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Erschienen in: European Child & Adolescent Psychiatry 12/2020

Open Access 08.02.2020 | Original Contribution

Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis

verfasst von: Runar Elle Smelror, Bjørn Rishovd Rund, Vera Lonning, Kjetil Nordbø Jørgensen, Kirsten Wedervang-Resell, Ole A. Andreassen, Torill Ueland, Anne M. Myhre, Ingrid Agartz

Erschienen in: European Child & Adolescent Psychiatry | Ausgabe 12/2020

Abstract

Neurocognitive deficits are associated with impaired global functioning and psychotic symptoms. However, whether symptoms can mediate the relationship between neurocognition and global functioning in adolescent psychosis is unclear. Here, we investigated if symptoms assessed with the Positive And Negative Syndrome Scale (PANSS), mediated the relationship between neurocognitive performance and global functioning in adolescents with non-affective early-onset psychotic disorders (EOP). Sixty-one adolescent EOP patients (age 12–18 years) from 2 Norwegian clinical cohorts were included. Linear regression models were applied to investigate associations between neurocognitive domains from the MATRICS Consensus Cognitive Battery (MCCB) and global functioning. PANSS symptoms were analyzed using the Wallwork/Fortgang five-factor model. Using the INDIRECT macro for SPSS, mediation effects were tested using bootstrapping with 95% bias corrected confidence intervals. Verbal learning was positively associated with global functioning (P < 0.001) and negatively associated with the disorganized symptom factor (P = 0.002), controlling for age, sex and cohort. Testing of indirect effects, controlling for age, sex and cohort, showed that the Negative (point estimate = 1.56, 95% CI 0.22, 3.47) and Disorganized (point estimate = 1.24, 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship between verbal learning and global functioning. We found that verbal learning, negative and disorganized symptoms influenced global functioning in adolescents with EOP, while reality-distorted positive symptoms did not. These results suggest that assessing these domains in EOP is helpful for planning treatment and rehabilitation programs focusing on functional outcome.
Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00787-020-01479-7) contains supplementary material, which is available to authorized users.

Introduction

Early-onset psychosis (EOP) includes psychotic disorders with age of onset before 18 years. Early-onset schizophrenia (EOS) is one of the leading causes of disease burden in adolescents between 15–19 years [1]. It is widely regarded as a neurodevelopmental disorder [27] with neurocognitive deficits as a core feature of the illness [8]. Neurocognitive deficits are present before the onset of illness [912], relatively stable over time [1316] and found in children with familial high risk of schizophrenia [17]. Although the neurocognitive deficits in EOP are similar to adult schizophrenia patients [18, 19], the deficits in adolescents seem to be greater than in adults [8, 20, 21]. These findings suggest that abnormal neurodevelopment in schizophrenia is present early in life in a period of extensive brain maturation and before the onset of illness [22]. EOP is thus important to investigate as adolescents are less influenced by any secondary effects of the disease, such as long-term medical treatment, unhealthy lifestyle, etc. Increased knowledge of cognitive functioning and neurodevelopment during this life period can provide new insight into the mechanisms contributing to impaired functional outcome and the development of psychosis [5, 6].
Long-term follow-up studies have showed that 42–74% of individuals with EOP had severely impaired functional outcome after 9–42 years (e.g. lived in a supervised home/institution, had symptoms most/all the time, had reduced/no work) [19, 2328]. Few studies have investigated putative associations between neurocognition and functional outcome in EOP. Two studies, including patients with EOS, found that neurocognitive deficits in speed of processing, verbal learning, attention, working memory and executive functioning were associated with impaired functional outcome at follow-up [19, 29]. As neurocognition is not part of the diagnostic criteria of psychotic disorders, symptom reduction on clinical rating scales (e.g. the Positive and Negative Syndrome Scale (PANSS) [30]) is often used as the only indicator of treatment success in clinical trials of schizophrenia. While the original PANSS includes three subscales, factor analyses show that five-factor models show better statistical validity, with the Wallwork/Fortgang model [31] showing the most optimal statistical fit for adult first-episode psychosis patients [32]. This model includes Positive, Negative, Disorganized/concrete, Excited and Depressed symptom factors, and separates reality-distorted positive symptoms (e.g. delusions and hallucinations) from disorganized symptoms (e.g. conceptual disorganization and reduced attention). This is in line with factor analyses suggesting that disorganized symptoms represent a different construct than positive symptoms [33, 34]. This is important as negative and disorganized symptoms have been more strongly associated with neurocognitive deficits than positive symptoms [35]. Stronger associations have also been found between negative symptoms and impaired functional outcome in EOP [36] and adult schizophrenia [37, 38], compared to positive symptoms. A recent study of adult first-episode psychosis patients and a former meta-analysis found that negative symptoms partially mediated the relationship between neurocognitive performance and global functioning in adult patients, while no significant association was found for reality-distorted positive symptoms [39, 40]. Disorganized symptoms were not assessed in these studies.
To the best of our knowledge, no studies have investigated if characteristic symptoms of psychosis mediate the relationship between neurocognitive performance and global functioning in adolescents with EOP. This may shed light on the nature of this relationship and help identify which psychotic symptoms are relevant predictors of functioning in adolescent psychosis. The present study examined whether neurocognitive performance, assessed with the MCCB, was associated with global functioning in EOP, and whether symptom domains from the Wallwork/Fortgang five-factor model mediated this relationship. Based on previous research in adolescent schizophrenia [19, 29], we hypothesized that speed of processing, verbal learning, attention, working memory and global cognition would be associated with global functioning in EOP. Furthermore, based on a previous systematic review [35] and research in adult schizophrenia [39, 40], we hypothesized that the Negative and Disorganized/concrete symptom factors would mediate this relationship, while no significant mediation effects would be found for positive symptoms.

Materials and methods

Participants

A total of 61 adolescents with early-onset non-affective psychotic disorders (EOP) were combined from 2 Norwegian clinical cohorts at the University of Oslo (the Thematically Organized Psychosis Study for Youth [Youth-TOP] and the Early-Onset Study). All participants were recruited from adolescent psychiatric inpatient units and outpatient clinics in the Oslo region from 2013–2016 (Youth-TOP) and 2005–2007 (Early-Onset Study). The Youth-TOP has an ongoing inclusion of participants and no neurocognitive patient data have previously been reported (see [41] for more information about patient characterization). Neurocognitive data from the Early-Onset Study have been published in previous papers, e.g. [15, 18, 42]. The inclusion criteria in both cohorts were: (1) Non-affective early-onset psychosis (schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder not otherwise specified, brief psychotic disorder), according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), (2) age between 12 and 18 years, (3) written informed consent obtained from participants, parents or guardians (if the participant was under 16 years), (4) language abilities to complete the interviews and self-rating questionnaires. The exclusion criteria in both cohorts were: (1) IQ below 70, (2) previous moderate/severe head injury, (3) a diagnosis of substance-induced psychosis, (4) organic brain disease. Demographic and clinical information of the participants are provided in Table 1.
Table 1
Demographic and clinical characteristics of the participants, and statistical tests for differences between the two cohorts
 
Youth-TOP
Early-Onset Study
Test statistics
 
N = 34
N = 27
 
Inclusion years
2013–2016
2005–2007
 
Diagnostic assessment
K-SADS-PLa
SCID-Ib
 
CGAS/GAF-Fc (SD)
43.2 (10.3)
48.0 (15.2)
t(44) = 1.41, P = 0.17
Sex, female (%)
21 (62)
14 (52)
χ2(1) = 0.61, P = 0.44
Hand dominance, right (%)
31 (91)
23 (85)
χ2(1) = 0.53, P = 0.47
Mother’s education, years (SD)
14.7 (2.7)
12.9 (2.8)
t(56) = − 2.51, P = 0.02
Age, years (SD)
16.2 (1.3)
15.9 (1.8)
t(59) = − 0.13, P = 0.53
IQ (SD)
100.4 (12.4)
95.2 (14.4)
t(59) = − 1.51, P = 0.14
Ethnicity, caucasian (%)
30 (88)
21 (78)
χ2(1) = 1.20, P = 0.27
Diagnosis (%)
  
χ2(4) = 3.75, P = 0.44
 Schizophrenia
21 (62)
12 (44)
 
 Schizoaffective disorder
1 (3)
3 (11)
 
 Schizophreniform disorder
0 (0)
1 (4)
 
 Brief psychotic disorder
1 (3)
1 (4)
 
 Psychosis not otherwise specified
11 (32)
10 (37)
 
Daily nicotine use, yes (%)
9 (27)
6 (23)
χ2(1) = 0.09, P = 0.76
Alcohol use, yes (%)
12 (35)
17 (63)
χ2(1) = 4.62, P = 0.03
Cannabis use, yes (%)
8 (24)
4 (15)
χ2(1) = 0.72, P = 0.40
Antipsychotic med., yes, n (%)
18 (53)
19 (70)
χ2(1) = 1.92, P = 0.17
 Aripiprazole
9 (50)
2 (11)
 
 Risperidone
3 (16)
2 (11)
 
 Quetiapine
4 (22)
6 (31)
 
 Olanzapine
1 (6)
6 (31)
 
 Ziprasidone
0 (0)
2 (11)
 
 Clozapine
1 (6)
1 (5)
 
Age of onset, mean years (SD)
14.3 (1.9)
14.1 (2.0)
t(59) = − 0.41, P = 0.68
DUPd, weeks (SD)
38.5 (47.6)
35.0 (51.5)
t(59) = 0.28, P = 0.78
PANSSe (SD)
 Positive
17.3 (4.1)
14.9 (4.2)
t(59) = − 2.26, P = 0.03
 Negative
19.2 (8.0)
12.2 (5.3)
t(57) = − 4.10, P < 0.001
 General
36.5 (8.1)
29.7 (7.4)
t(59) = − 3.37, P = 0.001
PANSS Wallwork/Fortgang (SD)
 Positive
2.9 (0.89)
2.5 (0.83)
t(59) = − 1.99, P = 0.05
 Negative
2.8 (1.18)
1.9 (0.76)
t(57) = − 3.45, P = 0.001
 Disorganized/concrete
2.2 (0.94)
1.6 (0.64)
t(58) = − 3.02, P = 0.004
 Excited
1.7 (0.55)
1.7 (0.63)
t(59) = − 0.04, P = 0.97
 Depressed
2.8 (0.88)
2.6 (1.13)
t(49) = − 0.87, P = 0.39
aSchedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL [43])
bStructured Clinical Instrument of Diagnosis for DSM-IV Axis I Disorders, modules A-D (First et al. [44])
cChildren’s Global Assessment Scale (CGAS) [45]. Global Assessment of Functioning (GAF) Scale (split DSM-IV version) [46]
dDuration of untreated psychosis
ePositive And Negative Syndrome Scale [30]
Bold values indicate P ≤ 0.05

Clinical measures

Diagnoses were confirmed using the Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime Version (K-SADS-PL) [43] in the Youth-TOP study and the Structural Clinical Instrument of Diagnosis for DSM-IV Axis I disorders (SCID-I), modules A-D [44], in the Early-Onset Study. For both cohorts, current psychopathology was assessed using the PANSS [30], and analyzed using the Wallwork/Fortgang five-factor model, consisting of Positive, Negative, Disorganized/concrete, Excited, and Depressed symptom factors [31]. Although the Wallwork/Fortgang model has not been validated in adolescents, it has shown the most optimal fit for adult first-episode schizophrenia patients, aged 18–65 years [32].
The interviewers in both studies were clinical psychologists or medical doctors who had completed an inter-rater reliability training course (≥ 80% inter-rater reliability) in PANSS assessment based on a training program developed at the University of California, Los Angeles. All interviewers participated in regular diagnostic consensus meetings led by a senior clinical researcher in the field of psychosis.

Global functioning

The participants’ level of global functioning was assessed using the Children’s Global Assessment Scale (CGAS) [45] in the Youth-TOP study and the Global Assessment of Functioning Scale, split DSM-IV version (GAF-F) [46, 47], in the Early-Onset Study. Both rating scales are based on the Global Assessment Scale [48], so the scoring of functioning is similar, ranging from 0 (lowest) to 100 (highest). The scales include behavior and activities indicative of daily functioning, such as social functioning, school performance and independent living [39, 49]. Despite minor differences in the naming of anchor points (e.g. scores from 51–60 are defined as “variable functioning” in the CGAS and “moderate functioning” in the GAF-F), the descriptions of functioning within each anchor point is similar between the scales (see [50] for more information about the scales). Although the anchor points in the CGAS contain both functioning and symptoms, while the GAF-F only contains functioning, we considered the two scales to be adequately comparable to allow us to merge for analysis of global functioning in the combined cohort. No significant differences were found between the CGAS and the GAF-F scores between the two cohorts (Table 1).

Neurocognitive measures

The participants underwent intelligence assessment using the Wechsler Abbreviated Scale of Intelligence [51]. Neurocognitive profiling was performed using a licensed translated version of the MATRICS Consensus Cognitive Battery (MCCB) [52], with the exception of the social cognition test Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT) [53]. The MCCB was developed for clinical trials of schizophrenia [54] and has been successfully used to assess cognitive functioning in children [55] and adolescents [18, 56]. The nine included tests covered six neurocognitive domains: (1) Speed of processing, measured with the BACS Symbol coding [57], Trail making test, part A (TMT-A) [58], and Category fluency: Animal naming [59], (2) Attention/vigilance, measured with the Continuous performance test, identical pairs (CPT-IP) [60], (3) Working memory, measured with the WMS-III Spatial span [61] and Letter-number span [62], (4) Verbal learning, measured with the Hopkins verbal learning test, revised (HVLT-R) [63], (5) Visual learning, measured with the Brief visuospatial memory test, revised (BVMT-R) [64], and (6) Reasoning and problem solving, measured with the NAB Mazes [65]. The HVLT-R test was originally validated for age ≥ 16 years but has been successfully used and standardized in children and adolescents [56, 66-68].

Statistical analyses

Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 25. All tests were two-tailed. Independent-sample t tests were used for analyses of cohort comparisons of continuous variables and chi-square (χ2) tests for comparisons of categorical data. We transformed the neurocognitive raw test scores from the MCCB in the total sample to standard scores (z scores) using the SPSS standardization function. High scores on the TMT-A test indicate impairment and were reversed. In domains containing more than one subtest and for the global cognition score, composite scores were calculated by summating the standard scores of relevant tests and transforming the sum scores to standard scores using the same procedure as described above. This procedure is in line with previous MCCB standardization studies [56, 69]. In the main analysis examining associations between neurocognition and global functioning, we applied separate linear regression models using the neurocognitive domains and global cognition as predictor variables and global functioning as the outcome variable. IQ was not included as it has been found to be moderately to highly correlated with the MCCB domains and the global cognition score [70, 71]. Age, sex and cohort were added as covariates as age and sex effects have been found in adolescent performance on the MCCB [56] and to avoid potential systematic cohort differences. Correction for multiple testing was performed using Bonferroni, in which P ≤ 0.007 was considered significant in the main analysis (P = 0.05/7 neurocognitive domains). Based on the results from the main analysis, we examined associations between (1) neurocognition and symptoms, using the mean symptom factor scores as predictor variables and the relevant neurocognitive domains as outcome variables, controlling for age, sex and cohort; and (2) symptoms and global functioning, using the symptom factors as predictor variables and global functioning as the outcome variable, controlling for age, sex and cohort. In both secondary analyses, P ≤ 0.01 was considered significant (P = 0.05/5 symptom factors). Lastly, to examine if symptoms mediated the relationship between the relevant neurocognitive domains and global functioning, we applied separate mediation analyses of the five symptom factors, controlling for age, sex and cohort, using the INDIRECT macro for SPSS [72]. The indirect effects were tested using 95% bias corrected (BC) bootstrap intervals with 5000 bootstrap samples. The indirect effects were considered statistically significant if the confidence interval of each point estimate did not include zero (null value). Bootstrapping was preferred over the product-of-coefficients approach (i.e. the Sobel test), because no assumptions of normal distributions are required [73] and because this approach is considered to be more valid for testing of indirect effects [74].

Results

Patient characteristics

Demographic and clinical characteristics of the two cohorts are provided in Table 1. The participants in the Youth-TOP study had significantly higher PANSS scores (Positive: t(59) = − 2.26, P = 0.03; Negative: t(57) = − 4.10, P < 0.001; General: t(59) = − 3.37, P = 0.001) and significantly higher scores on the Wallwork/Fortgang Positive [t(59) = − 1.99, P = 0.05], Negative [t(57) = − 3.45, P = 0.001] and Disorganized/concrete [t(58) = − 3.02, P = 0.004] symptom factors, compared to the participants in the Early-Onset Study. Furthermore, the participants in the Youth-TOP study had mothers with significantly more years of education than the participants in the Early-Onset Study [t(56) = − 2.51, P = 0.02], while a significantly higher proportion of participants in the Early-Onset Study had used alcohol compared to the participants in the Youth-TOP study [χ2 (1) = 4.62, P = 0.03]. When comparing neurocognitive performance between the two cohorts, the participants in the Youth-TOP study had significantly higher scores on the Spatial span test [t(58) = − 2.59, P = 0.01), Working memory domain [t(58) = − 2.55, P = 0.01] and on the Global cognition score [t(50) = − 2.73, P = 0.01] compared to the patients in the Early-Onset Study. MCCB test and domain scores are presented in Table 2.
Table 2
MCCB test and domain scores of the participants, and statistical tests for differences between the two cohorts
MCCB test and domain scores
Youth-TOP
Early-Onset Study
Test statistics
 
N = 34
N = 27
 
Speed of processing, Z score
0.15 (0.98)
− 0.19 (1.01)
t(57) = − 1.30, P = 0.20
 BACS symbol coding
49.61 (12.98)
46.59 (11.26)
t(58) = − 0.95, P = 0.35
 Animal naming
21.09 (5.44)
18.35 (5.46)
t(58) = − 1.93, P = 0.06
 Trail making test A
36.22 (12.74)
35.92 (14.61)
t(58) = − 0.08, P = 0.93
Attention/vigilance: CPT-IP d´
1.77 (0.68)
1.70 (0.70)
t(54) = − 0.38, P = 0.71
Working memory, Z score
0.28 (0.96)
− 0.36 (0.95)
t(58) = − 2.55, P = 0.01
 WMS-III spatial span
16.62 (2.67)
14.81 (2.70)
t(58) = − 2.59, P = 0.01
 Letter-number span
12.94 (3.14)
11.70 (2.32)
t(59) = − 1.71, P = 0.09
Verbal learning: HVLT-R
25.52 (5.19)
22.81 (5.50)
t(58) = − 1.95, P = 0.06
Visual learning: BVMT-R
25.38 (6.79)
22.93 (8.78)
t(48) = − 1.20, P = 0.24
Reasoning and problem-solving: NAB Mazes
20.29 (4.45)
17.85 (5.69)
t(59) = − 1.88, P = 0.07
Global cognition, Z score
− 0.34 (0.90)
− 0.37 (0.98)
t(50) = − 2.73, P = 0.01
Bold values indicate P ≤ 0.05

Associations between neurocognitive performance, global functioning, and symptoms

Verbal learning was the only neurocognitive domain significantly associated with global functioning, controlling for age, sex and cohort (β = 0.50, P < 0.001, R2 change = 0.20, model statistics (MS): F(4, 55) = 5.92, P < 0.001, R2 = 0.30, Fig. 1a), and thus the only domain included in the subsequent analyses. For the other domains and the global cognition score, no significant associations were found (Speed of processing: β = 0.22, P = 0.10, R2 change = 0.05, MS: F(4, 54) = 2.35, P = 0.07, R2 = 0.15; attention/vigilance: β = − 0.02, P = 0.87, R2 change = 0.00, MS: F(4, 51) = 1.04, P = 0.40, R2 = 0.08; working memory: β = 0.01, P = 0.93, R2 change = 0.00, MS: F(4, 55) = 1.70, P = 0.16, R2 = 0.11; visual learning: β = 0.13, P = 0.31, R2 change = 0.02, MS: F(4, 56) = 1.89, P = 0.12, R2 = 0.12; reasoning and problem solving: β = 0.09, P = 0.52, R2 change = 0.01, MS: F(4, 56) = 1.71, P = 0.16, R2 = 0.11; global cognition: β = 0.18, P = 0.25, R2 change = 0.03, MS: F(4, 47) = 1.42, P = 0.24, R2 = 0.11). When performing separate analyses of the two cohorts, verbal learning was the only neurocognitive domain significantly associated with global functioning in the Early-Onset Study after correcting for multiple testing. None of the associations between the neurocognitive domains and global functioning reached statistical significance in the Youth-TOP. The separate results for the two cohorts are presented in the supplemental material.
When investigating associations between the verbal learning domain and symptoms, controlling for age, sex and cohort, verbal learning was significantly negatively associated with the disorganized/concrete (β = − 0.40, P = 0.002, R2 change = 0.13, MS: F(4, 55) = 6.49, P < 0.001, R2 = 0.32) symptom factor (P ≤ 0.01 considered significant after Bonferroni correction). No significant associations were found for the other symptom factors after correcting for multiple testing (positive: β = − 0.08, P = 0.52, R2 change = 0.01, MS: F(4, 55) = 3.32, P = 0.02, R2 = 0.19; negative: β = − 0.32, P = 0.02, R2 change = 0.08, MS: F(4, 55) = 4.97, P = 0.002, R2 = 0.27; excited: β = − 0.11, P = 0.36, R2 change = 0.01, MS: F(4, 55) = 3.45, P = 0.01, R2 = 0.20; depressed: β = 0.06, P = 0.61, R2 change = 0.00, MS: F(4, 55) = 3.27, P = 0.02, R2 = 0.19).
When investigating associations between symptom factors and global functioning, controlling for age, sex and cohort, significant associations were found for the Negative (β = − 0.52, P < 0.001, R2 change = 0.20, MS: F(4, 56) = 6.13, P < 0.001, R2 = 0.30) and disorganized/concrete (β = − 0.39, P = 0.004, R2 change = 0.13, MS: F(4, 56) = 4.14, P = 0.005, R2 = 0.23) symptom factors (P ≤ 0.01 considered significant after Bonferroni correction). The other symptom factors did not reach statistical significance after correcting for multiple testing (Positive: β = − 0.20, P = 0.13, R2 change = 0.04, MS: F(4, 56) = 2.27, P = 0.07, R2 = 0.14; Excited: β = − 0.26, P = 0.04, R2 change = 0.07, MS: F(4, 56) = 2.83, P = 0.03, model R2 = 0.17; depressed: β = − 0.21, P = 0.12, R2 change = 0.04, MS: F(4, 56) = 2.30, P = 0.07, model R2 = 0.14).

Symptoms as mediators of the association between neurocognitive performance and global functioning

Verbal learning was the only neurocognitive domain significantly associated with global functioning and thus the only domain included in the mediation analyses for testing the indirect effects. The Negative (point estimate = 1.56, BC 95% CI 0.22, 3.47) and the Disorganized/concrete (point estimate = 1.24, BC 95% CI 0.05, 3.69) symptom factors significantly mediated the relationship (CI not including the null value) between verbal learning and global functioning, controlling for age, sex and cohort (i.e. testing the indirect effect of X on Y, through M, shown in Fig. 1b, c). For the other symptom factors, the indirect effects did not reach statistical significance (Positive: point estimate = 0.19, BC 95% CI − 0.33, 1.59; excited: point estimate = 0.34, BC 95% CI − 0.25, 1.81; depressed: point estimate = − 0.17, BC 95% CI − 1.54, 0.65). When performing separate mediation analyses of the two cohorts, the Excited symptom factor was the only factor significantly mediating the relationship between verbal learning and global functioning in the Early-Onset Study. None of the symptom factors significantly mediated the relationship between verbal learning and global functioning in the Youth-TOP. The separate results for the two cohorts are presented in the supplemental material.

Discussion

The purpose of this study was to examine associations between neurocognitive performance and global functioning, and to test whether symptoms mediated this relationship in adolescents with EOP. The main finding was that verbal learning was positively associated with global functioning, explaining 20% of the variance in the level of functioning, and that this association was significantly mediated by negative and disorganized symptoms. Our finding showing a significant association between verbal learning and global functioning is in accordance with two previous studies of patients with EOS [19, 29]. Our results are also in accordance with two previous studies including adult schizophrenia patients, showing that negative symptoms mediated the relationship between neurocognitive performance and global functioning, while positive symptoms did not [39, 40]. To the best of our knowledge, our study is the first to show that disorganized symptoms, as a separate construct from other positive symptoms, mediated the relationship between verbal learning and global functioning.
Verbal learning deficits are associated with earlier age of onset of psychosis [75] and transition to psychosis in high-risk individuals [76]. Deficits in this domain might be a predictor of, or contributing factor to, the clinical manifestation of negative and disorganized symptoms, which are considered to be a core feature of schizophrenia [7779]. It has been suggested that the clinical heterogeneity in schizophrenia is a representation of different underlying mechanisms categorized by a positive and negative syndrome. The positive syndrome includes mainly positive symptoms (hallucinations and delusions) and better functional outcome, while the negative syndrome includes mainly negative and disorganized symptoms, cognitive deficits, and poorer functional outcome [35, 7880]. Thus, the patients in our sample with verbal learning deficits, negative and disorganized symptoms could represent a negative subgroup with poorer global functioning [35, 7880] and a more general language deficit, possibly due to a dysfunction in the language-processing networks [81].
Contrary to our hypothesis, we did not find significant associations between global functioning and other neurocognitive domains or global cognition, which have been found in previous studies of EOS and in adult schizophrenia [19, 29, 49, 82]. One reason for the different results between our study and the two previous studies of adolescents [19, 29] may be that in the two previous studies, functional outcome was measured only at follow-up and compared with baseline neurocognitive functioning, while we only applied baseline data. Comparing our results to previous studies of adult patients [49, 82], the divergence in findings in our study might be due to different factors influencing neurocognitive functioning in adolescence as compared to in adulthood. For example, more supportive factors in the adolescents’ rearing environment could help them to maintain their level of functioning. Moreover, different measures of neurocognition and functional outcome were applied in our study and the previous studies. However, our analyses showed that verbal learning and global functioning were more strongly associated with negative and disorganized symptoms than other symptoms. These findings are in accordance with a previous study showing that negative and disorganized symptoms showed stronger associations with neurocognitive deficits, than positive symptoms [35]. Moreover, negative symptoms have also been more strongly associated with impaired functional outcome in EOP [36] and adult schizophrenia [37, 38], compared to positive symptoms.

Strengths and limitations

The main strength of this study is the large and well-characterized cohort of adolescent EOP patients. However, the study has several limitations. First, the study was naturalistic and cross-sectional, and no empirical assumptions of causality could be made, only investigations of statistical associations. We assume that baseline deficits in verbal learning and the presence of negative and disorganized symptoms will affect long-term global functioning in adolescents with EOP, but this must be investigated in a follow-up study. Second, global functioning was assessed using two different scales. Although the scales were considered to be sufficiently similar to merge and we controlled for cohort effects in the analyses, we cannot be certain that this did not bias the ratings of global functioning since no estimate of agreement between the two scales have been provided. Moreover, the ratings of functioning were based on the subjective impression of the interviewer. The interviewers were trained in scoring of CGAS and GAF, but no inter-rater reliability testing or observation of actual functioning was completed. Third, when performing separate analyses of the two cohorts, we found cohort differences in the regression and mediation analyses. Although cohort was added as a covariate in all the analyses, we cannot rule out that cohort differences may have biased the results. Fourth, it is unknown if medication effects have contributed to our findings as the combined cohort included medicated and unmedicated participants. Lastly, patient motivation was not assessed, although it has been shown to be related to cognitive performance in adult schizophrenia patients [83].

Conclusion

Our results confirm that verbal learning is an important neurocognitive domain for global functioning and that negative and disorganized symptoms mediate this relationship, while reality-distorted positive symptoms do not. Hence, our results support the notion that disorganized symptoms should be considered as an independent construct separate from other positive symptoms [33, 34]. Clinical implications of the study are that assessments of adolescents with EOP should include measures of verbal learning, negative and disorganized symptoms. This could be of value for cognitive remediation programs and in planning of psychosocial and psychopharmacological interventions aiming to improve global functioning.

Acknowledgements

Open Access funding provided by Oslo University & Oslo University Hospital. We would like to thank all the participants for their contribution to this study. We would also like to thank Thorny Olafsdottir for her help with data collection.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The Youth-TOP and the Early-Onset Study were approved by the South-East Regional Committee for Medical and Health Research Ethics and conducted in accordance with the Helsinki Declaration. Written informed consent was obtained from participants, parents or guardians (if the participant was under 16 years), prior to their inclusion in the studies.
Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creativecommons.​org/​licenses/​by/​4.​0/​.

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Literatur
2.
Zurück zum Zitat Murray RM, Lewis SW (1987) Is schizophrenia a neurodevelopmental disorder? Br Med J (Clinical research ed) 295(6600):681 Murray RM, Lewis SW (1987) Is schizophrenia a neurodevelopmental disorder? Br Med J (Clinical research ed) 295(6600):681
3.
Zurück zum Zitat Rapoport JL, Addington AM, Frangou S, Psych M (2005) The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 10(5):434 Rapoport JL, Addington AM, Frangou S, Psych M (2005) The neurodevelopmental model of schizophrenia: update 2005. Mol Psychiatry 10(5):434
4.
Zurück zum Zitat Owen MJ, O’donovan MC, Thapar A, Craddock N (2011) Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 198(3):173–175 Owen MJ, O’donovan MC, Thapar A, Craddock N (2011) Neurodevelopmental hypothesis of schizophrenia. Br J Psychiatry 198(3):173–175
5.
Zurück zum Zitat Insel TR (2010) Rethinking schizophrenia. Nature 468(7321):187 Insel TR (2010) Rethinking schizophrenia. Nature 468(7321):187
6.
Zurück zum Zitat Rapoport J, Giedd J, Gogtay N (2012) Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry 17(12):1228 Rapoport J, Giedd J, Gogtay N (2012) Neurodevelopmental model of schizophrenia: update 2012. Mol Psychiatry 17(12):1228
7.
Zurück zum Zitat Rund BR (2009) Is schizophrenia a neurodegenerative disorder? Nord J Psychiatry 63(3):196–201 Rund BR (2009) Is schizophrenia a neurodegenerative disorder? Nord J Psychiatry 63(3):196–201
8.
Zurück zum Zitat Nieto RG, Castellanos FX (2011) A meta-analysis of neuropsychological functioning in patients with early onset schizophrenia and pediatric bipolar disorder. J Clin Child Adolesc Psychol 40(2):266–280 Nieto RG, Castellanos FX (2011) A meta-analysis of neuropsychological functioning in patients with early onset schizophrenia and pediatric bipolar disorder. J Clin Child Adolesc Psychol 40(2):266–280
9.
Zurück zum Zitat Trotta A, Murray R, MacCabe J (2015) Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis. Psychol Med 45(2):381–394 Trotta A, Murray R, MacCabe J (2015) Do premorbid and post-onset cognitive functioning differ between schizophrenia and bipolar disorder? A systematic review and meta-analysis. Psychol Med 45(2):381–394
12.
Zurück zum Zitat Reichenberg A, Caspi A, Harrington H, Houts R, Keefe RS, Murray RM, Poulton R, Moffitt TE (2010) Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am J Psychiatry 167(2):160–169 Reichenberg A, Caspi A, Harrington H, Houts R, Keefe RS, Murray RM, Poulton R, Moffitt TE (2010) Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. Am J Psychiatry 167(2):160–169
14.
Zurück zum Zitat Jepsen JRM, Fagerlund B, Pagsberg AK, Christensen AMR, Nordentoft M, Mortensen EL (2010) Deficient maturation of aspects of attention and executive functions in early onset schizophrenia. Eur Child Adolesc Psychiatry 19(10):773–786 Jepsen JRM, Fagerlund B, Pagsberg AK, Christensen AMR, Nordentoft M, Mortensen EL (2010) Deficient maturation of aspects of attention and executive functions in early onset schizophrenia. Eur Child Adolesc Psychiatry 19(10):773–786
16.
Zurück zum Zitat Øie M, Sundet K, Rund BR (2008) Neurocognitive decline in early-onset schizophrenia compared with ADHD and normal controls: evidence from a 13-year follow-up study. Schizophr Bull 36(3):557–565 Øie M, Sundet K, Rund BR (2008) Neurocognitive decline in early-onset schizophrenia compared with ADHD and normal controls: evidence from a 13-year follow-up study. Schizophr Bull 36(3):557–565
17.
Zurück zum Zitat Hemager N, Plessen KJ, Thorup A, Christiani C, Ellersgaard D, Spang KS, Burton BK, Gregersen M, Søndergaard A, Greve AN, Gantriis DL, Poulsen G, Seidman LJ, Mors O, Nordentoft M, Jepsen JRM (2018) Assessment of neurocognitive functions in 7-year-old children at familial high risk for schizophrenia or bipolar disorder: the danish high risk and resilience study via 7. JAMA Psychiatry 75(8):844–852. https://doi.org/10.1001/jamapsychiatry.2018.1415CrossRef Hemager N, Plessen KJ, Thorup A, Christiani C, Ellersgaard D, Spang KS, Burton BK, Gregersen M, Søndergaard A, Greve AN, Gantriis DL, Poulsen G, Seidman LJ, Mors O, Nordentoft M, Jepsen JRM (2018) Assessment of neurocognitive functions in 7-year-old children at familial high risk for schizophrenia or bipolar disorder: the danish high risk and resilience study via 7. JAMA Psychiatry 75(8):844–852. https://​doi.​org/​10.​1001/​jamapsychiatry.​2018.​1415CrossRef
19.
Zurück zum Zitat Øie M, Sundet K, Ueland T (2011) Neurocognition and functional outcome in early-onset schizophrenia and attention-deficit/hyperactivity disorder: a 13-year follow-up. Neuropsychology 25(1):25 Øie M, Sundet K, Ueland T (2011) Neurocognition and functional outcome in early-onset schizophrenia and attention-deficit/hyperactivity disorder: a 13-year follow-up. Neuropsychology 25(1):25
20.
Zurück zum Zitat Rajji T, Ismail Z, Mulsant B (2009) Age at onset and cognition in schizophrenia: meta-analysis. Br J Psychiatry 195(4):286–293 Rajji T, Ismail Z, Mulsant B (2009) Age at onset and cognition in schizophrenia: meta-analysis. Br J Psychiatry 195(4):286–293
21.
Zurück zum Zitat Frangou S (2013) Neurocognition in early-onset schizophrenia. Child Adolesc Psychiatr Clin 22(4):715–726 Frangou S (2013) Neurocognition in early-onset schizophrenia. Child Adolesc Psychiatr Clin 22(4):715–726
22.
Zurück zum Zitat Bombin I, Mayoral M, Castro-Fornieles J, Gonzalez-Pinto A, de la Serna E, Rapado-Castro M, Barbeito S, Parellada M, Baeza I, Graell M, Payá B, Arango C (2013) Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses. Psychol Med 43(4):757–768. https://doi.org/10.1017/S0033291712001535CrossRef Bombin I, Mayoral M, Castro-Fornieles J, Gonzalez-Pinto A, de la Serna E, Rapado-Castro M, Barbeito S, Parellada M, Baeza I, Graell M, Payá B, Arango C (2013) Neuropsychological evidence for abnormal neurodevelopment associated with early-onset psychoses. Psychol Med 43(4):757–768. https://​doi.​org/​10.​1017/​S003329171200153​5CrossRef
23.
Zurück zum Zitat Maziade M, Gingras N, Rodrigue C, Bouchard S, Cardinal A, Gauthier B, Tremblay G, Cote S, Fournier C, Boutin P, Hamel M, Roy MA, Martinez M, Merette C (1996) Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset. Br J Psychiatry 169(3):361–370 Maziade M, Gingras N, Rodrigue C, Bouchard S, Cardinal A, Gauthier B, Tremblay G, Cote S, Fournier C, Boutin P, Hamel M, Roy MA, Martinez M, Merette C (1996) Long-term stability of diagnosis and symptom dimensions in a systematic sample of patients with onset of schizophrenia in childhood and early adolescence. I: nosology, sex and age of onset. Br J Psychiatry 169(3):361–370
24.
Zurück zum Zitat Gillberg IC, Hellgren L, Gillberg C (1993) Psychotic disorders diagnosed in adolescence. Outcome at age 30 years. J Child Psychol Psychiatry 34(7):1173–1185 Gillberg IC, Hellgren L, Gillberg C (1993) Psychotic disorders diagnosed in adolescence. Outcome at age 30 years. J Child Psychol Psychiatry 34(7):1173–1185
26.
Zurück zum Zitat Lay B, Blanz B, Hartmann M, Schmidt MH (2000) The psychosocial outcome of adolescent-onset schizophrenia: a 12-year followup. Schizophr Bull 26(4):801–816 Lay B, Blanz B, Hartmann M, Schmidt MH (2000) The psychosocial outcome of adolescent-onset schizophrenia: a 12-year followup. Schizophr Bull 26(4):801–816
27.
Zurück zum Zitat Röpcke B, Eggers C (2005) Early-onset schizophrenia. Eur Child Adolesc Psychiatry 14(6):341–350 Röpcke B, Eggers C (2005) Early-onset schizophrenia. Eur Child Adolesc Psychiatry 14(6):341–350
31.
Zurück zum Zitat Wallwork R, Fortgang R, Hashimoto R, Weinberger D, Dickinson D (2012) Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res 137(1–3):246–250 Wallwork R, Fortgang R, Hashimoto R, Weinberger D, Dickinson D (2012) Searching for a consensus five-factor model of the Positive and Negative Syndrome Scale for schizophrenia. Schizophr Res 137(1–3):246–250
32.
Zurück zum Zitat Langeveld J, Andreassen OA, Auestad B, Færden A, Hauge LJ, Joa I, Johannessen JO, Melle I, Rund BR, Røssberg JI (2013) Is there an optimal factor structure of the Positive and Negative Syndrome Scale in patients with first-episode psychosis? Scand J Psychol 54(2):160–165 Langeveld J, Andreassen OA, Auestad B, Færden A, Hauge LJ, Joa I, Johannessen JO, Melle I, Rund BR, Røssberg JI (2013) Is there an optimal factor structure of the Positive and Negative Syndrome Scale in patients with first-episode psychosis? Scand J Psychol 54(2):160–165
33.
Zurück zum Zitat Liddle PF (1987) Schizophrenic syndromes, cognitive performance and neurological dysfunction. Psychol Med 17(1):49–57 Liddle PF (1987) Schizophrenic syndromes, cognitive performance and neurological dysfunction. Psychol Med 17(1):49–57
34.
Zurück zum Zitat Bilder RM, Mukherjee S, Rieder RO, Pandurangi AK (1985) Symptomatic and neuropsychological components of defect states. Schizophr Bull 11(3):409–419 Bilder RM, Mukherjee S, Rieder RO, Pandurangi AK (1985) Symptomatic and neuropsychological components of defect states. Schizophr Bull 11(3):409–419
35.
Zurück zum Zitat Dominguez MdG, Viechtbauer W, Simons CJ, van Os J, Krabbendam L (2009) Are psychotic psychopathology and neurocognition orthogonal? A systematic review of their associations. Psychol Bull 135(1):157 Dominguez MdG, Viechtbauer W, Simons CJ, van Os J, Krabbendam L (2009) Are psychotic psychopathology and neurocognition orthogonal? A systematic review of their associations. Psychol Bull 135(1):157
36.
Zurück zum Zitat Díaz-Caneja CM, Pina-Camacho L, Rodríguez-Quiroga A, Fraguas D, Parellada M, Arango C (2015) Predictors of outcome in early-onset psychosis: a systematic review. npj Schizophr 1:14005 Díaz-Caneja CM, Pina-Camacho L, Rodríguez-Quiroga A, Fraguas D, Parellada M, Arango C (2015) Predictors of outcome in early-onset psychosis: a systematic review. npj Schizophr 1:14005
38.
Zurück zum Zitat Smith TE, Hull JW, Huppert JD, Silverstein SM (2002) Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills. Schizophr Res 55(3):229–237 Smith TE, Hull JW, Huppert JD, Silverstein SM (2002) Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills. Schizophr Res 55(3):229–237
39.
Zurück zum Zitat Ventura J, Hellemann GS, Thames AD, Koellner V, Nuechterlein KH (2009) Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res 113(2–3):189–199 Ventura J, Hellemann GS, Thames AD, Koellner V, Nuechterlein KH (2009) Symptoms as mediators of the relationship between neurocognition and functional outcome in schizophrenia: a meta-analysis. Schizophr Res 113(2–3):189–199
40.
41.
Zurück zum Zitat Wedervang-Resell K, Friis S, Lonning V, Smelror RE, Johannessen C, Reponen EJ, Lyngstad SH, Lekva T, Aukrust P, Ueland T, Andreassen OA, Agartz I, Myhre AM (2019) Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms. Psychoneuroendocrinology. https://doi.org/10.1016/j.psyneuen.2019.104513CrossRef Wedervang-Resell K, Friis S, Lonning V, Smelror RE, Johannessen C, Reponen EJ, Lyngstad SH, Lekva T, Aukrust P, Ueland T, Andreassen OA, Agartz I, Myhre AM (2019) Increased interleukin 18 activity in adolescents with early-onset psychosis is associated with cortisol and depressive symptoms. Psychoneuroendocrinology. https://​doi.​org/​10.​1016/​j.​psyneuen.​2019.​104513CrossRef
42.
Zurück zum Zitat Juuhl-Langseth M, Holmén A, Thormodsen R, Øie M, Rund BR (2014) Relative stability of neurocognitive deficits in early onset schizophrenia spectrum patients. Schizophr Res 156(2–3):241–247 Juuhl-Langseth M, Holmén A, Thormodsen R, Øie M, Rund BR (2014) Relative stability of neurocognitive deficits in early onset schizophrenia spectrum patients. Schizophr Res 156(2–3):241–247
43.
Zurück zum Zitat Kaufman J, Birmaher B, Brent D, Rao UMA, Flynn C, Moreci P, Williamson D, Ryan N (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988. https://doi.org/10.1097/00004583-199707000-00021CrossRef Kaufman J, Birmaher B, Brent D, Rao UMA, Flynn C, Moreci P, Williamson D, Ryan N (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36(7):980–988. https://​doi.​org/​10.​1097/​00004583-199707000-00021CrossRef
44.
Zurück zum Zitat First MB, Spitzer RL, Gibbon M, Williams JB (2002) Structured clinical interview for DSM-IV-TR axis I disorders, research version. Biometrics Research, New York State Psychiatric Institute, New York, NY First MB, Spitzer RL, Gibbon M, Williams JB (2002) Structured clinical interview for DSM-IV-TR axis I disorders, research version. Biometrics Research, New York State Psychiatric Institute, New York, NY
46.
Zurück zum Zitat Pedersen G, Hagtvet KA, Karterud S (2007) Generalizability studies of the Global Assessment of Functioning-Split version. Compr Psychiatry 48(1):88–94 Pedersen G, Hagtvet KA, Karterud S (2007) Generalizability studies of the Global Assessment of Functioning-Split version. Compr Psychiatry 48(1):88–94
47.
Zurück zum Zitat American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4thth ed., text rev edn. American Psychiatric Association, Washington American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders, 4thth ed., text rev edn. American Psychiatric Association, Washington
48.
Zurück zum Zitat Endicott J, Spitzer RL, Fleiss JL, Cohen J (1976) The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 33(6):766–771 Endicott J, Spitzer RL, Fleiss JL, Cohen J (1976) The Global Assessment Scale: a procedure for measuring overall severity of psychiatric disturbance. Arch Gen Psychiatry 33(6):766–771
49.
Zurück zum Zitat Fett A-KJ, Viechtbauer W, Penn DL, van Os J, Krabbendam L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 35(3):573–588 Fett A-KJ, Viechtbauer W, Penn DL, van Os J, Krabbendam L (2011) The relationship between neurocognition and social cognition with functional outcomes in schizophrenia: a meta-analysis. Neurosci Biobehav Rev 35(3):573–588
50.
Zurück zum Zitat Schorre BEH, Vandvik IH (2004) Global assessment of psychosocial functioning in child and adolescent psychiatry. Eur Child Adolesc Psychiatry 13(5):273–286 Schorre BEH, Vandvik IH (2004) Global assessment of psychosocial functioning in child and adolescent psychiatry. Eur Child Adolesc Psychiatry 13(5):273–286
51.
Zurück zum Zitat Wechsler D (2007) Wechsler abbreviated scale of intelligence (WASI), Norwegian Manual Supplement (trans. B. Ørbeck, K. Sundet). Harcort Asessment Inc., Stockholm Wechsler D (2007) Wechsler abbreviated scale of intelligence (WASI), Norwegian Manual Supplement (trans. B. Ørbeck, K. Sundet). Harcort Asessment Inc., Stockholm
52.
Zurück zum Zitat Nuechterlein KH, Green MF (2009) MATRICS consensus cognitive battery, Norwegian Version (trans. BR Rund, KS Sundet). MATRICS Assessment Inc, Los Angeles, CA Nuechterlein KH, Green MF (2009) MATRICS consensus cognitive battery, Norwegian Version (trans. BR Rund, KS Sundet). MATRICS Assessment Inc, Los Angeles, CA
53.
Zurück zum Zitat Mayer JD, Salovey P, Caruso D (2002) Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT© V2.0). Multi-Health Systems, Toronto Mayer JD, Salovey P, Caruso D (2002) Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT© V2.0). Multi-Health Systems, Toronto
54.
Zurück zum Zitat Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR (2008) The MATRICS consensus cognitive battery, part 1: test selection, reliability, and validity. Am J Psychiatry 165(2):203–213. https://doi.org/10.1176/appi.ajp.2007.07010042CrossRef Nuechterlein KH, Green MF, Kern RS, Baade LE, Barch DM, Cohen JD, Essock S, Fenton WS, Frese FJ 3rd, Gold JM, Goldberg T, Heaton RK, Keefe RS, Kraemer H, Mesholam-Gately R, Seidman LJ, Stover E, Weinberger DR, Young AS, Zalcman S, Marder SR (2008) The MATRICS consensus cognitive battery, part 1: test selection, reliability, and validity. Am J Psychiatry 165(2):203–213. https://​doi.​org/​10.​1176/​appi.​ajp.​2007.​07010042CrossRef
55.
Zurück zum Zitat Kelleher I, Clarke MC, Rawdon C, Murphy J, Cannon M (2013) Neurocognition in the extended psychosis phenotype: performance of a community sample of adolescents with psychotic symptoms on the MATRICS neurocognitive battery. Schizophr Bull 39(5):1018–1026. https://doi.org/10.1093/schbul/sbs086CrossRef Kelleher I, Clarke MC, Rawdon C, Murphy J, Cannon M (2013) Neurocognition in the extended psychosis phenotype: performance of a community sample of adolescents with psychotic symptoms on the MATRICS neurocognitive battery. Schizophr Bull 39(5):1018–1026. https://​doi.​org/​10.​1093/​schbul/​sbs086CrossRef
56.
Zurück zum Zitat Smelror RE, Jørgensen KN, Lonning V, Kelleher I, Cannon M, DeRosse P, Malhotra AK, Karlsgodt KH, Andreassen OA, Lundberg M, Edbom T, Cleland N, Ueland T, Myhre AM, Rund BR, Agartz I (2019) Healthy adolescent performance with standardized scoring tables for the MATRICS consensus cognitive battery: a multisite study. Schizophr Bull 45(4):773–783. https://doi.org/10.1093/schbul/sby131CrossRef Smelror RE, Jørgensen KN, Lonning V, Kelleher I, Cannon M, DeRosse P, Malhotra AK, Karlsgodt KH, Andreassen OA, Lundberg M, Edbom T, Cleland N, Ueland T, Myhre AM, Rund BR, Agartz I (2019) Healthy adolescent performance with standardized scoring tables for the MATRICS consensus cognitive battery: a multisite study. Schizophr Bull 45(4):773–783. https://​doi.​org/​10.​1093/​schbul/​sby131CrossRef
58.
Zurück zum Zitat Army Individual Test Battery (1944) Manual of directions and scoring. War Department, Washington, DC Army Individual Test Battery (1944) Manual of directions and scoring. War Department, Washington, DC
59.
Zurück zum Zitat Spreen O, Strauss E (1998) A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary, 2nd edn. Oxford University Press, New York Spreen O, Strauss E (1998) A Compendium of Neuropsychological Tests: Administration, Norms, and Commentary, 2nd edn. Oxford University Press, New York
61.
Zurück zum Zitat Wechsler D (1997) WMS-III: wechsler memory scale administration and scoring manual. The Psychological Corporation, London Wechsler D (1997) WMS-III: wechsler memory scale administration and scoring manual. The Psychological Corporation, London
62.
Zurück zum Zitat Gold JM, Carpenter C, Randolph C, Goldberg TE, Weinberger DR (1997) Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry 54(2):159–165 Gold JM, Carpenter C, Randolph C, Goldberg TE, Weinberger DR (1997) Auditory working memory and Wisconsin Card Sorting Test performance in schizophrenia. Arch Gen Psychiatry 54(2):159–165
63.
Zurück zum Zitat Brandt J, Benedict RHB (2001) Hopkins verbal learning test-revised: professional manual. Psychological Assessment Resources, Lutz Brandt J, Benedict RHB (2001) Hopkins verbal learning test-revised: professional manual. Psychological Assessment Resources, Lutz
64.
Zurück zum Zitat Benedict RHB (1997) Brief visuospatial memory test—revised. Psychological Assessment Resources, Odessa Benedict RHB (1997) Brief visuospatial memory test—revised. Psychological Assessment Resources, Odessa
65.
Zurück zum Zitat Stern RA, White T (2003) Neuropsychological assessment battery (NAB). Psychological Assessment Resources, Lutz Stern RA, White T (2003) Neuropsychological assessment battery (NAB). Psychological Assessment Resources, Lutz
66.
Zurück zum Zitat Stone WS, Mesholam-Gately RI, Giuliano AJ, Woodberry KA, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Perkins DO, Tsuang MT, Walker EF, Woods SW, McCarley RW, Heinssen R, Green MF, Nuechterlein K, Seidman LJ (2016) Healthy adolescent performance on the MATRICS consensus cognitive battery (MCCB): developmental data from two samples of volunteers. Schizophr Res 172(1):106–113. https://doi.org/10.1016/j.schres.2016.02.003CrossRef Stone WS, Mesholam-Gately RI, Giuliano AJ, Woodberry KA, Addington J, Bearden CE, Cadenhead KS, Cannon TD, Cornblatt BA, Mathalon DH, McGlashan TH, Perkins DO, Tsuang MT, Walker EF, Woods SW, McCarley RW, Heinssen R, Green MF, Nuechterlein K, Seidman LJ (2016) Healthy adolescent performance on the MATRICS consensus cognitive battery (MCCB): developmental data from two samples of volunteers. Schizophr Res 172(1):106–113. https://​doi.​org/​10.​1016/​j.​schres.​2016.​02.​003CrossRef
68.
Zurück zum Zitat Nagle AM, Everhart DE, Durham TW, McCammon SL, Walker M (2006) Deception strategies in children: examination of forced choice recognition and verbal learning and memory techniques. Arch Clin Neuropsychol 21(8):777–785 Nagle AM, Everhart DE, Durham TW, McCammon SL, Walker M (2006) Deception strategies in children: examination of forced choice recognition and verbal learning and memory techniques. Arch Clin Neuropsychol 21(8):777–785
72.
Zurück zum Zitat Preacher KJ, Hayes AF (2008) Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 40(3):879–891 Preacher KJ, Hayes AF (2008) Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 40(3):879–891
73.
Zurück zum Zitat Hayes AF (2009) Beyond Baron and Kenny: statistical mediation analysis in the new millennium. Commun Monogr 76(4):408–420 Hayes AF (2009) Beyond Baron and Kenny: statistical mediation analysis in the new millennium. Commun Monogr 76(4):408–420
74.
Zurück zum Zitat Hayes AF, Scharkow M (2013) The relative trustworthiness of inferential tests of the indirect effect in statistical mediation analysis: does method really matter? Psychol Sci 24(10):1918–1927 Hayes AF, Scharkow M (2013) The relative trustworthiness of inferential tests of the indirect effect in statistical mediation analysis: does method really matter? Psychol Sci 24(10):1918–1927
75.
Zurück zum Zitat Tuulio-Henriksson A, Partonen T, Suvisaari J, Haukka J, Lönnqvist J (2004) Age at onset and cognitive functioning in schizophrenia. Br J Psychiatry 185(3):215–219 Tuulio-Henriksson A, Partonen T, Suvisaari J, Haukka J, Lönnqvist J (2004) Age at onset and cognitive functioning in schizophrenia. Br J Psychiatry 185(3):215–219
78.
Zurück zum Zitat Andreasen NC (1985) Positive vs. negative schizophrenia: a critical evaluation. Schizophr Bull 11(3):380–389 Andreasen NC (1985) Positive vs. negative schizophrenia: a critical evaluation. Schizophr Bull 11(3):380–389
79.
Zurück zum Zitat Carpenter WT Jr, Heinrichs DW, Wagman AMI (1988) Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry 145(5):578 Carpenter WT Jr, Heinrichs DW, Wagman AMI (1988) Deficit and nondeficit forms of schizophrenia: the concept. Am J Psychiatry 145(5):578
81.
Zurück zum Zitat Brown M, Kuperberg GR (2015) A hierarchical generative framework of language processing: linking language perception, interpretation, and production abnormalities in schizophrenia. Front Hum Neurosci 9:643 Brown M, Kuperberg GR (2015) A hierarchical generative framework of language processing: linking language perception, interpretation, and production abnormalities in schizophrenia. Front Hum Neurosci 9:643
82.
Zurück zum Zitat Holshausen K, Bowie CR, Mausbach BT, Patterson TL, Harvey PD (2014) Neurocognition, functional capacity, and functional outcomes: the cost of inexperience. Schizophr Res 152(2–3):430–434 Holshausen K, Bowie CR, Mausbach BT, Patterson TL, Harvey PD (2014) Neurocognition, functional capacity, and functional outcomes: the cost of inexperience. Schizophr Res 152(2–3):430–434
83.
Zurück zum Zitat Moritz S, Klein J, Desler T, Lill H, Gallinat J, Schneider B (2017) Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills? Psychol Med 47(15):2602–2612 Moritz S, Klein J, Desler T, Lill H, Gallinat J, Schneider B (2017) Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills? Psychol Med 47(15):2602–2612
Metadaten
Titel
Negative and disorganized symptoms mediate the relationship between verbal learning and global functioning in adolescents with early-onset psychosis
verfasst von
Runar Elle Smelror
Bjørn Rishovd Rund
Vera Lonning
Kjetil Nordbø Jørgensen
Kirsten Wedervang-Resell
Ole A. Andreassen
Torill Ueland
Anne M. Myhre
Ingrid Agartz
Publikationsdatum
08.02.2020
Verlag
Springer Berlin Heidelberg
Erschienen in
European Child & Adolescent Psychiatry / Ausgabe 12/2020
Print ISSN: 1018-8827
Elektronische ISSN: 1435-165X
DOI
https://doi.org/10.1007/s00787-020-01479-7

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