Clinical and research implications of panic-bipolar comorbidity in children and adolescents.

A substantial portion of patients with juvenile bipolar disorder (BD) have a comorbid panic disorder (PD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. The sample comprised 224 referred children and adolescents with BD, 140 males (62.5%) and 84 females (37.5%), mean age 13.8+/-2.8 years, diagnosed with a clinical interview (K-SADS-PL), and followed up naturalistically for 6 months. Fifty-one BD patients (22.8%) had a lifetime diagnosis of comorbid PD. Subjects with BD+PD and those without BD (BD-noPD) did not differ according to index age, age at onset of BD and bipolar phenotype (episodic vs. continuous course, irritable vs. elated mood). BD+PD was more frequent in females, was less severe at baseline according to the Clinical Global Impression severity score, and was more frequently associated with BD type 2. Moreover, BD+PD presented higher rates of comorbid anxiety disorders (namely separation anxiety disorder) and lower rates of externalizing disorders, namely attention deficit disorder (ADHD) than BD-noPD. However, this different pattern of externalizing comorbidity did not affect severity and improvement. Our findings suggest that PD is frequently comorbid in juvenile BD and can influence severity, pattern of comorbidity and course of BD. The data are compatible with the hypothesis that Panic-BD and ADHD-BD might represent distinct developmental pathways of bipolar disorder. Further research on this question may prove rewarding.

Attention-deficit hyperactivity disorder -- bipolar comorbidity in children and adolescents.

OBJECTIVE: A substantial portion of juvenile bipolar disorder (BD) has a comorbid attention-deficit hyperactivity disorder (ADHD). The aim of our study was to analyze the cross-sectional and longitudinal implications of such comorbidity in children and adolescents with BD. METHODS: Ninety-eight refereed patients (mean age 13.7 +/- 3.0 years) with a diagnosis of BD by the Schedule for Affective Disorders and Schizophrenia for School-Age Children, Present and Lifetime version (K-SADS-PL) were followed for 6 months. RESULTS: Thirty-seven BD patients (37.8%) presented a lifetime diagnosis of comorbid ADHD. The mean age of onset of ADHD was 3.7 +/- 1.1 years, and the mean age of onset of BD was 10.0 +/- 3.2 years. Bipolar subjects with comorbid ADHD were predominantly male, younger, and had an earlier onset of BD (8.1 +/- 2.8 versus 11.1 +/- 2.9 years). Bipolar-ADHD patients presented more frequently a chronic rather than an episodic course of BD, with an irritable rather than an elated mood. They showed higher rates of oppositional defiant disorder/conduct disorder, lower rates of panic disorder, and less frequently received antidepressant medications. Finally, ADHD comorbidity was associated with a greater psychosocial impairment. CONCLUSIONS: ADHD comorbidity is frequent in juvenile BD and can influence age of onset, phenomenology, comorbidity, and course of BD. A timely diagnosis should improve our efforts regarding the outcome of these subjects.

The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction.

BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response.

Comorbidity of obsessive-compulsive disorder and attention-deficit/hyperactivity disorder in referred children and adolescents.

OBJECTIVE: The aim of this study was to explore whether comorbid attention-deficit/hyperactivity disorder (ADHD) affects the clinical expression and outcome of obsessive-compulsive disorder (OCD) in a clinical sample. METHOD: A consecutive series of 94 children and adolescents (mean age, 13.6 +/- 2.8 years) with current diagnosis of OCD were included in the study. Twenty-four (25.5%) patients were diagnosed as having a comorbid ADHD. Subjects with OCD plus ADHD were compared with subjects with OCD but without ADHD. RESULTS: Comorbid ADHD with OCD was significantly associated with a higher rate of males, an earlier onset of OCD, a greater psychosocial impairment, and a heavier comorbidity, namely, with bipolar disorder, tic disorder, and oppositional defiant disorder/conduct disorder. Phenomenology of obsessions and compulsions and outcome were not affected by ADHD comorbidity. CONCLUSIONS: A screening for ADHD should be performed in patients with OCD, as these patients and their parents are frequently not aware that the impairment may be partly due to a comorbid ADHD.

Developmental differences according to age at onset in juvenile bipolar disorder.

BACKGROUND: This study on a large sample of unselected, consecutive children and adolescents referred to a third-level hospital who received a diagnosis of bipolar disorder (BD) was aimed at exploring whether childhood-onset BD, as compared with adolescent-onset BD, presents specific clinical features in terms of severity, functional impairment, course, prevalent mood, pattern of co-morbidity, and treatment outcome. METHODS: A total of 136 patients, 81 males (59.6%) and 55 females (40.4%), mean age 13.5 +/- 2.9 years, meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) diagnosis of BD according to a structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (KSADS-PL), were included in the study. RESULTS: Eighty patients (58.8%) had a childhood-onset BD (before 12 years of age) and 56 (41.2%) had an adolescents-onset BD. Compared with the adolescent-onset BD, patients with childhood-onset were more frequently males and had a more frequent co-morbidity with attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). An episodic course was found in only 42.5% of bipolar children, but 76.8% of youngsters with adolescent-onset BD. Severity, 6-month treatment outcome, prevalent mood (elated versus irritable), and co-morbid anxiety did not differentiate the two groups. CONCLUSIONS: Our findings suggest that a very early age at onset may identify a form of BD with a more frequent subcontinuous course and a heavy co-morbidity with ADHD.

A naturalistic study of referred children and adolescents with obsessive-compulsive disorder.

OBJECTIVE: To report on clinical features, comorbidity, and response to pharmacotherapy in children and adolescents with obsessive-compulsive disorder (OCD) naturalistically followed and treated with serotonin reuptake inhibitors (SRIs). METHOD: A consecutive series of 94 patients (65 males, 29 females, age 13.6 +/- 2.8 years), referred in the period January 2001-April 2004, diagnosed with a clinical interview (Diagnostic Interview for Children and Adolescents-Revised), and followed for 10 +/- 6 months, were included in the study. RESULTS: Contamination obsessions and washing rituals were associated with less impairment than other subtypes of OCD. Aggressive sexual obsessions and checking rituals as well as symmetry obsessions and ordering-repeating rituals were more frequently comorbid with tic disorders. According to the Clinical Global Impressions-Improvement scale (score 1 or 2), 63 subjects (67%) were responders to treatment. Nonresponders were more severely impaired and had a higher number of comorbid disorders, namely, bipolar disorder and conduct disorder (p < .05). Forty-seven patients (50%) received an SRI monotherapy, whereas the other 47 (50%) needed other medications. Patients receiving SRI monotherapy were less severely impaired; had a later onset of OCD; were at a younger age at the visit, had higher rates of depression and anxiety and lower rates of bipolar disorder, attention-deficit/hyperactivity disorder, and conduct disorder (p < .05). CONCLUSIONS: Long-term naturalistic prospective studies in pediatric patients with OCD might represent an important source of information for everyday care regarding the effectiveness of a treatment over extended periods of time under routine clinical conditions.

Generalized anxiety disorder in referred children and adolescents.

OBJECTIVE: There are insufficient data on generalized anxiety disorder in children and adolescents. Symptoms and comorbidity of generalized anxiety disorder are described as a function of age, gender, and comorbidity in a consecutive series of referred children and adolescents. METHOD: One hundred fifty-seven outpatients (97 males and 60 females, 50 children and 107 adolescents, age range 7-18 years, mean age 13.4 +/- 2.7 years) were diagnosed as having generalized anxiety disorder, using historical information and a structured clinical interview (Diagnostic Interview for Children and Adolescents-Revised) according to the DSM-IV. RESULTS: Feelings of tension, apprehensive expectations, negative self-image, need for reassurance, irritability, and physical complaints were reported in more than 75% of the participants. Differences in symptomatology according to age and gender were nonsignificant. Depressive disorder was the most frequent comorbidity, being present in 56% of the patients. Comorbid anxiety disorders were present in about 75% of the patients, and 21% showed externalizing disorders. Subjects with comorbid depression had less anxiety comorbidity, subjects with comorbid separation anxiety disorder had higher rates of panic disorder, and subjects with comorbid externalizing disorders had higher rates of bipolar disorder. CONCLUSIONS: Referred children and adolescents with generalized anxiety disorder are heavily symptomatic and have frequent comorbidity. A more precise definition of the clinical picture may help early diagnosis and prevention of superimposed mental disorders.

Obsessive-compulsive bipolar comorbidity: focus on children and adolescents.

BACKGROUND: Growing evidence documents the frequent co-morbidity between Obsessive Compulsive Disorder (OCD) and Bipolar Disorder (BP) in adults. The aim of the present study is to explore some clinical aspects of this interface in children and adolescents, as it appears in a setting of routine clinical practice. METHOD: The sample comprised 102 consecutively referred children and adolescents, both inpatients and outpatients, with BP, OCD or co-morbid BP-OCD during a 3-year period. The mean age was 14.2 (SD=3.2); 65 (63.7%) were males. Diagnoses and clinical features were collected by means of structured interview according to DSM-IV (DICA-R) and a rating scale for OCD (CY-BOCS). Clinical outcome was evaluated prospectively by means of clinical global impression (CGI) as part of routine clinical care, throughout the follow-up. RESULTS: Thirty-seven (36.3%) patients (21 males and 16 females) were diagnosed as BP, 35 (34.3%) patients (26 males and 9 females) were diagnosed as OCD and 30 (29.4%) patients (18 males and 12 females) were diagnosed as BP-OCD. BP II, was more frequent in the BP-OCD than in BP. When OCD was co-morbid with BP, age of onset was significantly earlier than in the 'pure' OCD patients. On the contrary, age of onset of BP was not affected by co-morbid OCD. According to CGI baseline scores, OCD patients were significantly less impaired than BP-OCD and BP patients, while the severity of the symptomatology was similar in the last two groups. Severity scores at the end of the follow-up were significantly higher in BP-OCD patients than in OCD patients. Patients with pure BP showed lower rates of panic disorder-agoraphobia than BP-OCD patients and higher rates of ADHD-conduct disorder. Pure OCD patients showed lower rates of ADHD and higher rates of Generalized Anxiety Disorder. The number of obsessions did not differentiate the two groups, whereas pure OCD patients showed significantly more compulsions. 'Other' obsessions-e.g., existential, philosophical, odd and/or superstitious-were significantly more frequent in BP-OCD than in pure OCD patients. Ordering compulsions were significantly more frequent in pure OCD patients. LIMITATIONS: Possible low reliability of children's and their parents' recall of past episodes of mental disorder. CONCLUSIONS: In a tertiary care center, co-morbidity between OCD and BP is a significant clinical problem affecting a large number of patients. The correct identification of OCD-bipolar co-morbidity has relevant clinical implications as far as other concomitant disorders, symptomatological features, course, complications, and treatment management and outcome are concerned.

Predictors of treatment nonresponse in bipolar children and adolescents with manic or mixed episodes.

Even though juvenile bipolar disorder (BD) is reported to be more treatment-resistant than adult BD, predictors of nonresponse are not well studied. The aim of this study was to address this issue in a naturalistic sample of bipolar children and adolescents with manic or mixed episodes treated under the condition of routine clinical practice. This study was comprised of 40 patients (19 females and 21 males; mean age, 14.2 years; SD = 3.3; range, 7-18) with a Diagnostic and Statistical Manual of Mental Disorders-fourth edition (DSM-IV) diagnosis of manic (n = 23) or mixed episodes (n = 17). The clinical characteristics of 20 patients considered to be treatment responders, according to the Clinical Global Impression-Improvement (CGI-I) scores, were compared to those of the 20 nonresponders. The effect of predictors on the probability of treatment nonresponse was analyzed using the multiple stepwise logistic regression, backward procedure. Demographic variables (mean age, gender ratio, socioeconomic status), as well as the inpatients-outpatients ratio (75% versus 65%), duration of the follow-up (10.5 +/- 2.5 months versus 9.6 +/- 3.2 months), index episode (manic versus mixed), and rates of pharmacologic hypomania did not differentiate the 2 groups. According to stepwise logistic regression, predictors of nonresponse were the presence of comorbidity with conduct disorder (odd ratio, 3.36; 95% CI, 2.20-4.52), attention deficit hyperactivity disorder (ADHD) (odd ratio, 2.30; CI, 1.24-3.26), and the baseline CGI Severity score (odd ratio, 2.31; CI, 1.33-3.29). It is relevant to point out that patient age at the onset of BD, and at the first visit, and comorbid anxiety disorders did not influence treatment response. Follow-up studies with a larger sample size with BD and/or externalizing disorders appropriately managed with different treatment options and/or combinations are warranted.