Roberta Freeman

The long-term course of severe anorexia nervosa in adolescents: survival analysis of recovery, relapse, and outcome predictors over 10-15 years in a prospective study.

OBJECTIVE To assess the long-term course of recovery and relapse and predictors of outcome in anorexia nervosa. METHOD A naturalistic, longitudinal prospective design was used to assess recovery and relapse in patients ascertained through a university-based specialty treatment program. Patients were assessed semiannually for 5 years and annually thereafter over 10-15 years from the time of their index admission. Recovery was defined in terms of varying levels of symptom remission maintained for no fewer than 8 consecutive weeks. RESULTS Nearly 30% of patients had relapses following hospital discharge, prior to clinical recovery. However, most patients were weight recovered and menstruating regularly by the end of follow-up, with nearly 76% of the cohort meeting criteria for full recovery. Relapse after recovery was relatively uncommon. Of note, time to recovery was protracted, ranging from 57-79 months depending on definition of recovery. Among restrictors at intake, nearly 30% developed binge eating, occurring within 5 years of intake. A variety of predictors of chronic outcome and binge eating were identified. There were no deaths in the cohort. CONCLUSION The course of anorexia nervosa is protracted. Predictors of outcome are surprisingly few, but those identified are in keeping with previous accounts. The intensive treatment received by these patients may account for the lower levels of morbidity and mortality when considered in relation to other reports in the follow-up literature.

A family study of bipolar I disorder in adolescence: Early onset of symptoms linked to increased familial loading and lithium resistance

Lifetime rates of psychiatric illness were compared in relatives of adolescent probands with bipolar I disorder and in relatives of age-matched schizophrenic controls. Familial aggregation of major affective disorders was observed in bipolar probands, the rate of bipolar I disorder greatly exceeding that reported in relatives of adult bipolar probands. Adolescent probands with childhood onset of psychiatric disturbance were distinguished from probands who had no premorbid childhood psychiatric abnormality in two ways: (1) significantly increased aggregation of bipolar I disorder in first-degree relatives; and (2) poorer antimanic response to lithium carbonate. These data underscore important heterogeneity in adolescent-onset bipolar disorder.

Recovery and Relapse in Adolescents with Bipolar Affective Illness: A Five-Year Naturalistic, Prospective Follow-up

OBJECTIVE This study was a 5-year naturalistic prospective follow-up of 54 consecutive admissions of adolescents to a university inpatient service with a diagnosis of bipolar I affective illness. METHOD Subjects received structured clinical evaluations every 6 months after entry to establish time to recovery and subsequent relapse. Regression models were used to identify predictors of differential course. RESULTS Rate of recovery varied by polarity of episode at time of entry, with quick recovery observed in subjects with pure mania or mixed states, and a protracted index episode in subjects with pure depression. Multiple relapses were most often seen in subjects with mixed or cycling episodes at intake. CONCLUSIONS Polarity of illness may have utility in identifying bipolar adolescents with a more recurrent illness. Comparison with adult data suggests that recurrence risks may vary as a function of age at onset or stage of the disease process.

Early childhood attention deficit hyperactivity disorder predicts poorer response to acute lithium therapy in adolescent mania.

We compared the response to acute lithium therapy in 30 adolescents, 13-17 years of age, with mania and a prior history of early childhood attention deficit hyperactivity disorder (ADHD) to a sex- and age-matched control group of adolescent manics without premorbid psychiatric illness. Response to treatment was assessed daily over the course of 28 days using measures of global clinical improvement and severity ratings on the Bech-Rafaelsen Mania Scale (BRMS). BRMS scores decreased by a mean of 24.3 in the subgroup without prior ADHD compared to 16.7 in patients with ADHD (P = 0.0005). The average percent drop in BRMS scores over the study period in these two subgroups was 80.6% and 57.7%, respectively (P = 0.0005). Time to onset of sustained global clinical improvement was also assessed using Kaplan-Meier survival methods and possible covariates of time to improvement were tested in a Cox proportional hazards model. Median time to onset of sustained improvement was lengthened significantly in patients with early ADHD (23 days) compared to those without it (17 days; log rank chi2 = 7.2, P = 0.007). The results suggest that early childhood ADHD defines an important source of heterogeneity in bipolar illness with developmental, clinical, and neuropharmacogenetic implications.

Atypical anorexia nervosa: Separation from typical cases in course and outcome in a long-term prospective study

OBJECTIVE To assess differences in long-term course and outcome between typical and atypical cases of anorexia nervosa. METHOD A naturalistic, longitudinal prospective design was used to assess recovery, relapse, and onset of binge eating over 10 to 15 years in patients ascertained through a university-based specialty treatment program. Atypical anorexia nervosa was distinguished from the diagnostically prototypic form of the disorder based on the continuous absence of morbid fear of weight gain and body size distortion during the inpatient phase of treatment. Patients were assessed semiannually for 5 years then annually thereafter until the final visit. RESULTS Compared to pure cases of anorexia nervosa, atypical cases were less likely to drop weight after discharge, recovered more rapidly, and had lower cumulative risk for developing binge eating. CONCLUSION It has been argued recently that weight phobia and body image disturbance should not be viewed as critical to the diagnosis of anorexia nervosa. This study shows that the absence of these particular symptoms in patients presenting with malnutrition secondary to extreme dietary restriction predicts a less malignant course and outcome compared to typical cases of anorexia nervosa. These course differences suggest that the division of patients into typical versus atypical diagnostic subtypes may be nosologically valid and clinically useful.

The Pharmacotherapy of Depressive Illness in Adolescence: II. Effects of Lithium Augmentation in Nonresponders to Imipramine

The antidepressant value of lithium augmentation was assessed in a 3-week open trial involving 24 adolescents who remained highly depressed after 6 weeks of treatment with imipramine hydrochloride. Two patients responded dramatically during the first week, with an additional eight patients showing partial improvement during the 3-week trial. The overall magnitude of improvement in depression ratings was significantly greater than in an historical control group of nonresponders who continued to receive imipramine monotherapy during their hospital treatment. Results suggest the potential use of this adjunctive strategy in some tricyclic resistant adolescent depressives, although it appears less efficacious overall in this age group than in adults.

Binge eating in anorexia nervosa predicts later onset of substance use disorder: A ten-year prospective, longitudinal follow-up of 95 adolescents

The cooccurrence of binge eating and increased alcohol intake and substance abuse has been reported in clinical and community epidemiological samples. To further investigate the nature and causes of this comorbidity, we examined the 10-year prospective, longitudinal course of illness in 95 nonsubstance abusing adolescents hospitalized for treatment of anorexia nervosa. Survival analysis with Cox regression was used to quantitate the cumulative risk of developing substance use disorder (SUD) as a function of patterns of binge eating vs. dietary restraint within this cohort. Subjects who were binge eating at the time of intake were robustly distinguished from restrictors, having increased risk of SUD as well as greater likelihood of having at least one first-degree relative with SUD. The findings suggest binge eating that develops in the underweight stage of anorexia nervosa may reflect developmental, biological, and genetic risk processes shared in common with SUD.