaction time in the N-back test, with a

9 COGNITION, SYMPTOMS AND FUNCTION IN EARLY SCHIZOPHRENIA

a significant contribution to the model (TMT Table 4. Correlations between neurocognitive tests performance and results in PANSS and CGAS in EOS patients B: t= -0.26, p=.794; WCST percentage of conceptual level responses: t=1. 35, p=.190; WCST PANSS PANSS PANSS Neurocognitive tests Positive Negative General CGAS percentage of perseverative errors: t=0.74, WCST p=.465; N-back T: t=-0.048, p=.635). General % perseverative errors -0.19 0.38* 0.02 -0.40* psychopathology contributed to an increase % nonperseverative errors -0.16 0.03 0.02 -0.18 % total errors -0.21 0.24 0.03 -0.34 of the predictive value of the model (general % conceptual level responses 0.20 -0.25 -0.03 0.35* psychopathology: t=-0.082, p=.935). As TMT categories completed 0.13 -0.21 -0.07 0.31 trials to complete 1st category -0.23 -0.07 -0.13 0.02 B results were highly correlated with the CGAS score (as shown in Table 4), it is probable that N-back % number correct -0.12 -0.47*** -0.27* 0.55** CGAS eliminates TMT B as a weaker predic- % number wrong 0.12 0.47*** 0.27* -0.55** tor from this regression model. Table 5 shows reaction time (msec) 0.11 0.34 0.16 -0.42* the predictive value of cognitive abilities and TMT TMT A (sec) 0.05 0.33 0.27 -0.32 clinical variables on functional impairment in TMT B (sec) 0.24 0.53** 0.44* -0.60*** EOS patients. RAVLT trials I-V 0.00 -0.22 -0.25 0.44* recall after 20 min 0.05 -0.10 -0.11 0.33 DISCUSSION *p<.05; **p<.01; ***p<.001 Pearson correlation The obtained results indicate that EOS, even in of conceptual level responses. Likewise, they obtained the period of a partial remission of psychotic symptoms, is poorer results in all parameters of the N-back test, associated with a specific pattern of cognitive dysfunctions needed more time to perform TMT B, and showed and general functioning disturbances. In comparison with greater verbal memory disturbances in RAVLT (imme- healthy individuals, EOS adolescents showed significantly diate recall trials). poorer performance on all neurocognitive tests measur- The correlation between the CGAS score, the results ing working memory, executive functions, processing of cognitive tests, and clinical variables was calculated speed, verbal memory, and learning. Thereby our find- to identify potential predictors for regression analysis ings confirm the results of most other studies indicating (Table 5). Among the psychopathological symptoms in greater neurocognitive deficits in patients with early-onset the PANSS scale, the most significant correlations with schizophrenia, not only in comparison with healthy the CGAS score were found in relation to negative symp- controls but also with adult-onset schizophrenia patients toms (Pearson’s r = - 0.62; p<.001), positive symptoms (6, 15, 39, 40). Compared to their healthy peers, EOS (Pearson’s r =-0.41; p<.05), and general psychopathol- patients had significantly lower scores in all parameters ogy (Pearson’s r=- 0.55; p<.01). Further analysis was of the WCST: a higher percentage of perseverative errors based on the forward stepwise method. The variables indicating significant cognitive flexibility impairment and with significant correlations with CGAS scores were stereotyped reactions, a higher percentage of nonperse- adopted as potential predictors in the relevant block: verative errors that might be connected with attentional the PANSS negative, positive and general symptom dysfunctions, and a lower percentage of conceptual level scale score, parameters of the WCST (percentage of responses indicating significant difficulties in logical perseverative errors and percentage of conceptual level concept formation and a reduced ability to apply new responses), and the results of the N-back test (all parameters), TMT part B, and RAVLT Table 5. The forward stepwise method regression analysis examining the (number of words recalled in five repeti- contribution of clinical variables and the results of neuropsychological tests tions). The N-back percentage of incorrect to predict the CGAS score in adolescents with EOS Dependent variable = B SE Beta SE Beta t-value p- value responses, the number of words in RAVLT CGAS score trials I-V, and the PANSS negative and posi- N-back wrong -0.13 0.05 -0.36 0.13 -2.68 .013 tive symptom scores explained 63% of the RAVLT trials I-V (sum) 0.29 0.12 0.29 0.12 2.40 .024 variance of the total score in CGAS (adjusted PANSS Negative -0.34 0.15 -0.32 0.14 -2.21 .036 PANSS Positive -0.56 0.27 -0.26 0.12 -2.06 .049 R2=0.63; F(4)=12.96; p<.001). None of the other potential cognitive predictors made Adjusted R2=0. 63 F(4) =12.96, p=.00009

10 BEATA HINTZ AND ALINA BORKOWSKA information to the current situation in order to change morbid period of EOS patients, a delayed early childhood behavior. EOS patients also completed fewer categories development is observed with respect to motor functions in the WCST, which indicates a significantly decreased as well as to visuomotor and spatial coordination. Some effectiveness of reasoning. Our findings correspond to authors suspect that in certain patients cognitive deficits other results that established a significant impairment of occur before the first episode of the illness and that they frontal functions measured with the WCST in patients have a persistent character, while in other individuals with with an early onset of schizophrenia (41, 42). In our schizophrenia these disturbances may further develop in study, EOS patients also presented lower performance the course of the illness (50). This may, however, depend on visual working memory tests compared to the results on the intensity of CNS dysfunctions, the familial burden of the control group. In the N-back test, EOS patients of schizophrenia, and obstetric complications (51). achieved significantly poorer results with more incorrect It should be noted that the results of this study did responses and a longer mean reaction time. These findings not establish associations between the performance on indicate persistent impairment of visuospatial working neuropsychological tests and the intensity of positive memory and visuospatial processing. In various studies symptoms on the PANSS scale. However, a higher inten- using the N-back test, it was found that the performance sity of negative symptoms was found to correlate with of adult schizophrenic patients was significantly poorer poorer performance on working memory tests. These data in comparison with healthy subjects. Patients committed correspond with the results of other studies concerning more errors and had a longer reaction time, which was both EOS and AOS, which particularly identified a strong associated with abnormal functioning of the dorsolateral relationship between the negative symptoms of schizo- prefrontal cortex (43, 44). As recently established by phrenia and cognitive deficits, especially in the scope of Kyriakopoulos et al. (45), adolescents with EOS displayed working memory impairment (52-54). This may support reduced dorsolateral prefrontal and anterior cingulate the hypothesis expressed by Crow that negative symptoms cortex activity and reduced DLPFC connectivity within are associated mostly with neurocognitive dysfunctions the working memory network. and with greater prefrontal cortex disturbances (55). In TMT, a significant decline of psychomotor speed Some authors emphasize that negative symptoms are was observed (TMT A) as well as reduced performance more intense in AOS patients with more severe dysfunc- ability in visuospatial working memory and set shift- tions of premorbid psychosocial outcomes, a greater ing tasks (TMT B). These findings correspond with the severity of the illness, and a deeper cognitive dysfunction results of other studies in which EOS adolescents had (21, 56). It may be assumed that negative symptoms and significantly longer reaction times compared to healthy frontal deficit symptoms are crucial to poorer general controls (11, 46). functioning outcome in EOS schizophrenia since EOS EOS adolescents with a familial burden of psychosis is the more severe form of the illness characterized by presented greater cognitive deficits (especially in complex more serious clinical and functional outcomes (57). visuospatial skills) compared to patients without such a The previous studies performed on EOS patients also burden. This result may suggest that more severe visual showed that poor functioning in childhood, either nega- and visuospatial working memory and set shifting dys- tive or positive schizophrenic symptoms, as well as certain functions in patients with EOS may be associated with cognitive deficits without psychopathological symptoms, a hereditary predisposition to the illness and the coexis- may serve as predictors of functional outcome, but these tence of unfavorable factors in early CNS development, results were not confirmed by others (9, 25, 26, 28, 58). mainly associated with genetic conditions. Therefore, The main conclusion of the present study is that deficits our data may support the neurodevelopmental concept of visual working memory and verbal memory as well of schizophrenia (47), especially in light of the recent as a higher intensity of schizophrenia symptoms (both study by Shenton, Whitford and Kubicki (48), which negative and positive) have been found to be significant found subtle neurodegenerative changes in the frontal predictors of poor global functioning of EOS patients. and parietal lobes of EOS patients with schizophrenia. A cross-sectional study of EOS adolescents showed that Moreover, Kumra and colleagues (49) established a rela- 63% of the total CGAS variance was predicted by the tionship between the diminution of total cortical gray N-back percentage of incorrect responses, the RAVLT matter volume and a higher intensity of motor disorders trials I-V (number of words), and the PANSS negative and visual attention deficits in EOS patients. In the pre- and positive symptoms score. Our results are particularly

11 COGNITION, SYMPTOMS AND FUNCTION IN EARLY SCHIZOPHRENIA interesting in the light of the recent meta-analysis carried 2005;20:395-402. 4. Green MF. Stimulating the development of drug treatment to improve out by Ventura et al. (21), which showed an association cognition in schizophrenia. Ann Rev Clin Psychol 2007;3:159-180. between cognitive functions, negative symptoms, and 5. Vourdas A, Pipe R, Corrigall R, Frangou S. Increased developmental functional outcome exclusively in AOS patients. The deviance and premorbid dysfunction in early onset schizophrenia. authors suggest that negative symptoms mediate the Schizophr Res 2003; 62:13-22. 6. McClellan J, Prezbindowski A, Breiger D, McCurry C. connectivity between cognition and general functioning. Neuropsychological functioning in early onset psychotic disorders. However, EOS patients were not as extensively studied Schizophr Res 2004;68:21-26. as AOS individuals. In this light, our study offers new 7. 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