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母亲抑郁症对子女抑郁症的影响,151对,1年

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母亲抑郁症对子女抑郁症的影响,151对,1年 Article 1136 Am J Psychiatry 165:9, September 2008ajp.psychiatryonline.org This article is featured in this month’s AJP Audio and is discussed in editorials by Dr. Reiss (p. 1083) and Dr. Markowitz (p. 1086). Children of Depressed Mothers 1 Year After the Initia...
母亲抑郁症对子女抑郁症的影响,151对,1年
Article 1136 Am J Psychiatry 165:9, September 2008ajp.psychiatryonline.org This article is featured in this month’s AJP Audio and is discussed in editorials by Dr. Reiss (p. 1083) and Dr. Markowitz (p. 1086). Children of Depressed Mothers 1 Year After the Initiation of Maternal Treatment: Findings From the STAR*D-Child Study Daniel J. Pilowsky, M.D., M.P.H. Priya Wickramaratne, Ph.D. Ardesheer Talati, Ph.D. Min Tang, M.A. Carroll W. Hughes, Ph.D. Judy Garber, Ph.D. Erin Malloy, M.D. Cheryl King, Ph.D. Gabrielle Cerda, M.D. A. Bela Sood, M.D. Jonathan E. Alpert, M.D., Ph.D. Madhukar H. Trivedi, M.D. Maurizio Fava, M.D. A. John Rush, M.D. Stephen Wisniewski, Ph.D. Myrna M. Weissman, Ph.D. Objective: Maternal depression is a con- sistent and well-replicated risk factor for child psychopathology. The authors ex- amined the changes in psychiatric symp- toms and global functioning in children of depressed women 1 year following the initiation of treatment for maternal major depressive disorder. Method: Par t ic ipants were 1 ) 151 women with maternal major depression who were enrolled in the Sequenced Treatment Alternatives to Relieve Depres- sion (STAR*D) study and 2) their eligible offspring who, along with the mother, participated in the child STAR*D (STAR*D- Child) study (mother-child pairs: N=151). The STAR*D study was a multisite study designed to determine the comparative effectiveness and acceptability of various treatment options for adult outpatients with nonpsychotic major depressive dis- order. The STAR*D-Child study examined children of depressed women at baseline and involved periodic follow-ups for 1 year after the initiation of treatment for maternal major depressive disorder to as- certain the following data: 1) whether changes in children’s psychiatric symp- toms were associated with changes in the severity of maternal depression and 2) whether outcomes differed among the offspring of women who did and did not remit (mother-child pairs with follow-up data: N=123). Children’s psychiatric symp- toms in the STAR*D-Child study were as- sessed using the Schedule for Affective Disorders and Schizophrenia for School- Age Children—Present and Lifetime Ver- sion (K-SADS-PL), and maternal depres- sion severity in the STAR*D study was as- sessed by an independent clinician, using the 17-item Hamilton Depression Rating Scale (HAM-D). Results: During the year following the initiation of treatment, maternal depres- sion severity and children’s psychiatric symptoms continued to decrease over time. Decreases in the number of chil- dren’s psychiatric symptoms were signifi- cantly associated with decreases in mater- nal depression severity. When children’s outcomes were examined separately, a statistically significant decrease in symp- toms was evident in the offspring of women who remitted early (i.e., within the first 3 months after the initiation of treatment for maternal depression) or late (i.e., over the 1-year follow-up inter- val) but not in the offspring of nonremit- ting women. Conclusions: Continued efforts to treat maternal depression until remission is achieved are associated with decreased psychiatric symptoms and improved func- tioning in the offspring. (Am J Psychiatry 2008; 165:1136–1147) Maternal depression is a risk factor for child psy- chopathology that is consistent and well-replicated. The disorders among children of women with maternal de- pression vary according to the developmental stage of the affected offspring, with the average age at onset of anxiety and behavior disorders before puberty, the average age at onset of major depression in early adolescence, and the average age at onset of substance use disorders in late ad- olescence or early adulthood (1–4). Furthermore, mater- nal depression has been associated with less robust re- sponse to treatment among depressed adolescent offspring (5). Until recently, little has been known about the effect of treatment for depressed mothers on their off- spring (6–8). The Sequenced Treatment Alternatives to Re- lieve Depression (STAR*D) study provided a unique op- portunity to investigate whether successful treatment for depressed women would lead to improvement in psychi- atric disorders and symptoms among their offspring (9). The study of outcomes in these offspring is referred to as the child STAR*D (STAR*D-Child) study (10, 11). The main YYL 加亮 YYL 加亮 YYL 加亮 YYL 加亮 Am J Psychiatry 165:9, September 2008 1137 PILOWSKY, WICKRAMARATNE, TALATI, ET AL. ajp.psychiatryonline.org objective of the STAR*D study (12–14) was to determine which treatment or sequence of treatments would be ef- fective in adult patients with a diagnosis of major depres- sion who did not remit after first-line treatment with the antidepressant citalopram, a selective serotonin reuptake inhibitor. Remission was defined as a score of ≤7 on the 17-item Hamilton Depression Rating Scale (HAM-D [15]). At the initiation of maternal treatment, approximately one-third of the offspring (aged 7–17 years) of women in the STAR*D study had a current psychiatric disorder (10). Eligible offspring were independently assessed in the STAR*D-Child study by a team that was not involved with the mothers’ treatment. Three months after the initiation of treatment for maternal depression, we reported that re- mission among the mothers was associated with a signifi- cant decrease in the rates of children’s diagnoses as well as decreases in internalizing, externalizing, and total symp- toms (11). Interestingly, a ≥50% maternal response to treat- ment was required to detect improvement in the offspring. In the STAR*D-Child study, mothers and their offspring were followed every 3 months for 1 year after the initiation of treatment for maternal depression. The objective of the present study was to assess both maternal and child out- comes as reported in the STAR*D-Child study. We investi- gated two important issues that concern adult and child clinicians. First, we assessed whether those children of mothers who remitted by the 3-month follow-up re- mained well throughout the remainder of the 1-year fol- low-up interval. Second, we assessed whether those chil- dren of mothers who remitted after the 3-month follow-up similarly benefitted from maternal remission. In the present study, we refer to depressed mothers who remit- ted by the 3-month follow-up as early remitting subjects and to those who remitted after the 3-month follow-up as late remitting subjects. Most of the mothers (92%) who re- mitted by the 3-month follow-up were treated with citalo- pram (11). Late remitting subjects received two or more treatments as provided by the STAR*D protocol (12). We hypothesized that the following outcomes would oc- cur during the 1 year after the initiation of treatment for maternal depression: 1) mothers would show a significant decrease in HAM-D scores, with children showing a signif- icant decrease in offspring psychiatric symptoms, and changes in child outcomes would be associated with changes in maternal HAM-D scores; 2) children of early remitting subjects, who were shown to benefit from remis- sion of maternal depression 3 months after the initiation of treatment (11), would continue to demonstrate a lower prevalence of psychiatric symptoms relative to children of nonremitting subjects, providing that their mothers re- mained in remission; and 3) children of late remitting sub- jects would demonstrate intermediate outcomes. Method The STAR*D Study Design STAR*D (http://www.star-d.org) was a multisite study de- signed to determine the comparative effectiveness and accept- ability of different treatment options for a broadly representative group of outpatients with nonpsychotic major depressive disor- der (12, 14). STAR*D study participants were adults (age range: 18–75 years) with nonpsychotic major depressive disorder who did not have a lifetime diagnosis of bipolar, schizophrenia, or schizoaffective disorders. Initially, all study participants were treated with citalopram. Those subjects who did not remit with citalopram treatment or who were intolerant of citalopram were offered other treatments, including antidepressants, cognitive behavioral therapy, or a combination of treatments, using an equipoise-randomized design as described elsewhere (16, 17). The STAR*D-Child Study Design Among the 14 STAR*D regional centers, seven participated in the STAR*D-Child study. The STAR*D study recruited 824 women (age range: 25–60 years) at these seven regional centers. Among the women recruited, 808 (98%) were screened to ascertain whether they had at least one child between the ages of 7 and 17 years. Of these women, 177 (22%) had children in this age range. Among the 177 women with at least one child aged 7–17 years, 174 (98%) met all eligibility criteria, and 151 (87%) entered the child study. The STAR*D-Child assessors were 1) not involved with the mothers’ treatment, 2) blind to their remission status, and 3) in- dependent of the team that treated these mothers. Since the as- sessors were involved with multiple assessments of children over time, they were not blind to child status from prior assessments. The mothers’ clinical assessments were conducted by STAR*D staff who were not involved with the children’s assessments. Base- line assessments (Figure 1) were conducted before or within 2 weeks following the initiation of treatment for maternal depres- sion and every 3 months thereafter (3, 6, 9, and 12 months). Subjects Mothers (age range: 25–60 years) were adult outpatients with nonpsychotic major depressive disorder who were enrolled as participants in the STAR*D study. Mothers of children aged 7–17 FIGURE 1. STAR*D-Child Study Designa a Data are based on the year following the initiation of treatment for maternal depression. Baseline Assessment Treatment of maternal depression Remission Non- Remission Assessed every 3 months Follow-up ends a year after remission Assessed every 3 months Follow-up ends two years after baseline assessment Baseline assessment Treatment of maternal depression Remission Non-remission Assessed every 3 months Follow-up ends 1 year after remission Assessed every 3 months Follow-up ends 2 years after baseline assessment Depressed Mothers Depressed mothers 1138 Am J Psychiatry 165:9, September 2008 CHILDREN OF DEPRESSED MOTHERS ajp.psychiatryonline.org years were invited to participate in the STAR*D-Child study with one eligible child. These mothers provided separate written in- formed consent. If a mother had more than one offspring in the age range of eligibility, one child was randomly selected. Addi- tional data pertaining to the STAR*D-Child study sample are available elsewhere (10). Maternal Assessments Maternal assessments were conducted as part of a comprehen- sive battery of tests for all STAR*D participants (17). A diagnosis of current nonpsychotic major depressive disorder was established by a clinical interview and confirmed using a symptom checklist based on DSM-IV criteria (17). The HAM-D was used to assess the severity of depressive symptoms (15). The HAM-D has good reli- ability, and scores are highly correlated with the results from other observer-rated instruments (18). In the STAR*D study, re- mission of maternal depression was defined as a HAM-D score ≤7, and relapse was defined as a HAM-D score ≥14 any time after remission. Mothers who were in remission during and after the first 3 months of follow-up were considered early and late remit- ting subjects, respectively, provided that they remained in remis- sion for the entire 1-year follow-up interval. Remission and treatment response were assessed using HAM- D scores that were obtained from the STAR*D study. In cases in which mothers discontinued their participation in the adult study but remained in the child study, HAM-D scores were not avail- able. In these cases and whenever HAM-D scores were unavail- able, we converted the mothers' Quick Inventory of Depressive Symptomatology—Self-Report scores to HAM-D scores. Quick Inventory of Depressive Symptomatology—Self-Report scores were obtained via interactive voice response (13) through the use of a method based on item response theory analysis of the rela- tionship between this self-report and HAM-D, as employed by the STAR*D study (9, 19, 20). The following HAM-D scores were un- available for assessment: 0 at baseline and 51/121, 9/87, 4/61, and 22/79 at 3, 6, 9, and 12 months, respectively. Child Assessments Children were assessed with the Schedule for Affective Disor- ders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL). The K-SADS-PL is a semistructured diagnostic interview used to assess children at baseline and at 3- month intervals (21). Among the K-SADS diagnostic measures, K- SADS-PL, a downward extension of the adult SADS, is the most widely used version currently available (22, 23). It is a valid and re- liable diagnostic instrument, with test-retest reliability kappa co- efficients in the good to excellent range (0.63–1.00) for present and lifetime diagnoses (21). K-SADS-PL includes a screening section and supplements for children who screen positive for one or more disorders. In addition, all sections are available online (www.wpic.pitt.edu/ksads/default.htm). Furthermore, the mother (or parent) and child are interviewed separately, and symptoms are scored separately (as absent or present) at the threshold or subthreshold level. Because STAR*D was an effective- ness study and mimicked clinical practice, we were required to minimize the number of assessments. Thus, we selected the fol- lowing sections of the K-SADS-PL that focus on disorders that are highly prevalent among children of depressed parents: affective, anxiety, and disruptive behavior disorders (2, 3). The qualifica- tions, training of interviewers, and reliability of diagnostic assess- ments of children have been reported elsewhere (10). The variable child symptoms consisted of a simple count of the child-reported symptoms from the screening interview that were present at the threshold (definite symptoms) or subthreshold level. We created a similar variable based on the mother’s clinical interview about the child (mother-reported child symptoms) and TABLE 1. Baseline Demographic and Clinical Characteristics of Depressed Mothers and Their Offspring (N=123) Characteristic and Assessment Measure Mother-Child Pair Assessment Before (or within) 2 Weeks After Initiation of Treatment for Maternal Depression Maternal Mean SD Range Median Age (years) 37.7 6.6 24.0–52.0 36.0 HAM-D score 24.6 5.2 14.0–42.0 25.0 N % Range Median Race African American 45 36.6 White 52 42.3 Hispanic 22 17.9 Other 4 3.3 Education 90 indicate superior functioning, and scores <70 indicate impaired global functioning. Data Analysis Changes in maternal and child outcomes. Changes in ma- ternal HAM-D scores and in child C-GAS scores, which are con- tinuous variables, were modeled using longitudinal mixed-effect regression models with random coefficients. The changes in HAM-D scores of each individual mother over time were first modeled using a polynomial regression model, with the individ- ual HAM-D score at each specific time as the dependent variable and the number of months after baseline assessment as the inde- pendent variable. In addition, household income was included as a potential confounding variable. The polynomial regression model posits that the individual treatment response of each mother was a function of the number of months since the base- line assessment. This model was used to estimate 1) the average pattern of change (e.g., linear, quadratic) in HAM-D scores over time and 2) the extent of variation around regression parameters. Initially, each regression parameter was treated as a random coef- ficient to determine whether these parameters varied between mothers. If there was no significant variation, the coefficients were treated as fixed. A similar approach was used to model child C-GAS scores, with children’s age, gender, and family household income included as potential confounding variables. All longitu- dinal mixed-models were performed using the PROC MIXED pro- cedure of the SAS system (SAS, Cary, N.C.). Changes in child symptoms were modeled using Poisson re- gression analysis, which is appropriate for modeling count data. The logarithm of a child’s symptom count at each specific time was considered the dependent variable, and the number of weeks after the baseline assessment was treated as an independent con- tinuous variable. Changes in child diagnoses were similarly mod- eled using logistic regression analyses, which are appropriate for modeling dichotomous outcomes. Both Poisson and logistic re- gression analyses were conducted within the framework of the generalized estimating equation approach to adjust for correla- tions between repeated observations over time using an ex- changeable correlation matrix, as suggested by Asarnow et al. (25), and were performed using the PROC GENMOD procedure of the SAS system (SAS, Cary, N.C.). For all models, the potential confounding variables (children’s age, gender, and household in- come) were included in the analysis. For exploratory analysis of changes in symptoms over time in children with at least one definite symptom at baseline, we used 1) a log (x+1) transformation to normalize the data and 2) relevant random regression analyses as described previously. Associations between maternal HAM-D scores and child outcomes. The series of analyses conducted allowed us to de- termine whether mother and child outcomes improved over the mother’s treatment/follow-up period. However, if there was a sig- nificant change over time in the mother’s HAM-D score and in the child’s outcome variables, we sought to determine whether changes in child outcomes over time were related to changes in maternal HAM-D scores over time. This was initially accom- plished by fitting 1) a Poisson regression model to child symp- toms; 2) a logistic regression model to child diagnoses; and 3) a random regression model to child functioning, as described pre- viously except for the inclusion of the mother’s HAM-D score at current assessment as a time-dependent covariate. We were able to infer that changes in child outcomes were at least partially re- lated to changes in the mother’s current HAM-D score if 1) the es- timate of the coefficient corresponding to time (i.e., the nu
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