Prevention of Depression in At-Risk Adolescents: Moderators of Long-term Response.

In a randomized controlled trial, we found that a cognitive behavioral program (CBP) was significantly more effective than usual care (UC) in preventing the onset of depressive episodes, although not everyone benefitted from the CBP intervention. The present paper explored this heterogeneity of response. Participants were 316 adolescents (M age = 14.8, SD = 1.4) at risk for depression due to having had a prior depressive episode or having current subsyndromal depressive symptoms and having a parent with a history of depression. Using a recursive partitioning approach to baseline characteristics, we (Weersing et al. 2016) previously had identified distinct risk clusters within conditions that predicted depressive episodes through the end of the continuation phase (month 9). The present study used the same risk clusters that had been derived in the CBP group through month 9 to reclassify the UC group and then to examine group differences in depression through month 33. We found that in this overall very high-risk sample, the CBP program was superior to UC among youth in the low-risk cluster (n = 33), characterized by higher functioning, lower anxiety, and parents not depressed at baseline, but not in the middle (n = 95) and high-risk (n = 25) clusters. Across conditions, significantly more depression-free days were found for youth in the low-risk cluster (M = 951.9, SD = 138.8) as compared to youth in the high-risk cluster (M = 800.5, SD = 226.7). Identification of moderators, based on purely prognostic indices, allows for more efficient use of resources and suggests possible prevention targets so as to increase the power of the intervention.

A randomized trial of a group cognitive intervention for preventing depression in adolescent offspring of depressed parents.

BACKGROUND: Adolescent offspring of depressed parents are at high risk for development of depression. Cognitive restructuring therapy holds promise for preventing progression to depressive episodes. METHODS: A randomized, controlled trial was conducted to prevent depressive episodes in at-risk offspring (aged 13-18 years) of adults treated for depression in a health maintenance organization (HMO). Potential adult cases were found by reviewing the HMO pharmacy records for dispensation of antidepressant medication and the mental health appointment system. Medical charts were reviewed for a depression diagnosis. Recruitment letters signed by treating physicians were mailed to adults. Eligible offspring had subdiagnostic depressive symptoms insufficient to meet full DSM-III-R criteria for affective disorder and/or a past mood disorder. These youth were randomized to usual HMO care (n = 49) or usual care plus a 15-session group cognitive therapy prevention program (n = 45). RESULTS: We detected significant treatment-by-time (program) effects for the Center for Epidemiological Studies Depression Scale (P=.005) and the Global Assessment of Functioning scores (P =.04). Survival analysis of incident major depressive episodes during a median 15-month follow-up found a significant advantage (P =.003) for the experimental condition (9.3% cumulative major depression incidence) compared with the usual-care control condition (28.8%). CONCLUSION: A brief, group cognitive therapy prevention program can reduce the risk for depression in the adolescent offspring of parents with a history of depression.

Patient selection for in vitro fertilization: physical and psychological aspects.

The impact of maternal age, previous childbearing, and the type of underlying pathology on the success rate of an IVF program is explored. There is no difference in the pregnancy rate or in the abortion rate with increasing maternal age, and a similar result is seen in relation to previous childbearing. A reduced fertilization rate is seen in couples classified as having unexplained infertility, dyspermia, and male immobilizing sperm antibodies. The pregnancy rates in the first two groups are satisfactory once fertilization has occurred, but there have been no ongoing pregnancies if there are circulating sperm immobilizing antibodies present in either the male or the female. The psychological problems facing the infertile patient are discussed with special reference to in vitro fertilization.

The Adolescents Training and Learning to Avoid Steroids (ATLAS) prevention program. Background and results of a model intervention.

OBJECTIVE: To develop and test a school-based intervention to prevent anabolic androgenic steroid use among high-risk adolescent athletes. DESIGN: Nonrandom controlled trial. SETTING: Two urban high schools. PARTICIPANTS: Fifty-six adolescent football players at the experimental school and 24 players at the control school. INTERVENTION: Eight weekly, 1-hour classroom sessions delivered by the coach and adolescent team leaders, and eight weight-room sessions delivered by research staff. The intervention addressed sports nutrition and strength training as alternatives to steroid use, drug refusal role play, and antisteroid media campaigns. OUTCOME MEASURES: A preintervention and postintervention questionnaire that assessed attitudes toward and intent to use steroids and other drugs; knowledge of drug effects; and diet, exercise, and related constructs. RESULTS: Compared with controls, experimental subjects were significantly less interested in trying steroids after the intervention, were less likely to want to use them even if their friends used them, were less likely to believe steroid use was a good idea, believed steroids were more dangerous, had better knowledge of alternatives to steroid use, had improved body image, increased their knowledge of diet supplements, and had less belief in these supplements as beneficial. CONCLUSIONS: Significant beneficial effects were found despite the sample size, suggesting that the effects of the intervention was large. This outcome trial demonstrates an effective anabolic androgenic steroid prevention program for adolescent athletes, and the potential of team-based interventions to enhance adolescents' health.

Posttraumatic stress disorder across two generations of Cambodian refugees.

OBJECTIVE: To examine the expression of war-related trauma as manifested by DSM-III-R rates of posttraumatic stress disorder (PTSD) and major depressive disorder in two generations of Cambodian refugees living in the western United States. METHOD: A probability sample of 209 Khmer adolescents and one of their parents were interviewed using portions of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version and the PTSD section of the Diagnostic Interview for Children and Adolescents. Interviews were conducted in English by a master's-level clinician with a Khmer interpreter. RESULTS: PTSD was found to be significantly related across parent-child generations. A nonsignificant generational trend was also found for depressive disorders. A number of environmental variables measured in the study (amount of reported war trauma, loss, living arrangements, treatment received, socioeconomic status) were not related to these findings. Parents were more likely to report an earlier onset of PTSD symptoms. CONCLUSIONS: This study suggests that PTSD in refugees may cluster in families. Whether this phenomenon is caused by a genetic susceptibility to trauma awaits further research. PTSD and depressive disorders in refugee populations, while often comorbid, appear to follow different courses over time.

Does PTSD transcend cultural barriers? A study from the Khmer Adolescent Refugee Project.

OBJECTIVE: To determine whether the factor structure of the posttraumatic stress disorder (PTSD) syndrome in Cambodian refugee youth resembles earlier reported factor studies in Caucasian samples. METHOD: 194 Khmer adolescent refugees who reported prior significant trauma (most of it massive war trauma as children) were administered the PTSD module of the Diagnostic interview for Children and Adolescents, as part of an epidemiological study on the effects of war on this group of refugees. RESULTS: The following four factors were found: arousal, avoidance, intrusion, and numbing. A confirmatory factor analysis using data from the parents of this sample yielded a good fit for the four-factor solution based on the youth data. CONCLUSIONS: The four-factor solution from this sample resembled earlier studies on traumatized Caucasian and African-American adults. These results lend further credibility to the veracity of this diagnosis with refugee samples. PTSD as a result of prior war trauma appears to surmount the barriers of culture and language in this sample.

Major depression in community adolescents: age at onset, episode duration, and time to recurrence.

OBJECTIVE: This paper presents retrospective and prospective data regarding time course parameters of major depressive disorder (MDD) in community adolescents (14 to 18 years old): time to onset and recovery and, among those who recovered, time to recurrence. METHOD: Diagnostic interviews were conducted with 1,508 randomly selected high school students. Three hundred sixty-two had experienced at least one past or current episode of MDD. RESULTS: Mean age at onset of first episode was 14.9 (SD = 2.8). Early MDD onset was associated with female gender and suicidal ideation. MDD episode duration ranged from 2 to 520 weeks, with a mean of 26.4 weeks (SE = 3.3) and a median of 8.0 weeks. Longer episodes were observed in those whose depression occurred early (at or before age 15), whose depression had been accompanied by suicidal ideation, and for whom treatment was sought. Of the adolescents who recovered, 5% relapsed within 6 months, 12% within 1 year, and approximately 33% within 4 years. Shorter time to recurrence was associated with prior suicidal ideation and attempt and with later first onset. CONCLUSIONS: Risk of MDD is low in childhood, increasing substantially with adolescence. The majority of episodes in community adolescents are relatively brief, although the risk of recurrence is substantial. Suicidal behaviors are important mediators of episode duration and of recurrence.

The Khmer Adolescent Project: III. A study of trauma from Thailand's Site II refugee camp.

OBJECTIVE: To determine the prevalence rates of posttraumatic stress disorder (PTSD) and depression in a sample of 99 Cambodian youths, aged 18 to 25 years, living in the Site II refugee camps along the Thai-Cambodian border; to compare these rates to data collected in a similarly aged sample of Cambodian refugees living in the United States; and to illustrate the findings with case vignettes and a brief description of the refugee camp at Site II. METHOD: The senior author describes the main features of life in the Site II camp while being employed in one of its medical clinics. A Khmer translated version of the depression section of the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version and the PTSD section of Diagnostic Interview Schedule for Children and Adolescents were used in interview format by trained bilingual research assistants. Khmer versions of the Beck Depression Inventory and the Impact of Events Scale were also administered. RESULTS: The enduring nature of PTSD was evident in this sample of Khmer youths who had survived the Pol Pot regime as children. Similar rates of Pol Pot-related PTSD were found when compared to rates from the US sample. Subclinical forms of PTSD were found in those who reported their worst trauma during life in the camp, while the full PTSD syndrome was associated with those who reported trauma occurring during the earlier Pol Pot regime. Extremely high rates of depressive disorder were found which were interpreted as related to the repatriation back to Cambodia as this study was undertaken. CONCLUSION: PTSD in this sample appears to be specifically related to earlier war trauma, while depressive symptoms appear more related to recent stressors. As with other findings from the Khmer adolescent project, this study reaffirms the strong connection between the diagnosis of current PTSD and earlier war trauma in an additional sample of youths at Site II, Thailand. Depressive symptoms, on the other hand, appear to be related to the vicissitudes of recent stressful events in this refugee population.

Impact of comorbidity on a cognitive-behavioral group treatment for adolescent depression.

OBJECTIVE: Examine hypotheses concerning the negative impact of lifetime psychiatric comorbidity on participation in, and benefit from, a cognitive-behavioral group treatment for depression in adolescents (e.g., greater severity at intake, less recovery and more recurrence, less participation in treatment). METHOD: Across two previous studies conducted between 1986 and 1993, 151 depressed adolescents (aged 14-18) were randomly assigned to one of three treatment conditions (two active treatments and a waitlist control) and followed for 24 months posttreatment. Forty percent of participants had one or more lifetime comorbid diagnoses at intake. RESULTS: Comorbid anxiety disorders were associated with higher depression measure scores at intake and greater decrease in depression scores by posttreatment. Overall lifetime comorbidity was unrelated to diagnostic recovery, but lifetime substance abuse/dependence was associated with slower time to recovery. Participants with attention-deficit and disruptive behavior disorders were more likely to experience depression recurrence posttreatment. Associations between comorbidity and participation or therapy process measures were nonsignificant. CONCLUSIONS: Although some outcomes were worse for some comorbid diagnoses, the reassuring overall conclusion is that the presence of psychiatric comorbidity is generally not a contraindication for the use of structured group cognitive-behavioral interventions for depressed adolescents.

Targeted prevention of unipolar depressive disorder in an at-risk sample of high school adolescents: a randomized trial of a group cognitive intervention.

OBJECTIVES: This investigation attempted to prevent unipolar depressive episodes in a sample of high school adolescents with an elevated risk of depressive disorder. METHOD: Adolescents at risk for future depressive disorder by virtue of having elevated depressive symptomatology were selected with a two-stage case-finding procedure. The Center for Epidemiologic Studies-Depression Scale (CES-D) was administered to 1,652 students; adolescents with elevated CES-D scores were interviewed with the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Subjects with current affective diagnoses were referred to nonexperimental services. The remaining 150 consenting subjects were considered at risk for future depression and randomized to either a 15-session cognitive group prevention intervention or an "usual care" control condition. Subjects were reassessed for DSM-III-R diagnostic status after the intervention and at 6- and 12-month follow-up points. RESULTS: Survival analyses indicated a significant 12-month advantage for the prevention program, with affective disorder total incidence rates of 14.5% for the active intervention, versus 25.7% for the control condition. No differences were detected for nonaffective disorders across the study period. CONCLUSION: Depressive disorder can be successfully prevented among adolescents with an elevated future risk.

Cognitive-behavioral treatment of adolescent depression: efficacy of acute group treatment and booster sessions.

OBJECTIVE: This trial examined the effects of both acute and maintenance cognitive-behavioral therapy (CBT) for depressed adolescents. METHOD: Adolescents with major depression or dysthymia (N = 123) were randomly assigned to 1 of 3 eight-week acute conditions: adolescent group CBT (16 two-hour sessions); adolescent group CBT with a separate parent group; or waitlist control. Subsequently, participants completing the acute CBT groups were randomly reassigned to 1 of 3 conditions for the 24-month follow-up period: assessments every 4 months with booster sessions; assessments only every 4 months; or assessments only every 12 months. RESULTS: Acute CBT groups yielded higher depression recovery rates (66.7%) than the waitlist (48.1%), and greater reduction in self-reported depression. Outcomes for the adolescent-only and adolescent + parent conditions were not significantly different. Rates of recurrence during the 2-year follow-up were lower than found with treated adult depression. The booster sessions did not reduce the rate of recurrence in the follow-up period but appeared to accelerate recovery among participants who were still depressed at the end of the acute phase. CONCLUSIONS: The findings, which replicate and expand upon a previous study, support the growing evidence that CBT is an effective intervention for adolescent depression.

Screening for anxiety and depression in early adolescence.

OBJECTIVE: To examine the level of diagnostic and discriminative accuracy of three dimensional rating scales for detecting anxiety and depressive disorders in a school-based survey of 9th grade youths. METHOD: Classroom screening instruments, the Center for Epidemiologic Studies-Depression Scale (CES-D), the Revised Children's Manifest Anxiety Scale (RCMAS), and the Multidimensional Anxiety Scale for Children (MASC) were administered to 632 youths from three sites in 1998. On the basis of rating scale results, samples of high-scoring and non-high-scoring youths were invited to participate in a diagnostic interview conducted within 2 months of the screening sessions. RESULTS: MASC scores were most strongly associated with individual anxiety disorders, particularly among females, whereas the CES-D composite score was associated with a diagnosis of major depression, after controlling for comorbid disorders. The RCMAS was least successful in discriminating anxiety and depression. When receiver operator characteristic curves were examined, diagnostic accuracy was moderate. CONCLUSIONS: The ability of the MASC and CES-D to discriminate within and between categorically defined diagnostic groups has important implications for the accurate identification of youths in need of services.

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

OBJECTIVE: To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. METHOD: After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20-40 mg), imipramine (gradual upward titration to 200-300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score < or = 8 or > or = 50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. RESULTS: Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score < or = 8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent- or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. CONCLUSIONS: Paroxetine is generally well tolerated and effective for major depression in adolescents.

Lack of association between sperm antibodies and recurrent spontaneous abortion.

The results of this investigation did not confirm the previous report by Witkin and Chaudhry (1). In contrast, they indicate that women with a history of recurrent SABs have a significantly lower incidence of circulating sperm antibodies. This finding is consistent with the considerable amount of evidence indicating that sperm antibodies can interfere with sperm function.

Intracytoplasmic sperm injection for treating infertility associated with sperm autoimmunity.

OBJECTIVE: To determine whether intracytoplasmic sperm injection (ICSI) can be used to achieve normal fertilization, embryo cleavage, and pregnancies in cases of sperm autoimmunity. DESIGN: A retrospective analysis of ICSI results in sperm antibody-positive and randomly selected antibody-negative groups. SETTING: University- and hospital-based reproductive research laboratory and tertiary referral IVF program. PATIENT(S): Thirty-nine couples selected on the basis of a strongly positive result for sperm antibodies of immunoglobulin (Ig) G and/or IgA immunoglobulin class in the male partner and a control group of 140 antibody-negative couples. INTERVENTION(S): Human menopausal gonadotropin, hCG and Lucrin (Abbott Australasia, Kurnell, NSW, Australia) were given by injection. Oocyte collection was by transvaginal ovarian puncture. Blood was collected for beta-hCG measurement. MAIN OUTCOME MEASURE(S): Normal fertilization, embryo cleavage, establishment of clinical pregnancy, and delivery. RESULT(S): There were no significant differences in fertilization rates (62% versus 58%) or clinical pregnancy rates (19% versus 12%) between sperm antibody-positive and sperm antibody-negative patient groups. CONCLUSION: Intracytoplasmic sperm injection is an effective treatment for patients with severe sperm autoimmunity.

Effect of sperm antibodies in females on human in vitro fertilization.

The effect of sperm antibodies derived from the female partner's serum on fertilization and embryo cleavage was evaluated by analyzing the Royal Women's Hospital in vitro fertilization (IVF) data. The results suggest that antispermatozoal isoantibodies detected by the immunobead test (IBT) can interfere with IVF. Thus, in a group of patients with IBT-IgG and IBT-IgA sperm antibody titers of greater than or equal to 10 in serum, a low fertilization rate (15%) was obtained when the wife's serum was used as serum supplement in the IVF culture medium. Where replacement (antibody-negative donor or cord) serum was used in the culture medium, a higher fertilization rate (69%) was obtained (P less than 0.01). These results underline the importance of using replacement serum in cases where the wife has significant sperm antibody levels in her serum. Six pregnancies were obtained in the antibody-positive group (n = 20), five of which occurred in patients with IBT-IgG and IBT-IgA-titers less than 10, for a pregnancy rate of 5/9 in this subgroup. Four of these patients delivered (4/9). Analysis of larger groups of antibody-positive patients is required for further evaluation of these results and ascertainment of the likelihood of occurrence of posttransfer effects of sperm antibodies on the embryo.

Normal fertilization and embryo development by intracytoplasmic sperm injection of round-headed acrosomeless sperm.

OBJECTIVE: To investigate the ability of round-headed acrosomeless sperm to bind to the human zona pellucida (ZP) and oolemma and to fertilize human oocytes by intracytoplasmic sperm injection. DESIGN: Oocytes that had failed to fertilize in IVF were used for sperm-ZP and spermoolemma binding tests. Sperm from a fertile donor was used as a control for oocyte variability. Intracytoplasmic sperm injection was used for assisted fertilization. SETTING: University- and hospital-based reproductive research laboratory and tertiary referral IVF program. PATIENTS: Case study of a couple in which the man has 100% round-headed acrosomeless sperm in the ejaculate. MAIN OUTCOME MEASURE: Fertilization and embryo development and the ability of sperm to bind to the ZP and oolemma. RESULTS: No ZP or oolemma binding was achieved, but normal fertilization and embryo development was obtained after intracytoplasmic injection of round-headed acrosomeless sperm. However, no pregnancy was achieved after the transfer of two cleaving embryos. CONCLUSIONS: Normal fertilization and embryo development from round-headed acrosomeless sperm is possible with intracytoplasmic sperm injection. However, it remains to be reported whether pregnancy can result from fertilization with this type of sperm defect.

Inhibition of human sperm-zona pellucida and sperm-oolemma binding by antisperm antibodies.

The results of this preliminary investigation suggest that antisperm antibodies interfere predominantly with sperm-zona pellucida binding. The observation of similar numbers of control (Ab-) and test (Ab+) sperm bound to the oolemma implies that the antibody-mediated inhibition of capacitation, acrosome reaction, or oolemma binding may not be major causes of failed fertilization with sperm autoimmunity. However, only seven patients were studied, and further investigation with larger numbers of subjects are required.

Sperm antibodies and human in vitro fertilization.

In order to directly evaluate the effects of sperm antibodies in human in vitro fertilization (IVF), the authors preincubated donor sperm in female sera containing sperm antibodies and then inseminated supernumerary human oocytes from a gamete intrafallopian transfer (GIFT) program. The sperm were incubated for 30 minutes in medium containing 20% serum with antisperm activity (Test); or no antisperm activity (Control) as assessed by the immunobead test (IBT). Each oocyte was inseminated with 1 to 2 X 10(5)/ml of the preincubated motile sperm with Control or Test treatments allocated on a random basis. Six positive sera were tested in 17 experiments, resulting in a fertilization rate of 41% (25/61) versus 84% (36/43) for controls (P less than 0.001). When considered individually, three of six positive sera caused significant inhibition. The only serum that gave complete inhibition had the highest titer for IgG (10,000) and lower IgA (100). Absorption with protein A reduced the IgG titer to less than 10 and removed the fertilization inhibitory activity. These results confirm that sperm antibodies from female sera can inhibit human IVF.

Assessment of the Sperm Quality Analyzer.

OBJECTIVE: To assess the relationship between the results of the Sperm Quality Analyzer (United Medical Systems Inc., Santa Ana, CA), which measures motile sperm concentration by light scattering, conventional manual semen analysis characteristics, and computer-assisted sperm motility analyses. DESIGN: Sperm Quality Analyzer measurements and manual and computer-assisted semen analyses were performed on 150 (50, 62, and 38) samples in three laboratories and the results were compared. SETTING: The study was performed in the Andrology Laboratory of Prince Henry's Institute of Medical Research, Monash Medical Centre, and Andrology Laboratory and Reproductive Biology Unit at the Royal Women's Hospital, Melbourne, Victoria, Australia. PATIENTS: Patients presented to the laboratories for routine fertility evaluation in the male and were selected at random to reflect the range of normal and abnormal samples seen in the laboratories. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Sperm count, motility (percent motility, motility index, velocity, and amplitude of lateral head displacement [ALH]), morphology, and normal acrosomes were evaluated by manual and computer-assisted semen analysis and sperm quality analyzer motility index. RESULTS: Spearman nonparametric univariate analysis showed strong correlations between sperm motility index and manual sperm concentration, motility, abnormal morphology, and normal acrosomes by Pisum sativum agglutinin; and computer-assisted sperm motility analysis sperm concentration, motile concentration, and percent static. Curvilinear velocity, straight-line velocity (VSL), and linearity also were related significantly to sperm motility index values. By multiple regression analysis, the significant covariates of the sperm motility index were motile sperm concentration, abnormal morphology, ALH, and straight-line velocity and these accounted for 85.5% of the variance of the sperm motility index. CONCLUSIONS: The Sperm Quality Analyzer is easy to use. The good correlation between the sperm motility index, motile sperm concentration, and, in addition, a number of other semen parameters supports the use of the Sperm Quality Analyzer for screening patients and in situations that warrant a rapid verification of semen quality, such as in the IVF or artificial insemination clinic. Further investigation of the Sperm Quality Analyzer in the management of male infertility is warranted.