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Objective: The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths)., Method: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders., Results: Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion., Conclusions: Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

Objective: The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring")., Method: High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years)., Results: Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data., Conclusions: Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Objective: The study compared use of specialty outpatient mental services among children ages six and seven and children ages eight through 12 and investigated predictors of differences in the patterns of service use by age., Methods: Eligible children were first-time patients of clinics participating in the Longitudinal Assessment of Manic Symptoms who were between ages six and 12 and who were English speaking. Children who screened positive for symptoms of mania (N=1,124) were invited to participate, and families of 621 (55%) children consented. A matched sample of 86 children without a positive screen for mania also participated. Baseline interviews assessed sociodemographic characteristics of the child and family and the child's functioning, diagnoses, and use of services., Results: Of the 707 children, 30% were younger, and 50% used multiple types of specialty outpatient services. Younger children were more likely to be male, have Medicaid insurance, and have two parents with mental health problems. Use of multiple types of services was related to study site, high depression scores, fewer minor health issues, and fewer stressful life events among younger children and with parental stress, primary diagnosis, poor functioning, and not living with both parents among older children. Younger children were much more likely than older children to have used services before age six., Conclusions: Younger children showed very early use of multiple types of services for mental health problems and a pattern of persistent impairment despite long-standing use of services. These data argue strongly for focusing on emotional and behavioral issues among young children.

Objective: This study evaluated demographic and clinical correlates and predictors of polypharmacy at baseline assessment in the Longitudinal Assessment of Manic Symptoms (LAMS) sample, a cohort of children age six to 12 years at their first outpatient mental health visit at university-affiliated clinics., Methods: Use of medications in four classes (mood stabilizers, antidepressants, antipsychotics, and stimulants) was assessed, and the Service Assessment for Children and Adolescents classified lifetime and current use of various services. Analyses examined correlates of the number of medications prescribed and odds of polypharmacy, defined as use of two or more concurrent medications., Results: In the total sample, 201 of 698 participants (29%) were prescribed two or more medications. These participants had lower Children's Global Assessment Scale scores, more comorbid disorders, and higher baseline parent-reported mood symptoms than those prescribed no or one medication. White youths were three times as likely as nonwhite youths to be receiving two or more psychotropics, even after adjustment for other demographic and clinical characteristics. Of 262 participants (38% of sample) not being treated with medications, 252 (96%) had a diagnosis of at least one psychiatric disorder (74% had two or more)., Conclusions: Findings suggest that patients with greater severity and comorbidity were more likely to receive two or more medications. However, 38% of these children with serious disorders were not receiving psychotropic medication at the time of this assessment. Results counter findings suggesting overtreatment with medications of children with psychiatric disorders in the community.

Objective: The authors examined the association of demographic and clinical characteristics, family history, and type of treatment among children receiving outpatient mental health services and parents' perception of treatment benefit. They also examined whether perceived benefit was related to continued use of services at six-month follow-up., Methods: Parents of children age six to 12 years who were first-time patients at one of nine clinics participating in the Longitudinal Assessment of Manic Symptoms (LAMS) study completed the Parent General Behavior Inventory Ten-Item Mania Scale. Parents of children with scores of 12 or higher (N=1,124) were invited to participate in a follow-up study, and 621 agreed. During baseline assessment after the first outpatient visit and at six-month follow-up, the parents were asked about children's sociodemographic and diagnostic characteristics and use of services and asked to rate how much their children had benefited from the most recent outpatient treatment., Results: Data were available for 573 children. At baseline, parents of 167 (29%) children reported that the treatment provided a lot of benefit, and perceived benefit was related to receiving medication (with or without therapy) versus just therapy, higher scores on functioning, LAMS site, no history of comorbid diagnoses, living with both biological parents, and having no parents or siblings with a prior hospitalization for a psychiatric illness. At six-month follow-up, perceived benefit was related to continued use of services (p<.001)., Conclusions: Medication with or without therapy was perceived as more beneficial than therapy alone. Perceived benefit was strongly related to continued use of treatment.

Objective: The study described service utilization among children with emotional and behavioral disorders making a first visit to outpatient mental health clinics in four Midwest cities., Methods: Data were from the Longitudinal Assessment of Manic Symptoms study. A total of 707 youths aged six to 12 years 11 months and their parents completed diagnostic assessments; demographic information and mental health service use was self-reported. Analyses examined the relationship of demographic variables, diagnoses, impairment, and comorbidity with type and level of services utilized., Results: Utilization was multimodal; half the youths had received outpatient and school services during their lifetime. Factors unrelated to need (age, sex, race, and insurance) were associated with service type. Children with a bipolar spectrum disorder had higher use of inpatient services than those with depressive or disruptive disorders and were more likely to currently use two or more services. More than half of youths with bipolar or depressive disorders had lifetime use of both medication and therapy, whereas youths with a disruptive behavior disorder were more likely to have used only therapy. Impairment and comorbidity were not related to service utilization., Conclusions: Use of services began at a very young age and occurred in multiple service sectors. Type of service used was related to insurance and race, underscoring the need for ongoing disparities research. Contrary to findings from administrative data analyses, use of medication alone was infrequent. The low rate of use of combination therapy suggests that clinicians and families need to be educated about the effectiveness of multimodal treatment.

Objective: The authors evaluated lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity of depressive and manic symptoms at intake in preschool offspring of parents with bipolar I and II disorders., Method: A total of 121 offspring ages 2-5 years from 83 parents with bipolar disorder and 102 offspring of 65 demographically matched comparison parents (29 with non-bipolar psychiatric disorders and 36 without any lifetime psychopathology) were recruited for the study. Parents with bipolar disorder were recruited through advertisements and adult outpatient clinics, and comparison parents were ascertained at random from the community. Participants were evaluated with standardized instruments. All staff were blind to parental diagnoses., Results: After adjustment for within-family correlations and both biological parents' non-bipolar psychopathology, offspring of parents with bipolar disorder, particularly those older than age 4, showed an eightfold greater lifetime prevalence of attention deficit hyperactivity disorder (ADHD) and significantly higher rates of having two or more psychiatric disorders compared to the offspring of the comparison parents. While only three offspring of parents with bipolar disorder had mood disorders, offspring of parents with bipolar disorder, especially those with ADHD and oppositional defiant disorder, had significantly more severe current manic and depressive symptoms than comparison offspring., Conclusions: Preschool offspring of parents with bipolar disorder have an elevated risk for ADHD and have greater levels of subthreshold manic and depressive symptoms than children of comparison parents. Longitudinal follow-up is warranted to evaluate whether these children are at high risk for developing mood and other psychiatric disorders.

Objective: The authors sought to assess the longitudinal course of youths with bipolar spectrum disorders over a 4-year period., Method: At total of 413 youths (ages 7-17 years) with bipolar I disorder (N=244), bipolar II disorder (N=28), and bipolar disorder not otherwise specified (N=141) were enrolled in the study. Symptoms were ascertained retrospectively on average every 9.4 months for 4 years using the Longitudinal Interval Follow-Up Evaluation. Rates and time to recovery and recurrence and week-by-week symptomatic status were analyzed., Results: Approximately 2.5 years after onset of their index episode, 81.5% of the participants had fully recovered, but 1.5 years later 62.5% had a syndromal recurrence, particularly depression. One-third of the participants had one syndromal recurrence, and 30% had two or more. The polarity of the index episode predicted that of subsequent episodes. Participants were symptomatic during 60% of the follow-up period, particularly with subsyndromal symptoms of depression and mixed polarity, with numerous changes in mood polarity. Manic symptomatology, especially syndromal, was less frequent, and bipolar II was mainly manifested by depressive symptoms. Overall, 40% of the participants had syndromal or subsyndromal symptoms during 75% of the follow-up period, and 16% of the participants experienced psychotic symptoms during 17% the follow-up period. Twenty-five percent of youths with bipolar II converted to bipolar I, and 38% of those with bipolar disorder not otherwise specified converted to bipolar I or II. Early onset, diagnosis of bipolar disorder not otherwise specified, long illness duration, low socioeconomic status, and family history of mood disorders were associated with poorer outcomes., Conclusions: Bipolar spectrum disorders in youths are characterized by episodic illness with subsyndromal and, less frequently, syndromal episodes with mainly depressive and mixed symptoms and rapid mood changes.

Objective: Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a 1H spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder., Method: The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age=15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age=17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo 1H spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference., Results: Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites., Conclusions: These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset.

Objective: In vivo imaging studies have suggested anatomical and functional abnormalities in the anterior cingulate in adults with mood disorders. This anatomical magnetic resonance imaging study examined the cingulate cortex in children and adolescents with bipolar disorder and matched healthy comparison subjects., Method: Sixteen patients (mean age=15.5 years, SD=3.4) with DSM-IV bipolar disorder and 21 matched healthy comparison subjects (mean age=16.9 years, SD=3.8) were studied. Three-dimensional gradient echo imaging was performed (TR=25 msec, TE=5 msec, slice thickness=1.5 mm) in a 1.5-T GE Signa magnet. Cingulate volumes were compared by using analysis of covariance, with age and intracranial volume as covariates., Results: The patients with bipolar disorder had significantly smaller mean volumes relative to the healthy subjects in the left anterior cingulate (mean=2.49 cm(3 [SD=0.28] versus 3.60 cm3 [SD=0.12], respectively), left posterior cingulate (2.53 cm3 [SD=0.32] versus 2.89 cm3 [SD=0.09]), and right posterior cingulate (2.19 cm3 [SD=0.13] versus 2.28 cm3 [SD=0.08]). No significant between-group difference was found for the right anterior cingulate (2.64 cm3 [SD=0.21] versus 2.71 cm3 [SD=0.10])., Conclusions: The findings indicate smaller cingulate volumes in children and adolescents with bipolar disorder, suggesting that such abnormalities may be present early in the illness course.