The Efficacy of Cognitive-Behavioral Intervention in Reducing Positive and Negative Symptoms in Adolescents with Schizophrenia:

doi:10.21203/rs.3.rs-4811956/v1

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The Efficacy of Cognitive-Behavioral Intervention in Reducing Positive and Negative Symptoms in Adolescents with Schizophrenia:

https://doi.org/10.21203/rs.3.rs-4811956/v1

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Background: There is limited research on cognitive-behavioral interventions for treating individuals under 18 years of age with schizophrenia using single-subject methodology.

Method: This study employed a single-case experimental design with a multiple baseline approach. The participants were three adolescents under 18 years old diagnosed with schizophrenia. They participated in the baseline, treatment, and follow-up phases sequentially. The sampling method was purposive. During the study, participants were assessed using the PANSS (Positive and Negative Syndrome Scale) four times during the baseline phase, four times during the treatment phase, and once during the follow-up phase. Data were analyzed using graphical analysis, percentage of improvement, Cohen's d effect size, percentage of non-overlapping data (PND), and percentage of all non-overlapping data (PAND).

Results: The findings indicated a significant reduction in PANSS scores for positive and negative symptoms in all three participants after the cognitive-behavioral intervention, compared to the baseline scores.

Conclusion: Cognitive-behavioral therapy is effective in treating schizophrenia in adolescence, both during the intervention and follow-up phases.

Schizophrenia

Adolescence

Cognitive-Behavioral Intervention

Single-subject Study

Schizophrenia is a chronic and common mental disorder and one of the top ten causes of disability worldwide (Arango et al., 2022). According to the World Health Organization, 24 million people suffer from this disorder globally (Kumari & Tinger, 2020). The prevalence of schizophrenia spectrum disorders in Iran ranges from 0.5% to 0.89% (Rahim Mokar et al., 2014). Statistically, it is estimated that 765,400 individuals in Iran suffer from psychosis (Davari Nejad et al.). Schizophrenia is also the most costly mental disorder, with annual expenditures exceeding $155 billion in the United States (Mahmoud et al., 2021).

Schizophrenia in adolescence is often more severe than in adulthood (Morrison et al., 2020). A recent meta-analysis indicated that one-third of individuals develop this disorder before the age of 18 (Armando et al., 2015). Early-onset schizophrenia (ages 13-17) and very early-onset schizophrenia (before age 13) are associated with higher levels of auditory hallucinations, negative symptoms, more frequent relapses, poorer social functioning, severe cognitive deficits, and bizarre behaviors (Arango, 2022). These individuals often fail to achieve developmental and social milestones. Therefore, early -Onset schizophrenia may have a poorer prognosis and higher treatment needs compared to adult- onset schizophrenia. Failure to address the problem in adolescence can lead to more complicated treatments, increased disease rates, financial losses, and reduced quality of life for affected individuals and society. Prevention and treatment, especially non-pharmacological interventions, are crucial solutions. The National Institute for Health and Care Excellence (NICE) recommends that all patients with schizophrenia undergo a course of cognitive-behavioral therapy (Lee et al., 2015).

Cognitive-behavioral theories of delusions, as delineated by Garety et al. (2001), fall into two categories: motivational theories and deficit theories (Mackie et al., 2007). The motivational approach to delusions posits that these beliefs are attempts to cope with and reduce stress (Mahler, 1974; Gregory et al., 2010). Conversely, the deficit view attributes delusions to brain inefficiencies, suggesting that individuals experiencing hallucinations have intrusive thoughts and suffer from meta-worry—worry about worrying (Beechwood, 1994). Meta-analyses have demonstrated that cognitive-behavioral therapy (CBT) significantly impacts negative symptoms of schizophrenia (Velthorst et al., 2015). Despite advancements in schizophrenia treatment, complete recovery remains low, with only one in seven patients achieving full remission (Jääskeläinen et al., 2013). Some patients continue to exhibit symptoms and do not fully respond to medication (Correll et al., 2020), suffering from numerous distressing symptoms (Melle et al., 2005). Given these challenges, incorporating psychological interventions for individuals with schizophrenia is highly valuable. Meta-analyses have shown that CBT is one of the most effective psychological interventions for schizophrenia spectrum disorders and is recognized as a gold standard (Mehl et al., 2015). This therapy effectively reduces psychotic symptoms, associated disabilities, hospitalization frequency (Toomey et al., 2020), stress, and improves coping strategies and patients' quality of life (Rector et al., 2011). Compared to other psychological treatments, CBT has greater efficacy for individuals with schizophrenia, with an effect size of 0.16 (Wykes et al., 2014). A study concluded that individuals receiving continuous CBT over nine months showed improvement in delusions and hallucinations. Although CBT for psychosis has strong empirical support, there are inconsistent findings regarding its effectiveness in improving positive and negative psychotic symptoms, reducing symptom recurrence, lowering rehospitalization rates, and enhancing patients' mental health status (Jones et al., 2012; Krakowek, 2013).

At present, studies on the effectiveness of psychological treatments for early-onset psychosis in adolescents are limited. Most research has focused on adults, with insufficient studies on treatment and follow-up specifically for adolescents (Anderson et al., 2003; Stauffer et al., 2011; Morrison et al., 2020; Kazdin, 2021). There are very few studies utilizing a multiple baseline single-subject methodology to examine cognitive-behavioral therapy (CBT) for adolescents with schizophrenia, making such research quite rare (Shahram Vahedi & Ghojazzadeh, 2019; Carter & Wells, 2018). CBT for psychosis is predominantly conducted in group settings and less frequently on an individual basis (Saksa et al., 2009; Velthorst et al., 2006).

Furthermore, CBT is an emerging and scarce treatment, especially for adolescent schizophrenia in inpatient settings in Iran, where pharmacological approaches are the predominant mode of treatment. As a result, this study aims to determine whether cognitive-behavioral interventions are effective in reducing positive and negative symptoms in adolescents with schizophrenia.

Participants

The study involved three adolescents (two females and one male) diagnosed with schizophrenia.

Participant 1: A 17-year-old unmarried female, in her third year of high school, with a history of one hospitalization. Her predominant clinical presentation included auditory hallucinations and delusions, specifically believing that her mother was poisoning her food and that people from the television would come out and kill her.

Participant 2: A 14-year-old female, in her second year of middle school, also with a history of one hospitalization. Her clinical presentation included disorganized behavior and delusions. Disorganized behaviors were characterized by eating her menstrual blood and feces and public nudity. Her delusions included beliefs that her parents were not her real parents and that she would never die. She also had a history of suicidal thoughts, with symptoms beginning two years prior to the study.

Participant 3: A 17-year-old male, with an education level of the third grade of middle school, with symptoms starting four years prior. He had a history of attention deficit hyperactivity disorder (ADHD) from childhood, multiple hospitalizations, and a paternal diagnosis of schizophrenia. His predominant symptoms included grandiose delusions, paranoid delusional systems, believing that his neighbor was a witch, auditory hallucinations, inappropriate laughter, and suicidal thoughts.

Measures

Clinical Measures

K-SADS-PL Diagnostic Interview: The K-SADS-PL is a semi-structured diagnostic interview designed to provide detailed information on recent symptoms, age of onset, duration, and severity of psychiatric disorders in children and adolescents aged 6-17 years, based on the DSM-IV criteria. Studies conducted in Iran have demonstrated that the K-SADS-PL is a reliable tool with sufficient test-retest and inter-rater reliability (Ghanizadeh et al., 2006).

Positive and Negative Syndrome Scale (PANSS): This scale was developed to measure the severity of positive and negative symptoms in patients with schizophrenia. It consists of 33 items rated on a 7-point scale, assessing positive symptoms, negative symptoms, and other dimensions based on a semi-structured clinical interview (Kay et al., 1987). The alpha coefficients for the positive and negative subscales are 0.73 and 0.83, respectively, with Cronbach's alpha for the overall scale in Iran reported as 0.80 (Abolghasemi, 2007). Its validity has also been confirmed through factor analysis (Ghamari et al., 2010; Mirzaei et al., 2014)

Therapeutic Protocol: The intervention protocol was derived from the "Cognitive-Behavioral Therapy for Severe Mental Illness: A Comprehensive Manual" (Wright et al., 2009Refer to table number 1 below. The intervention sessions were conducted at the child and adolescent outpatient clinic of Razi Psychiatric University Hospital in Tabriz-Iran.

Table 1 Description of Cognitive-Behavioral Therapy Sessions

Session	Content and Assignments
1	Establishing rapport, obtaining case history, normalizing strategies, introducing therapy content, committing to session attendance, reading educational handouts on the therapy process.
2	Teaching mental health hygiene and explaining the rationale for therapy, functional analysis of psychotic symptoms, case summary, designing the treatment plan, completing the treatment goals worksheet.
3	Assessing the PANSS scale, educating on the impact of thoughts and beliefs on emotions and problem-solving abilities, creating a list of the individual’s delusions, challenging delusional thoughts.
4	Employing techniques to gather supporting and opposing evidence for delusional beliefs, using creative methods for reality testing, conducting behavioral experiments to test beliefs
5	Providing alternative interpretations, using techniques to assess supporting and opposing evidence for delusions and adopting different perspectives, assignment: daily thought recording in a three-column format, teaching the ABC model and problem-solving skills.
6	Assessing the PANSS scale, designing reality-testing experiments, identifying and modifying schemas, coping with resistant delusions, completing problem-solving worksheets, engaging in daily activities, normalizing hallucinations, evaluating hallucinations, interpreting the patient’s hallucinations, daily voice note-taking.
7	Using alternative explanations for hallucinations, employing the strategy of expanding logical interpretations, introducing strategies for 1) distraction (music, drawing) and 2) refocusing (correcting cognitive distortions related to voices, gathering supporting and opposing evidence for the content of voices), assignment: questioning a close person and recording voices, reading a booklet on the causes of hearing voices.
8	Introducing the third strategy: schema-based/metacognitive approach for dealing with hallucinations and cognitive continuum, using a coping card, completing two-column interpretations for hallucinations (ineffective interpretations, effective interpretations).
9	Assessing the PANSS scale, identifying negative schemas, coping with hallucinations using schema-based and metacognitive strategies, activating and increasing participation in pleasurable activities, reducing avoidance patterns, practicing confrontation and coping strategies for hallucinations, providing an activity planning worksheet.
10	Teaching behavioral skills and stress reduction, developing a self-care plan, thought table, step-by-step assignments, setting realistic goals for behavioral activation, setting attainable and hopeful goals, teaching social skills.
11	Empowering the patient to cope with lack of motivation and regain control over life, enhancing social functioning, identifying personal motivations, setting short-, mid-, and long-term goals, reviewing the relapse prevention plan, reinforcing learned skills, discussing realistic future goals, and setting strategies to maintain progress.
12	Assessing the PANSS scale, planning for the future, implementing relapse prevention strategies tailored to positive and negative symptoms, consolidating skills and techniques, reinforcing strategies to prevent relapse, ensuring treatment adherence, correcting negative cognitions about the illness.
13	Strengthening coping strategies, assessing PANSS, monitoring progress, addressing any ongoing challenges, planning for self-management, and monitoring early warning signs.

Procedure

This study employed a single- subject experimental design with a multiple baseline approach across different participants and continuous assessment. Participants underwent baseline, treatment, and follow-up phases sequentially. The sampling method was purposive, selecting participants based on specific inclusion and exclusion criteria.

Inclusion Criteria:

A- Diagnosed with schizophrenia according to DSM-IV criteria. Participants were initially selected based on a preliminary clinical diagnosis, followed by a structured diagnostic interview using the K-SADS-PL conducted by a child and adolescent psychiatrist. B- Age range of14-17 years. C- Minimum educational level of middle school completion. D- Normal IQ.

Exclusion Criteria:

A-Prior experience with psychological therapies, particularly CBT. B- Diagnosis of bipolar disorder, schizoaffective disorder, or other organic mental disorders. C- Concurrent personality disorders.

All three participants were evaluated using the PANSS scale after reaching medication stabilization (minimum of 2 months) before the commencement of CBT. Participants simultaneously entered the baseline phase and were randomized regarding the sequence of entering CBT, with each entering treatment one session (one week) apart. For instance, the first participant began treatment after two baseline assessment sessions in the third week. The second participant began in the second session of the first participant, and the third participant began in the second session of the second participant and the third session of the first participant.

Each participant underwen baseline assessment, 12 sessions of CBT intervention, and a follow-up session. Assessments were conducted during baseline, four times during treatment (sessions 3, 6, 9, and 12), and one follow-up session using research instruments. Written consent was obtained from the parents and participants for their participation in therapy sessions throughout the study. The study received ethical approval from Research Ethics Committee of Islamic Azad University - Tabriz Branch (ID IR.IAU.TABRIZ.1403.197)

Data analysis and efficacy determination were performed using visual representation methods or graphical analysis, improvement percentage, Cohen's d effect size, percentage of non-overlapping data (PND), and percentage of all non-overlapping data (PAND). Visual representation of data, adhering to criteria, indicates that observed changes are reliable and valid, resulting from the intervention rather than other factors (Kazdin et al., 2021).

Table 2 presents the descriptive statistics (mean, standard deviation, etc.) for the study participants during the baseline and intervention phases for both positive and negative symptoms. Each participant was assessed during three phases: baseline, intervention, and follow-up. Baseline assessments were continued until data stabilization was achieved. For some assessments, stability was reached after two data points, for others after three or more. To ensure stability in the baseline phase data, a stability envelope was plotted. When over 80% of the data points fell within the stability envelope, the baseline data were considered stable. As shown in Tables 3, 100% of the data for all participants' positive and negative symptoms fell within the stability envelope during the baseline phase.The same procedure was applied during the intervention phase for all three participants. For the intervention phase data, stability was assessed every three sessions (i.e., sessions three, six, nine, and twelve). If over 80% of the data points fell within the stability envelope, the data were deemed stable. If fewer than 80% of the data points were within the envelope, indicating that more than 20% of the data points were outside the envelope, the intervention phase data were considered variable. This variability in the intervention phase data indicates that the treatment resulted in significant changes in the participants' conditions.

After this intra-situational analysis for each phase (baseline and intervention) and each participant, an inter-situational analysis was conducted. As shown in Tables 4, and 5,and 6, the relative level change, absolute level change, mean level change, and the percentage of non-overlapping data (PND) and percentage of overlapping data (POD) were calculated. The goal of the present study was to reduce symptoms, aiming for a downward trend in symptom severity. As shown in these tables, the intervention led to a statistically significant reduction in symptoms for all participants, indicating the effectiveness of the intervention.Figures 1 and 2 illustrate the multiple baseline designs for three participants' positive and negative symptoms across the three experimental phases: baseline, intervention, and follow-up. As depicted in the graphs, data points for all participants were lower in the intervention phase compared to the baseline phase. Thus, cognitive-behavioral therapy was effective in reducing both positive and negative symptoms (each arrow in the chart represents an effect). The effects persisted into the follow-up phase, demonstrating the sustained impact of the intervention.

According to Table 5 (improvement percentage and effect size for positive symptoms), the intervention results for the first participant showed a Cohen's d effect size of 0.66, with a PAN (percentage of all non-overlapping data) of 99.5% and a PAND (percentage of all overlapping data) of 99.84%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were 70 and 73, respectively, which were statistically significant, indicating a high effect size and significant improvement in positive schizophrenia symptoms. Similarly, for the second participant, Cohen's d was 3.24, with PAN and PAND both at 100%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were 62 and 53, respectively, which were statistically significant. For the third participant, Cohen's d was 4.74, with PAN and PAND both at 100%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were 75 and 58, respectively, which were statistically significant.The overall improvement percentages for all participants during the intervention phase indicate a high improvement rate. Therefore, it can be concluded that the positive symptoms of the participants decreased compared to the initial assessment. The intervention led to an improvement in the behavioral performance of the participants in terms of positive symptoms.

Table 6 shows the improvement percentages and effect sizes for negative symptoms. For the first participant, the Cohen's d effect size was 15.71, with a PAN of 75% and a PAND of 99.8%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were both 74, which were statistically significant, indicating a high effect size and significant improvement in negative schizophrenia symptoms. Similarly, for the second participant, Cohen's d was 8.46, with PAN and PAND both at 100%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were 68, which were statistically significant. For the third participant, Cohen's d was 3.66, with PAN and PAND both at 100%, indicating a large effect size. The improvement percentages during the intervention and follow-up phases were 75 and 77, respectively, which were statistically significant.The patients demonstrated a significant reduction in the severity of negative symptoms during the intervention phase, leading to improved behavioral performance. This study utilized standard behavioral analysis techniques, including visual data point analysis through level and trend analysis. Initially, the results from the level analysis of the data points were examined, followed by trend lines using White's median split method.

Figures 1 and 2 illustrate the level and trend analysis results for the study participants across the three phases: baseline, intervention, and follow-up for both positive and negative symptoms. As depicted in Figure 1, the level of positive symptoms for the first participant showed a significant decrease from baseline to the intervention phase, with median behavior scores dropping from 28.5 during the baseline to 11.5 during the intervention phase, indicating a substantial reduction. Similarly, the level of positive symptoms for the second participant decreased from a median of 22 during the baseline phase to 12.5 during the cognitive-behavioral therapy (CBT) phase for schizophrenia. The follow-up phase score was 10, showing further reduction compared to the intervention phase.

The level analysis for the third participant revealed performance similar to that of the first and second participants. The median behavior scores for the third participant decreased from 30.5 during the baseline phase to 13.25 during the intervention phase, showing a significant reduction. Overall, the third participant demonstrated a marked decrease in symptoms during the treatment phase compared to the baseline, indicating a reduction in schizophrenia symptoms over the course of the therapeutic intervention and follow-up. The follow-up phase continued to show a sustained therapeutic trend.As shown in Figure 2, the level of negative symptoms for the first participant significantly decreased from the baseline to the intervention and follow-up phases. The median behavior scores dropped from 24.5 during the baseline phase to 8.5 during the intervention phase. Similarly, the level of negative symptoms for the second participant decreased from a median of 25 during the baseline phase to 8.16 during the CBT phase, with a follow-up phase score of 8, indicating further reduction compared to the baseline phase. The level analysis for the third participant indicated a sharp decrease in symptoms during the CBT phase compared to the baseline. Comparison of the performance levels of this participant between the baseline and intervention phases showed a reduction in schizophrenia symptoms over the course of the therapeutic intervention for negative symptoms, with continued improvement observed during the follow-up phase.

This study demonstrates the significant impact of cognitive-behavioral therapy in reducing both positive and negative symptoms in patients with schizophrenia. Visual and statistical analyses, including level and trend analysis, revealed substantial improvements across all participants. The intervention resulted in marked decreases in symptom severity, with effects persisting into the follow-up phase. These findings underscore the potential efficacy of cognitive-behavioral therapy in managing schizophrenia symptoms and improving behavioral performance in this population. Future studies with larger samples and diverse demographics are recommended to further validate these results and enhance their generalizability.

As shown in Figure 2, the level of negative symptoms for the first participant significantly decreased from the baseline to the intervention and follow-up phases. The median behaviors in the baseline phase were 24.5, which decreased to 8.5 during the intervention phase. Similarly, the level of behaviors for the second participant decreased from a median of 25 in the baseline phase to 8.16 during the cognitive-behavioral therapy intervention phase, with a follow-up phase score of 8, indicating a reduction compared to the baseline phase. The overall level of the third participant showed a sharp decrease during the cognitive-behavioral therapy phase compared to the baseline. Comparison of the performance levels of this participant between the baseline and intervention phases indicates a reduction in schizophrenia symptoms over the course of the therapeutic intervention for negative symptoms, with a continued decrease observed during the follow-up phase.

Table2 Percentage of descriptive data for participant during experimental phases

	Phases		Baseline	Intervention
	Participants	Index	Baseline	Intervention
Participants with Positive Symptoms	1	Mean	28.5	12.25
		Standard Deviation	1.5	8.07
		median	28.5	11.5
		Maxi	30	29
		Minimum Score	27	9
		Range	3	19
	2	Mean	23.66	12.25
		Standard Deviation	1.88	4.28
		median	22	12.5
		Maxi	25	16
		Minimum Score	21	8
		Range	4	8
	3	Mean	30	13.25
		Standard Deviation	3.5	3.56
		median	30.5	13.5
		Maxi	32	18
		Minimum Score	27	8
		Range	5	10
Participants with negative Symptoms	1	Mean	29	12.5
		Standard Deviation	2	0.38
		median	28.5	8
		Maxi	31	27
		Minimum Score	27	7
		Range	4	20
	2	Mean	24.6	8.5
		Standard Deviation	2.8	0.86
		median	25	8/16
		Maxi	28	10
		Minimum Score	21	8
		Range	7	2
	3	Mean	36.5	18.75
		Standard Deviation	2.06	6.53
		median	30.5	19.5
		Maxi	39	26
		Minimum Score	34	10
		Range	5	30

Note: The minimum score for both positive and negative symptoms is 7 and the maximum score for both positive and negative symptoms is 94.

Table 3 In-situ visual analysis variables for participants in positive and negative symptoms

Participant with positive symptoms	position sequence	Baseline stage			Intervention stage
	Participants	First	Second	Third	First	Second	Third
	Number of sessions	2	3	4	4	4	4
	style
	Stability chamber	34.2-22.8	30-20	36/6-24/4	13.8-9.2	15-10	16.2-10/8
	The percentage of dat in the stability chamber	100%	100%	100%	50%	50%	50%
	The range of stability chamber changes	Stable	Stable	Stable	Unstable	Unstable	Unstable
	Change of style
	Relative style change	3	4	3	10	4.5	5.5
	Absolute style change	3	4	5	17	8	10
	Process
	direction	at the same level	at the same level	at the same level	Descending	Descending	Descending
	Stability	Stable	Stable	Stable	Variable	Variable	Variable
	The percentage of dat in the stability chamber	100	100	100	50	50	50
Participants with negative symptoms	Style
	Stability chamber	34.2-22.8	30-20	43.8-29.2	9.6-6.4	9.8-6.5	23.4-15.6
	The percentage of dat in the stability chamber	100%	100%	100%	75%	75%	75%
	The range of stability chamber changes	Stable	Stable	Stable	Unstable	Unstable	Unstable
	Change of style
	Relative style change	-4	3.5	4	10	1	12.5
	Absolute style change	4	7	5	20	2	16
	Process
	direction	at the same level	at the same level	at the same level	Descending	Descending	Descending
	Stability	Stable	Stable	Stable	variable	variable	variable
	The percentage of dat in the stability chamber	100	100	100	75%	75%	75%

Table 4 Visual analysis between situations for clients in positive and negative symptoms

Comparison of the situation	Baseline and intervention phase
Participants	First	Second	Third
Trend changes
Changing Direction
Trend type	negative	negative	negative
Trend type	Stable to variable	Stable to variable	Stable to variable
change of style in positive symptoms
Relative style change	27 to 19.5	25 to 14	28.5 to 15.5
Absolute style change	27 to 26	25 t0 16	27 to 18
middle change	28.5 to 11.5	25 to 12.5	30.5 to 13.5
Average change	28.5 to 14.5	23.6 to 12.25	30 to 13.25
change of style in negative symptoms
Relative style	31 t0 17.5	24.5 to 9	34.5 t0 25
Absolute style	31 to 27	21 to 10	34 to24
middle change	29 to 8	25 to 8	36.5 to 19.5
Average change	29 to 12.5	24.6 to 8.5	36.5 to 18.75

Table 5 Recovery percentage and effect size of positive symtoms for research participants

	score			Mean		Standard Deviation		Recovery Percentage		PND	POD	PAND	Effect Size
Participant	Final Baseline	Intervention	Follow-up	Baseline	Intervention	Baseline	intervention	Intervention	Follow-up	Intervention	Intervention	Intervention	Intervention
1	27	9	8	28.5	15.25	1.5	8.07	70%*	73%^*	99.5	0.5	99.84	0.66*
2	25	8	10	23.6	12.25	1.8	4.28	62*	53*	100	0	100	3.24*
3	30	8	13	30	13.25	3.5	3.56	75*	58*	100	0	100	4.74*

Note: All numbers with asterisks are significant

Table 6 Recovery percentage and effect size of negative symptoms for research participants

	score			Mean		Standard Deviation		Recovery Percentage		PND	POD	PAND	Effect Size
Participant	Final Baseline	Intervention	Follow-up	Baseline	Intervention	Baseline	Baseline	Intervention	Follow-up	Intervention	Intervention	Intervention	Intervention
1	31	7	7	29	12.5	2	0.38	74%*	74%*	75%	25%	99.8%	15.71*
2	21	8	8	24.6	8.5	2.8	0.86	68%*	68%*	100%	0	100%	8.46*
3	37	10	9	36.5	18.7	2.06	6.5	75%*	77%*	100%	0	100%	3.66*

Note: All numbers with asterisks are significant

This study aimed to evaluate the efficacy of cognitive-behavioral therapy (CBT) in altering the symptoms of adolescents with schizophrenia. Supporting our hypothesis, we found that all three participants showed significant improvement and changes in positive symptoms following the CBT intervention. Visual data analysis indicated that positive symptoms decreased during the intervention phase for all three adolescent participants compared to the baseline, suggesting that CBT effectively reduced positive schizophrenia symptoms during adolescence. These findings align with the claims of proponents of CBT, who argue that it targets cognitive-behavioral factors effectively (Zafar Bekiroglu & Larion, 2019; Jones et al., 2020; Muller et al., 2020; Khakbaz, 2023).

Conversely, some studies have shown that the efficacy of CBT on positive symptoms of schizophrenia is not entirely satisfactory (Zimmerman et al., 2005; Jauhar et al., 2014). These studies suggest that while CBT shows promise as an adjunctive treatment, its impact on positive symptoms may be limited, highlighting the need for further investigation and the development of alternative interventions. Additionally, another study (Startup, 2004) found that CBT had limited acceptance among patients with schizophrenia. Krakovic et al. demonstrated that group CBT for psychotic symptoms in 45 patients improved both positive and negative symptoms, maintaining this improvement for up to 12 months. However, symptoms recurred post this period, challenging the efficacy of this treatment, particularly for negative symptoms and auditory hallucinations. Jauhar et al. (2014) also showed that the efficacy of CBT for psychosis is not always verifiable, necessitating more trials for schizophrenia patients.

Some studies, such as those by Ikio and Jauhar (Wu et al., 2005), found CBT to be effective for all psychotic symptoms. However, studies by Van der Gaag and Zimmerman (Van der Gaag et al., 2018; Zimmerman et al., 2005) refuted this, showing CBT's efficacy only for positive psychotic symptoms. Moreover, according to a study, the effect sizes from efficacy studies may not be generalizable to different clinical settings or populations (Morrison et al., 2004).

The follow-up results in this study also showed significant changes in positive symptoms, demonstrating CBT's efficacy one month post-intervention. These follow-up findings align with some studies (Gumley et al., 2003; Klingberg et al., 2011) but differ from others (Smith et al., 2003). Our hypothesis also indicated that the reduction in participants' scores on the PANSS scale from baseline to the end of the twelfth session illustrates the impact of CBT on negative schizophrenia symptoms in all three adolescents. These findings align with the proponents' claims that CBT targets cognitive-behavioral factors (Klingberg et al., 2008 & 2011; Wykes et al., 2008; Guo et al., 2017; Makanjuola et al., 2020; Khakbaz, 2023), creating significant changes in negative symptoms. However, our findings differ from recent studies (Velthorst et al., 2015), which did not show significant reductions in negative symptoms.

Most recent studies (post-2004) did not report significant reductions in negative symptoms, though some did report notable improvements (with moderate to large effect sizes). Velthorst et al. identified individualized interventions (such as single-subject designs) as more successful than group interventions in reducing negative symptoms. This suggests that single-subject approaches are better suited for addressing maladaptive thinking patterns (social withdrawal) (Kazdin, 2021). Hence, using the single-subject method for adolescents with schizophrenia is a strength of this study and, as far as we know, is unique in evaluating the efficacy of CBT on both positive and negative symptoms in adolescents with schizophrenia. The follow-up results also showed significant changes in negative symptoms for adolescents with schizophrenia, consistent with other studies (Farooq Naeem et al., 2016; Zafar Bekiroglu & Goulari, 2019; Gumley et al., 2003; Pretiolitis et al., 2009; Muller et al., 2020; Xu et al., 2023), but differing from others (Zimmerman et al., 2005; Klingberg et al., 2008).

Overall, this study's findings show significant reductions in PANSS scores for both positive and negative symptoms in all three patients compared to baseline and follow-up scores. These results can be observed in the trend change charts of positive and negative symptoms, improvement percentages, and effect sizes in treatment targets. This study aligns with Morrison's (2020) findings, which demonstrated that CBT significantly reduces general and specific symptoms in schizophrenia patients, even those who refuse antipsychotic medications. Furthermore, Wykes (2014) in a meta-analysis review showed that CBT not only impacts positive and psychotic symptoms but also other symptoms such as functioning. Our findings align with Melissa (2019), who recommended medication and psychological interventions, particularly family and cognitive-behavioral interventions, for adolescents, considering psychological interventions a significant advancement in treating adolescent schizophrenia. Our findings also align with McCarthy (2018), who suggested that CBT reduces positive and negative symptoms, highlighting CBT's potential in treating psychotic symptoms and combining CBT with cognitive remediation for schizophrenia.

In adolescent schizophrenia treatment, Sarrin (2011) applied three therapeutic methods: antipsychotic medication, CBT, and a combined approach in adolescents aged 14-18. The results showed that the combined treatment had the most significant impact. Sarrin also found significant efficacy of psychological treatments over medication alone in adolescents aged 14-18. Clinically, CBT is essential as it aims to change dysfunctional thoughts and replace them with realistic and adaptive thoughts, reducing patients' engagement with delusions and hallucinations (Farooq Naeem et al., 2016). Hence, according to specialists (Smith et al., 2003), CBT through cognitive restructuring, exposure, coping cards, questioning delusional beliefs, reassessing personal experiences, developing alternative strategies, and normalization techniques effectively reduces negative emotions related to positive and negative symptoms, changing lifestyles, and improving patients' quality of life. CBT's positive effects may be due to its techniques such as normalization and changing dysfunctional cognitions and behaviors (Warmann et al., 2003). These skills learned during sessions can be used by patients post-treatment. Moreover, the mechanism of homework execution leads to therapeutic changes (Lee et al., 2015). Clinically, for treating schizophrenia, it should be noted that adolescents experiencing the first episode of schizophrenia (FES) respond better to treatment compared to patients with recurrent episodes. This means that individuals newly diagnosed with schizophrenia are more likely to improve symptoms during treatment. Adequate response to treatment in FES is associated with favorable outcomes, indicating that early intervention and effective management strategies can significantly impact the disease's progression (Shena et al., 2012). Early intervention along with adherence to treatment, including CBT, can lead to better quality of life, improved outcomes, symptom management, and overall well-being for adolescents with schizophrenia. Adherence to treatment can help adolescents with schizophrenia experience improved social, academic, and professional functioning (Lutz et al., 2021)

The main Limitation of this study was the sample size due to the low prevalence of adolescent schizophrenia. It took approximately two years to select and enroll adolescent schizophrenia samples simultaneously. Also, due to ethical considerations, it was impossible to implement CBT Without pharmacotherapy. The findings of this study cannot be generalized to the entire population; therefore, it is recommended that the study be conducted With a larger sample size and a Wider geographic range for generalizability. Moreover, the same therapeutic method should be applied to samples not voluntarily taking medication for more precise results, and the number of intervention and follow-up sessions should be increased to examine the intervention’s effects’ continuity. A strength of this study is the single- subject design, which focuses on the intervention’s efficacy on individual patients and strictly controls interfering factors, highlighting the efficacy of CBT for adolescents with schizophrenia and starting treatment after medication stabilization.

Cognitive-behavioral therapy was effective in reducing positive and negative symptoms in adolescents with schizophrenia during both the CBT intervention and the follow-up period.

Conflict of Interest: The authors declare that they have no conflict of interest.

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The Efficacy of Cognitive-Behavioral Intervention in Reducing Positive and Negative Symptoms in Adolescents with Schizophrenia:

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