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Disponible online el 13 de Enero de 2022
Disorganization in first episode affective psychosis: Treatment response and clinical considerations from a 2-year follow-up study in a “real world” setting
Desorganización en el primer episodio de psicosis afectiva: respuesta al tratamiento y consideraciones clínicas de un estudio longitudinal de 2 años en el «mundo real»
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Lorenzo Pelizzaa,
Autor para correspondencia
lorpelizza@ausl.pr.it

Corresponding author.
, Emanuela Leucia, Davide Maestria, Emanuela Quattronea, Silvia Azzalib, Giuseppina Paulilloa, Pietro Pellegrinia
a Department of Mental Health and Pathological Addiction, Azienda USL di Parma, Largo Palli n. 1/A, 43100 Parma, Italy
b Department of Mental Health and Pathological Addiction, Azienda USL-IRCCS di Reggio Emilia, Via Amendola n.2, 43100 Reggio Emilia, Italy
Recibido 05 julio 2021. Aceptado 13 diciembre 2021
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Tablas (4)
Table 1. Clinical, sociodemographic and psychopathological characteristics of the FEAP total sample (n=75) at baseline.
Table 2. Baseline associations of PANSS “Disorganization” dimension score with psychopathology, functioning, sociodemographic and clinical features in the FEAP total group (n=75).
Table 3. Baseline associations of PANSS “Disorganization” dimension score with sociodemographic and clinical features in the FEAP total group (n=75).
Table 4. PANSS “Disorganization” dimension subscores and their associations with specialized treatment components of the Pr-EP program, functioning, psychopathology, clinical and sociodemographic characteristics along the 2-year follow-up period in the FEAP total sample (n=75).
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Abstract
Introduction

Disorganization is a crucial domain in affective psychoses. However, it has received poor research attention, especially at the illness onset. The aims of this study were: (a) to monitor the longitudinal course of disorganization in young people with first episode affective psychosis (FEAP) across 2 years of follow-up, and (b) to investigate any relevant correlation of disorganized symptoms with psychopathology, functioning and the specific treatment elements of an “Early Intervention in Psychosis” (EIP) protocol along the follow-up period.

Materials and methods

Seventy-five FEAP participants (aged 12–35 years) completed the Positive And Negative Syndrome Scale (PANSS) and the Global Assessment of Functioning (GAF). Spearman's rank correlation coefficients were calculated.

Results

During the follow-up, disorganized symptoms showed significant enduring positive correlations with PANSS items representing delusional thought content and uncooperativeness, as well as a persistent negative association with the GAF score. Across the 2-year follow-up period, FEAP individuals also had a relevant reduction in disorganization levels. This symptom decrease was specifically related with the combination of antipsychotic medication with the specific psychosocial components of our EIP intervention offered to FEAP patients during the first 12 months of treatment.

Conclusions

Disorganization is relevant in FEAP subjects already at their enrollment in specialized EIP protocols. However, it decreases over time, together with the delivery of specific, combined (person-tailored) EIP interventions.

Keywords:
Disorganization
First episode psychosis
Affective psychosis
Follow-up
Treatment response
Resumen
Introducción

La desorganización es un síntoma crucial en las psicosis afectivas que ha recibido poca atención de la investigación, especialmente al inicio de la enfermedad. Los objetivos de este estudio son: a) monitorear el curso longitudinal de la desorganización en los jóvenes con primer episodio de psicosis afectiva (PEPA) durante 2 años de seguimiento; b) examinar cualquier correlación relevante de la desorganización con la psicopatología general, el funcionamiento y los elementos específicos de tratamiento ofrecido en un programa de intervención temprana en psicosis (ITP) durante los 2 años de seguimiento.

Materiales y métodos

Un total de 75 participantes con PEPA (12-35 años) completaron la Positive And Negative Syndrome Scale (PANSS) y la Global Assessment of Functioning (GAF) y calculamos los coeficientes de correlación de Spearman.

Resultados

Durante el seguimiento, la desorganización mostró correlaciones positivas, significativas y duraderas con los ítems de la PANSS relacionados con el contenido delirante del pensamiento y la falta de cooperación, así como una asociación negativa pertinente y persistente con la puntuación de la GAF. Durante el seguimiento, los individuos con PEPA también tuvieron una reducción longitudinal significativa en los niveles de desorganización. Esta disminución se relacionó específicamente con la combinación de medicación antipsicótica y los componentes psicosociales específicos del tratamiento ofrecido a los pacientes con PEPA durante los primeros 12 meses de intervención.

Conclusiones

La desorganización es relevante en los pacientes con PEPA, ya en su inscripción en los protocolos especializados de ITP. En todo caso, la desorganización disminuye con el tiempo, junto con la realización de intervenciones específicas y combinadas de ITP (es decir, adaptadas a la persona).

Palabras clave:
Desorganización
Primer episodio de psicosis
Psicosis afectiva
Seguimiento
Respuesta al tratamiento
Texto completo
Introduction

In recent years, disorganization obtained increasing attention in psychosis research, due to its detrimental effect on daily functioning and social interactions.1,2 Disorganized dimension is frequent in patients with severe bipolar disorder (especially during manic episodes), in which it has been considered as an index of a core biological defect in information processing involving selective attention.3 Specifically, the ability to select/discard trivial sensory input appears to be lost in severe mania, resulting in the experience of flight of ideas, racing thoughts and “confusion”, also typically described by interviewers as a pressure of speech extending to thought incoherence and disorganization.4 Moreover, impaired ability to think, concentrate or make decisions is commonly reported by patients with major depressive episodes (especially in agitated depression).5 Recent empirical evidence also found that disorganized symptoms are common in adolescents and young people with early-onset bipolar disorder (especially in both first manic and first depressive episodes with psychotic features), where they are associated with more hospitalizations, lower inter-episodic functioning and poorer prognosis.2,6

However, despite assessing disorganized features in early-onset bipolar disorder has been considered a crucial issue in both research and clinical setting, reliable investigations on disorganization in first episode affective psychosis (FEAP) are still currently relatively scarce.7 This relatively lack of interest can be traced back to the relevance of disorganized symptoms within the traditional conceptualization of schizophrenia psychopathology.8 Moreover, another possible reason may be due to the fact that most of the widely used measures of disorganized symptoms in psychosis were primarily extracted with factor analysis methods using psychometric instruments specifically developed on the traditional, dichotomic (negative vs. positive) model of psychosis psychopathology.9 These scales were not calibrated for the specific assessment of disorganized features and the statistically extracted “Disorganization” factors often included items not typically representing disorganized symptoms (e.g. the “Disorientation” item of the Positive And Negative Syndrome Scale [PANSS]).10

Another critical area concerns whether disorganization and impairment in cognitive functions are discrete constructs. The nature of this link is still currently unclear.11 An important issue is the potential overlap between neurocognitive functioning and specific items commonly used for assessing disorganized symptoms in patients with psychosis (e.g. the PANSS “Difficulty in Abstract Thinking”, “Stereotyped Thought” and “Poor Attention” items).12

Finally, studies on disorganization have been mainly conducted in clinical samples of subjects with prolonged psychosis. To date, research in the early stages of illness (especially in FEAP individuals) is relatively scarce. Moreover, most of these investigations had a cross-sectional design. A lack of knowledge still affects the longitudinal course of disorganization in FEAP and its related treatment response. An in-depth knowledge on disorganization at the psychosis onset may also have the potential to inform specialized person-tailored interventions and to improve their effectiveness (also on long-term outcome and daily functioning).13

Starting from this background, the aim of this research was two-fold:

  • (a)

    to monitor the longitudinal stability of disorganization in young patients with FEAP along a 2-year follow-up period;

  • (b)

    to examine any relevant association of disorganization with functioning, psychopathology and sociodemographic characteristics, as well as with the specialized treatment components of an “Early Intervention in Psychosis” (EIP) program in FEAP individuals across the 2 years of follow-up.

To the best of our knowledge, no longitudinal study specifically investigating disorganized symptoms in young FEAP patients has been reported in the literature to date. We hypothesized a longitudinal decrease in disorganization severity during the follow-up period, together with the provision of specialized, evidence-based EIP interventions specifically targeting on functioning and major psychopathological aspects.

Materials and methodsSetting and participants

All the participants were recruited within the “Parma-EarlyPsychosis” (Pr-EP) program between January 2013 and May 2019. Pr-EP is an EIP protocol implemented in all adolescent and adult mental healthcare centers of the Parma Department of Mental Health, in Northern Italy (for details on the Pr-EP program, see Leuci et al., 2019).14 All FEAP subjects were in a subacute phase of the current illness episode and were under pharmacological treatment (i.e. antipsychotics, antidepressants or mood stabilizers []if necessary) for less than 2 months.

Inclusion criteria of the present research were: (a) age between 12 and 35 years; (b) specialist help-seeking request; (c) presence of FEAP within the DSM-IV-TR criteria for affective (bipolar or major depressive) psychosis (APA, 2000); and (d) a Duration of Untreated Psychosis ([DUP] defined as the time interval [in weeks] between the onset of psychotic symptoms and the first antipsychotic intake)15 of <2 years. Specifically, this DUP length was selected because it is usually considered the limit to start specific EIP interventions.16 In the present study, we decided to include FEAP patients with first psychotic episode of both mania and major depression because such psychopathological syndromes may alternatively characterize the early-onset of a bipolar disorder, especially in adolescence and young adulthood.17 Indeed, it has been reported that disorganization is relatively common in FEAP adolescents and young adults (i.e. in both first manic or first depressive episodes with psychotic features).2,6

Exclusion criteria were: (a) previous psychotic episodes within DSM-IV-TR diagnoses of both non-affective and affective psychosis18 or any other previous manic or major depressive episode without psychotic symptoms; (b) past exposure to antipsychotics (i.e. in a previous illness episode, before the Pr-EP recruitment) or first antipsychotic intake for more than 2 months in the current psychotic episode; (c) known intellectual disability (i.e. Intelligence Quotient <70); (d) current DSM-IV-TR substance dependence; and (e) neurological disorders or any other medical condition with psychiatric symptoms. Specifically, we considered past exposure to antipsychotic medication as an equivalent of past psychotic episode, in line with what was proposed by Yung and colleagues,19 who defined the psychosis threshold as essentially that at which antipsychotics would probably be started in the common clinical practice.

All subjects (and their parents, if minors) gave their informed consent prior to their inclusion in this study. Local relevant ethical approvals were obtained for the research (AVEN Ethics Committee: protocol n. 36102/09.09.2019). The present study has been also carried out in accordance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments including humans. The data that support the findings of the current research are available on request from the corresponding author. The data are not publicly available due to privacy/ethical restrictions.

Assessment

Psychopathological evaluation of this research included the PANSS and the Global Assessment of Functioning (GAF) scale.18 These instruments were administered by trained Pr-EP team members both at baseline and every 12 months during the 2-year follow-up period. Regular supervision sessions were used to ensure the inter-rater reliability (for details on the Pr-EP assessment battery, see also Landi et al., 2020).20

The PANSS is a widely used 30-item clinical interview for evaluating the severity of psychosis psychopathology. In accordance with what proposed by Shafer and Dazzi21 in a recent meta-analysis on the PANSS factor structure, the “Disorganization” dimension specifically included the following eight PANSS items: P2 “Conceptual Disorganization”, N5 “Difficulty in Abstract Thinking”, N7 “Stereotyped Thinking”, G5 “Mannerisms and Posturing”, G10 “Disorientation”, G11 “Poor Attention”, G13 “Disturbance of Volition” and G15 “Preoccupation”. The PANSS showed good psychometric properties in clinical populations of young Italian patients with first episode psychosis.22

The GAF is a widely used scale to specifically rate socio-occupational and clinical functioning in patients with mental disorders. Scores range from 1 (“severely impaired functioning”) to 100 (“extremely high functioning”). This instrument showed good validity and reliability in Italian clinical samples with early psychosis.23,24

Procedures and data analysis

At baseline, the axis-I diagnosis was made by at least two trained Pr-EP team members using the Structured Clinical Interview for DSM-IV-TR axis I Disorders (SCID-I).25 Subsequently, all FEAP individuals were then assigned to a specialized, multi-professional team (including a clinical psychologist, a psychiatrist and a case-manager for early rehabilitation), generally within 3 weeks from the enrollment in the Pr-EP protocol.26 To all FEAP participants, it was then offered a 2-year comprehensive intervention program including a psychopharmacological treatment (based on their symptom severity) and a multi-component psychosocial intervention (combining psychoeducational sessions for family members, individual psychotherapy oriented on cognitive-behavioral principles and a recovery-oriented case management), in accordance with current guidelines on the topic.27 Specifically, low-dose atypical antipsychotics were used as first-line treatment.28 Antidepressants, benzodiazepines and mood stabilizers were also used to treat anxiety, insomnia, depression and mood elevation.

Data were analyzed using the Statistical Package for Social Science (SPSS) for Windows, version 15.0.29 All tests were two-tailed with a significance level set at 0.05. In the FEAP total sample, Spearman's correlation coefficients were calculated to investigate any relevant association of disorganization with sociodemographic characteristics, functioning and psychopathology (both at baseline and across the 2-year follow-up period), as well as with the specific treatment components provided within the Pr-EP program. In accordance with a conventional approach proposed by Schober and colleagues,30 we defined the strength of the Spearman's correlation values as follows: 0.90–1.00=very strong correlation, 0.70–0.89=strong correlation, 0.40–0.69=moderate correlation, and 0.10–0.39=weak correlation. The Mann–Whitney U test was performed to compare continuous parameters in inter-subgroup analyses. The Wilcoxon test for repeated measures was used to investigate the longitudinal stability of disorganization along the 2-year follow-up period. The Holm–Bonferroni p value correction was performed to control the problem of multiple comparisons.31

Results

Over the course of this research, 75 FEAP patients (41 [54.7%] males; 64 [85.3%] white Caucasian) entered the Pr-EP protocol. According to the DSM-IV-TR criteria, 49 (65.3%) of them had a manic episode with psychotic features, while 26 (34.7%) had a major depressive episode with psychotic features. Sociodemographic and clinical features of the FEAP total sample at entry are shown in the Table 1. No difference in PANSS “Disorganization” dimension scores was found between FEAP patients with manic episode and those with major depressive episode both at baseline and at the end of the 2-year follow-up period (baseline: median [interquartile range]=21 [16–25] vs 18 [14–27], z=−0.704, p=0.481; 2-year assessment time=13 [9.50–16.50] vs 11 [8–15], z=−0.726, p=0.468).

Table 1.

Clinical, sociodemographic and psychopathological characteristics of the FEAP total sample (n=75) at baseline.

Variable  Total sample 
Gender (males)  41 (54.7%) 
Ethnic group (white Caucasian)  64 (85.3%) 
Age at entry (in years)  27 (21–34) 
Education (in years)  13 (10–13) 
DUP (in weeks)  36 (13–60) 
Hospitalization (as source of Pr-EP referral)  37 (49.3%) 
Past specialist contact  35 (46.7%) 
GAF score  45 (40–51) 
PANSS dimension scores
Positive dimension  17 (13–22) 
Negative dimension  22 (15–30) 
Disorganization  19 (14–25.25) 
Depressive dimension  15 (12–20) 
Excitement dimension  9 (6–12) 
PANSS total score  64 (54–78) 

Legend: Frequencies (percentages) and median (interquartile range) are reported. FEAP=First Episode Affective Psychosis; DUP=Duration of Untreated Psychosis; Pr-EP=“Parma-Early Psychosis” program; GAF=Global Assessment of Functioning, PANSS=Positive And Negative Syndrome Scale.

Baseline results

At the initial assessment (T0), PANSS “Disorganization” dimension subscore had significant positive correlations with PANSS total score and PANSS “Delusions”, “Unusual Thought Content”, “Hostility”, “Uncooperativeness” and “Tension” item subscores (Table 2). Moreover, it showed a statistically relevant negative correlation with the GAF score, regardless of the severity of manic and depressive symptoms, Indeed, also controlling for PANSS “Depression” and “Excitement” dimension subscores, negative correlation between disorganization and GAF score remained statistically significant (controlling for PANSS “Excitement” dimension subscore: ρ=−0.326, p=0.005; controlling for PANSS “Depression” dimension subscore: ρ=−0.385, p=0.001). Furthermore, no baseline associations of disorganization with negative symptoms, depression and excitement item subscores, sociodemographic and clinical characteristics (including hospitalization as source of Pr-EP referral and past specialist contact [i.e. in previous illness episodes, before the Pr-EP enrollment]) were observed (Table 3).

Table 2.

Baseline associations of PANSS “Disorganization” dimension score with psychopathology, functioning, sociodemographic and clinical features in the FEAP total group (n=75).

Variables  PANSS “Disorganization” factor score (ρ
PANSS items
P1 Delusions  0.462* 
P3 Hallucinations  0.332 
P4 Excitement  0.192 
P5 Grandiosity  0.211 
P6 Suspiciousness/Persecution  0.340 
P7 Hostility  0.422* 
N1 Blunted Affect  0.295 
N2 Emotional Withdrawal  0.332 
N3 Poor Rapport  0.302 
N4 Passive/Apathetic Social Withdrawal  0.243 
N6 Lack of Spontaneity/Flow of Conversation  0.142 
G1 Somatic Concern  0.140 
G2 Anxiety  0.270 
G3 Guilt Feelings  0.278 
G4 Tension  0.435* 
G6 Depression  0.070 
G7 Motor retardation  0.263 
G8 Uncooperativeness  0.522* 
G9 Unusual Thought Content  0.468* 
G12 Lack of Judgment and Insight  0.092 
G14 Poor Impulse Control  0.102 
G16 Active Social Avoidance  0.137 
PANSS Total Score  0.639* 
GAF  −0.414** 
Age at entry  0.085 
Years of education  −0.233 
DUP (in weeks)  −0.019 

Legend: PANSS=Positive And Negative Syndrome Scale; FEAP=First Episode Affective Psychosis; GAF=Global Assessment of Functioning scale; DUP=Duration of Untreated Psychosis; * Holm–Bonferroni corrected p value <0.001; ** Holm–Bonferroni corrected p value <0.01. Spearman's rank correlation coefficient (ρ) values are reported. Statistically significant correlations are in bold. Strength of the Spearman's correlation values are defined as follows: 0.90–1.00=very strong correlation, 0.70–0.89=strong correlation, 0.40–0.69=moderate correlation, and 0.10–0.39=weak correlation.

Table 3.

Baseline associations of PANSS “Disorganization” dimension score with sociodemographic and clinical features in the FEAP total group (n=75).

Males(n=41)  Females(n=34)  z(PANSS “Disorganization” subscale score) 
19 (14–27)  19 (14–22.25)  −0.750 
White Caucasians(n=64)  Other ethnic group(n=11)  z(PANSS “Disorganization” subscale score) 
19 (14–26)  17 (14–22)  −0.472 
Hospitalization(as source of PrEP referral)(n=37)  Other source of Pr-EP referral(n=38)  z(PANSS “Disorganization” subscale score) 
20.50 (15–26)  17.50 (13.75–22)  −1.370 
Past specialist contact(n=35)  No past specialist contact(n=40)  z(PANSS “Disorganization” subscale score) 
20 (15–26)  18 (14–25)  −0.629 

Legend: PANSS=Positive And Negative Syndrome Scale; FEAP=First Episode Affective Psychosis; Pr-EP=Parma early Psychosis program. Median (interquartile range) and Mann–Whitney U test (z) values are reported.

Additionally, also exclusively considering FEAP participants with manic episode, no significant baseline correlation of PANSS “Disorganization” subscale score with PANSS item subscores representing specific excitement features was found (PANSS “Excitement” item score: ρ=0.246; p=0.089; PANSS “Grandiosity” item score: ρ=0.309; p=0.097). Similarly, only considering FEAP patients with major depression, no baseline association of disorganization with PANSS item subscores capturing specific depressive characteristics was observed (PANSS “Depression” item score: ρ=−0.227; p=276; PANSS “Guilt Feelings” item score: ρ=0.183; p=0.379).

In the FEAP total group at entry, we notably found high prevalence rates of previous specialist contact (n=35; 46.7%) and hospitalization (n=37; 49.3%) (Table 1). Specifically, the most frequent DSM-IV-TR diagnoses in previous specialist contact were depressive disorders (n=14; 40%), conduct disorder (n=8; 22.8%), anxiety disorders (n=7; 20%) and learning disabilities (n=4; 11.4%).

Follow-up results

All FEAP subjects concluded the 2-year follow-up period. After the first year of treatment (T1), the median of individual psychotherapy sessions was 13.50 (interquartile range=9–19.75), the median of psychoeducational sessions for family members was 5 (interquartile range=2.50–8.50) and the median of case management sessions was 16 (interquartile range=9–24). At entry, 70 (93.3%) out of 75 FEAP participants were taking antipsychotics (mean equivalent dose of chlorpromazine=162.18±120.54mg/day). At the 1-year follow-up assessment time, antipsychotic medication was still prescribed to 53 (70.7%) FEAP patients (mean equivalent dose of chlorpromazine=123.35±114.88mg/day).

At the end of the 2-year follow-up period (T2), the median of individual psychotherapy sessions was 23 (interquartile range=15–30.25), the median of psychoeducational sessions for family members was 8.50 (interquartile range=7–12.75) and the median of case management sessions was 30 (interquartile range=15.17–46). At the T2 assessment, antipsychotic medication was still prescribed to 39 (52%) FEAP individuals (mean equivalent dose of chlorpromazine=162.50±122.96mg/day).

Across the 2 years of follow-up, a significant decrease in the PANSS “Disorganization” subscale score was observed (Table 4). Furthermore, the difference (delta) between T0 and T2 PANSS “Disorganization” dimension scores (i.e. the longitudinal improvement in disorganization levels) maintained statistically relevant positive correlations with deltas in T0 and T2 PANSS total scores and PANSS “Uncooperativeness” and “Tension” item subscores, as well as a significant negative correlation with the delta in T0 and T2 GAF scores. No longitudinal associations of PANSS “Disorganization” domain scores with negative symptoms, positive symptoms, depression and excitement item subscores, baseline clinical and sociodemographic features were found.

Table 4.

PANSS “Disorganization” dimension subscores and their associations with specialized treatment components of the Pr-EP program, functioning, psychopathology, clinical and sociodemographic characteristics along the 2-year follow-up period in the FEAP total sample (n=75).

Variable  Baseline (T0)  2-year (T2) follow-up assessment time  z 
PANSS “Disorganization” scores  19 (14–25.25)  11 (8.50–16.50)  −4.845* 
Variables(T0-T2 Delta PANSS scores)  T0-T2 Delta PANSS “Disorganization” score(ρ
PANSS items
P1 Delusions  0.372 
P3 Hallucinations  0.299 
P4 Excitement  0.327 
P5 Grandiosity  0.306 
P6 Suspiciousness/Persecution  0.243 
P7 Hostility  0.402 
N1 Blunted Affect  0.428 
N2 Emotional Withdrawal  0.360 
N3 Poor Rapport  0.200 
N4 Passive/Apathetic Social Withdrawal  0.157 
N6 Lack of Spontaneity/Flow of Conversation  0.159 
G1 Somatic Concern  0.215 
G2 Anxiety  0.389 
G3 Guilt Feelings  0.272 
G4 Tension  0.459** 
G6 Depression  0.195 
G7 Motor retardation  0.415 
G8 Uncooperativeness  0.428** 
G9 Unusual Thought Content  0.405 
G12 Lack of Judgment and Insight  0.179 
G14 Poor Impulse Control  0.176 
G16 Active Social Avoidance  0.094 
PANSS Total Score  0.700* 
GAF  −0.433** 
Variables  T0-T1 Delta PANSS “Disorganization” score(ρ) 
T0 equivalent dose of Chlorpromazine (mg/day)  0.228 
T1 equivalent dose of Chlorpromazine (mg/day)  0.124 
T1 number of individual psychotherapy sessions  0.085 
T1 number of family psychoeducational sessions  0.228 
T1 number of case management sessions  0.097 
Pr-EP combined interventions  0.401*** 
Variables  T0-T2 Delta PANSS “Disorganization” score(ρ
T0 equivalent dose of Chlorpromazine (mg/day)  0.026 
T1 equivalent dose of Chlorpromazine (mg/day)  0.154 
T2 equivalent dose of Chlorpromazine (mg/day)  0.102 
T2 number of individual psychotherapy sessions  −0.232 
T2 number of family psychoeducational sessions  0.090 
T2 number of case management sessions  0.009 
Pr-EP combined interventions  0.202 
Age at entry  −0.042 
Education (in years)  −0.124 
DUP (in weeks)  0.066 
T2 days of hospitalization  −0.227 
Males(n=41)  Females(n=34)  z(T0-T2 Delta PANSS “Disorganization” score) 
6.50 (2–10.50)  7 (3.75–10)  −0.288 
White Caucasian(n=64)  Other Ethnic Group(n=11)  z(T0-T2 Delta PANSS “Disorganization” score) 
6 (2–10)  9 (4.75–9.50)  −0.775 

Legend: PANSS=Positive And Negative Syndrome Scale; Pr-EP=Parma-Early Psychosis Program; FEAP=First Episode Affective Psychosis; T0=baseline; T1=1-year follow-up assessment time; T2=2-year follow-up assessment time; Pr-EP combined interventions=antipsychotic therapy+psychosocial treatments; median (interquartile range), Wilcoxon test (z), Sperarman's rank correlation coefficient (ρ) and Mann–Whitney U test (z) values are reported; ** Holm–Bonferroni corrected p value <0.001; ** Holm–Bonferroni corrected p value <0.01; *** Holm–Bonferroni corrected p value <0.05. Statistically significant results are in bold. Strength of the Spearman's correlation values are defined as follows: 0.90–1.00=very strong correlation, 0.70–0.89=strong correlation, 0.40–0.69=moderate correlation, and 0.10–0.39=weak correlation.

However, exclusively considering FEAP patients with manic episode, statistically relevant longitudinal correlations of the difference in T0 and T2 PANSS “Disorganization” subscale scores with deltas in T0 and T2 PANSS item subscores describing specific clinical characteristics of excitement were found (T0-T2 Delta PANSS “Excitement” item score: ρ=0.512; p=0.002; T0-T2 delta PANSS “Grandiosity” item score: ρ=0.513; p=0.002). Differently, only considering FEAP participants with major depression, no longitudinal associations of disorganization with deltas in T0 and T2 PANSS item subscores representing describing specific depressive features were observed (PANSS “Depression” item score: ρ=0.014; p=0.276; PANSS “Guilt Feelings” item score: ρ=0.133; p=0.610).

Finally, the delta in T0 and T1 PANSS “Disorganization” dimension scores had a statistically relevant positive correlation with the simultaneous delivery of the specific treatments (i.e. antipsychotic therapy+psychosocial intervention) offered to FEAP patients during the first year of the Pr-EP program (Table 4). However, this significant association was not confirmed at the end of the 2-year follow-up period.

Discussion

Our results showed a significant baseline correlation between disorganization levels and PANSS total score in FEAP patients. This suggests that disorganized symptoms may be overall considered as early psychopathological indices of global clinical severity in young people with FEAP already at their enrollment in specialized EIP programs.32,33 This finding is also in line with previous evidence on association between high baseline levels of disorganization and later transition to overt psychosis in individuals with at-risk mental states.34,35 In the present research, the link between disorganized symptoms and PANSS global severity was also enduring over time.

Psychopathological suggestions

We found significant enduring correlations (i.e. both at baseline and along the 2-year follow-up period) between disorganization and delusional thinking (specifically, PANSS “Delusions” and “Unusual Though Content” item scores [but not with the PANSS “Grandiosity” item subscore]). This supports that disorganized and positive symptoms may be considered as salient, comorbid psychopathological characteristics also in early-onset affective psychosis (i.e. in adolescents and young adults with early psychosis outside schizophrenia spectrum disorders).36,37 Therefore, differential diagnosis with schizophrenia should be routinely formulated in case of early-onset first episode psychosis.38 It remains to be clarified in our young FEAP population how commonly psychotic depression may precede psychotic mania. Indeed, depressive episodes are frequent at the onset of bipolar disorder, with incidence rates that vary from 50% to 80% in different studies.39

Furthermore, in the FEAP total group, no relevant correlations of disorganization with PANSS items specifically describing core features of excitement, depressive and negative symptom dimensions were observed. Only an enduring association between disorganized symptoms and PANSS “Tension” subscore (typically depicting a specific somatic characteristic of anxiety)10 was also found. Therefore, disorganization, negative symptoms, excitement and depression seem to be independent domains in the psychopathology of young FEAP patients. As the only exception, exclusively considering FEAP individuals with manic episode, persistent associations of severity in disorganized features with excitement and grandiosity were reported over time.

Our results also showed relevant baseline correlations of disorganized symptoms with some PANSS items representing clinical aspects involved in treatment resistance (i.e. hostility and uncooperativeness). In line with what has been previously reported in individuals with prolonged psychosis,40 this finding seems to suggest that severity in disorganization levels could play a negative role in treatment adherence in FEAP patients, already at their first specialist contact with specific EIP programs. Our evidence of an enduring relationship between disorganization and uncooperativeness also suggests that a longitudinal improvement in disorganized symptoms may contribute to increase compliance with specialized, evidence-based EIP interventions over time.

Moreover, results of this study showed a significant, persistent correlation between disorganization and decline in daily functioning, right from the patient's recruitment in a dedicated EIP program. This reduction seems to be independent from the baseline severity of manic or depressive symptoms. Longitudinal association between disorganization and functioning deterioration is in line with what was observed in previous research on individuals with prolonged bipolar disorder or chronic psychosis, suggesting that the most severely disorganized subjects have greater difficulties in real-world functioning.1,11 However, our evidence of a longitudinal improvement in disorganized symptoms matched an overtime increase in patient's daily functioning.

Finally, no associations of disorganization with hospitalization (as source of Pr-EP referral), DUP and sociodemographic features at entry were also found. On the contrary, Buoli and colleagues39 recently observed that duration of untreated illness in bipolar disorder resulted to be longer in individuals with early-onset psychotic symptoms (also including disorganized features). In this respect, Moller41 also found that high levels of disorganization in young people with first-episode psychosis were associated to a shortened DUP and could reduce treatment delay. However, as observed in our previous studies,20,42 the median DUP in young subjects with first episode psychosis decreased during the first six years of Pr-EP clinical activity. This could partially affect the difference in DUP results.

Treatment suggestions

Our results showed a decrease in disorganized dimension across a 2-year follow-up period. In the first year of treatment, this symptom reduction was significantly correlated with the simultaneous delivery of the psychosocial components of the Pr-EP program (i.e. family psychoeducation+individual psychotherapy+case management) and antipsychotic medication (although no specific Pr-EP intervention alone appeared to individually play a key role in the longitudinal decrement of disorganization levels). This seems to suggest the relevance of integrating specialized psychosocial treatments with antipsychotic therapy already at the onset of FEAP,43 together with the need of including specific therapeutic modules on disorganization in psychosocial interventions within EIP services, especially for better managing the severity of disorganized symptoms and other related, critical clinical dimensions (e.g. functioning deterioration, compliance with treatment, engagement in mental healthcare pathways),44 and to favor patients’ clinical and functional recovery, right from the FEAP onset. The intensity of EIP treatment sessions in the first years of intervention also seems to be a crucial parameter for improving patient's resilience and reducing the “drop-out” phenomenon.45 However, this interesting finding was not confirmed at the end of our follow-up. Considering that most of the Pr-EP psychosocial treatment sessions were provided within the first year of intervention,20 maintaining the same intensity of engagement in mental healthcare pathways at least still along 2–3 years of our Pr-EP protocol could further consolidate the longitudinal decrease in disorganized symptoms and the clinical/functional recovery of young FEAP patients.

Limitations

A first limitation was related to the assessment of the PANSS “Disorganization” dimension, which it has been mainly validated in patients with schizophrenia spectrum disorders. Although using this meta-analytic factor could be reasonable, it should be administered with caution across non-schizophrenia diagnostic groups. Further research is needed to determine the extent to which this structure model can be accurately applied outside schizophrenia spectrum disorders.

Moreover, another limitation involves the longitudinal stability of the disorganized construct along the illness course. Indeed, it has been reported a potential change in the PANSS “Disorganization” dimension structure overtime. In this respect, Amoretti and co-workers46 observed that disorganization factor did not have the same item composition at baseline and after a 2-year follow-up period in a clinical population of young patients with first episode psychosis. This potential factor instability could partially interfere with our longitudinal findings. Third, even if a strength of this research could be to have participants with FEAP within a “real-world” setting mainly engaged in providing optimal mental healthcare pathways within public, community psychiatric services, it should also be noted that our results are not also generalizable to individuals in different illness course (e.g. patients with prolonged affective psychosis and long-term medication).

Fourth, the current study was developed within an EIP protocol not specifically focused on disorganization. Indeed, psychometric assessment of major psychopathology in our research used the PANSS, which is a clinical instrument commonly administered in clinical populations with early psychosis, but not originally developed for disorganization. However, despite the lack of scales specifically centered on disorganization in young people with first episode psychosis and given the widespread use of the PANSS to assess psychopathology in such clinical samples, our findings have the potential to be replicated in other FEAP populations and offer a lead to further investigate disorganized symptoms in the early phases of affective psychosis. This is of crucial importance, since empirical studies on this topic are still relatively scarce and disorganized dimension has a detrimental effect on daily functioning and is predictive of poor prognosis.

Another weakness of this research is that we could not evaluate the potential link between neurocognitive functioning and disorganized symptoms (even if recent studies reported that they seem to be separate dimensions).8 Therefore, further investigations examining this relationship also in FEAP patients are needed. However, known intellectual disability was an exclusion criterion in this research.

Finally, another limitation was also the relatively small sample size. Thus, further research in larger clinical populations with FEAP to confirm our promising results are needed.

Conclusions

Disorganization is a relevant psychopathological dimension in young patients with FEAP already at their enrollment in specialized EIP programs, where it seems to be a stable, longitudinal index of psychopathological severity. Specifically, disorganized symptoms in FEAP patients show persistent correlations with decline in daily functioning and poor treatment adherence. However, improvement in disorganized features appears to be responsive to the simultaneous delivery of antipsychotic medication and specific psychosocial interventions provided to FEAP subjects in the first year of our EIP treatment.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Conflict of interest

None declared.

Acknowledgments

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sectors. The Pr-EP program was partly financed through a special, treatment-oriented regional fund: “Progetto Esordi Psicotici della Regione Emilia Romagna”.

For their facilitating technical and administrative support in the Pr-EP program, the authors gratefully acknowledge the “Early Psychosis Facilitators Group” members (Sabrina Adorni, Andrea Affaticati, Anahi Alzapiedi, Paolo Ampollini, Patrizia Caramanico, Maria Teresa Gaggiotti, Tiziana Guglielmetti, Mauro Mozzani, Matteo Rossi, Lucilla Maglio, Matteo Tonna, Fabio Vanni and Matteo Zito) and the “Quality Staff Group” members (Patrizia Ceroni, Stefano Giovanelli, Leonardo Tadonio) of the Parma Department of Mental Health and Pathological Addictions. The authors also wish to thank all the patients and family members who actively participated to the Pr-EP program.

References
[1]
P. de Sousa, W. Sellwood, M. Griffiths, R.P. Bentall.
Disorganisation, thought disorder and socio-cognitive functioning in schizophrenia spectrum disorders.
Br J Psychiatry, 214 (2019), pp. 103-112
[2]
L. Pelizza, E. Leuci, D. Maestri, E. Quattrone, S. Azzali, G. Paulillo, et al.
Examining disorganization in patients with first episode psychosis: findings from a 1-year follow-up of the “Parma early Psychosis” program.
Early Interv Psychiatry, (2021),
[3]
A.M. McIntosh, L.K. Harrison, K. Forrester, S.M. Lawrie, E.C. Johnstone.
Neuropsychological impairments in people with schizophrenia or bipolar disorder and their unaffected relatives.
Br J Psychiatry, 186 (2005), pp. 378-385
[4]
C.R. Lake.
Disorders of thought are severe mood disorders: the selective attention defect in mania challenges the Kraepelinian dichotomy: a review.
Schizophr Bull, 34 (2008), pp. 109-117
[5]
G. Sampogna, V. Del Vecchio, V. Giallonardo, M. Luciano, A. Fiorillo.
Diagnosis, clinical features and therapeutic implications of agitated depression.
Psychiatr Clin North Am, 43 (2020), pp. 47-57
[6]
E. Vieta, E. Salagre, I. Grande, A.F. Carvalho, B.S. Fernandes, M. Berk, et al.
Early Intervention in bipolar disorder.
Am J Psychiatry, 75 (2018), pp. 411-426
[7]
L. Pelizza, E. Leuci, D. Maestri, E. Quattrone, S. Azzali, G. Paulillo, et al.
Disorganization in first episode schizophrenia: treatment response and psychopatyhological findings from the 2-year follow-up of the “Parma Early Psychosis” program.
J Psychiatr Res, 141 (2021), pp. 293-300
[8]
A.R. Van Meter, C. Burke, E.A. Youngstrom, G.L. Faedda, C.U. Correll.
The bipolar prodrome: meta-analysis of symptom prevalence prior to initial or recurrent mood episodes.
J Am Acad Child Adolesc Psychiatry, 55 (2016), pp. 543-555
[9]
P.F. Liddle.
The symptoms of chronic schizophrenia: a re-examination of the positive-negative dichotomy.
Br J Psychiatry, 151 (1987), pp. 145-151
[10]
S.R. Kay, A. Fiszbein, L.A. Opler.
The Positive and Negative Syndrome Scale (PANSS) for schizophrenia.
Schizophr Bull, 13 (1987), pp. 261-276
[11]
P. Rocca, S. Galderisi, A. Rossi, A. Bertolino, P. Rucci, D. Gibertoni, et al.
Disorganization and real-world functioning in schizophrenia: results from the multicenter study of the Italian Network for Research on Psychoses.
Schizophr Res, 201 (2018), pp. 105-112
[12]
K.S. Minor, P.H. Lysaker.
Necessary, but non sufficient: links between neurocognition, social cognition and metacognition in schizophrenia are moderated by disorganized symptoms.
Schizophr Res, 159 (2014), pp. 198-204
[13]
M. Tonna, P. Ossola, C. Marchesi, E. Bettini, A. Lasalvia, C. Bonetto, et al.
Dimensional structure of first episode psychosis.
Early Interv Psychiatry, 13 (2019), pp. 1431-1438
[14]
E. Leuci, E. Quattrone, P. Pellegrini, L. Pelizza.
The “Parma-Early Psychosis” program: general description and process analysis after 5 years of clinical activity.
Early Interv Psychiatry, 14 (2019), pp. 356-364
[15]
L. Levi, M. Bar Haim, S. Burshtein, I. Winter-Van Rossum, S. Heres, M. Davidson, et al.
Duration of untreated psychosis and response to treatment: an analysis of response in the OPTiMiSE cohort.
Eur Neuropsychopharmacol, 32 (2020), pp. 131-135
[16]
P. Fusar-Poli, G. Salazar de Pablo, C.U. Correll, A. Meyer-Lindenberg, M.J. Millan, S. Borgwardt, et al.
Prevention of psychosis: advances in detection, prognosis, and intervention.
JAMA Psychiatry, 77 (2020), pp. 755-765
[17]
C. O’Donovan, M. Alda.
Depression preceding diagnosis of bipolar disorder.
Front Psychiatry, 11 (2020), pp. 500
[18]
American Psychiatric Association (APA).
Diagnostic and statistical manual of mental disorders, IV edition, Text Revision (DSM-IV-TR).
APA Press, (2000),
[19]
A.R. Yung, Y.P. Yuen, P.D. McGorry, L.J. Phillips, D. Kelly, M. Dell’Olio, et al.
Mapping the onset of psychosis: the comprehensive assessment of at-risk mental states.
Aust N Z J Psychiatry, 39 (2005), pp. 964-971
[20]
G. Landi, E. Leuci, E. Quattrone, S. Azzali, C. Pellegrini, P. Pellegrini, et al.
The “Parma-Early Psychosis” programme: characterization of help-seekers with first episode psychosis.
Early Interv Psychiatry, (2020),
[21]
A. Shafer, F. Dazzi.
Meta-analysis of the Positive and Negative Syndrome Scale (PANSS) factor structure.
J Psychiatr Res, 115 (2019), pp. 113-120
[22]
L. Pelizza, D. Maestri, E. Leuci, E. Quattrone, S. Azzali, G. Paulillo, et al.
Negative symptom configuration within and outside schizophrenia spectrum disorders: results from the “Parma Early Psychosis” program.
[23]
M. Poletti, L. Pelizza, S. Azzali, F. Paterlini, S. Garlassi, I. Scazza, et al.
Clinical high risk for psychosis in childhood and adolescence: findings from the 2-year follow-up of the ReARMS project.
Eur Child Adolesc Psychiatry, 28 (2019), pp. 957-971
[24]
L. Pelizza, C. Pellegrini, E. Quattrone, S. Azzali, G. Landi, P. Pellegrini, et al.
Suicidal ideation in patients experiencing a first-episode psychosis: findings from the 2-year follow-up of the “Parma Early Psychosis” program.
Suicide Life Threat Behav, 50 (2020), pp. 838-855
[25]
M.B. First, R.L. Spitzer, M. Gibbon, J.B.W. Williams.
Structured clinical interview for DSM-IV-TR axis I disorders (SCID-I).
New York State Psychiatric Institute, (2002),
[26]
E. Leuci, L. Pelizza, G. Landi, E. Quattrone, D. Maestri, S. Azzali, et al.
Personal health budget in patients with first episode psychosis: a new rehabilitation model based on a community care system in Italy.
Early Interv Psychiatry, (2021),
[27]
E. Miglietta, A. Lasalvia, C. Bonetto, C. Comacchio, D. Cristofalo, S. Tosato, et al.
Pathways to care, DUP and types of interventions over 5 years following psychosis onset: findings from a naturalistic study conducted in routine generalist mental health services.
Soc Psychiatry Psychiatr Epidemiol, 55 (2020), pp. 175-186
[28]
C.S. Yee, E.R. Hawken, R.J. Baldessarini, G.H. Vázquez.
Maintenance pharmacological treatment of juvenile bipolar disorder: review and meta-analyses.
Int J Neuropsychopharmacol, 22 (2020), pp. 531-540
[29]
SPSS Inc..
Statistical Package for Social Science (SPSS) for windows, version 15.0.
SPSS Inc. Press, (2010),
[30]
P. Schober, C. Boer, L. Schwarte.
Correlation coefficients: appropriate use and interpretation.
Anesth Analg, 126 (2018), pp. 1763-1768
[31]
S.A. Holm.
A simple sequentially rejective multiple test procedure.
Scand J Stat, 6 (1979), pp. 65-70
[32]
C. Rosen, R. Marvin, J.L. Reilly, O. Deleon, M.S.H. Harris, S.K. Keedy, et al.
Phenomenology of first-episode psychosis in schizophrenia, bipolar disorder, and unipolar depression: a comparative analysis.
Clin Schizophr Relat Psychoses, 6 (2012), pp. 145-151
[33]
L. Pelizza, S. Azzali, F. Paterlini, S. Garlassi, I. Scazza, L.R. Chiri, et al.
Characterization of young people with first episode psychosis or at ultra-high risk: the Reggio Emilia At-Risk Mental States (ReARMS) program.
Riv Psichiatr, 54 (2019), pp. 254-263
[34]
A. Raballo, B. Nelson, A. Thompson, A. Yung.
The comprehensive assessment of at-risk mental states: from mapping the onset to mapping the structure.
Schizophr Res, 127 (2011), pp. 107-114
[35]
A. Polari, S. Lavoie, H.P. Yuen, P. Amminger, G. Berger, E. Chen, et al.
Clinical trajectories in the ultra-high risk for psychosis population.
Schizophr Res, 197 (2018), pp. 550-556
[36]
A. Picardi, F. Battisti, G. de Girolamo, P. Morosini, B. Norcio, R. Bracco, et al.
Symptom structure of acute mania: a factor study of the 24-item Brief Psychiatric Rating Scale in a national sample of patients hospitalized for a manic episode.
J Affect Dis, 108 (2008), pp. 183-189
[37]
I.L. Fu-, W.S. Gurgel, S.C. Caetano, R. Machado-Vieira, Y.P. Wang.
Psychotic and affective symptoms of early-onset bipolar disorder: an observational study of patients in first manic episode.
Braz J Psychatry, 42 (2020), pp. 168-174
[38]
M. Poletti, L. Pelizza, S. Azzali, F. Paterlini, S. Garlassi, I. Scazza, et al.
Overcoming the gap between child and adult mental health services: the Reggio Emilia experience in an early intervention in psychosis program.
Early Interv Psychiatry, (2020),
[39]
M. Buoli, B.M. Cesana, A. Fagiolini, U. Albert, G. Maina, A. de Bartolomeis, et al.
Which factors delay treatment in bipolar disorder? A nationwide study focused on duration of untreated illness.
Early Interv Psychiatry, (2020),
[40]
A. Nestsiarovich, V. Obyedkov, H. Kandratsenka, M. Siniauskaya, I. Goloenko, N. Waszkiewicz.
Disorganization at the stage of schizophrenia clinical outcome: clinical-biological study.
Eur Psychiatry, 42 (2020), pp. 44-48
[41]
P. Moller.
First-episode schizophrenia: do grandiosity, disorganization and acute initial development reduce duration of untreated psychosis? An exploratory naturalistic case study.
Compr Psychiatry, 41 (2000), pp. 184-190
[42]
L. Pelizza, E. Leuci, G. Landi, D. Maestri, G. Paulillo, P. Ceroni, et al.
Personal Health Budget as a new rehabilitation model for severe mental illness within a caring community: an Italian evaluation study of beneficial effects.
Aust N Z J Psychiatry, 55 (2021), pp. 602-612
[43]
N. Albert, M.A. Weibell.
The outcome of early intervention in first episode psychosis.
Int Rev Psychiatry, 31 (2019), pp. 413-424
[44]
M.P. Marggraf, P.H. Lysaker, M.P. Salyers, K.S. Minor.
The link between formal thought disorder and social functioning in schizophrenia: a meta-analysis.
Eur Psychiatry, 63 (2020), pp. e34
[45]
L. Pelizza, M.L. Ficarelli, E. Vignali, S. Artoni, M.C. Franzini, S. Montanaro, et al.
Implementation of individual placement and support in Italy: the Reggio Emilia experience.
Community Ment Health J, 56 (2020), pp. 1128-1138
[46]
S. Amoretti, M. Verdolini, G. Mezquida, F.D. Rabelo-da-Ponte, M.J. Cuesta, L. Pina-Camacho, et al.
Identifying clinical clusters with distinct trajectories in first episode psychosis through an unsupervised machine learning technique.
Eur Neuropsychopharmacol, 47 (2021), pp. 112-129
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