A controlled family history study of prepubertal major depressive disorder

First-degree (N = 195) and second-degree (N = 785) adult relatives of prepubertal children with major depression (N = 48), children with nonaffective psychiatric disorders (N = 20), and normal children (N = 27) were assessed by the Family History-Research Diagnostic Criteria method (FH-RDC), except for the adult informant (usually the mother), who was directly interviewed. Compared with normal controls, prepubertal children with major depressive disorder (MDD) had significantly higher familial rates of psychiatric disorders in both first- and second-degree relatives, especially MDD, alcoholism, and "other" (mostly anxiety) diagnoses. Relatives of children in the nonaffective psychiatric control (PC) group had low rates of alcoholism, high rates of other (anxiety) disorder diagnoses, and intermediate rates of MDD (accounted for by those children with separation anxiety). This suggests that prepubertal onset of major depression may be especially likely in families with a high aggregation of affective disorders when these families also have a high prevalence of alcoholism, and that a proportion of children without affective disorder but with separation anxiety disorder in this study were at high risk for the development of affective illness later in life. These results support the validity of prepubertal-onset depressive illness as a diagnostic category, and are consistent with high familial rates of MDD and other psychiatric disorders found in family studies of adolescent and early-onset adult probands with major affective disorders, and with studies of the offspring of parents with major affective disorders. Within the child MDD group substantial heterogeneity was found. Low familial rates of MDD were associated with suicidality and comorbid conduct disorder in the child probands. The highest familial rates of MDD, approximately threefold those in the normal controls, and all the bipolar relatives, were found in the families of prepubertal probands with MDD who never had a concrete suicidal plan or act and who were without comorbid conduct disorder. A useful nosological continuum in which to classify prepubertal MDD may be to place at one end those patients with comorbid conduct disorder and at the other end those patients with manifestations related to bipolarity, including hypomania, mania, and psychotic subtype.     

Early onset psychiatric disorder in high risk children and increased familial morbidity

The relationship between child psychopathology and familial morbidity in second degree relatives was examined for children considered at risk on the basis of parental affective illness. Second degree relatives in high-risk families with no child psychopathology were no different from low-risk families in their rates of depression and anxiety. Second degree relatives in high-risk families positive for child psychopathology had significantly higher rates of depression and anxiety than relatives of low-risk children and relatives of high-risk children with no disorder. The implications of these findings are discussed with respect to risk status, prepubertal onset of psychopathology, and familial morbidity for specific psychiatric disorders.     

Selective serotonin reuptake inhibitors and depression in the child and adolescent

Child and adolescent depression is a serious psychiatric disorder with a considerable impact on psychosocial functioning, and an associated risk of mortality due to suicide. The potential interest of selective serotonin reuptake inhibitors (SSRI) for child and adolescent depression treatment is now well recognized. Since a recent date, this class of antidepressants is recommended as first-line medication (18, 24). Open studies have shown a response rate to SSRI from 60% to 75% and their efficiency was demonstrated through a controlled trial of high methodological quality, conducted by Emslie et al. in 1997 (10). The side effects of SSRI are generally mild and seldom require to discontinue the treatment. Research on this domain is tending toward increasing data on the efficacy, safety and pharmacokinetics of SSRI on children and adolescents. The different SSRI specificities and the potentialisation of these compounds by a molecule of the same class, or by other medications (lithium, buspirone, triodothyronine), are currently studied. It seems useful to us to do a review of this category of antidepressants, even though data are incomplete; it has not gone through AMM approval in children below the age of 15, but it appears to be efficient and promising.     

抗抑郁药物治疗儿童青少年抑郁症的临床试验进展

本文目的是归纳并总结新型抗抑郁药物治疗儿童青少年抑郁症的效果和安全性,为儿童青少年抑郁症的药物干预提供参考。抑郁症是儿童青少年常见的精神疾病之一,严重影响患者的健康成长,可造成自杀等严重不良后果。使用抗抑郁药物是治疗儿童青少年抑郁症的重要手段,然而可用于儿童青少年的抗抑郁药物种类较少,临床应用受到一定限制。本文就近十年抗抑郁药物治疗儿童青少年抑郁症的临床试验进展进行综述。     

Clinical guidelines for depressive disorders in childhood and adolescence

 Major depressive and dysthymic disorders are recurrent and sometimes persistent unipolar mood disorders, which often present in childhood and adolescence. Depressive episodes may increase in severity and duration with recurrence and are associated with substantial morbidity and risk of suicide. The role of child and adolescent mental health services in early intervention and management is thus of major importance. This paper draws together current research evidence and common clinical practice, in guidelines for the specialist management of depressive disorders in childhood and adolescence. Both psychotherapy and pharmacotherapy have been found to be beneficial for the acute treatment of children and adolescents with depressive disorders. Based on current evidence, psychotherapy may be the first treatment for most depressed youngsters, but antidepressants should be considered for those with severe depression. All patients need continuation therapy, and some will need maintenance treatment. Evidence supporting the efficacy of psychological and psychopharmacological treatments are reviewed. An integration of approaches is suggested as a guideline for treatment planning. Accepted: 15 February 2000     

Genetic screening for susceptibility to depression: can we and should we?

OBJECTIVE: To summarize current knowledge about genetic susceptibility to mood disorders and examine ethical and policy issues that will need to be addressed if robustly replicated susceptibility alleles lead to proposals to screen and intervene with persons at increased genetic risk of developing mood disorders. METHOD: Empirical studies and reviews of the genetics of unipolar and bipolar depression were collected via MEDLINE and psycINFO database searches. RESULTS: A number of candidate genes for depression have been identified, each of which increases the risk of mood disorders two- or threefold. None of the associations between these alleles and mood disorders have been consistently reported to date. CONCLUSIONS: Screening the population for genetic susceptibility to mood disorders is unlikely to be a practically useful policy (given plausible assumptions). Until there are effective treatments for persons at increased risk, screening is arguably unethical. Screening within affected families to advise on risks of developing depression would entail screening children and adolescents, raising potentially serious ethical issues of consent and stigmatization. Genetic research on depression should continue under appropriate ethical guidelines that protect the interests of research participants.     

A secular increase in child and adolescent onset affective disorder.

Both longitudinal and cross-sectional studies utilizing population and family study samples have found evidence for a secular increase in major affective disorders in adults. Applying techniques used in cross-sectional studies in adults to family study data of children and adolescents, the authors demonstrate evidence of a parallel secular increase for child and adolescent onset affective disorders. Normal and depressed prepubertal probands were identified. All full siblings were directly interviewed for lifetime episodes of affective disorder. Analysis of the siblings (probands not further analyzed in this article) by the Cox proportional hazards model demonstrates that the risk for affective disorder is higher in siblings born more recently.     

Childhood stimulant treatment and teen depression: is there a relationship?

Recent preclinical data have raised the possibility that prepubertal treatment of attention-deficit/hyperactivity disorder (ADHD) with stimulant medication might increase risk for later depression. The current longitudinal study investigated whether children with ADHD who were treated with stimulant medication displayed heightened levels of adolescent depression. Adolescents diagnosed with ADHD during childhood who had received a minimum of 1 year of treatment with stimulant medication were compared to adolescents with a childhood history of ADHD who were never treated with stimulants and a demographically matched comparison group on self-reports of depressive symptoms and diagnoses of depressive disorders. Both subgroups with childhood ADHD reported significantly higher dimensional ratings of depression and categorical rates of depressive disorders relative to the comparison group (all p<0.05), yet those who were and were not medicated did not differ from one another. Results indicate that, while childhood ADHD increases risk for adolescent depression, stimulant treatment for ADHD neither heightens nor protects against such risk.     

Maternal expressed emotion and parental affective disorder: risk for childhood depressive disorder, substance abuse, or conduct disorder

Expressed emotion (EE) refers to a set of emotional aspects of speech for which ratings have been derived. Seven independent studies have established that higher EE ratings in the relatives of patients with schizophrenia predict higher rates of relapse in these patients and two studies have established an association of higher EE in spouses with relapse of depression in their mate. There are no previous studies of parental EE as a predictor of childhood affective disorder or other disorders not in the schizophrenia spectrum. In this study we investigated the relationship between the level of maternal EE and the incidence of DSM-III affective disorder (major depression or mania or dysthymia), substance abuse, or conduct disorder in 273 children. We found that a higher degree of maternal expressed emotion was associated with a three-fold increase in a child's risk (odds multiplier) for having at least one of the following diagnoses: depressive disorder (major depression or dysthymia), substance abuse, or conduct disorder. This increased risk acts in addition to the increased risk of child diagnosis associated with parental affective illness. Research and clinical implications are discussed.     

Experimental animal modeling of depression and anxiety

Experimental animal models have been introduced to study aspects of psychiatric symptoms of depression and anxiety; however, there is no comprehensive animal model for these conditions. The models introduced may simulate certain symptoms (despair), be used to evaluate behavioral theories (cognitive theory of learned helplessness), allow study of underlying neurochemical mechanisms (CSF metabolites, genetic, neurotransmitter model), be used to evaluate developmental issues, and lead to finding new treatments through preclinical pharmacologic trials. A variety of models are needed, as each one attempts to deal with a particular aspect of a syndrome. Pharmacologic models, the model of uncontrollability, separation models, and genetic approaches have been summarized. Depression is viewed as a complex, multifactorial illness. Anxiety models have focused on pharmacologic treatment of motivational conflict and the elicitation of fear and panic through environmental and drug manipulations. The most recent investigations in this area address separation calls and alarm calls in primates as potential models for separation distress and panic symptomatology, arguing that the behavioral context as well as the specific behavior be considered. Animal models have emphasized adult psychopathology in the past. However, with increased recognition of psychiatric disorders in children and adolescents, animal modeling of disorders that begin in the development period assumes importance. Studies in the animal modeling of depression and anxiety involving genetic models, psychosocial models, and stress-induction models are the focus of continuing investigations and may be pertinent to child and adolescent psychopathology. They offer hope for learning more about the neurobiologic mechanisms involved in these conditions and for testing new treatment approaches.     

Major depressive disorder in adolescence: a brief review of the recent treatment literature.

OBJECTIVE: Treating adolescents with depression remains a major clinical and public health challenge. Because of the serious morbidity and mortality associated with adolescent major depressive disorder (MDD), there is a need to review the published literature on treatment efficacy to establish effective treatment choices for these adolescents. METHOD: We reviewed the recent literature on the treatment of MDD in adolescents using the Medline and PsycINFO computerized databases. RESULTS: Results of open studies of MDD treatment in adolescents suggested therapeutic efficacy; however, later, better-controlled studies are more difficult to interpret, owing to the high rate of improvement with placebo. Currently, there is limited evidence of robust, effective therapeutic interventions in children and in adolescent depressive disorders. CONCLUSIONS: Despite limitations, current findings from studies investigating selective serotonin reuptake inhibitors (SSRIs), cognitive-behavioural therapy, and interpersonal therapy generally support these treatments as safe and effective for adolescent MDD. Still, further investigations into these treatments for adolescent depression are warranted.     

Depressive disorders in children and adolescents

Depressive disorders in children and adolescents are valid clinical entities which can be identified using adult diagnostic criteria. Recent research has resulted in significant progress in the areas of diagnosis, epidemiology, family pathology, pharmacokinetics and psychopharmacology. Many rating instruments have been developed to screen, diagnose and measure changes of depression in children and adolescents. The prevalence of depressive disorders in prepubertal children is about 2% and in adolescents about 5%. Depressive episodes are usually of long duration, with high rates of relapse. These relapses are usually associated with school, family and social failure. Follow-up studies of depressed adolescents indicated that about half of the patients continue to suffer from mood disturbances and psycho-social adaptational problems. In North America suicidal behaviour in adolescents has increased 300% in the past 30 years. However, its relationship to depression is more complex than in adults. There is a significant excess of affective illness and alcoholism in the families of depressed adolescents. Similarly, there is a high rate of impairment among children of parents with affective disorders. During depressive episodes, prepubertal children show abnormalities of growth hormone and cortisol secretion. However, DST findings are contradictory. Polysomnographic findings in childhood depression appear unremarkable. In adolescent depression these findings are similar to those in depressed adults. Biological manifestations of depressive disorders may be significantly affected by developmental and hormonal changes. Antidepressants have been effective in the therapy of several disorders in childhood. These include enuresis, school phobias, attention deficit, conduct disorders and obsessive-compulsive disorders. Open drug studies suggest that antidepressants are useful in depressed children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concomitant pharmacotherapy among youths treated in routine psychiatric practice

OBJECTIVES: The aim of this study was to assess rates and correlates of concomitant pharmacotherapy in children and adolescents treated by psychiatrists in a broad range of clinical settings. METHODS: Cross-sectional data on 392 child and adolescent patients aged 2-17 years from the 1997 and 1999 American Psychiatric Practice Research Network Study of Psychiatric Patients and Treatments were used, and weighted estimates are provided. RESULTS: Findings indicate that 84% of child and adolescent patients received one or more psychopharmacologic medications; 52% of patients treated with medications received concomitant pharmacotherapy (i.e., two or more medications). Patients who were treated with psychopharmacologic treatments received a median of 2 medications (range, 1-6). Highest rates of concomitant pharmacotherapy were among patients with bipolar disorder (87%). Correlates of concomitant pharmacotherapy included: (1) having a diagnosis of bipolar disorder, (2) having co-occurring Axis I or II disorders or general medical conditions, and (3) currently receiving treatment in an inpatient setting. CONCLUSIONS: Over 40% of child and adolescent patients of psychiatrists were prescribed two or more psychopharmacologic medications. Patients with chronic and clinically complex conditions were more likely to receive concomitant pharmacotherapy. Most often, efficacy of U.S. Food and Drug Administration (FDA)-approved medications has been examined as monotherapy, and cautions on drug interactions and off-label use derived from multiple sources accompany each product. With high rates of concomitant pharmacotherapy among children and adolescents in psychiatric care, additional research on efficacy and safety of this treatment strategy is necessary.     

Depression and bipolar support alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in children and adolescents

OBJECTIVE: To focus attention on the critical unmet needs of children and adolescents with mood disorders and to make recommendations for future research and allocation of healthcare resources. METHOD: The 36-member Consensus Development Panel consisted of experts in child/adolescent or adult psychiatry and psychology, pediatrics, and mental health advocacy. Reviews of the literature concerning youth mood disorders were performed on the subjects of risk factors, prevention, diagnosis, treatment, and services delivery, and opinions and experiences of mental health advocates were obtained. RESULTS: The Consensus Development Panel listened to presentations and participated in discussions. Independent workgroups of clinicians, scientists, and mental health advocates considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed by the entire group and edited to incorporate input from all participants. CONCLUSIONS: Evidence suggests high rates of unmet needs for children and adolescents with depression or bipolar disorder. Training is largely limited to child mental health specialists; general psychiatrists, pediatricians, and other primary care physicians receive little or no training. As a result, treatment patterns may reflect adult treatment plans that are not validated for youths. Effective treatments have been identified and some preliminary prevention models have been developed, but they are not yet widely applied. Patients experience limited exposure to clinicians adequately trained to address their problems and little information to guide care decisions, particularly concerning bipolar disorder. National efforts are required to restructure healthcare delivery and provider training and to immediately develop more advanced research on pathophysiology, prevention, and services delivery effectiveness.     

Eating disorders in children and adolescents: pharmacological therapies

Anorexia nervosa and bulimia nervosa do exist in childhood, frequently have their onset in adolescence, and can result in serious medical and psychiatric sequelae that impede physical, emotional, and behavioral development. Although we use the same Diagnostic and Statistical Manual of Mental Disorders-Version 4 [DSM-IV] definitions to diagnose eating disorders in children, adolescents, and adults, these disorders may be expressed somewhat differently in younger populations, requiring assessment and treatment procedures that are tailored to their developmental needs. Significant advances have been made in recent years in our understanding of treatments for eating disorders in adults, and specifically pharmacological treatments for these disorders. Multiple double-blind, placebo-controlled studies have documented the short-term efficacy of antidepressant medications in bulimia nervosa. While the usefulness of pharmacological treatments for the acute treatment of anorexia nervosa is less clear, recent evidence suggests a role for medication in the relapse-prevention stage of the illness. The majority of the medication trials for the eating disorders have been conducted with adults, and the literature on the pharmacological treatment of children and adolescents with these disorders is very limited. This review article summarizes the current literature on the role of medication in the treatment of anorexia nervosa and bulimia nervosa, with particular emphasis on studies conducted in child and adolescent populations.

     

Prevalence of affective disorders in children and adolescents: findings from the Zurich Epidemiological Studies

OBJECTIVE: Affective disorders were studied in two epidemiological studies of children and adolescents in the Canton of Zurich, Switzerland. METHOD: In the Zurich Epidemiological Study of Child and Adolescent Psychopathology Study (ZESCAP) in 1994 a representative cohort of 1964 pupils aged 7-16 years was studied. The Zurich Adolescent Psychology and Psychopathology Study (ZAPPS) included 1089 adolescents aged 15-19 years who were assessed in 1997. A two-stage approach with questionnaire screening of the entire sample in stage 1 and consecutive interviews in stage 2 was used in both studies. Diagnoses according to DSM-III-R were derived from structured parent interviews in the ZESCAP and from both parent and adolescent interviews in the ZAPPS. RESULTS: The total prevalence rate for affective disorders in the ZESCAP was 0.66% (SE 0.25) whereas it was 5.1% based on adolescent interviews and 1.2% based on parent interviews in the ZAPPS. Adolescent girls have significantly higher prevalence rates for affective disorders than boys (9.4 vs. 1.1%). CONCLUSION: These findings are in accordance with various other international epidemiological studies on affective disorders in children and adolescents.     

Time trends in child and adolescent mental disorders

PURPOSE OF REVIEW: 1995 saw the publication of a major review of time trends in psychosocial disorders of youth across the second half of the twentieth century. It found evidence for substantial increases in rates of youth crime, alcohol and drug use, depression and suicide in most industrialized countries in the decades following the Second World War, slowing in some instances in the 1980s. Ten years on, we review findings on more recent trends in rates of these and other indicators of child and adolescent mental health. RECENT FINDINGS: Prevalence estimates for autism spectrum disorders have increased in recent decades, as has public and professional awareness of hyperactivity and attention deficits. Trends in adolescent conduct problems, and in alcohol and drug use, appear to reflect culture-specific influences. Rates of suicide among young males, and self-harm among females have risen in many countries in recent years; trends in emotional disorders are more varied, but there is little evidence for any rise in rates of anorexia nervosa. Although some contributors to these trends have been identified, much remains to be learned about the key risks involved. SUMMARY: Monitoring time trends in child and adolescent mental health is essential for service planning; knowledge of changing trends can also provide important pointers to potential risk factors. Current data sources allow relatively reliable tracking of trends in some areas, but remain severely limited in others. Further research is needed to understand the mechanisms underlying recently identified trends in child and adolescent mental health.     

Adolescent Bulimia Nervosa

Onset of bulimia nervosa (BN) typically occurs in adolescence and is frequently accompanied by medical and psychiatric sequelae that may have detrimental effects on adolescent development. Potentially serious medical consequences and high comorbid rates of mood disorders and suicidality underscore the need for early recognition and effective treatments. Research among adolescents with BN has lagged behind that of adults, although evidence is accumulating to support the efficacy of family-based interventions and cognitive behavioral treatments that are adapted for use with adolescent populations. The aim of the current article is to provide an overview of recent research on epidemiology, risk factors, diagnostic issues, and treatment interventions focusing on adolescent BN, and to highlight areas for future research.     

Outcomes of suicidal behaviors

Research issues associated with outcomes of suicidal behavior include: the appropriate length of time to follow subjects is at least two years, psychiatric controls without a history of suicide attempt are a recommended comparison group, quantitation of traits such as aggression or impulsivity is desirable. Clinical issues include the following: the diathesis for suicide is a trait, the most universal risk factor across groups is the presence of depression, yet under-treatment, such as inadequate dosing of antidepressants and high rates of drop-out from psychotherapy, is a major problem. Other issues include that treatment must take a lifelong perspective, there is an ongoing need for psychoeducation of practitioners and the public, outreach to institutions such as schools, hospitals and jails is needed, when a child or adolescent exhibits suicidal behavior, parents should be screened for psychiatric illness, there is an urgent need to remedy barriers to treatment including insurance coverage obstacles, long wait-lists, and fragmentation of mental healthcare. Improvements should include a focus on step-down treatments and the integration of primary care and mental healthcare. Establishing a national registry of serious suicidal behavior to aid research, and clinical trials of treatments for suicidal behavior is important. Subpopulations for study include children, adolescents, the elderly, institutionalized persons, community samples (as distinct from clinical samples), persons with a family history of suicide (for genetic linkage studies), attempters versus completers, single versus multiple attempters and persons who drop out of treatment.     

A review of pharmacotherapy of major depression in children and adolescents

OBJECTIVE: The review examined the historical progression and current status of pharmacotherapy of child and adolescent major affective disorder. METHODS: A MEDLINE search was used to identify double-blind, placebo-controlled studies of child and adolescent major depression. Only studies that used reliable diagnostic and recovery parameters were included. RESULTS: Few well-designed studies have compared placebo and tricyclic antidepressants in the treatment of major depressive disorder in children and adolescents. However, results consistently suggest that tricyclic antidepressants are not efficacious. Early results of double-blind placebo-controlled trials with fluoxetine and paroxetine have shown a significant drug effect. However, the results are inconsistent, which could reflect the ways that response to medication is defined, the ways that rating scales measure recovery, and uncertainties of dosing strategies with second-generation antidepressants. Hypothesized reasons for the unique response pattern in youths include the changing hormonal status of children, the differential maturation of the noradrenergic versus serotonergic neurotransmitter systems, and the possibility that a large proportion of depressed youths are in the early stages of bipolar disorder, which is not effectively treated by these medications. CONCLUSIONS: Tricyclic antidepressants are not superior to placebo for the treatment of child and adolescent major depressive disorder. Although two of three trials of second-generation antidepressants in this age group have had negative results, data suggest that these drugs may be more promising. It is too early in our investigation to know whether these agents will be effective in treating major depressive disorder in children and adolescents.