Evidence from Family Genetic Studies Further evidence that a subtype of CD linked to bipolar disorder could be identified derives from pilot familial-risk analyses (Biederman, Faraone, Wozniak, & Monuteaux, 2000; Wozniak, Biederman, Faraone, Blier, & Monuteaux, 2001). These results showed that relatives of probands with bipolar disorder had an increased risk for bipolar disorder but not CD, whereas relatives of probands with CD had an increased risk for CD but not for bipolar disorder; relatives of probands with CD plus bipolar disor - der had an elevated risk for both disorders (Wozniak et al., 2001). Among relatives in this latter group, bipolar disorder and antisocial disorders showed significant cosegregation, that is, relatives with one disorder were highly likely to have the other. As a result of this cosegregation, CD plus bi - polar disorder was significantly elevated among relatives of probands with CD plus bipolar disorder but was rare among the relatives of the other proband groups. Probands with the combined condition of CD and bipolar disorder also had high rates of conduct or antisocial disorders without bi- polar disorder among the relatives, suggesting a genetic loading with two subtypes of CD: with and without bipolar disorder. The family study results support the concept of heterogeneity of bipo- lar disorder and CD. Whereas the rates of bipolar disorder in relatives were identical in both bipolar disorder proband groups, the relatives of probands with CD plus bipolar disorder had almost exclusively the comorbid type of bipolar disorder (CD/antisocial personality disorder plus bipolar disorder) and relatives of the probands with bipolar disorder had higher rates of bi- polar disorder without CD/antisocial personality disorder (Wozniak et al., 2001). These results provide compelling evidence that subtypes of CD and of bipolar disorder can be identified based on patterns of comorbidity with the other disorder. Notably, both CD and bipolar disorder show both a within-patient and a familial association with ADHD, suggesting that their co-occurrence may correspond to a distinct familial syndrome (Biederman et al., 2000; Wozniak et al., 2001; Faraone, Biederman, Mennin, Wozniak, & Spencer, 1997; Faraone, Biederman, Mennin, & Russell, 1998; Faraone, Biederman, & Monuteaux, 2001). Familial-risk analysis also found strong support for the hypothesis that bipolar disorder in probands is a risk factor for substance use disorders (SUDs) in relatives, independently of the comorbidity with CD in probands (Biederman et al., 2000). After accounting for CD in probands, bipolar dis - order in probands was a risk factor for SUDs, including both drug and al - cohol addiction, in relatives. In contrast, after accounting for bipolar disor - der in probands, CD in probands was a risk factor for alcohol dependence in relatives but not for drug dependence, independently of comorbid bipo - lar disorder in the probands. The effects of bipolar disorder and CD in probands combined additively to predict the risk for SUDs in relatives. Treatment Implications 245 Familial-risk data also showed that regardless of the presence of CD in probands with bipolar disorder, relatives of these probands were at risk for substance dependence onset in their teenage years. In contrast, the risk for alcohol dependence imparted by probands with CD becomes evident only during adulthood. These data suggest that the familial disposition to bipo - lar disorder—and not CD—is associated with early-onset SUDs, making it especially relevant for prevention programs aimed at adolescents. Management Rather than pharmacotherapy, the treatment of CD in youths primarily uti - lizes psychosocial interventions. A recent report (Tcheremissine & Lieving, 2006) addressing the pharmacological aspects of the treatment of CD in children and adolescents concludes that pharmacological interventions will be most effective when combined with behavioral and psychosocial inter - ventions. These authors write that “a multidisciplinary approach to the treatment of CD, which includes behavioral parent training, interpersonal skills training, family therapy and the use of psychotropic agents targeted at a particular cluster of symptoms, can increase the overall effectiveness of each of the applied interventions” (Tcheremissine & Lieving, 2006, p. 459). The authors go on to suggest that the best targets for psychopharma- cological intervention are aggression, hyperactivity, impulsivity, and mood symptoms and that antipsychotics, antidepressants, mood stabilizers, anti- epileptics, stimulants, and adrenergic medications should be used for the comorbidity associated with the CD. Although a small literature addresses the pharmacotherapy of CD, no- tably these studies generally utilize treatments that are considered mood stabilizers, raising the question of whether responders in these studies suffer additionally from a bipolar spectrum disorder. A review of prevention, treatment, and service configurations for juvenile maladaptive aggression (i.e., conduct problems) indicates, as in the preceding report, that preven - tion programs and psychosocial treatments are useful in reducing aggres - sion in children and adolescents (Connor et al., 2006). However, in addi - tion, these authors cite the antimanic agents (along with stimulants when ADHD is present) as the pharmacological treatments with the most robust empirical support in the treatment of aggression, suggesting that the aggres - sion could be symptom of mania. The delineation of a subgroup of children with mania and CD would have important clinical implications. It could lead to improvement in our efforts to ameliorate the guarded outcome of some youths with CD. Be - cause mania may respond to specific pharmacological treatments, correctly identifying those children with mania and CD may afford the opportunity to introduce these medications in the treatment of antisocial and aggressive youths. 246 COMORBID DISORDERS AND SPECIAL POPULATIONS Indeed, our preliminary treatment data from extensive chart reviews of children with mania suggest that mood stabilizers and atypical antipsy - chotics, the very medications most commonly recommended for the treat - ment of CD, are important for the clinical stabilization of difficult-to-treat patients with bipolar disorder (Wozniak & Biederman, 1996; Biederman et al., 1998). Campbell and Cueva’s (1995) review concluded that for children and adolescents, the antimanic agent lithium is useful for reducing a key symptom of CD, aggression. Consistent with this, their double-blind, pla - cebo-controlled study showed lithium to be effective in the treatment of hospitalized aggressive children with CD. In another review, Sheard (1975) noted that lithium had been successfully used to improve aggressive behav - ior in childhood, and Worrall, Moody, and Naylor (1975) reported that lithium could effectively treat aggressive, nonmanic adolescents. A small literature suggesting that antipsychotic medications such as haloperidol and molindone were helpful in decreasing aggression in youths with CD (Campbell, Anderson, & Green, 1983) has led to the use of the atypical antipsychotic agents in treating CD with aggressive features. An open-label pharmacokinetic study by Findling et al. (2006) examined quetiapine in 6- to 12-year-olds with the primary diagnosis of CD. The out- come measures included the Rating of Aggression Against People and/or Property Scale (RAAPPS), the Nisonger Child Behavior Rating Form (NCBRF), the Clinical Global Impression Scale of Improvement (CGI-I) and Severity (CGI-S), and the Connors Parent Rating Scale (CPRS-48). Scores on the RAAPPS and the CGI-S improved significantly by week 8 and five of the six problem scales of the NCBRF improved significantly as well. The Conduct, Learning and Hyperactivity scales of the CPRS improved from baseline to week 8, and the Psychosomatic, Impulse, and Anxiety scales improved but not significantly. Several trials indicate that risperidone can be useful for CD, especially the aggressive features, in both short-term and long-term use (Aman, De Smedt, Derivan, Lyons, & Findling, 2002; Findling, Aman, Eerdekens, Derivan, & Lyons, 2004; Croonenberghs, Fegert, Findling, De Smedt, & Van Dongen, 2005; Findling et al., 2000; Turgay, Binder, Snyder, & Fisman, 2002). These reports, from the Risperidone Disruptive Behavior Study Group, examine the use of risperidone in children with severe disrup - tive behaviors and below-average IQ in double-blind, placebo-controlled short-term studies and open-label long-term studies. Included children had a clinician-confirmed DSM-IV diagnosis of CD, oppositional defiant disor - der, or disruptive behavior disorder not otherwise specified, as well as ele - vated scores on the Conduct Problem subscale of the NCBRF. In addition, included children had a DSM-IV Axis II diagnosis of mild mental retarda - tion, moderate mental retardation, or borderline intellectual functioning (IQ of 36–84) and a low score on the Vineland Adaptive Behavior Scale. These studies concluded that risperidone was effective in the short- and Treatment Implications 247 long-term treatment of disruptive behavior disorders based on statistically significant improvement in the Conduct Problem subscale of the NCBRF. However, a post-hoc analysis of data from the placebo-controlled 6- week study (N = 110) examined 24 candidate affective symptoms extracted from the 64-item NCBRF (Biederman et al., 2006). These symptoms re - flected the bipolar symptoms of explosive irritability, agitation, expansive - ness, grandiosity, and depression. Risperidone was also effective in treating these putative symptoms of mania. This analysis raises the question of whether studies that examine the effects of antimanic agents on CD may in - clude participants with comorbid bipolar spectrum illness and, further, whether the improvement in CD symptoms is a function in part of the im - provement in bipolar disorder symptoms. Consistent with this notion, an open-label trial of risperidone in chil - dren and adolescents with bipolar disorder concluded that risperidone was associated with significant short-term improvement of symptoms of pediat - ric bipolar disorder but, in addition, reported that 55% of participants with comorbid CD were “much” or “very much” improved on the CGI-S for CD (Biederman, Mick, Wozniak, et al., 2005). Nine of the 30 partici- pants with bipolar disorder (30%) treated with risperidone had impairment at baseline on conduct symptoms. In open-label studies of olanzapine and risperidone in preschool-age participants (4–6 years; Biederman, Mick, Hammerness, et al., 2005) the authors reported rapid reduction of symp- toms of mania in preschool children. At baseline, 39% of the 16 partici- pants on risperidone and 57% of the 15 participants on olanzapine had symptoms of CD as indicated by a CGI-S score of 3 or more. At follow-up evaluation 8 weeks later, 50% of the 5 risperidone-treated participants with CD and 38% of the 8 olanzapine-treated participants with CD were “much” or “very much” improved on the CGI-I scale for CD. OPPOSITIONAL DEFIANT DISORDER High rates with bidirectional overlap of comorbid oppositional defiant dis - order (ODD) and bipolar disorder are reported by various studies. Rates of ODD in the population with bipolar disorder range from 47–88% (Woz - niak et al., 1995; Findlay et al., 2001; Geller et al., 2000), and, conversely, 20% of children with ODD are reported to have comorbid bipolar disorder (Greene & Doyle, 1999). A recent meta-analysis reported that among sam - ples of children and adolescents with bipolar disorder, ODD was the sec - ond most common comorbidity after ADHD, with weighted rate of 53% (Kowatch et al., 2005). Diagnosis of ODD in the context of mania is challenging, as, noso - logically, ODD shares overlapping symptoms with mania, without any symptom specific to ODD that could diagnostically differentiate it from 248 COMORBID DISORDERS AND SPECIAL POPULATIONS mania. Because ODD is so frequently comorbid with pediatric bipolar dis - order, understanding of ODD’s relationship with bipolar disorder ranges from ODD being a secondary disorder as a consequence of bipolar illness or being a prodrome or early manifestation of bipolar disorder to repre - senting a “true independent” comorbid psychopathological phenomenon. However, many children with disruptive behavior disorders do not go on to develop bipolar disorder (Biederman et al., 1996), suggesting that different forms of disruptive behavior disorders may exist—one that could be prodromal to bipolar disorder and another form that is not. More work is needed to further evaluate this issue. A clinical inquiry summarized eight reviews of ODD treatment in chil - dren and found improved behavior, with 20–30% decrease in disruptive or aggressive behaviors with parenting interventions and behavioral therapy, including cognitive-behavioral therapy, social problem-solving skills train - ing, and parent management training involving child and/or parent for 12– 25 sessions (Farley et al., 2005). Though treatment for ODD is primarily behavioral in nature, when it is comorbid with other medication-responsive psychiatric conditions (bipolar disorder, ADHD), pharmacological treat- ment of the comorbid disorder often reduces overall symptoms. A double- blind crossover randomized controlled trial evaluating children with either CD or ODD with explosive temper and mood lability reported significant reduction in aggressive behaviors and anger and hostility following dival- proex treatment (Donovan et al., 2000). There are currently no data avail- able on the treatment of ODD in the context of bipolar disorder comor- bidity. Further prospective studies addressing course and treatment of ODD when comorbid with bipolar disorder are warranted. ENURESIS Significantly higher rates of enuresis have been observed with pediatric bi - polar disorder. Epidemiological studies report high prevalence of enuresis in children and adolescents (5–8% of 7- to 17-year-olds) (Bellman, 1966; Costello et al., 1996; Linna, Moilanen, Keistinen, Ernvall, & Karppinen, 1991; Shaffer et al., 1996; Spee-van der Wekke, Hirasing, Meulmeester, & Radder, 1998). Higher than expected rates (21.5%) of enuresis are reported with bipolar disorder (Klages, Geller, Tillman, Bolhofner, & Zimerman, 2005; Henin et al., 2006) and other common childhood-onset disorders such as ADHD (21–32% of 6- to 17-year-olds) (Klages et al., 2005; Biederman et al., 1995; Robson, Jackson, Blackhurst, & Leung, 1997). Ge - netic factors appear to be important in the pathophysiology of enuresis, as evidenced by family studies reporting that enuretics versus nonenuretics had a significantly higher prevalence of familial aggregation of enuresis. This is evident both in the general population and in populations with bi - Treatment Implications 249 polar disorder (Klages et al., 2005; Arnell et al., 1997; Loeys et al., 2002). It is unlikely that enuresis is part of the symptom picture of a severe manic episode or due to medication (lithium) side effects, because of this evidence of familial aggregation plus evidence that onset of enuresis tends to occur prior to onset of mania (Klages et al., 2005; Henin et al., 2006). Medication treatment may play a role in this comorbidity as well. High rates of bipolar disorder occurring in youths with enuresis have been suggested to be a result of hypomania induced by antidepressant treatment for enuresis in youths. Conversely, psychotropic treatment for mania in youths, such as lithium treatment, may result in enuresis as a side effect. The issue of enuresis in youths with bipolar disorder secondary to anti - manic psychotropic treatment has been addressed by Klages et al. (2005), who examined the temporal relationship between onset of enuresis and treatment with lithium in youths with bipolar disorder and reported that no participant with enuresis had received lithium before the onset of enuresis. These authors concluded that enuresis in youths with bipolar dis - order is not secondary to treatment with lithium. The risk of antidepres- sant-induced hypomania should be considered when treating enuresis in children at risk of bipolar disorder with tricyclic antidepressants. Alterna- tive treatment with desmopressin could be the treatment of choice for enuretic children with enuresis with or at risk for bipolar disorder. ANXIETY DISORDERS The presence of anxiety disorders in individuals who suffer from bipolar disorder has been underrecognized and understudied. One reason for this lack of recognition could be the notion that it is counterintuitive to suggest that bipolar disorder, which is characterized by high levels of disinhibition, could coexist with anxiety, which is characterized by fear and inhibition. However, in the first study to demonstrate the high frequency (16%) of bi - polar disorder in an outpatient pediatric psychopharmacology clinic (Wozniak et al., 1995) 56% of the children with bipolar disorder suffered from two or more lifetime anxiety disorders (multiple anxiety disorders) comorbidly. These findings have been replicated in a larger sample (Biederman et al., 2004). Furthermore, a recent detailed analysis of the comorbidity between pediatric bipolar disorder and anxiety disorders revealed that 75% of youths with bipolar disorder have one or more anxiety disorders comorbid with their bipolar disorder. In a community sample, Lewinsohn et al. (1995) reported that a third of nonreferred adolescents with bipolar disor - der had comorbid anxiety disorders, a significantly higher rate than that found in those without a history of mania. Similar findings were reported by Faraone, Biederman, Mennin, et al. (1997), who found that 56% of adoles - cents with a diagnosis of bipolar disorder had multiple anxiety disorders. 250 COMORBID DISORDERS AND SPECIAL POPULATIONS This association is also evident in adults, as demonstrated by Simon and colleagues, who reported in one of the largest studies of bipolar adults to date that over half of their sample had at least one anxiety disorder (Si - mon et al., 2003; Simon et al., 2005). Anxiety has been found to occur rela - tively frequently in both the manic and depressive phases of bipolar disor - der in adults (Cassidy, Forest, Murry, & Carroll, 1998; Cassidy, Murry, Forest, & Carroll, 1998). Data from both ECA (Chen & Dilsaver, 1995) and the National Comorbidity Survey (NCS) document higher than ex - pected rates of several anxiety disorders in participants with bipolar disor - der (OCD, social phobia, panic disorder, PTSD). Because the anxiety disorders are heterogeneous (eight are included in the DSM-IV; American Psychiatric Association, 1994), uncertainties remain as to which anxiety disorders are associated with bipolar disorder, and most studies lump them together. Various clinical and epidemiological stud - ies in adult and pediatric populations have identified a wide range of anxi - ety disorders associated with bipolar disorder, including generalized anxiety disorder, panic disorder, agoraphobia, simple phobia, social phobia, separa- tion anxiety disorder, PTSD, and OCD. Rates of comorbid association range between 12.5 and 56% (McElroy et al., 2001; Lewinsohn et al., 1995; Chen & Dilsaver, 1995; Johnson, Cohen, & Brook, 2000; Masi et al., 2001; Faedda, Baldessarini, Glovinsky, & Austin, 2004; Harpold et al., 2005; Tillman et al., 2003; Wozniak, Biederman, Monuteaux, Richards, & Faraone, 2002; Biederman, Faraone, Marrs, et al., 1997; Faraone, Bieder- man, Wozniak, et al., 1997; Feske et al., 2000; Kessler, Sonnega, Bromet, Hughest, & Nelson, 1995; Kessler, Stang, Wittchen, Stein, & Walters, 1999; Perugi, 1999; Masi et al., 2004; Wozniak et al., 1999; Judd et al., 1002; Perugi, Akiskal, Toni, Simonini, & Gemignani, 2001; Perugi, Frare, Toni, Mata, & Akiskal, 2001). A specific association in youths between separation anxiety disorder and bipolar disorder is suggested by Tillman et al. (2003). However, Harpold et al. (2005) found high rates of anxiety dis - orders in 297 clinically referred youths with bipolar disorder with no spe - cific link to any particular anxiety disorder over others. Thus more infor - mation is needed as to whether the association between bipolar disorder and anxiety disorders in youths is limited to a single anxiety disorder or is more extensive and includes other anxiety disorders as well. Panic Disorder A preponderance of investigators have suggested that a particular link ex - ists between bipolar disorder and panic disorder in adults (Chen & Dilsaver, 1995; Goodwin & Hoven, 2002; Goodwin, Hamilton, Milne, & Pine, 2002) and children (Birmaher et al., 2002). Data from adult studies report a lifetime prevalence of panic disorder in 21–33% of individuals with bipolar disorder (Chen & Dilsaver, 1995; Goodwin & Hoven, 2002; Treatment Implications 251 Goodwin et al., 2002; Kessler, Davis, & Kendler, 1997; Kessler et al., 1998) and, conversely, lifetime bipolar disorder in 6–23% of individuals with panic disorder (Perugi, 1999; Rowen, South, & Hawkes, 1994). MacKinnon and colleagues (MacKinnon et al., 1998; MacKinnon et al., 2002) utilize family genetic methodology in 57 families to argue that panic disorder with bipolar disorder is a genetic subtype of bipolar disorder. Savino et al. (1993) system - atically explored the intraepisodic and longitudinal comorbidity of 140 adults with panic disorder, and the reported comorbidity with bipolar disor - der in 13.5% of the patients with panic disorder. They also note that an ad - ditional 34.3% met features of “hyperthymic temperament,” a possible bi - polar spectrum condition. Likewise, a recent report by Birmaher et al. (2002) suggested a specific association between bipolar disorder and panic disorder in youths, and Biederman, Faraone, Marrs, et al. (1997) reported high rates of panic disorder (52%) among youths with bipolar disorder. There is growing evidence that anxiety comorbidity is a frequent, al - beit a hitherto neglected, precursor for pediatric-onset bipolar disorder (Masi et al., 2001; Bashir, Russell, & Johnson, 1987; Geller, Biederman, Griffin, Jones, & Lefkowitz, 1996). In a longitudinal study, Johnson et al. (2000) found that having an anxiety disorder as an adolescent increased the risk of developing bipolar disorder in early adulthood. Posttraumatic Stress Disorder Individuals who work with trauma victims make the clinical observation that mood swings are common in this group. Although a considerable liter- ature implicates psychosocial stresses in the onset and recurrence of bipolar disorder (Kraepelin, 1921; Brown & Harris, 1982; Hlastala et al., 2000), there is paucity of research on the association of PTSD with bipolar disor - der. Findings from the National Comorbidity Survey (NCS) estimate the lifetime prevalence of PTSD in the general population as 7.8% (Kessler et al., 1995). By contrast, reported rates of PTSD comorbidity in patients with bipolar disorder have varied widely from 7 to 50%. Although many studies have looked at possible links between early traumatic events and development of psychopathology over the life span (Breslau et al., 1998; Bryer, Nelson, Miller, & Krol, 1987; Grilo, Sanislow, Fehon, Martino, & McGlashan, 1999; Kaplan et al., 1998; Kessler et al., 1997; Levitan et al., 1998), few studies have examined the potential role of early traumatic life stresses on the development of bipolar disorder and PTSD. Emerging evidence suggests that trauma significantly compromises the course of bipolar disorder. Leverich et al. (2006) evaluated 631 outpa - tients with bipolar disorder and reported that nearly half of the females (49%) and one-third of the males (36%) reported early sexual and physical abuse. Those who endorsed a history of child or adolescent physical or sex - ual abuse, compared with those who did not, had significantly higher rates 252 COMORBID DISORDERS AND SPECIAL POPULATIONS of comorbid PTSD, a history of an earlier onset of bipolar illness, and a higher rate of suicide attempts. On the other hand Geller et al. (2000) re - ported high rates (43%) of the symptom of hypersexuality (higher in pu - bertal vs. prepubertal bipolar disorder population) and low rates (< 1%) of history of sexual abuse in their prepubertal and early-adolescent bi - polar disorder cohort, suggesting that the symptom of hypersexuality in pe - diatric bipolar disorder is etiologically unrelated to sexual abuse and more reflective of mania and puberty. Similarly, Garno, Goldberg, Ramirez, and Ritzler (2005) studied 100 adult patients with bipolar disorder, and half (51%) reported a history of abuse, whereas a quarter suffered from comorbid PTSD (24%). A report by Wozniak et al. (1999) raises the question as to whether a diagnosis of bipolar disorder may pose a risk factor for trauma. Using data from a large longitudinal sample of well-characterized boys with and with - out ADHD, these authors failed to find meaningful associations between ADHD, trauma, and PTSD. Instead, they identified early bipolar disorder as an important antecedent to later trauma. When traumatized children present with severe irritability and mood lability, clinicians may have a ten- dency to attribute these symptoms to having experienced a trauma. These longitudinal results, in contrast, suggest the opposite: Mania may be an an- tecedent risk factor for later trauma (possibly because of the attendant reckless, disinhibited state) rather than representing a reaction to the trauma. If confirmed, these results could help dispel the commonly held no- tion that mania-like symptoms in youths represent a reaction to trauma and would further suggest that children with bipolar disorder should be monitored closely to prevent trauma. Obsessive–Compulsive Disorder Minimal extant literature and no systematic data exist on the challenging clinical dilemma of children and adolescents presenting with comorbid OCD and bipolar disorder. Descriptions of OCD symptoms in patients with bipolar disorder date back to the 19th century (Morel, 1860). Most data on comorbid OCD and bipolar disorder are not based on systematic studies (Goodwin & Jamison, 1990; Rasmussen & Eisen, 1992) but consist of documentation from naturalistic studies. In adults, evidence of a higher- than-expected overlap between OCD and bipolar disorder first came from the ECA study, in which 23% of those with bipolar disorder also met crite - ria for OCD (Robins & Price, 1991). Subsequent studies have consistently found the overlap between OCD and bipolar disorder to be as high as 15– 35% (Chen & Dilsaver, 1995; Perugi et al., 1997; Kruger, Cooke, Hasey, Jorne, & Persad, 1995). When comorbid with bipolar disorder, OCD in adults has a more episodic course, often featuring higher rates of sexual and religious obsessions, lower rates of checking rituals, greater frequency Treatment Implications 253 of concurrent major depressive episodes, and panic disorder. These individ - uals also exhibit increased rates of suicidality, more frequent hospitaliza - tions, and more complex pharmacological interventions than those without bipolar disorder (Chen & Dilsaver, 1995; Perugi et al., 1997; Perugi et al., 2002; Centorrino et al., 2006). A recent survey conducted among the French Association of OCD Patients provides corroborating evidence for this comorbidity in participants who gave retrospective childhood reports. The authors, while reporting a high prevalence of comorbid lifetime bipo - larity, also noted that many of these participants had had a juvenile onset of OCD (Hantouche et al., 2002; Kochman et al., 2002). Until recently, the presence of comorbid OCD and bipolar disorder in children and adolescents had drawn little attention. Recently, several sepa - rate studies have reported a bidirectional overlap between bipolar disorder and OCD in children at rates greater than expected. Masi and colleagues in 2001 reported that 44% of their pediatric patients with bipolar disorder had a lifetime diagnosis of OCD, which usually preceded the onset of mood symptoms. In 2005, Masi et al. reported that 24.5% of their pediatric pop- ulation with OCD had comorbid bipolar disorder. Geller et al. (1996; Geller, 1996) also found high rates of bipolar disorder (27%), as well as disruptive behavior disorders, in a pediatric population with OCD. Simi- larly, recent findings in a pediatric population with bipolar disorder reveal rates of comorbid OCD in the range of 15–27% (Faedda et al., 2004; Harpold et al., 2005; Tillman et al., 2003). On the other hand, Reddy and colleagues (2000) reported a much lower rate of bipolar disorder (1.9%) in their pediatric population with OCD that was largely treatment naïve and of moderate severity. Inconsistency in the rate of co-occurrence of the two disorders could be attributed to selection and/or referral bias and suggests that a true comorbidity risk may have been overlooked in these patients. Although the available literature suggests substantial impact on clini - cal presentation, global functioning, and treatment decisions when bipolar disorder and OCD co-occur in young patients (Masi et al., 2004), the na - ture of this relationship remains unknown. For example, the agitation, rac - ing thoughts, and feelings of distress that can be associated with severe OCD could mimic a bipolar picture; conversely, the manic symptom of increase in goal-directed activity (“mission mode” behavior) or repetitive, unwanted hypersexual thoughts in a child or adolescent with bipolar disor - der could mimic an OCD presentation. There is a paucity of systematic data addressing the clinical character - istics of the comorbid OCD and bipolar disorder in a pediatric population. One of the two studies that address this comorbid presentation comes from Masi et al. (2004), who conducted a naturalistic prospective 3-year follow- up study of 102 children and adolescents with OCD, bipolar disorder, and bipolar disorder plus OCD; the other study examined 228 youths ascer - tained to have OCD and bipolar disorder for clinical features, patterns of 254 COMORBID DISORDERS AND SPECIAL POPULATIONS [...]... genetic linkage between OCD and bipolar disorder Coryell (1981) reported an equal incidence (2.3%) of mania in families of probands with OCD and in families of probands with bipolar disorder Similarly, an increased incidence of obsessional traits has been reported in the offspring of probands with bipolar disorder (Klein, Depue, & Slater, 1985) Treatment Implications Improving the understanding of the... anxiety disorders and bipolar disorder in youths has important treatment implications Because bipolar disorder and anxiety disorders respond to different treatments, identification of the comorbid state is essential for proper treatment 256 COMORBID DISORDERS AND SPECIAL POPULATIONS and for achieving optimal functioning In addition, children and adolescents with comorbid bipolar disorder and anxiety disorders... examine the treatment response of mania to atypical antipsychotics in children and adolescents with comorbid bipolar disorder and anxiety disorders by comparing the antimanic response to olanzapine of youths with bipolar disorder in the context of comorbidity status with OCD and generalized anxiety disorder (GAD) and concluded that the comorbid presence of lifetime OCD, but not GAD, in children and adolescents. .. Rett syndrome and childhood disintegrative disorder Literature is limited, and no systematic data exist on the diagnosis and treatment of comorbid bipolar disorder and PDD in children and adolescents In the absence of systematic research on comorbid bipolar disorder and PDD, indirect evidence suggestive of comorbid bipolar disorder in pediatric populations with PDD comes from high rates of aggressive... bipolar disorder and PDD in 21% of the participants with PDD and 11% of the participants with mania They also observed striking homology in the phenotypic features of PDD irrespective of comorbidity with bipolar disorder, and, similarly, phenotypic features of mania were analogous in youths with bipolar disorder with and without PDD comorbidity, suggesting that bipolar disorder and PDD are bona fide disorders... 109(4), 77 7 78 6 Isaac, G (1992) Misdiagnosed bipolar disorder in adolescents in a special educational school and treatment program Journal of Clinical Psychiatry, 53(4), 133–136 Joffe, R T., & Swinson, R P (19 87) Carbamazepine in obsessive-compulsive disorder Biological Psychiatry, 22(9), 1169–1 171 Johnson, J G., Cohen, P., & Brook, J S (2000) Associations between bipolar disorder and other psychiatric disorders... and Anxiety, 21(2), 71 77 Geller, B (1996) The high prevalence of bipolar parents among prepubertal mood-disordered children necessitates appropriate questions to establish bipolarity Current Opinion in Psychiatry, 9, 239–240 Geller, B., Fox, L., & Clark, K (1994) Rate and predictors of prepubertal bipolarity during follow-up of 6- to 12-year-old depressed children Journal of the American Academy of. .. alterations in the behavior of the preschool-age offspring of parents with bipolar disorder has been provided (Hirshfeld-Becker et al., 2006) In a study of the young children of adults with bipolar disorder, higher rates of observed behavioral disinhibition were found in preschoolers who had a parent with bipolar disorder compared with low-risk controls These findings demonstrate that behaviors suggestive of. .. Journal of the American Academy of Child and Adolescent Psychiatry, 34(6), 71 5 72 3 Kowatch, R A., Fristad, M., Birmaher, B., Wagner, K D., Findling, R L., & Hellander, M (2005) Treatment guidelines for children and adolescents with bipolar disorder Journal of the American Academy of Child and Adolescent Psychiatry, 44(3), 213–235 Kraepelin, E (1921) Manic-depressive insanity and paranoia Edinburgh,... intervene using particular skills and desired goals (i.e., increasing or decreasing duration and/ or intensity of emotion) of treatment In this vein, we used the emotional reactivity curve model to guide selection of skills determined to be necessary for parents to learn in order to assist their child in regulating emotions in a more competent and adaptive fashion These skills and the corresponding points/portion . reduction of symp- toms of mania in preschool children. At baseline, 39% of the 16 partici- pants on risperidone and 57% of the 15 participants on olanzapine had symptoms of CD as indicated by a CGI-S. (2.3%) of mania in families of probands with OCD and in families of probands with bipolar disorder. Similarly, an increased incidence of obsessional traits has been reported in the offspring of probands. examine the use of risperidone in children with severe disrup - tive behaviors and below-average IQ in double-blind, placebo-controlled short-term studies and open-label long-term studies. Included