Ronald A. Weller

Depression in adolescents growing pains or true morbidity

This review discusses the prevalence and characteristics of depression in childhood and adolescence. Depression in this age group is a major public health concern, but is often under-recognised and dismissed as growing pains. Interviewing the patient and their parents is essential for accurate diagnosis and structured interviews may be helpful. Prevalence increases with age. Risk of recurrence is high and is influenced by family conflict. Childhood onset depression has a 60-70% risk of continuing into adulthood and 20-40% develop bipolar disorder within 5 years. The nature of the disorder is affected by family history and symptoms vary with age. Comorbidity is common and influences treatment choice and long-term outcome. It is hoped that complications such as poor academic performance, impaired social functioning, and substance abuse may be prevented by early intervention.

An open-label trial of divalproex in children and adolescents with bipolar disorder

OBJECTIVEnThis study evaluated the safety and effectiveness of divalproex sodium (Depakote ) in the treatment of youths with bipolar disorder.nnnMETHODnForty bipolar disorder patients aged 7 to 19 years, with a manic, hypomanic, or mixed episode, enrolled in an open-label study of divalproex (2-8 weeks), followed by a double-blind, placebo-controlled period (8 weeks).nnnRESULTSnTwenty-two subjects (61%) showed > or =50% improvement in Mania Rating Scale (MRS) scores during the open-label period. Significant ( <.001) improvements from baseline were seen for mean scores of all efficacy measures, including the MRS, Manic Syndrome Scale, Behavior and Ideation Scale, Brief Psychiatric Rating Scale, Clinical Global Impressions Severity scale, and Hamilton Rating Scale for Depression. Of the 23 subjects who discontinued the study during the open-label period, 6 (15%) discontinued for ineffectiveness, 6 (15%) for intolerance, 6 (15%) for noncompliance, and 6 (15%) for other reasons. Adverse events were generally mild or moderate in severity, with the most common being headache, nausea, vomiting, diarrhea, and somnolence. Laboratory data results were unremarkable. Too few subjects participated in the double-blind period for statistical analysis.nnnCONCLUSIONnThis study provides preliminary support for the safety and effectiveness of divalproex in the treatment of bipolar disorder in youths.

Treatment for Adolescents with Depression Study (TADS): Rationale, design, and methods

OBJECTIVESnA rapidly growing empirical literature on the treatment of major depressive disorder (MDD) in youth supports the efficacy of short-term treatment with depression-specific cognitive-behavioral therapy or medication management with a selective serotonin reuptake inhibitor. These studies also identify a substantial probability of partial response and of relapse, which might be addressed by more intensive, longer-term treatments.nnnMETHODnFunded by the National Institute of Mental Health, the Treatment for Adolescents With Depression Study (TADS) is a multicenter, randomized, masked effectiveness trial designed to evaluate the short-term (12-week) and long-term (36-week) effectiveness of four treatments for adolescents with MDD: fluoxetine, cognitive-behavioral therapy, their combination, and, acutely, pill placebo. A volunteer sample of 432 subjects aged 12-17 years (inclusive) with a primary DSM-IV diagnosis of MDD who are broadly representative of patients seen in clinical practice will enter the study. The primary dependent measures rated blindly by an independent evaluator are the Childrens Depression Rating Scale and, for responder analysis, a dichotomized Clinical Global Impressions-Improvement score. Consistent with an intent-to-treat analysis, all patients, regardless of treatment status, return for all scheduled assessments.nnnRESULTSnThis report describes the design of the trial, the rationale for the design choices made, and the methods used to carry out the trial.nnnCONCLUSIONnWhen completed, TADS will improve our understanding of how best to initiate treatment for adolescents with MDD.

The Treatment for Adolescents With Depression Study (TADS): outcomes over 1 year of naturalistic follow-up.

OBJECTIVEnThe Treatment for Adolescents With Depression Study (TADS) evaluates the effectiveness of fluoxetine, cognitive-behavioral therapy (CBT), and their combination in adolescents with major depressive disorder. The authors report effectiveness outcomes across a 1-year naturalistic follow-up period.nnnMETHODnThe randomized, controlled trial was conducted in 13 academic and community sites in the United States. Stages I, II, and III consisted of 12, 6, and 18 weeks of acute, consolidation, and continuation treatment, respectively. Following discontinuation of TADS treatments at the end of stage III, stage IV consisted of 1 year of naturalistic follow-up. The participants were 327 subjects between the ages of 12 and 17 with a primary DSM-IV diagnosis of major depressive disorder. No TADS treatment was provided during the follow-up period; treatment was available in the community. The primary dependent measures, rated by an independent evaluator blind to treatment status, were the total score on the Childrens Depression Rating Scale-Revised and the rate of response, defined as a rating of much or very much improved on the Clinical Global Impressions improvement measure.nnnRESULTSnSixty-six percent of the eligible subjects participated in at least one stage IV assessment. The benefits seen at the end of active treatment (week 36) persisted during follow-up on all measures of depression and suicidality.nnnCONCLUSIONSnIn contrast to earlier reports on short-term treatments, in which worsening after treatment is the rule, the longer treatment in the TADS was associated with persistent benefits over 1 year of naturalistic follow-up.

Suicide-bereaved children and adolescents: ii. parental and family functioning

OBJECTIVEnThe current study extends the authors earlier examination of suicide-bereaved (SB) children from the Grief Research Study, a longitudinal study of childhood bereavement after parental death, by examining the childrens family history of psychopathology and family environment before and after death.nnnMETHODnTwenty-six SB children, aged 5 to 17 years, and their 15 surviving parents were compared with 332 children bereaved from parental death not caused by suicide (NSB) and their 201 surviving parents in interviews 1, 6, 13, and 25 months after the death.nnnRESULTSnSuicide completers evidenced more psychopathology than parents who died from reasons other than suicide. Contrary to expectations, surviving SB parents were not more impaired than NSB parents. Before the death, SB families were less stable than NSB families and relationships with the decreased SB parent were compromised. However, no differences were detected between groups in childrens relationships with their surviving parents. Likewise, few differences were found in social support or changes in religious beliefs.nnnCONCLUSIONSnSB children generally come from families with a history of psychopathology and substantial family disruption. However, surviving SB parents do not exhibit higher rates of psychopathology than other bereaved parents and many have positive relationships with their children.

BIPOLARITY IN CHILDREN

Childhood and adolescent bipolar disorder have been less studied than adult onset bipolar illness. However, case reports of mania in childhood can be found as early as the mid 19th century. Historically, several factors have made the accurate diagnosis of bipolar disorder in childhood difficult: clinical bias against the diagnosis of mania in children; low base rate of disorder; symptom overlap between bipolar disorder and other more prevalent childhood-onset psychiatric disorders; and developmental constraints and variability in clinical presentation. The epidemiology of juvenile-onset bipolar disorder remains an open topic for research. The disorder appears to increase in prevalence with advancing age until young adulthood. Reported phenomenology of bipolar disorder in children and adolescents indicates a highly variable presentation with a developmental trend towards increased resemblance to the adult phenotype with increasing age of onset. Diagnostic accuracy for the disorder is improved by adherence to diagnostic and statistical manual of mental disorders (DSM) criteria and may be aided by structured or semistructured diagnostic interviews. The course of bipolar disorder in children and adolescents has also received limited systematic study. However, research to date supports a clinical picture of a relapsing, recurrent illness with substantial morbidity. Systematic studies of pharmacologic treatments of acute mania in children and adolescents are limited in number and scope. Clinical justification for the use of acute antimanic treatments such as lithium and valproic acid is still based upon studies conducted in adults. There remains an immediate and significant need for additional research into all aspects of juvenile-onset bipolar disorder.

Depression in children and adolescents two months after the death of a parent

BACKGROUNDnThis study examined depressive symptoms in bereaved children and adolescents two months after the death of a parent.nnnMETHODSnParticipants were 325 children and adolescents bereaved of a parent approximately two months prior to the study. They were compared to 129 non-bereaved community controls and 110 non-bereaved depressed controls. Participants and their parents were interviewed regarding the childs depressive symptoms. Possible moderating factors for depression in bereaved children were examined.nnnRESULTSn25% of the bereaved participants experienced a major depressive episode (MDE) compared to 1% of the community controls. An additional 24% of the bereaved participants experienced a sub-syndromal depressive episode, defined as 3 or 4 depressive symptoms, compared to 4% of the community controls. Factors correlated with occurrence of MDE in the bereaved children in exploratory analyses were (1) history of MDE in the child and (2) history of alcoholism in a parent. Guilt/worthlessness, psychomotor disturbance, and low energy in the context of an MDE predicted membership in the depressed control group over the bereaved group.nnnLIMITATIONSnThe relationship between an MDE in the bereaved child and parent history of alcoholism is exploratory, as the p-value for this correlation was greater than the α adjusted for multiple comparisons. The bereaved childs history of MDE was based on the childs and parents memories of depressive symptoms.nnnCONCLUSIONSnThe death of a parent is a risk factor for depressive symptoms and depressive episodes in children and adolescents two months after the death.

Affective disorders and other psychiatric diagnoses in children and adolescents with 22q11.2 Deletion Syndrome.

BACKGROUNDn22q11.2 Deletion Syndrome (22qDS) is a common chromosome deletion syndrome that has been associated with severe psychopathology, including bipolar disorder and schizophrenia, in adults. Assessment of psychiatric diagnoses in children and adolescents with 22qDS is in the early stages of investigation.nnnMETHODSn24 children and adolescents with 22qDS established by chromosomal analysis were randomly selected from a 22qDS clinic. Children and their parents were interviewed by trained psychometricians with a standardized structured diagnostic interview. A diagnosis was considered present if DSM-IV diagnostic criteria were met on either the parent or the child interview.nnnRESULTSn24 22qDS subjects (mean age 9.7+/-3.3 years) had a mean of two DSM-IV psychiatric disorders. 79% met criteria for at least one DSM-IV psychiatric disorder and over one third had three or more diagnoses. 12.5% met criteria for major depression but none had bipolar disorder. Anxiety disorders (54%), attention-deficit/hyperactivity disorder (38%), and oppositional defiant disorder (38%) were common. Although 29% reported at least one psychotic-like symptom, none met criteria for a psychotic disorder.nnnLIMITATIONSnSmall sample size may have obscured significant associations. Other limitations included non-blinded interviewers and lack of a simultaneously studied control group.nnnCONCLUSIONnAffective, anxiety, attentional, and behavioral disorders were relatively common in this randomly selected group of children and adolescents with 22qDS. No child met criteria for bipolar disorder or schizophrenia. Prospective, longitudinal study is needed to determine whether early psychiatric symptomatology in children with 22qDS predicts continuing or more severe psychopathology later in life. Early psychiatric screening and monitoring appears warranted in 22qDS patients.

Occurrence of affective disorders compared to other psychiatric disorders in children and adolescents with 22q11.2 deletion syndrome

BACKGROUNDn22q11.2 deletion syndrome (22qDS) is a common genetic disorder with highly variable clinical manifestations that may include depression, bipolar disorder and schizophrenia. Studies of psychiatric disorders in youth with 22qDS often had methodological limitations. This study reviewed clinical studies with the currently best available methodology to determine the occurrence of affective disorders compared to other psychiatric disorders in youth with 22qDS.nnnMETHODnA PubMed search was performed to identify psychiatric studies published from 2000 through 2009 of children and adolescents with genetically confirmed 22qDS who underwent systematic psychiatric assessments. Studies that met defined inclusion/exclusion criteria were selected for further analysis.nnnRESULTSnSeven studies with a total of 323 children and adolescents with 22qDS (mean age=10.8 years) met the defined inclusion/exclusion criteria. Depressive disorders, but not bipolar spectrum disorders, were increased compared to community-based rates in youth without 22qDS. Anxiety disorders and attention-deficit/hyperactivity disorder were the most frequent disorders. Although psychotic-like phenomena and schizotypical traits were reported, only two adolescents (<1%) had a psychotic disorder.nnnLIMITATIONSnUnknown selection and assessment factors may have impacted on occurrence rates.nnnCONCLUSIONnThe elevated occurrence of depressive, anxiety, and attention disorders in children with 22qDS, compared to community-based rates in children without 22qDS, suggest that psychiatric screening is needed. Longitudinal study is needed to determine if these childhood psychiatric disorders will resolve, continue into adulthood, or develop into more serious psychopathology.

Treatment options in the management of adolescent depression.

Treatment for depression in children and adolescents often requires pharmacotherapy with tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs), followed by psychotherapy. Most studies have not found the TCAs to be more effective than placebo in the treatment of depression in children and adolescents. Initial reports, however, have found the SSRIs to be more effective and better tolerated. In the small proportion of children who have treatment-resistant depression, TCAs plus lithium, monoamine oxidase inhibitors (MAOIs) or electroconvulsive therapy (ECT) may be useful. More studies on the treatment of depression in children and adolescents are needed, as adult data cannot simply be extrapolated.