Trajectories of callous-unemotional traits from childhood to adolescence in referred youth with a disruptive behavior disorder who received intensive multimodal therapy in childhood.

PURPOSE: Our aims were to explore the developmental trajectories of callous-unemotional (CU) traits using a growth curve analysis in Italian children with disruptive behavior disorders treated with a multimodal intervention, and to test both predictors and distal outcomes of CU traits trajectories. PATIENTS AND METHOD: One hundred and sixty-eight children were enrolled, of whom 24 were lost in the follow-up and 144 were followed up from ages 8-9 to 14-15 years with four assessment points. Patients included 128 males (88.9%) with a mean age of 8.7 years, 96 with oppositional defiant disorder (66.7%) and 48 with conduct disorder (CD) (33.3%). The developmental trajectories of CU traits were assessed with the Inventory of Callous-Unemotional Traits (ICU). RESULTS: Our findings revealed that CU features were likely to fit a quadratic model from childhood to adolescence. The CU traits tended to decrease during childhood, with stabilization in adolescence and a significant variability in the growth curves. Pretreatment CD and higher levels of externalizing behavioral problems were associated with higher level of CU traits at baseline, whereas positive parenting was associated with lower levels. No significant effects were found for all the other predictors (socioeconomic status, negative parenting, combined pharmacotherapy). Regarding outcomes into adolescence, both higher levels of CU traits at the baseline and a lower decrease of CU traits across time points predicted a higher risk of CD diagnosis, and higher rate of referrals to mental health services and of substance use. Furthermore, pretreatment CD and negative parenting predicted a higher risk of substance use into adolescence. CONCLUSION: Our findings suggest that a close monitoring of CU traits in referred children with disruptive behavior disorders may help to detect the patients at higher risk of poor outcome.

A NATURALISTIC EXPLORATORY STUDY OF OBSESSIVE-COMPULSIVE BIPOLAR COMORBIDITY IN YOUTH.

BACKGROUND: Growing evidence supports the comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) in children and adolescents. Our aim is to further explore clinical and treatment implications of this comorbidity, as it appears in clinical practice. METHOD: The sample included 429 consecutive patients with BD and/or OCD as primary diagnoses, followed for a mean period of 6 months (range 4-9 months), 172 with BD (102 males, mean age 13.7±2.9 years), 169 with OCD (118 males, mean age of 13.2±2.7 years) and 88 with comorbid BD+OCD (56 males, mean age 14.2±2.6 years, 52 with BD as the primary diagnosis), followed for a mean period of 6 months (range 4-9 months). The comorbid group was compared to pure BD and OCD groups, to explore differential clinical and treatment features. RESULTS: The BD-OCD comorbidity was found in 33.8% of the BD patients and in 34.2% of the OCD patients. Age at onset of BD and OCD were not different in pure and "comorbid" groups. The comorbid group presented a higher occurrence of BD type II and hoarding symptoms, and more frequently received a psychotherapy and second generation antipsychotics, but it presented the poorest outcome in terms of response to treatments. Severity at baseline (clinical severity and functional impairment), hoarding obsessions and compulsions, and conduct disorder comorbidity were associated with a treatment non-response. LIMITATIONS: A selection bias may have increased the rate of comorbidity, as most of the patients were referred to our tertiary hospital for severe BD and/or OCD and pharmacological treatment. We have used CGI-I as an outcome measure, not a specific measure of BD or OCD symptoms' severity and improvement. The short duration of the follow-up may limit our conclusions. CONCLUSIONS: The timely identification of BD-OCD comorbidity may have relevant clinical implications in terms of symptomatology, course, treatment and outcome.

A Naturalistic Comparison of Methylphenidate and Risperidone Monotherapy in Drug-Naive Youth With Attention-Deficit/Hyperactivity Disorder Comorbid With Oppositional Defiant Disorder and Aggression.

BACKGROUND/PURPOSE: Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are frequently co-occurring in youth, but data about the pharmacological management of this comorbidity are scarce, especially when impulsive aggression is prominent. Although stimulants are the first-line medication for ADHD, second-generation antipsychotics, namely, risperidone, are frequently used. We aimed to assess effectiveness and safety of monotherapy with the stimulant methylphenidate (MPH) and risperidone in a consecutive sample of 40 drug-naive male youths diagnosed as having ADHD-combined presentation, comorbid with ODD and aggression, without psychiatric comorbidities, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). METHODS: Twenty males treated with MPH (mean age, 8.95 ± 1.67 years) and 20 males treated with risperidone (mean age, 9.35 ± 2.72 years), followed up to 6 months, were assessed according to efficacy measures (Child Behavior Checklist [CBCL], Clinical Global Impression-Severity [CGI-S] and Improvement [CGI-I], Children Global Assessment Scale), and safety measures. At the end of the follow-up, both medications were similarly effective based on CBCL subscales of aggression and rule-breaking behaviors, on Diagnostic and Statistical Manual of Mental Disorders-oriented oppositional defiant problems and conduct problems, and on CGI-S, CGI-I, and Children Global Assessment Scale, but only MPH was effective on CBCL attention problems and attention-deficit/hyperactivity problems. Risperidone was associated with weight gain and elevated prolactin levels. IMPLICATIONS/CONCLUSIONS: Although the nonrandomized, nonblind design limits the conclusions of our exploratory study, our findings suggest that when ADHD is comorbid with ODD and aggression MPH and risperidone are both effective on aggressive behavior, but only stimulants are effective on ADHD symptoms.

Evaluation of Improvement in Externalizing Behaviors and Callous-Unemotional Traits in Children with Disruptive Behavior Disorder: A 1-Year Follow Up Clinic-Based Study.

Multi-component interventions based on cognitive behavioral principles and practices have been found effective in reducing behavioral problems in children with disruptive behavior disorders (oppositional defiant disorder and conduct disorder). However, it is still unclear if these interventions can affect children's callous-unemotional traits, which are predictive of subsequent antisocial behavior. Furthermore, it could be important to identify empirically supported treatment protocols for specific disorders addressed by child mental health services. The present study aimed to test the following two hypotheses: first, the Coping Power (CP) treatment program is able to reduce externalizing behaviors in children with disruptive behavior disorders treated in a mental health care unit; second, the CP program can reduce children's callous unemotional traits. The sample included 98 Italian children, 33 treated with the CP program; 37 with a less focused multi-component intervention, and 28 with child psychotherapy. The results showed that the CP program was more effective than the other two treatments in reducing aggressive behaviors. Furthermore, only the CP program was associated with a decrease in children's callous unemotional traits. The CP program was also associated with lower rate of referrals to mental health services at one-year follow-up. These findings support the importance of disseminating manualized and focused intervention programs in mental health services.

Combined pharmacotherapy-multimodal psychotherapy in children with Disruptive Behavior Disorders.

Although multi-component psychotherapeutic interventions are first-line treatments for Disruptive Behavior Disorders (DBD), pharmacotherapy is often associated for more severe patients. Our aim was to explore effectiveness of an associated pharmacotherapy in referred children with DBD receiving a one-year psychotherapeutic intervention. Aggression, callous unemotional (CU) traits and emotional dysregulation were outcome measures. The sample included 144 children, aged 8-12 years, 41 (29%) with an ADHD comorbidity. Fifty-five (38%) patients received an additional pharmacotherapy with one medication, methylphenidate, a second generation antipsychotic, or a mood stabilizer. Data were collected before and after the one-year treatment. According to the Child Behavior Checklist (CBCL), aggressive behaviors, rule-breaking behaviors and emotional dysregulation improved in the whole group, as well as parent- and child-reported CU traits. The hierarchical regression model showed that additional pharmacotherapy significantly predicted lower scores at the CBCL aggressive behaviors and emotional dysregulation, but not CU traits at the end of the treatment. The interaction between methylphenidate and ADHD comorbidity predicted lower aggressive behaviors after the treatment. In summary, this naturalistic investigation suggest that an additional pharmacotherapy significantly improved aggression and emotional dysregulation, but not CU traits. When ADHD was comorbid, methylphenidate was more effective than antipsychotics or mood stabilizers in reducing aggression.

Callous unemotional traits in children with disruptive behavior disorder: Predictors of developmental trajectories and adolescent outcomes.

The present study investigated trajectories of Callous Unemotional (CU) traits in youth with Disruptive Behavior Disorder diagnosis followed-up from childhood to adolescence, to explore possible predictors of these trajectories, and to individuate adolescent clinical outcomes. A sample of 59 Italian referred children with Disruptive Behavior Disorder (53 boys and 6 girls, 21 with Conduct Disorder) was followed up from childhood to adolescence. CU traits were assessed with CU-scale of the Antisocial Process Screening Device-parent report. Latent growth curve models showed that CU traits are likely to decrease linearly from 9 to 15 years old, with a deceleration in adolescence (from 12 to 15). There was substantial individual variability in the rate of change of CU traits over time: patients with a minor decrease of CU symptoms during childhood were at increased risk for severe behavioral problems and substance use into adolescence. Although lower level of socio-economic status and lower level of parenting involvement were associated to elevated levels of CU traits at baseline evaluation, none of the considered clinical and environmental factors predicted the levels of CU traits. The current longitudinal research suggests that adolescent outcomes of Disruptive Behavior Disorder be influenced by CU traits trajectories during childhood.

Child behaviour checklist emotional dysregulation profiles in youth with disruptive behaviour disorders: clinical correlates and treatment implications.

Two Child Behaviour Checklist (CBCL) profiles were correlated to poor self-regulation, Deficient Emotional Self-Regulation (DESR) (elevation between 1 and 2 Standard Deviations (SD) in Anxiety/Depression, Aggression, Attention subscales), and Dysregulation Profile (DP) (elevation of 2 Standard Deviations or more). We explored youths with Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) whether these profiles are associated with specific clinical features. The sample included 57 patients with DESR profile and 41 with DP profile, ages 9 to 15 years, all assigned to a non-pharmacological Multimodal Treatment Program. No differences resulted between groups in demographic features, diagnosis ratio, and comorbidities with Attention Deficit Hyperactivity Disorder (ADHD), Bipolar Disorder (BD), and Anxiety Disorder. The DP group was associated with higher scores in Withdrawn, Social Problem, Thought, Rule Breaking, and Somatic CBCL subscales, and higher scores in Narcissism and Impulsivity (but not Callous-Unemotional (CU)), according to the Antisocial Process Screening Device (APSD). After treatment, patients with DESR improved their personality traits (Narcissistic and Callous-Unemotional, but not Impulsivity), while changes in CBCL scales were modest. Patients with DP improved scales of Attention, Aggression, Anxiety-Depression, Rule Breaking, Withdrawal, Social Problem and Thought, while personality features did not change. These results suggest diagnostic implications of CBCL profiles, and indications for targeted treatment strategies.

First adaptation of coping power program as a classroom-based prevention intervention on aggressive behaviors among elementary school children.

Children with high levels of aggressive behavior create a major management problem in school settings and interfere with the learning environment of their classmates. We report results from a group-randomized trial of a program aimed at preventing aggressive behaviors. The purpose of the current study, therefore, was to determine the extent to which an indicated prevention program, Coping Power Program, is capable of reducing behavioral problems and improving pro-social behavior when delivered as a universal classroom-based prevention intervention. Nine classes (five first grade and four second grade) were randomly assigned to intervention or control conditions. Findings showed a significant reduction in overall problematic behaviors and in inattention-hyperactivity problems for the intervention classes compared to the control classes. Students who received Coping Power Program intervention also showed more pro-social behaviors at postintervention. The implications of these findings for the implementation of strategies aimed at preventing aggressive behavior in school settings are discussed.

Efficacy of a multimodal treatment for disruptive behavior disorders in children and adolescents: focus on internalizing problems.

Disruptive Behavior Disorders (DBDs) are among the most common reasons for youth referrals to mental health clinics. Aim of this study is to compare short and medium term efficacy of a multimodal treatment program (MTP), compared to community care (treatment-as-usual, TAU). The sample included 135 youths with DBDs (113 males, age range 9-15 years, mean age 12±2.5 years) were assigned either to a MTP (n=64), or addressed to community care for a TAU (n=71). Outcome measures were the Child Behaviour Checklist (CBCL) and the Children's Global Assessment Scale (C-GAS). All subjects were assessed at the baseline (T0), after 1-year treatment (T1) and after a 2-year follow-up (T2). Compared with patients receiving TAU, youths in the MTP showed, both at T1 and T2, significantly lower scores on CBCL Externalizing Scale, Internalizing Scale, Anxious/Depressed, Social Problems, and Aggressive Behavior, and higher scores at the C-GAS. Improvement in Internalizing Scales was particularly evident, with a shift from the clinical to the non-clinical range. Rate of use of mental health services and scholastic failure were reduced in the MTP. It is suggested that the improvement of the Internalizing symptoms is a crucial component of the therapeutic process in this MTP.

Quetiapine monotherapy in adolescents with bipolar disorder comorbid with conduct disorder.

Bipolar Disorders (BD) are often comorbid with disruptive behaviour disorders (DBDs) (oppositional-defiant disorder or conduct disorder), with negative implications on treatment strategy and outcome. The aim of this study was to assess the efficacy of quetiapine monotherapy in adolescents with BD comorbid with conduct disorder (CD). A consecutive series of 40 adolescents (24 males and 16 females, age range 12-18 years, mean age 14.9 ± 2.0 years), diagnosed with a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime Version [K-SADS-PL]) according to American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision (DSM-IV-TR) criteria were included. All the patients were treated with quetiapine monotherapy (mean final dose 258 ± 124 mg/day, range 100-600 mg/day). At the end-point (3 months), 22 patients (55.0%) were responders (Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2 and CGI-Severity [CGI-S] ≤ 3 and improvement of at least 30% Children's Global Assessment Scale [C-GAS] during 3 consecutive months). Both CGI-S and C-GAS significantly improved (p<0.0001). Nine out of the 16 patients with suicidality (56.3%) had a reduction in this severe symptom during the follow-up. Nonresponders were more frequently males, and more frequently had an attention-deficit/hyperactivity disorder (ADHD) comorbidity. Eight patients (20.0%) experienced moderate to severe sedation and eight (20.0%) experienced increased appetite and weight gain. In these severely impaired adolescents, quetiapine monotherapy was well tolerated and effective in>50% of the patients.

Response to treatments in youth with disruptive behavior disorders.

OBJECTIVE: Predictors of poor response to treatments in youths with disruptive behavior disorders (DBDs), including conduct disorder (CD) and oppositional defiant disorder (ODD), are under-studied. Multimodal psychosocial interventions are the best option, but a significant portion of patients needs adjunctive pharmacotherapy. The concept of "psychopathy", and namely, the callous (lack of empathy and guilt) and unemotional (shallow emotions) trait, has been considered a possible specifier indicating a more severe subgroup of patients. We explored whether the callous-unemotional trait (CU) may affect the response to multimodal treatment in referred youths with DBDs. METHOD: 118 youths (102 males, age range 6-14years, mean age 11.1±2.5years) completed a 12-month multimodal intervention, 48 of whom (41%) needed an associated pharmacotherapy. The patients were assessed according to psychopathological profile (Child Behavior Checklist, CBCL), severity and improvement (Clinical Global Impression-Severity and Improvement scores, CGI-S and CGI-I), functional impairment (Children-Global Assessment Scale, C-GAS), and psychopathic dimension (Antisocial Process Screening Device, APSD), including CU dimension. RESULTS: 58 patients (49.2%) were non-responders. They had more frequently a diagnosis of CD than ODD, presented a comorbid mood disorder, higher CBCL scores in rule-breaking behavior, and higher APSD ("psychopathic") scores. Subjects with higher or lower CU differed only according to the rate of responders (35% vs. 60%, p<.05). The linear blockwise regression indicated that pre-treatment functional impairment (C-GAS) and baseline CU trait were predictors of non-response. The logistic regression indicated that only the value of baseline APSD-CU trait was a predictor of non-response. CONCLUSIONS: A careful assessment of baseline clinical functioning and psychopathological features, namely the psychopathic traits, can identify the most problematic patients, and has specific prognostic and treatment implications.

Predictors of nonresponse to psychosocial treatment in children and adolescents with disruptive behavior disorders.

OBJECTIVE: A crucial issue in youths with disruptive behavior disorders, including oppositional defiant disorder and conduct disorder, is the refractoriness to treatments. A multimodal approach with individual therapy to improve social skills and self-control and family and school interventions is the best psychosocial treatment. Predictors of poor response to psychosocial treatment remain understudied. We aimed at exploring whether callous (lack of empathy and guilt) and unemotional (shallow emotions) (CU) trait and type of aggression (predatory vs. affective) can affect response to psychosocial treatment in referred youths with disruptive behavior disorders. METHODS: The sample consisted of 38 youths (28 boys and 10 girls, age range: 6-14 years, mean age: 13.1 ± 2.6 years) diagnosed as having oppositional defiant disorder or conduct disorder according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria and a clinical interview (Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version), who completed a 6-month therapeutic program at our hospital. Patients were assessed according to severity and improvement (Clinical Global Impressions-Severity score [CGI-S] and CGI-Improvement score), functional impairment (Children's Global Assessment Scale [C-GAS]), type of aggression, predatory versus affective (Aggression Questionnaire), and CU dimension (Antisocial Process Screening Device and the Inventory of CU Traits). RESULTS: Among the 38 patients, 21 (55.3%) were responders and 17 (44.7%) were nonresponders, according to CGI-Improvement score and CGI-S. Nonresponders were more impaired at the baseline according to CGI-S and C-GAS. Nonresponders presented higher scores of predatory aggression, whereas affective aggression did not differ between groups. Nonresponders presented higher scores in CU trait of Antisocial Process Screening Device and in Inventory of CU total score (callous trait), but these differences did not survive Bonferroni correction. CONCLUSIONS: Severity at the baseline and predatory aggression are negative predictors of psychosocial treatment, but the role of the callous trait needs more exploration in larger samples. Further research may increase our diagnostic and prognostic capacities, thus improving our treatment strategies.

Effectiveness of lithium in children and adolescents with conduct disorder: a retrospective naturalistic study.

BACKGROUND: The most severe forms of conduct disorder (CD) are disabling conditions, often resistant to treatment and likely to evolve into antisocial behaviours. Mood stabilizers and atypical antipsychotics are often used to treat severe cases of CD, as are antidepressants and psychostimulants less frequently, despite a relative lack of efficacy data. Use of lithium in hospitalized children and adolescents with CD has been evaluated in a small number of studies. AIM: To explore the efficacy and tolerability of lithium (administered either as monotherapy or in association with atypical antipsychotics) in children and adolescents with CD and to identify variables associated with positive or negative responses to such treatment. METHODS: This retrospective study included 60 consecutive patients (46 males and 14 females; range 8-17 years; mean age 14.2 +/- 2.4 years) who were treated with lithium for CD diagnosed on the basis of the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime (K-SADS-PL) clinical interview and the DSM-IV criteria for CD. The sample consisted of 44 inpatients (who remained in hospital during the first 2 or 3 weeks of treatment and were then assessed as outpatients) and 16 outpatients; the follow-up period was 6-12 months (mean 8.4 +/- 2.2 months). While all patients were initially treated with lithium, an atypical antipsychotic could be added if necessary to achieve satisfactory control of symptoms. Outcome measures included the Modified Overt Aggression Scale (MOAS), the Clinical Global Impression-Severity (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, and the Aggression Questionnaire (which assessed the type of aggression, i.e. predatory vs affective). Patients were considered responders to pharmacological treatment at the end of the follow-up period if they satisfied all of the following criteria: >or=50% decrease in MOAS score, CGI-I score of 1 or 2 ('very much improved' or 'much improved') and CGI-S score of 0.8 indicates good treatment efficacy). RESULTS: At the end of follow-up, 29 of 60 patients (48.3%) were classified as responders (10 receiving lithium monotherapy and 19 receiving lithium plus atypical antipsychotic therapy). For the sample as a whole, mean total MOAS score improved significantly (p < 0.001) and the effect size (pre- vs post-treatment) was 1.03. Mean MOAS verbal, and physical towards objects and other persons aggression scores, both in patients taking lithium as monotherapy and those also taking an add-on atypical antipsychotic, also improved significantly (p < 0.001) and the effect size was >or=0.80 for all items. Improvement in mean MOAS self-aggression score (p < 0.001) and an effect size of 0.59 was found when an atypical antipsychotic was added to lithium therapy. Predictors of a positive response to treatment were less severe disease at baseline, lower MOAS aggression scores and an impulsive (affective, nonpredatory) type of aggression. Gastrointestinal adverse effects, polydipsia and increased urinary frequency, tremor and increased thyroid stimulating hormone levels were the most frequently reported adverse effects. Two patients discontinued treatment because of adverse effects (vomiting and thyroid dysfunction). CONCLUSION: Lithium alone or in combination with an atypical antipsychotic may reduce aggressive behaviours in children and adolescents with CD. The adverse effects of such therapy are relatively common but rarely severe.

Comorbidity of conduct disorder and bipolar disorder in clinically referred children and adolescents.

OBJECTIVE: The co-occurrence of conduct disorder (CD) and bipolar disorder (BD) has been frequently reported in referred children and adolescents. We address the implications of this comorbidity in a naturalistic sample of youths with BD, CD, and CD+BD. METHODS: The sample consisted of 307 patients (216 males and 91 females, age range 8-18 years, mean age 13.5 +/- 2.6 years) referred during a 5-year period and followed-up for at least 6 months, 106 with CD without BD, 109 with BD without CD, and 92 with CD+BD, diagnosed with a structured clinical interview (K-SADS-PL). RESULTS: Patients with CD alone were more predominantly males and with the lowest socio-economic status. Patients with CD without BD were the least severe at the baseline, while patients with BD alone presented the greatest improvement during the follow-up, and those with CD+BD had the poorest response. Patients with CD+BD presented higher rates of global aggression at the baseline, namely impulsive aggression, compared with CD alone, and the highest risk of substance abuse. Patients with BD alone presented higher rates of comorbid panic disorder and obsessive compulsive disorder, while patients with CD, with or without BD, had higher rates of ADHD. CONCLUSIONS: Bipolar-conduct disorder comorbidity may have meaningful implications in children and adolescents, in terms of presentation, course, and treatments.

Conduct disorder in referred children and adolescents: clinical and therapeutic issues.

OBJECTIVE: Studies on referred children and adolescents with conduct disorder (CD) have relevant implications for prevention and treatment. We addressed this issue in a large sample of youths with CD, considering age at onset, sex, and response to treatments as variables. METHODS: The sample consisted of 198 patients (153 males and 45 females; age range, 8-18 years; mean age, 13.2 +/- 2.6 years), consecutively diagnosed as having CD during a 5-year period. The diagnoses were based on fulfillment of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, according to historical information, prolonged observations, and a clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version). Three subtypes of aggressive behaviors-"predatory" (controlled, planned, and goal-oriented), "affective" (impulsive, explosive, and unprofitable), and "mixed" (with both the features)-were considered in this study. RESULTS: Patients with prepubertal onset were younger at referral and had a poorer socioeconomic status. Their condition was more severe at the baseline, but their response to treatments did not differ from those with adolescent onset. Predatory and affective aggression and attention deficit hyperactivity disorder comorbidity were higher in children with prepubertal-onset CD. Regarding to sex, females were older and had a lower socioeconomic status. Their condition was more severe at the baseline and presented higher scores in self-aggression, but they responded better to treatments. Rates of attention deficit hyperactivity disorder were significantly lower in females, whereas other comorbidities (including substance abuse) were similar between sexes. Nonresponders to treatments received less frequently a psychosocial intervention, have more severe condition at the baseline, presented a more severe verbal and physical aggression, a lower affective/predatory index, and a higher rate of substance abuse. CONCLUSIONS: Age at onset and sex may be critical variables for prognosis of CD. Psychosocial intervention can significantly improve the treatment response.