Joan Kaufman

Childhood and Adolescent Depression: A Review of the Past 10 Years. Part II

OBJECTIVE To qualitatively review the literature of the past decade covering the epidemiology, clinical characteristics, natural course, biology, and other correlates of early-onset major depressive disorder (MDD) and dysthymic disorder (DD). METHOD A computerized search for articles published during the past 10 years was made and selected studies are presented. RESULTS Early-onset MDD and DD are frequent, recurrent, and familial disorders that tend to continue into adulthood, and they are frequently accompanied by other psychiatric disorders. These disorders are usually associated with poor psychosocial and academic outcome and increased risk for substance abuse, bipolar disorder, and suicide. In addition, DD increases the risk for MDD. There is a secular increase in the prevalence of MDD, and it appears that MDD is occurring at an earlier age in successive cohorts. Several genetic, familial, demographic, psychosocial, cognitive, and biological correlates of onset and course of early-onset depression have been identified. Few studies, however, have examined the combined effects of these correlates. CONCLUSIONS Considerable advances have been made in our knowledge of early-onset depression. Nevertheless, further research is needed in understanding the pathogenesis of childhood mood disorders. Toward this end, studies aimed at elucidating mechanisms and interrelationships among the different domains of risk factors are needed.

The Psychosocial Functioning and Family Environment of Depressed Adolescents

OBJECTIVE This study examined measures of functional impairment and family relations in a sample of 62 adolescents with major depressive disorder (MDD) and 38 normal controls with no history of psychiatric illness. METHOD Ratings of the following domains were obtained: mother-child relations, father-child relations, spousal relations, sibling relations, peer relations, and school performance. Ratings of each domain for the 3-month period preceding the assessment were derived from information obtained using a semistructured interview administered independently to the adolescents and one of their parents. RESULTS Adolescents with MDD were found to have severe difficulties in all areas. Ninety percent of the depressed adolescents had scores greater than 2 SD above the mean of the normal controls on one or more of the domain ratings. In addition, adolescents with difficulties in parent-child relations were more likely than those adolescents without problems in family relations to have difficulties in peer relations and school performance. CONCLUSIONS The authors discuss the importance of systematically examining psychosocial variables in future studies of the etiology, course, and treatment of MDD in adolescents.

The Corticotropin-Releasing Hormone Challenge in Depressed Abused, Depressed Nonabused, and Normal Control Children

Hypothalamic-pituitary-adrenal (HPA) axis disturbances in depressed children with a history of abuse were examined. Thirteen depressed abused, 13 depressed nonabused, and 13 normal control children were given 1.0 microgram/kg of human corticotropin-releasing hormone (CRH) intravenously. Blood samples for corticotropin (ACTH) and cortisol were obtained at nine intervals. When compared to depressed nonabused and normal control children, depressed abused children had significantly greater peak, total, and net ACTH secretion post-CRH. Increased ACTH secretion was only observed in depressed abused children experiencing ongoing chronic adversity (marital violence, emotional abuse, poverty, lack of supports). The pattern of findings of the depressed abused children experiencing ongoing adversity parallels the pattern of HPA axis dysregulation reported in animal studies of chronic stress. They add to a growing body of literature suggesting measures of past trauma and current adversity are important sources of variability in psychobiological correlates of major depression.

Problems defining resiliency: Illustrations from the study of maltreated children

In this article, operational definitions of resiliency used in previous studies are reviewed. Data from a sample of 56 maltreated school-age children are then explored to highlight how variations in the source, type, and number of assessments obtained affect the rates of children classified as resilient. Assessments were obtained in three domains: academic achievement, social competence, and clinical symptomatology. Two sources of information were used to assess each domain, and three different data integration procedures were used to calculate rates of resiliency in the maltreated cohort. It is concluded that the most appropriate definition of resiliency to be used in future investigations depends on the aims of the study. If the goal of the study is to assess overall functioning, there is an advantage to using more broad, multidimensional assessments. If, in contrast, the goal of the study is to determine why some high-risk children develop particular types of problems, to identify underlying etiological processes associated with different outcomes, there is an advantage to using narrower definitions.

The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression

This study examined the relationship between longitudinal clinical course and sleep and cortisol findings in adolescent unipolar major depressive disorder (MDD). Subjects were 28 adolescents (15.4 +/- 1.3 years) systematically diagnosed with unipolar MDD and 35 group-matched normal controls who participated in EEG sleep and neuroendocrine studies. Follow-up clinical assessments were conducted 7.0 +/- 0.5 years later in 94% of the original cohort. Although initial group comparisons failed to show significant differences in biologic measures, analyses incorporating clinical follow-up reveal that changes in sleep and cortisol measures are associated with differential longitudinal course. Normal controls who would develop depression after the biologic studies had shown significantly higher density of rapid eye movements (REM) and a trend for reduced REM latency compared to controls with no psychiatric disorder at follow-up. Depressed subjects with a recurrent unipolar course showed a trend towards elevated plasma cortisol near sleep onset compared to MDD subjects with no further episodes during the follow-up interval.

The use of multiple informants to assess children's maltreatment experiences

Most researchers rely exclusively on the reports of protective service workers to determine childrens abuse history. In this report, information about childrens maltreatment experiences is obtained from protective service workers and three supplementary sources of data: parents, medical records, and clinical observations. Fifty-six children from 34 families receiving protective services for verified reports of physical abuse, neglect, sexual abuse, and/or emotional maltreatment participated in the study, with most children known to have experienced more than one type of abuse. The supplementary data provided important information about the range and severity of childrens maltreatment experiences. Review of the parent and medical record data led to identification of 28 children who had additional types of maltreatment experiences that were not reported by their protective services workers—nine cases of physical abuse, two cases of neglect, five cases of sexual abuse, and 12 cases of emotional maltreatment. Supplementary data also revealed information about incidents of specific types of abuse that were more severe than those reported by the childrens protective service workers in an additional 24 cases. A method was devised to synthesize information provided from the different sources of data examined in this report to derive 0–4 point ratings of four categories of maltreatment experiences: (1) physical abuse, (3) neglect, (3) sexual abuse, and (4) emotional maltreatment. The Kappa reliability coefficients for each of these scales were .88, .73, .83, and .90, respectively. Data demonstrating the relationship between these maltreatment ratings and various indices of the childrens socioemotional and cognitive functioning were also presented to provide preliminary support for the validity of these scales. The findings from this study suggest that multiple sources of data should be examined in order to obtain accurate assessments of childrens maltreatment experiences, and that independent raters can synthesize discrepant data to obtain reliable and valid estimates of childrens abuse history. Clinical and methodological issues relevant to the improved assessment of childrens maltreatment experiences are also discussed.

Corticotropin-releasing hormone challenge in prepubertal major depression

This study investigates cortisol and ACTH (corticotropin) responses to an infusion of human CRH (corticotropin-releasing hormone) in prepubertal children with major depressive disorder (MDD). Following a period of 24 hours of adaptation to the laboratory environment with an intravenous catheter in place, 34 children with MDD and 22 healthy controls received 1 microgram/kg of human CRH at 5:00 PM. Blood samples for cortisol and ACTH were measured at baseline and post-CRH. Overall, there were no significant differences between the MDD and the normal controls in baseline or post CRH stimulation values of either cortisol or ACTH. Melancholic (n = 4) patients had significantly higher baseline cortisol levels than nonmelancholic (n = 24) patients. Compared with the outpatients and the nonmelancholics, the inpatients (n = 10) and the melancholics showed significantly lower total ACTH secretion (effect size: 0.9 and 1.4, respectively) after CRH infusion. These results are consistent with a broad literature suggesting that the HPA axis abnormalities occur less frequently in early-onset depression than reported in adult studies. The pattern of results in the subgroups of inpatients and in melancholic children, however, raise questions about possible continuities with adult studies.

The Dexamethasone Suppression Test in children and adolescents: A review and a controlled study

Dexamethasone Suppression Test (DST) studies conducted in children and adolescents are reviewed, together with factors hypothesized to explain discrepancies in rates of DST nonsuppression across studies. These factors are then examined in a controlled study of 27 adolescents with major depressive disorder (MDD) and 34 normal controls (NC). Subjects were given 1 mg of dexamethasone at 11:00 PM, and the following day serum samples for cortisol were collected each hr from 8 AM to 11 PM through an indwelling catheter. There were no significant differences found between the MDD and NC subjects on any postdexamethasone cortisol measure. Further, cortisol suppressors and nonsuppressors were not distinguished by any of the hypothesized factors identified from the review, including inpatient status, presence of suicidality, endogenous features, psychotic symptoms, or prior history of MDD. Questions about the appropriateness of the 1 mg dose of dexamethasone (currently the standard dose used with adolescents) are raised, together with a discussion of the effects of stress on DST findings.

Psychopathology in the relatives of depressed-abused children.

OBJECTIVE To determine if the type of symptomatology abused children manifest is related to family history of psychopathology. METHOD Lifetime history of psychopathology was assessed in the relatives of 26 preadolescents--13 depressed abused (MDD-AB) and 13 depressed nonabused (MDD-NA) children. Rates of disorder in the relatives of these children were compared to published rates of psychopathology in relatives of 27 normal control (NC) children. Data were obtained on 104 first-degree relatives (MDD-AB = 25, MDD-NA = 29, NC = 50) and 503 second-degree relatives (MDD-AB = 127, MDD-NA = 117, NC = 259). The Schedule for Affective Disorders and Schizophrenia was used to assess psychopathology in parents, and Family History method was used to obtain lifetime psychiatric data for all other relatives. RESULTS When compared to first-degree relatives of NC children, first-degree relatives of MDD-AB children had approximately a nine-fold increased risk for major depression, and a three- to nine-fold increased risk for other disorders associated with the familial subtype of affective illness known as Depression Spectrum Disease (e.g., antisocial personality, alcohol and substance dependence). Similar findings were reported in second-degree relatives, and comparisons between the relatives of MDD-NA and NC children. CONCLUSION The findings extend results of prior research and (1) suggest familial vulnerability factors influence the symptom profile of abused children; and (2) highlight the value of incorporating psychiatric formulations into multidisciplinary models of child abuse research and treatment programs.

BASELINE THYROID HORMONES IN DEPRESSED AND NON-DEPRESSED PRE- AND EARLY-PUBERTAL BOYS AND GIRLS

OBJECTIVE To examine baseline thyroid hormones in a large group of well-characterized pre- and early-pubertal boys and girls who met criteria for major depressive disorder (MDD) and a comparison group of normal children without psychiatric disorders. METHODS 45 children with MDD (10.6 years +/- 1.4 year) and 56 healthy controls (10.0 +/- 1.7 year) who participated in a large, psychobiologic protocol are included in this report. As part of the screening for eligibility, baseline samples were drawn for thyroxine (T4), triiodothyronine (T3) uptake, and thyroid stimulating hormone (TSH). Free thyroxine index (FTI) also was computed. RESULTS Between-group analyses were carried out controlling for various demographic variables significantly related to thyroid hormones [e.g. age, gender, body mass index (BMI) and their interactions]. For many hormones there were significant effects for age and gender. For T4, MDD boys had lower T4 compared with boys in the normal group. No differences were noted between MDD girls and normal girls. For TSH, MDD boys had lower concentrations compared with normal boys while no differences were noted in girls. For T3 uptake, the MDD group had lower uptake compared with the normal group. For FTI, there were no group differences. Similar to most studies of adults with depression, all our subjects were euthyroid. Unlike the adult studies, we found lower T4 concentrations in the MDD group rather than higher. Group differences in thyroid hormones were noted primarily in boys. The large sample size of this study allowed for the control of multiple variables, which has not been done in past studies. Without such controls, true findings may be masked in other studies of depression. Thus, our findings suggest the possibility of developmental differences in the relation of thyroid hormone and depression.