This paper examines the relationship between plasma concentration of antidepressant and both clinical response and adverse effects in treatment-resistant depressed adolescents. Adolescents (n = 334) with major depression who had not responded to a selective serotonin reuptake inhibitor (SSRI) were randomized to 1 of 4 treatments: switch to another SSRI (fluoxetine, citalopram, or paroxetine), switch to venlafaxine, switch to SSRI plus cognitive behavior therapy, or switch to venlafaxine plus cognitive behavior therapy. Adolescents who did not improve by 6 weeks had their dose increased. Plasma concentrations of medication and metabolites were measured at 6 weeks in 244 participants and at 12 weeks in 204 participants. Adolescents treated with citalopram whose plasma concentration was equal to or greater than the geometric mean (GM) showed a higher response rate compared to those with less than the GM, with parallel but nonsignificant findings for fluoxetine. A dose increase of citalopram or fluoxetine at week 6 was most likely to result in response when it led to a change in concentration from less than the GM at 6 weeks to the GM or greater at week 12. Plasma levels of paroxetine, venlafaxine, or O-desmethylvenlafaxine were not related to clinical response. Exposure was associated with more cardiovascular and dermatologic side effects in those receiving venlafaxine. Antidepressant concentration may be useful in optimizing treatment for depressed adolescents receiving fluoxetine or citalopram.
major depressive disorder; adolescents; plasma concentration; drug exposure; optimization
To assess whether relative severity of irritability symptoms versus elation symptoms in mania is stable and predicts subsequent illness course in youth with DSM-IV bipolar I or II disorder or operationally defined bipolar disorder not otherwise specified.
Investigators used the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children to assess the most severe lifetime manic episode in bipolar youth aged 7–17 years who were recruited from 2000 to 2006 as part of the Course and Outcomes of Bipolar Youth prospective cohort study (N = 361), conducted at university-affiliated mental health clinics. Subjects with at least 4 years of follow-up (N = 309) were categorized as irritable-only (n = 30), elated-only (n = 42), or both irritable and elated (n = 237) at baseline. Stability of this categorization over follow-up was the primary outcome. The course of mood symptoms and episodes, risk of suicide attempt, and functioning over follow-up were also compared between baseline groups.
Most subjects experienced both irritability and elation during follow-up, and agreement between baseline and follow-up group assignment did not exceed that expected by chance (κ = 0.03; 95% CI, −0.06 to 0.12). Elated-only subjects were most likely to report the absence of both irritability and elation symptoms at every follow-up assessment (35.7%, versus 26.7% of irritable-only subjects and 16.9% of those with both irritability and elation; P = .01). Baseline groups experienced mania or hypomania for a similar proportion of the follow-up period, but irritable-only subjects experienced depression for a greater proportion of the follow-up period than did subjects who were both irritable and elated (53.9% versus 39.7%, respectively; P = .01). The groups did not otherwise differ by course of mood episode duration, polarity, bipolar diagnostic type, suicide attempt risk, or functional impairment.
Most bipolar youth eventually experienced both irritability and elation irrespective of history. Irritable-only youth were at similar risk for mania but at greater risk for depression compared with elated-only youth and youth who had both irritability and elation symptoms.
This study aims to characterize patterns of mental health service utilization within a sample of bipolar youth. Demographic variables, youth bipolar characteristics, youth comorbid conditions, and parental psychopathology were examined as predictors of treatment utilization across different levels of care.
A total of 293 bipolar youth (aged 7–17 years) and their parents completed a diagnostic interview, family psychiatric history measures, and an assessment of mental health service utilization. Demographic and clinical variables were measured at baseline and mental health service use was measured at the six-month follow-up.
Approximately 80% of bipolar youth attended psychosocial treatment services over the span of 6 months. Of those who attended treatment, 67% attended only outpatient services, 22% received inpatient/partial hospitalization, and 12% received residential/therapeutic school-based services. Using multinomial logistic regression, older age, female gender, and bipolar characteristics, including greater symptom severity and rapid cycling, were found to predict higher levels of care. Youth suicidal and non-suicidal self-injurious behavior, comorbid conduct disorder, and parental substance use disorders also predicted use of more restrictive treatment settings.
Results underscore the importance of assessing for and addressing suicidality, comorbid conduct disorder, and parental substance use disorders early in the treatment of bipolar youth to potentially reduce the need for more restrictive levels of care.
adolescence; bipolar disorder; childhood; service utilization
Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder, but, to our knowledge, no studies examined the course of anxiety disorders in youth and adults with bipolar disorder.
As part of the Course and Outcome of Bipolar Youth study, 413 youth, ages 7 to 17 years who met criteria for Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) bipolar I disorder (n = 244), bipolar II disorder (n = 28), and operationally defined bipolar disorder not otherwise specified (n = 141) were recruited primarily from outpatient clinics. Subjects were followed on average for 5 years using the Longitudinal Interval Follow-Up Evaluation. We examined factors associated with the persistence (> 50% of the follow-up time) and onset of new anxiety disorders in youth with bipolar disorder.
Of the 170 youth who had anxiety at intake, 80.6% had an anxiety disorder at any time during the follow-up. Most of the anxiety disorders during the follow-up were of the same type as those present at intake. About 50% of the youth had persistent anxiety, particularly generalized anxiety disorder (GAD). Persistence was associated with multiple anxiety disorders, less follow-up time in euthymia, less conduct disorder, and less treatment with antimanic and antidepressant medications (all P values ≤ .05). Twenty-five percent of the sample who did not have an anxiety disorder at intake developed new anxiety disorders during follow-up, most commonly GAD. The onset of new anxiety disorders was significantly associated with being female, lower socioeconomic status, presence of attention-deficit/hyperactivity disorder and substance use disorder, and more follow-up time with manic or hypomanic symptoms (all P values ≤ .05)
Anxiety disorders in youth with bipolar disorder tend to persist, and new-onset anxiety disorders developed in a substantial proportion of the sample. Early identification of factors associated with the persistence and onset of new anxiety disorders may enable the development of strategies for treatment and prevention.
Individuals with early onset of bipolar disorder are at high risk for suicide. Yet, no study to date has examined factors associated with prospective risk for suicide attempts among youth with bipolar disorder.
To examine past, intake, and follow-up predictors of prospectively observed suicide attempts among youth with bipolar disorder.
We interviewed subjects, on average, every 9 months over a mean of 5 years using the Longitudinal Interval Follow-up Evaluation.
Outpatient and inpatient units at 3 university centers.
A total of 413 youths (mean [SD] age, 12.6 [3.3] years) who received a diagnosis of bipolar I disorder (n=244), bipolar II disorder (n=28), or bipolar disorder not otherwise specified (n=141).
Main Outcome Measures
Suicide attempt over prospective follow-up and past, intake, and follow-up predictors of suicide attempts.
Of the 413 youths with bipolar disorder, 76 (18%) made at least 1 suicide attempt within 5 years of study intake; of these, 31 (8% of the entire sample and 41% of attempters) made multiple attempts. Girls had higher rates of attempts than did boys, but rates were similar for bipolar subtypes. The most potent past and intake predictors of prospectively examined suicide attempts included severity of depressive episode at study intake and family history of depression. Follow-up data were aggregated over 8-week intervals; greater number of weeks spent with threshold depression, substance use disorder, and mixed mood symptoms and greater number of weeks spent receiving outpatient psychosocial services in the preceding 8-week period predicted greater likelihood of a suicide attempt.
Early-onset bipolar disorder is associated with high rates of suicide attempts. Factors such as intake depressive severity and family history of depression should be considered in the assessment of suicide risk among youth with bipolar disorder. Persistent depression, mixed presentations, and active substance use disorder signal imminent risk for suicidal behavior in this population.
The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment.
Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants.
Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was 2 weeks, predicted by previous history of nonsuicidal self-injury. While there were no main effects of treatment, venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation. Adjunctive use of benzodiazepines, while in a small number of participants (N=10) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events.
Since predictors of suicidal adverse events also predict poor response to treatment, and many of these events occurred early in treatment, improving the speed of response to depression, by targeting of family conflict, suicidal ideation, and drug use may help to reduce their incidence. The relationship of venlafaxine and of benzodiazepines to selfharm events requires further study and clinical caution.
This exploratory study assessed whether maternal recall of childhood feeding and eating practices differed across anorexia nervosa (AN) subtypes. Participants were 325 women from the Genetics of Anorexia Nervosa study whose mothers completed a childhood feeding and eating questionnaire. Multinomial logistic regression analyses were used to predict AN subtype from measures related to childhood eating: (a) infant feeding (breastfed, feeding schedule, age of solid food introduction), (b) childhood picky eating (picky eating before age one and between ages one and five), and (c) infant gastrointestinal problems (vomiting and colic). Results revealed no significant differences in retrospective maternal report of childhood feeding and eating practices among AN subtypes.
Anorexia Nervosa; Anorexia Nervosa Subtype; Feeding; Maternal Report; Infancy
Follow-up studies of eating disorders (EDs) suggest outcomes ranging from recovery to chronic illness or death, but predictors of outcome have not been consistently identified. We tested 5151 single-nucleotide polymorphisms (SNPs) in approximately 350 candidate genes for association with recovery from ED in 1878 women. Initial analyses focused on a strictly defined discovery cohort of women who were over age 25 years, carried a lifetime diagnosis of an ED, and for whom data were available regarding the presence (n=361 ongoing symptoms in the past year, ie, ‘ill') or absence (n=115 no symptoms in the past year, ie, ‘recovered') of ED symptoms. An intronic SNP (rs17536211) in GABRG1 showed the strongest statistical evidence of association (p=4.63 × 10−6, false discovery rate (FDR)=0.021, odds ratio (OR)=0.46). We replicated these findings in a more liberally defined cohort of women age 25 years or younger (n=464 ill, n=107 recovered; p=0.0336, OR=0.68; combined sample p=4.57 × 10−6, FDR=0.0049, OR=0.55). Enrichment analyses revealed that GABA (γ-aminobutyric acid) SNPs were over-represented among SNPs associated at p<0.05 in both the discovery (Z=3.64, p=0.0003) and combined cohorts (Z=2.07, p=0.0388). In follow-up phenomic association analyses with a third independent cohort (n=154 ED cases, n=677 controls), rs17536211 was associated with trait anxiety (p=0.049), suggesting a possible mechanism through which this variant may influence ED outcome. These findings could provide new insights into the development of more effective interventions for the most treatment-resistant patients.
GABA; anorexia nervosa; recovery from eating disorders; genetic association; single nucleotide polymorphisms; eating/metabolic disorders; GABA; eating/metabolic disorders; neurogenetics; biological psychiatry; genetic association; anorexia nervosa; recovery from eating disorders; single-nucleotide polymorphisms; phenomic association
To determine the rate of diagnostic conversion from an operationalized diagnosis of Bipolar Disorder Not Otherwise Specified (BP-NOS) to Bipolar I or Bipolar II Disorders (BP-I/II) in youth over prospective follow-up and to identify factors associated with conversion.
Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months.
Diagnostic conversion to BP-I/II occurred in 63 subjects (45%): 32 (23%) to BP-I (9 of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p=.006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes.
Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II disorders. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.
Mood Disorders - Bipolar; Child Psychiatry; Adolescents; Diagnosis; Classification
Comorbidity among eating disorders, traumatic events, and post traumatic stress disorder (PTSD) has been reported in several studies. The main objectives of this study were to describe the nature of traumatic events experienced and to explore the relation between PTSD and anorexia nervosa (AN) in a sample of women.
Eight hundred twenty-four participants from the National Institutes of Health funded Genetics of Anorexia Nervosa Collaborative Study were assessed for eating disorders, PTSD, and personality characteristics.
From a final sample of 753 women with AN, 13.7% (n=103) met DSM-IV criteria for PTSD. The sample mean age was 29.5 years (SD=11.1). In pairwise comparisons across AN subtypes, the odds of having a PTSD diagnosis were significantly lower in individuals with restricting AN (RAN) than individuals with purging AN without binge eating (PAN) (OR=0.49, 95% CI=0.30, 0.80). The majority of participants with PTSD reported the first traumatic event before the onset of AN (64.1%, n=66). The most common traumatic events reported by those with a PTSD diagnosis were sexual related traumas during childhood (40.8%) and during adulthood (35.0%).
AN and PTSD do co-occur and traumatic events tend to occur prior to the onset of AN. Clinically, these results underscore the importance of assessing trauma history and PTSD in individuals with AN and raise the question of whether specific modifications or augmentations to standard treatment for AN should be considered in a subgroup to address PTSD-related psychopathology.
PTSD; anorexia nervosa; trauma; prevalence; comorbid; epigenetic
This analysis is a follow-up to an earlier investigation of 182 genes selected as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN). As those initial case-control results revealed no statistically significant differences in single nucleotide polymorphisms, herein we investigate alternative phenotypes associated with AN. In 1762 females using regression analyses we examined: (1) lowest illness-related attained body mass index; (2) age at menarche; (3) drive for thinness; (4) body dissatisfaction; (5) trait anxiety; (6) concern over mistakes; and (7) the anticipatory worry and pessimism vs. uninhibited optimism subscale of the harm avoidance scale. After controlling for multiple comparisons, no statistically significant results emerged. Although results must be viewed in the context of limitations of statistical power, the approach illustrates a means of potentially identifying genetic variants conferring susceptibility to AN because less complex phenotypes associated with AN are more proximal to the genotype and may be influenced by fewer genes.
covariates; eating disorders; association studies; personality; genetic
The purpose of this study was to report on the outcome of participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial after 24 weeks of treatment, including remission and relapse rates and predictors of treatment outcome.
Adolescents (ages 12–18 years) with selective serotonin reuptake inhibitor (SSRI)-resistant depression were randomly assigned to either a medication switch alone (alternate SSRI or venlafaxine) or a medication switch plus cognitive-behavioral therapy (CBT). At week 12, responders could continue in their assigned treatment arm and nonresponders received open treatment (medication and/or CBT) for 12 more weeks (24 weeks total). The primary outcomes were remission and relapse, defined by the Adolescent Longitudinal Interval Follow-Up Evaluation as rated by an independent evaluator.
Of 334 adolescents enrolled in the study, 38.9% achieved remission by 24 weeks, and initial treatment assignment did not affect rates of remission. Likelihood of remission was much higher (61.6% versus 18.3% ) and time to remission was much faster among those who had already demonstrated clinical response by week 12. Remission was also higher among those with lower baseline depression, hopelessness, and self-reported anxiety. At week 12, lower depression, hopelessness, anxiety, suicidal ideation, family conflict, and absence of comorbid dysthymia, anxiety, and drug/alcohol use and impairment also predicted remission. Of those who responded by week 12, 19.6% had a relapse of depression by week 24.
Continued treatment for depression among treatment-resistant adolescents results in remission in approximately one-third of patients, similar to adults. Eventual remission is evident within the first 6 weeks in many, suggesting that earlier intervention among non-responders could be important.
Extensive population-based genome-wide association studies have identified an association between the FTO gene and BMI; however, the mechanism of action is still unknown. To determine whether FTO may influence weight regulation through psychological and behavioral factors, seven single nucleotide polymorphisms (SNPs) of the FTO gene were genotyped in 1085 individuals with anorexia nervosa (AN) and 677 healthy weight controls from the international Price Foundation Genetic Studies of Eating Disorders. Each SNP was tested in association with eating disorder phenotypes and measures that have previously been associated with eating behavior pathology: trait anxiety, harm-avoidance, novelty seeking, impulsivity, obsessionality, compulsivity, and concern over mistakes. After appropriate correction for multiple comparisons, no significant associations between individual FTO gene SNPs and eating disorder phenotypes or related eating behavior pathology were identified in cases or controls. Thus, this study found no evidence that FTO gene variants associated with weight regulation in the general population are associated with eating disorder phenotypes in AN participants or matched controls.
Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder (BP). We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with BP.
As part of the Course and Outcome of Bipolar Youth study (COBY), 446 youth ages 7 to 17, who met DSM-IV criteria for BP-I (n=260), BP-II (n=32) or operationalized criteria for BP not otherwise specified (BP-NOS; n=154) were included. Subjects were evaluated for current and lifetime Axis-I psychiatric disorders at intake using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children–Present and Lifetime version (K-SADS-PL), and standardized instruments to assess functioning and family history.
Forty-four percent (n=194) of the sample met DSM-IV criteria for at least one lifetime anxiety disorder, most commonly Separation Anxiety (24%) and Generalized Anxiety Disorders (16%). Nearly 20% met criteria for two or more anxiety disorders. Overall, anxiety disorders predated the onset of BP. BP-II subjects were more likely than BP-I or BP-NOS subjects to have a comorbid anxiety disorder. After adjusting for confounding factors, BP youth with anxiety were more likely to have BP-II, longer duration of mood symptoms, more severe ratings of depression, and family history of depression, hopelessness and somatic complaints during their worst lifetime depressive episode than those without anxiety.
Comorbid anxiety disorders are common in youth with BP, and most often predate BP onset. BP-II, a family history of depression, and more severe lifetime depressive episodes distinguish BP youth with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in BP youth.
Youth; anxiety; bipolar disorder; prevalence; clinical correlates
The purpose of this study is to examine the prevalence and correlates of non-suicidal self-injury (NSSI) among children and adolescents diagnosed with bipolar disorder (BP).
Four hundred-thirty two youth with a diagnosis of BP and their parents, including 193 children and 239 adolescents, completed a diagnostic interview and instruments to assess youth clinical and illness history, youth comorbidity, parental mood disorder, and psychosocial functioning.
Approximately 22% of children and 22% of adolescents reported NSSI during the course of their most recent mood episode. In a multivariate model controlling for global impairment, among children, a BPI or BPII diagnosis (versus BPNOS), psychosis, separation anxiety disorder, and greater severity of depressive symptoms were found to be associated with NSSI. Among adolescents, a mixed episode, a suicide attempt, greater severity of depressive symptoms, and poor psychosocial functioning were found to be associated with NSSI. Neither the presence of a youth comorbid disruptive behavior disorder nor a parental mood disorder was associated with NSSI.
The primary limitations of this study include the use of a cross-sectional study design, lack of a control group, and limited generalizability of study results to non-clinical and ethnically diverse samples.
NSSI is not uncommon among youth with BP, particularly those who present with BPI or BPII, psychosis, a mixed episode, suicidal behavior, severe depressive symptoms, separation anxiety, and/or poor psychosocial functioning. However, the relative importance of these factors in relation to NSSI may vary with age. Treatments for BP that are developmentally sensitive, examine the function of NSSI for each youth, and teach adaptive skills to address emotional and social needs, may prove to be most successful.
Bipolar Disorder; Self-Injury; Suicide; Comorbidity; Psychosocial
We investigated sociodemographic characteristics in women with and without lifetime eating disorders.
Participants were from a multi-site international study of eating disorders (N = 2096). Education level, relationship status, and reproductive status were examined across eating disorder subtypes and compared with a healthy control group.
Overall, women with eating disorders were less educated than controls, and duration of illness and age of onset were associated with educational attainment. Menstrual status was associated with both relationship and reproductive status, but eating disorder subtypes did not differ significantly from each other or from healthy controls on these dimensions.
Differences in educational attainment, relationships, and reproduction do exist in individuals with eating disorders and are differentially associated with various eating disorder symptoms and characteristics. These data could assist with educating patients and family members about long-term consequences of eating disorders.
Children; relationship; education; anorexia nervosa; bulimia nervosa; amenorrhea
Despite the high morbidity associated with bipolar disorder (BP), few studies have prospectively studied the course of this illness in youth.
To assess the longitudinal course of BP spectrum disorders (BP-I, BP-II, and not otherwise specified [BP-NOS]) in children and adolescents.
Subjects were interviewed, on average, every 9 months for an average of 2 years using the Longitudinal Interval Follow-up Evaluation.
Outpatient and inpatient units at 3 university centers.
Two hundred sixty-three children and adolescents (mean age, 13 years) with BP-I (n = 152), BP-II (n = 19), and BP-NOS (n = 92).
Main Outcome Measures
Rates of recovery and recurrence, weeks with syndromal or subsyndromal mood symptoms, changes in symptoms and polarity, and predictors of outcome.
Approximately 70% of subjects with BP recovered from their index episode, and 50% had at least 1 syndromal recurrence, particularly depressive episodes. Analyses of weekly mood symptoms showed that 60% of the follow-up time, subjects had syndromal or subsyndromal symptoms with numerous changes in symptoms and shifts of polarity, and 3% of the time, psychosis. Twenty percent of BP-II subjects converted to BP-I, and 25% of BP-NOS subjects converted to BP-I or BP-II. Early-onset BP, BP-NOS, long duration of mood symptoms, low socioeconomic status, and psychosis were associated with poorer outcomes and rapid mood changes. Secondary analyses comparing BP-I youths with BP-I adults showed that youths significantly more time symptomatic and had more mixed/cycling episodes, mood symptom changes, and polarity switches.
Youths with BP spectrum disorders showed a continuum of BP symptom severity from subsyndromal to full syndromal with frequent mood fluctuations. Results of this study provide preliminary validation for BP-NOS.
We examined the long-term outcome of participants in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study, a randomized trial of 334 adolescents (aged 12-18 years) with DSM-IV-defined major depression disorder initially resistant to selective serotonin reuptake inhibitor (SSRI) treatment who were and subsequently treated for 12 weeks with another SSRI, venlafaxine, another SSRI + cognitive behavioral therapy (CBT), or venlafaxine + CBT. Responders then continued with the same treatment through week 24, while non-responders were given open treatment.
For the current study, patients were reassessed 48 (N=116) and 72 (N=130) weeks from intake. Data were gathered from February 2011 to February 2007. Standardized diagnostic interviews and measures of depression, suicidal ideation, related psychopathology and level of functioning were periodically administered. Remission was defined as ≥ 3 weeks with ≤ 1 clinically significant symptom and no associated functional impairment (score of 1 on the adolescent version of the Longitudinal Interval Follow-Up Evaluation [A-LIFE], and relapse as ≥ 2 weeks with probable or definite depressive disorder (score of 3 or 4 on the A-LIFE). Mixed effects regression models were applied to estimate remission, relapse, and functional recovery.
By 72 weeks, an estimated 61.1% of the randomized youths had reached remission. Randomly assigned treatment (first 12 weeks) did not influence remission rate or time to remission, but the group assigned to SSRI's had a more rapid decline in self-reported depressive symptoms and suicidal ideation than those assigned to venlafaxine (p<.05). Participants with more severe depression, greater dysfunction, and alcohol/drug use at baseline were less likely to remit. The depressive symptom trajectory of the remitters diverged from that of non-remitters by the first 6 weeks of treatment (p<.001). Of the 130 participants in remission at week 24, 25.4% relapsed in the subsequent year.
While most adolescents achieved remission, more than one-third did not, and one-fourth of remitted patients experienced a relapse. More effective interventions are needed for patients who do not show robust improvement early in treatment.
depression; adolescents; treatment; resistance
To describe sexual functioning in women with eating disorders.
We assessed physical intimacy, libido, sexual anxiety, partner and sexual relationships in 242 women from the International Price Foundation Genetic Studies relative to normative data.
Intercourse (55.3%), having a partner (52.7%), decreased sexual desire (66.9%), and increased sexual anxiety (59.2%) were common. Women with restricting and purging anorexia nervosa had a higher prevalence of loss of libido than women with bulimia nervosa and eating disorder not otherwise specified (75%, 74.6%, 39% and 45.4%, respectively). Absence of sexual relationships was associated with lower minimum lifetime body mass index (BMI) and earlier age of onset; loss of libido with lower lifetime BMI, higher interoceptive awareness and trait anxiety; and sexual anxiety with lower lifetime BMI, higher harm avoidance and ineffectiveness. Sexual dysfunction in eating disorders was higher than in the normative sample.
Sexual dysfunction is common across eating disorders subtypes. Low BMI is associated with loss of libido, sexual anxiety, and avoidance of sexual relationships.
anorexia nervosa; eating disorders; sexual behavior; sexual dysfunction
We examined prevalence of substance use disorders (SUD) in women with: (1) anorexia nervosa (AN) restricting type (RAN); (2) AN with purging only (PAN); (3) AN with binge eating only (BAN); and (4) lifetime AN and bulimia nervosa (ANBN). Secondary analyses examined SUD related to lifetime purging behavior and lifetime binge eating.
Participants (N = 731) were drawn from the International Price Foundation Genetic Studies.
The prevalence of SUD differed across AN subtypes, with more in the ANBN group reporting SUD than those in the RAN and PAN groups. Individuals who purged were more likely to report substance use than those who did not purge. Prevalence of SUD differed across lifetime binge eating status.
SUD are common in AN and are associated with bulimic symptomatology. Results underscore the heterogeneity in AN, highlighting the importance of screening for SUD across AN subtypes.
eating disorders; anorexia nervosa; bulimia nervosa; drug use; alcohol related disorders; cannabis
Extremely low body mass index (BMI) values are associated with increased risk for death and poor long-term prognosis in individuals with AN. The present study explores childhood personality characteristics that could be associated with the ability to attain an extremely low BMI.
Participants were 326 women from the Genetics of Anorexia Nervosa (GAN) Study who completed the Structured Interview for Anorexia Nervosa and Bulimic Syndromes and whose mother completed the Child Behavioral Check List and/or Revised Dimensions of Temperament Survey.
Children who were described as having greater fear or anxiety by their mothers attained lower BMIs during AN (p <0.02). Path analysis in the GAN and a validation sample, Price Foundation Anorexia Nervosa Trios Study, confirmed the relation between early childhood anxiety, caloric restriction, qualitative food item restriction, excessive exercise, and low BMI. Path analysis also confirmed a relation between childhood anxiety and caloric restriction, which mediated the relation between childhood anxiety and low BMI in the GAN sample only.
Fearful or anxious behavior as a child was associated with the attainment of low BMI in AN and childhood anxiety was associated with caloric restriction. Measures of anxiety and factors associated with anxiety-proneness in childhood may index children at risk for restrictive behaviors and extremely low BMIs in AN.
Anorexia Nervosa; Anxiety; Body Mass Index
We performed association studies with 5,151 SNPs that were judged as likely candidate genetic variations conferring susceptibility to anorexia nervosa (AN) based on location under reported linkage peaks, previous results in the literature (182 candidate genes), brain expression, biological plausibility, and estrogen responsivity. We employed a case–control design that tested each SNP individually as well as haplotypes derived from these SNPs in 1,085 case individuals with AN diagnoses and 677 control individuals. We also performed separate association analyses using three increasingly restrictive case definitions for AN: all individuals with any subtype of AN (All AN: n = 1,085); individuals with AN with no binge eating behavior (AN with No Binge Eating: n = 687); and individuals with the restricting subtype of AN (Restricting AN: n = 421). After accounting for multiple comparisons, there were no statistically significant associations for any individual SNP or haplotype block with any definition of illness. These results underscore the importance of large samples to yield appropriate power to detect genotypic differences in individuals with AN and also motivate complementary approaches involving Genome-Wide Association (GWA) studies, Copy Number Variation (CNV) analyses, sequencing-based rare variant discovery assays, and pathway-based analysis in order to make up for deficiencies in traditional candidate gene approaches to AN.
single nucleotide polymorphisms; probands; anorexia nervosa; bulimia nervosa
To study the relationship between negative life events and demographic and clinical variables in youth with bipolar I disorder, bipolar II disorder, and bipolar disorder not otherwise specified (NOS), as well as to compare the rates of life events in youth with bipolar disorder, depressive and/or anxiety disorders (DEP-ANX), and healthy controls.
Subjects included 446 youth, aged 7 to 17 years, meeting DSM-IV criteria for bipolar I, bipolar II, or an operationalized definition of bipolar disorder NOS, and were enrolled in the Course and Outcome of Bipolar Illness in Youth study. Subjects completed the Life Events Checklist. Sixty-five DEP-ANX and 65 healthy youth were obtained from previous studies using similar methodology. The study was conducted from October 2000 to July 2006.
Older age, lower socioeconomic status, living with nonintact family, non-Caucasian race, anxiety, and disruptive disorders were associated with greater number of total negative life events. Specifically, increased independent, dependent, and uncertain negative life events were associated with lower socioeconomic status, nonintact family, and comorbid disruptive disorders. Increased independent negative life events were additionally associated with non-Caucasian race and comorbid anxiety disorders. Increased dependent and uncertain negative life events were also associated with older age. DEP-ANX youth reported a similar rate of negative life events as bipolar youth, and both groups had more negative life events than the healthy controls. Bipolar youth reported fewer total and dependent positive life events compared to DEP-ANX and healthy youths.
Similar to DEP-ANX youth, bipolar youth are exposed to excessive negative independent and dependent life events which may have implications in the long-term outcome and negative consequences associated with this disorder.
To determine whether some children with bipolar disorder (BP) manifest irritability without elation and whether these children differ on socio-demographic, phenotypic, and familial features from those who have elation and no irritability and from those who have both.
361 BP youth recruited from three sites, University of Pittsburgh, Brown, and UCLA were assessed at baseline and for most severe past symptomatology using standardized semi-structured interviews. BP subtype was identified and frequency and severity of manic symptoms quantified. Subjects were required to have episodic mood disturbance to be diagnosed with BP. The sample was then re-classified, and compared, based upon the most severe lifetime manic episode into three subgroups: elated only, irritable only, and both elated and irritable.
Irritable only and elated only subgroups constituted 10% and 15% of the sample, respectively. Except for the irritable only subjects being significantly younger than the other two subgroups, there were no other between groups socio-demographic differences. There were no significant between-group differences in the BP subtype, rate of psychiatric comorbidities, severity of illness, duration of illness, and family history of mania in first/second-degree relatives and other psychiatric disorders in first degree relatives with the exception of depression and alcohol abuse occurring more frequently in the irritability only subgroup. The elated only group had higher scores on most DSM-IV mania criterion B items.
The results of this study support the DSM-IV A criteria for mania in youth. Irritable-only mania exists, particularly in younger children, but similar to elated-only mania it occurs infrequently. The fact that the irritable only subgroup has similar clinical characteristics and family histories of BP, as compared to subgroups with predominant elation, provides support for continuing to consider episodic irritability in the diagnosis of pediatric BP.
Overweight (OW) and obesity (OB) is highly prevalent among adults with bipolar disorder (BP), and has been associated with illness severity. Little is known regarding OW/OB among youth with BP.
Subjects were 348 youth ages 7 to 17 years old, with BP-I, BP-II, or study-operationalized criteria for BP-NOS enrolled in the Course and Outcome of Bipolar Youth study. Ageand sex-adjusted body mass index (BMI) was computed according to International Obesity Task Force cut points, based on self- and parent-reported height and weight, to determine OW/OB.
OW/OB was prevalent among 42% of subjects. The most robust predictors of OW/OB in a logistic regression model were younger age, non-Caucasian race, lifetime physical abuse, substance use disorders, psychiatric hospitalizations, and exposure to ≥2 medication classes associated with weight-gain.
The prevalence of OW/OB among youth with BP may be modestly greater than the general population. Moreover, similar to adults, OW/OB among youth with BP may be associated with increased psychiatric burden. These preliminary findings underscore the importance of early identification of OW/OB among youth with BP. Future studies are needed to clarify the direction of the associations between OW/OB and the identified predictors, and to compare the prevalence of OW/OB among youth with BP versus other psychiatric disorders.
bipolar disorder; child; adolescent; pediatric; overweight; obesity