Children's Depression Rating Scale-Revised Research Articles

Randomized, placebo-controlled trial of cognitive-behavioral therapy alone or combined with sertraline in the treatment of pediatric obsessive–compulsive disorder

BackgroundTo examine the efficacy of sequential sertraline and cognitive-behavioral therapy (CBT) treatment relative to CBT with pill placebo over 18 weeks in children and adolescents with obsessive–compulsive disorder (OCD). MethodsForty-seven children and adolescents with OCD (Range = 7–17 years) were randomized to 18-weeks of treatment in one of three arms: 1) sertraline at standard dosing + CBT (RegSert + CBT); 2) sertraline titrated slowly but achieving at least 8 weeks on the maximally tolerated daily dose + CBT (SloSert + CBT); or 3) pill placebo + CBT (PBO + CBT). Assessments were conducted at screening, baseline, weeks 1–9, 13, and 17, and post-treatment. Raters and clinicians were blinded to sertraline (but not CBT) randomization status. Primary outcomes included the Children's Yale-Brown Obsessive–Compulsive Scale, and response and remission status. Secondary outcomes included the Child Obsessive Compulsive Impact Scale–Parent/Child, Children's Depression Rating Scale-Revised, Multidimensional Anxiety Scale for Children, and Clinical-Global Impressions-Severity. ResultsAll groups exhibited large within-group effects across outcomes. There was no group by time interaction across all outcomes suggesting that group changes over time were comparable. ConclusionsAmong youth with OCD, there was no evidence that sequentially provided sertraline with CBT differed from those receiving placebo with CBT. ClinicalTrials.gov IdentifierNCT00382291.

Escitalopram in the Treatment of Adolescent Depression: A Randomized, Double-Blind, Placebo-Controlled Extension Trial

The purpose of this study was to evaluate the extended efficacy, safety, and tolerability of escitalopram relative to placebo in adolescents with major depressive disorder (MDD). Adolescents (12-17 years) who completed an 8-week randomized, double-blind, flexible-dose, placebo-controlled, lead-in study of escitalopram 10-20 mg versus placebo could enroll in a 16-24-week, multisite extension trial; patients maintained the same lead-in randomization (escitalopram or placebo) and dosage (escitalopram 10 or 20 mg/day, or placebo) during the extension. The primary efficacy was Children's Depression Rating Scale-Revised (CDRS-R) change from the lead-in study baseline to treatment week 24 (8-week lead-in study plus 16-week extension); the secondary efficacy was Clinical Global Impressions-Improvement (CGI-I) score at week 24. All efficacy analyses used the last observation carried forward (LOCF) approach; sensitivity analyses used observed cases (OC) and mixed-effects model for repeated measures (MMRM). Safety was evaluated via adverse event (AE) reports and the clinician-rated Columbia-Suicide Severity Rating Scale (C-SSRS). Following lead-in, 165 patients enrolled in the double-blind extension (82 placebo; 83 escitalopram); 40 (48.8%) placebo and 37 (44.6%) escitalopram patients completed treatment. CDRS-R total score improvement was significantly greater for escitalopram than for placebo (p=0.005, LOCF; p=0.014; MMRM). Response rates (CDRS-R ≥ 40% reduction from baseline [adjusted and unadjusted] and CGI-I ≤ 2) were significantly higher for escitalopram than for placebo (LOCF); remission rates (CDRS-R ≤ 28) were 50.6% for escitalopram and 35.7% for placebo (p=0.002). OC analyses were not significantly different between groups. The most frequent escitalopram AEs (≥ 5% and more frequent than placebo) were headache, nausea, insomnia, vomiting, influenza-like symptoms, diarrhea, and urinary tract infection. Most AEs were mild/moderate and not related to the study drug. AEs suggestive of self-harm occurred in 5.7% and 7.1% of placebo and escitalopram patients. Occurrence of suicidal behavior and/or suicidal ideation assessed by C-SSRS was 10.9% (14/128) for placebo and 14.5% (19/131) for escitalopram. Extended use of escitalopram was generally safe and resulted in modest improvement in efficacy in adolescents with MDD.

Suicidal ideation of psychiatrically hospitalized adolescents has one-year predictive validity for suicide attempts in girls only.

Clinicians commonly incorporate adolescents' self-reported suicidal ideation into formulations regarding adolescents' risk for suicide. Data are limited, however, regarding the extent to which adolescent boys' and girls' reports of suicidal ideation have clinically significant predictive validity in terms of subsequent suicidal behavior. This study examined psychiatrically hospitalized adolescent boys' and girls' self-reported suicidal ideation as a predictor of suicide attempts during the first year following hospitalization. A total of 354 adolescents (97 boys; 257 girls; ages 13-17years) hospitalized for acute suicide risk were evaluated at the time of hospitalization as well as 3, 6, and 12months later. Study measures included the Suicidal Ideation Questionnaire-Junior, Multidimensional Anxiety Scale for Children, Children's Depression Rating Scale-Revised, Beck Hopelessness Scale, Youth Self-Report, and Personal Experiences Screen Questionnaire. The main study outcome was presence and number of suicide attempt(s) in the year after hospitalization, measured by the Diagnostic Interview Schedule for Children. Results indicated a significant interaction between suicidal ideation, assessed during first week of hospitalization, and gender for the prediction of subsequent suicide attempts. Suicidal ideation was a significant predictor of subsequent suicide attempts for girls, but not boys. Baseline history of multiple suicide attempts was a significant predictor of subsequent suicide attempts across genders. Results support the importance of empirically validating suicide risk assessment strategies separately for adolescent boys and girls. Among adolescent boys who have been hospitalized due to acute suicide risk, low levels of self-reported suicidal ideation may not be indicative of low risk for suicidal behavior following hospitalization.

Prospective Relationship Between Obsessive–Compulsive and Depressive Symptoms During Multimodal Treatment in Pediatric Obsessive–Compulsive Disorder

The present study examined the prospective relationship between obsessive-compulsive and depressive symptoms during a multimodal treatment study involving youth with obsessive-compulsive disorder (OCD). Participants included fifty-six youth, aged 7-17 years (M = 12.16 years) who were enrolled in a two-site randomized controlled pharmacological and cognitive behavioral therapy treatment trial. Obsessive-compulsive severity was measured using the Children's Yale-Brown Obsessive-Compulsive Scale, and depressive symptoms were rated using the Children's Depression Rating Scale-Revised. Multi-level modeling analyses indicated that, on average over the course of treatment, variable and less severe obsessive-compulsive symptoms significantly predicted a decrease in depressive symptoms. Additionally, week-to-week fluctuations in OCD severity did not significantly predict weekly changes in depressive symptom severity. Level of baseline depressive symptom severity did not moderate these relationships. Findings suggest that when treating youth with OCD with co-occurring depression, therapists should begin by treating obsessive-compulsive symptoms, as when these are targeted effectively, depressive symptoms diminish as well.

Severity of depressive symptomatology and functional impairment in children and adolescents with temporal lobe epilepsy

ObjectiveDepression is a frequent psychiatric disorder in children with temporal lobe epilepsy (TLE). However, severity of depressive symptoms (DS) is frequently neglected in these patients. This study aimed to determine severity of DS and global functioning by using quantitative measures and to establish their correlation with patients’ demographics and clinical variables. Methods31 children (mean age of 11.8±2.3 years) with TLE were assessed with K-SADS-PL for axis I DSM-IV diagnosis. Severity of DS was measured by Children Depression Rating Scale-Revised – CDRS-R. Global functional impairment was evaluated with Child Global Assessment Scale-CGAS. Results25 patients (56% boys; 12±2.3 years) had current DS, moderate or severe in 84% according to CDRS-R T-Score. Severity of DS was not correlated with age (p=0.377), gender (p=0.132), seizure control (p=0.936), age of onset (p=0.731), duration of epilepsy (p=0.602) and the presence of hippocampal sclerosis (p=0.614). Patients had moderate to major functional impairment measured by CGAS (48.7±8.8), being adolescents more impaired than children (p=0.03). Impairment of global functioning was not associated with epilepsy variables (p>0.05). ConclusionChildren with TLE had moderate to severe DS early in the course of their disease with a relevant impact on their global functional activities, especially considering adolescents. Epilepsy severity seems not to be correlated to the severity of DS, contradicting the idea of a cause–consequence relationship. More systematic research is needed to better understand the association of depressive disorders in children and adolescents with TLE.

Depressed Adolescents Treated with Exercise (DATE): A pilot randomized controlled trial to test feasibility and establish preliminary effect sizes

The Depressed Adolescents Treated with Exercise (DATE) study evaluated a standardized aerobic exercise protocol to treat nonmedicated adolescents that met DSM-IV-TR criteria for major depressive disorder. From an initial screen of 90 individuals, 30 adolescents aged 12–18 years were randomized to either vigorous exercise (EXER) (>12 kg/kcal/week [KKW]) or a control stretching (STRETCH) activity (<4 KKW) for 12 weeks. The primary outcome measure was the blinded clinician rating of the Children's Depression Rating Scale – Revised (CDRS-R) to assess depression severity and Actical (KKW) accelerometry 24hr/7days a week to assess energy expenditure and adherence. Follow-up evaluations occurred at weeks 26 and 52. The EXER group averaged 77% adherence and the STRETCH group 81% for meeting weekly target goals for the 12 week intervention based on weekly sessions completed and meeting KKW requirements. There was a significant increase in overall weekly KKW expenditures (p < .001) for both groups with the EXER group doubling the STRETCH group in weekly energy expenditure. Depressive symptoms were significantly reduced from baseline for both groups with the EXER group improving more rapidly than STRETCH after six weeks (p < .016) and nine weeks (p < .001). Both groups continued to improve such that there were no group differences after 12 weeks (p = .07). By week 12, the exercise group had a 100% response rate (86% remission), whereas the stretch group response rate was 67% (50% remission) (p = .02). Both groups had improvements in multiple areas of psychosocial functioning related to school and relationships with parents and peers. Anthropometry reflected decreased waist, hip and thigh measurements (p = .02), more so for females than males (p = .05), but there were no weight changes for either gender. The EXER group sustained 100% remission at week 26 and 52. The STRETCH group had 80% response and 70% remission rates at week 26 and by week 52 only one had not fully responded. The study provides support for the use of exercise as a non-medication intervention for adolescents with major depressive disorders when good adherence and energy expenditure (KKW) are achieved.

Evidence for Increased Glutamatergic Cortical Facilitation in Children and Adolescents With Major Depressive Disorder

Converging lines of evidence implicate the glutamate and γ-aminobutyric acid neurotransmitter systems in the pathophysiology of major depressive disorder. Transcranial magnetic stimulation cortical excitability and inhibition paradigms have been used to assess cortical glutamatergic and γ-aminobutyric acid-mediated tone in adults with major depressive disorder, but not in children and adolescents. To compare measures of cortical excitability and inhibition with 4 different paradigms in a group of children and adolescents with major depressive disorder vs healthy controls. Cross-sectional study examining medication-free children and adolescents (aged 9-17 years) with major depressive disorder compared with healthy controls. Cortical excitability was assessed with motor threshold and intracortical facilitation measures. Cortical inhibition was measured with cortical silent period and intracortical inhibition paradigms. University-based child and adolescent psychiatry clinic and neurostimulation laboratory. Twenty-four participants with major depressive disorder and 22 healthy controls matched for age and sex. Patients with major depressive disorder were medication naive and had moderate to severe symptoms based on an evaluation with a child and adolescent psychiatrist and scores on the Children's Depression Rating Scale-Revised. Motor threshold, intracortical facilitation, cortical silent period, and intracortical inhibition. Compared with healthy controls, depressed patients had significantly increased intracortical facilitation at interstimulus intervals of 10 and 15 milliseconds bilaterally. There were no significant group differences in cortical inhibition measures. These findings suggest that major depressive disorder in children and adolescents is associated with increased intracortical facilitation and excessive glutamatergic activity.

A prospective open-label trial of paliperidone monotherapy for the treatment of bipolar spectrum disorders in children and adolescents

Treatment studies for the management of pediatric bipolar disorder are limited. This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders. An 8-week, prospective, open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders (depression, psychosis, attention-deficit/hyperactivity disorder [ADHD]). Assessments included the Young Mania Rating Scale (YMRS), Clinical Global Impression scale (CGI), Children's Depression Rating Scale-Revised (CDRS-R), and Brief Psychiatric Rating Scale (BPRS). Adverse events were assessed through spontaneous self-reports, vital signs, weight monitoring, and laboratory analysis. Fifteen youth with bipolar spectrum disorders (YMRS at entry: 32.8 ± 6.1) were enrolled in the study and 11 (73 %) completed the 8-week trial. The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects. Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores (-18.7 ± 13.9, p < 0.001) at endpoint. Paliperidone treatment also resulted in significant improvement in the severity of ADHD and psychotic symptoms. Although treatment with paliperidone was generally well tolerated and was not associated with clinically significant change in cardiovascular or metabolic parameters, increases in body weight (4.1 ± 5.5 lb) were substantial. Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth. Future placebo-controlled studies are warranted to confirm these findings.

Neural correlates of treatment response in depressed bipolar adolescents during emotion processing

Depressive mood in adolescents with bipolar disorder (BDd) is associated with significant morbidity and mortality, but we have limited information about neural correlates of depression and treatment response in BDd. Ten adolescents with BDd (8 females, mean age = 15.6 ± 0.9) completed two (fearful and happy) face gender labeling fMRI experiments at baseline and after 6-weeks of open treatment. Whole-brain analysis was used at baseline to compare their neural activity with those of 10 age and sex-matched healthy controls (HC). For comparisons of the neural activity at baseline and after treatment of youth with BDd, region of interest analysis for dorsal/ventral prefrontal, anterior cingulate, and amygdala activity, and significant regions identified by wholebrain analysis between BDd and HC were analyzed. There was significant improvement in depression scores (mean percentage change on the Child Depression Rating Scale-Revised 57% ± 28). Neural activity after treatment was decreased in left occipital cortex in the intense fearful experiment, but increased in left insula, left cerebellum, and right ventrolateral prefrontal cortex in the intense happy experiment. Greater improvement in depression was associated with baseline higher activity in ventral ACC to mild happy faces. Study sample size was relatively small for subgroup analysis and consisted of mainly female adolescents that were predominantly on psychotropic medications during scanning. Our results of reduced negative emotion processing versus increased positive emotion processing after treatment of depression (improvement of cognitive bias to negative and away from positive) are consistent with the improvement of depression according to Beck's cognitive theory.

Neurocognitive Effects of Repetitive Transcranial Magnetic Stimulation in Adolescents with Major Depressive Disorder

Objectives: It is estimated that 30–40% of adolescents with major depressive disorder (MDD) do not receive full benefit from current antidepressant therapies. Repetitive transcranial magnetic stimulation (rTMS) is a novel therapy approved by the US Food and Drug Administration to treat adults with MDD. Research suggests rTMS is not associated with adverse neurocognitive effects in adult populations; however, there is no documentation of its neurocognitive effects in adolescents. This is a secondary post hoc analysis of neurocognitive outcome in adolescents who were treated with open-label rTMS in two separate studies.Methods: Eighteen patients (mean age, 16.2 ± 1.1 years; 11 females, 7 males) with MDD who failed to adequately respond to at least one antidepressant agent were enrolled in the study. Fourteen patients completed all 30 rTMS treatments (5 days/week, 120% of motor threshold, 10 Hz, 3,000 stimulations per session) applied to the left dorsolateral prefrontal cortex. Depression was rated using the Children’s Depression Rating Scale-Revised. Neurocognitive evaluation was performed at baseline and after completion of 30 rTMS treatments with the Children’s Auditory Verbal Learning Test (CAVLT) and Delis–Kaplan Executive Function System Trail Making Test.Results: Over the course of 30 rTMS treatments, adolescents showed a substantial decrease in depression severity. Commensurate with improvement in depressive symptoms was a statistically significant improvement in memory and delayed verbal recall. Other learning and memory indices and executive function remained intact. Neither participants nor their family members reported clinically meaningful changes in neurocognitive function.Conclusion: These preliminary findings suggest rTMS does not adversely impact neurocognitive functioning in adolescents and may provide subtle enhancement of verbal memory as measured by the CAVLT. Further controlled investigations with larger sample sizes and rigorous trial designs are warranted to confirm and extend these findings.

A Pilot Double Blind Randomized Placebo Controlled Trial of a Prototype Computer-Based Cognitive Behavioural Therapy Program for Adolescents with Symptoms of Depression

Depressive disorder is common in adolescents and largely untreated. Computers offer a way of increasing access to care. Computerized therapy is effective for depressed adults but to date little has been done for depressed adolescents. The objective of this study was to examine the feasibility, acceptability, and effects of The Journey, a computerized cognitive behavioural therapy (cCBT) program for depressed adolescents. Thirty-four adolescents (mean age 15.2 years, SD = 1.5) referred by school counsellors were randomly assigned to either cCBT or a computer-administered attention placebo program with psychoeducational content (CPE). Participants completed the intervention at school. Data were collected at baseline, post-intervention and at a 1-month follow-up. The primary outcome measure was the Child Depression Rating Scale Revised (CDRS-R); secondary outcome measures were: RADS-2; Pediatric Quality of Life Inventory; Adolescent Coping Scale (short form); response and remission rates on CDRS-R. Completion rates and self-reported satisfaction ratings were used to assess feasibility and acceptabililty of the intervention. Ninety-four percent of cCBT and 82% of CPE participants completed the intervention. Eighty-nine percent liked The Journey a lot or thought it was "okay" and 89% of them would recommend it for use with others as is or after some improvement. Adolescents treated with cCBT showed greater symptom improvement on CDRS-R than those treated with CPE program (mean change on cCBT = 17.6, CI = 14.13-21.00; CPE = 6.06, CI = 2.01-10.02; p< .001). It is feasible, acceptable and efficacious to deliver computerized CBT to depressed adolescents in a school setting. Generalizability is limited by the size of the study.

Psychosocial factors associated with depression severity in pregnant adolescents

Adolescent depression during pregnancy is associated with increased morbidity for the teen and her infant. This cross-sectional study explored the relationships among the independent histories of alcohol use, drug use, depression, and abuse (physical or sexual) on depression severity in a diverse group of 116 pregnant adolescents (mean age = 16) who attended an urban prenatal clinic. Ever having had an alcoholic drink was a significant predictor of higher depressive scores on Children's Depression Rating Scale-Revised, β = 3.3 (0.8, 5.7); p < 0.05. History of abuse was associated with a significant 4.3-point higher mean depressive score, β = 4.3 (1.8, 6.7), p < 0.001, and remained a statistically significant predictor of more severe depressive symptoms after adjustment for history of alcohol use, history of drug use, and history of depression. This study identified that a history of physical or sexual abuse is a significant factor related to the severity of depressive symptoms in pregnant adolescents, independent of a history of alcohol, drug use, or depression. These findings suggest that an assessment of history of alcohol use, as well as abuse history, may increase the likelihood of identifying adolescents at risk for antenatal depression.

Children's depression rating scale-revised (CDRS-R): Preliminary data on the validity of the Arabic version

Children's depression rating scale-revised (CDRS-R): Preliminary data on the validity of the Arabic version

Convergence of Children's Depression Rating Scale-revised Scores and Clinical Diagnosis in Rating Adolescent Depressive Symptomatology.

The Children’s Depression Rating Scale-Revised (CDRS-R) is a widely used instrument for research on depression in minors. A raw score of ≥40 has often been used as indicator of depressive symptomatology. As a validated German version of the CDRS-R has recently became available, we assessed CDRS-R raw summary scores of a video taped interview session in two different rater groups and compared them with clinical ratings of International Classification of Diseases (ICD-10) depression diagnosis as observed by a third independent group. We found that for the German version a raw score between 35 and 40 is indicative for mild depressive symptomatology as described by the ICD-10. CDRS-R scores show potential clinical applicability to deduct levels of depression.

Do sub-syndromal manic symptoms influence outcome in treatment resistant depression in adolescents? A latent class analysis from the TORDIA study

To identify distinct depressive symptom trajectories in the TORDIA study and determine their correlates. Latent Class Growth Analysis (LCGA) using the Children's Depression Rating Scale-Revised (CDRS-R) through 72 weeks from intake. 3 classes were identified: (1) little change in symptomatic status ("NO"), comprising 24.9% of participants, with a 72-week remission rate of 25.3%; (2) slow, steady improvement ("SLOW"), comprising 47.9% of participants, with a remission rate of 60.0%, and (3) rapid symptom response ("GO"), comprising 27.2% of participants, with a remission rate of 85.7%. Higher baseline CDRS-R (p<0.001) and poorer functioning (p=0.03) were the strongest discriminators between NO and GO. Higher baseline CDRS (p<0.001) and scores on the Mania Rating Scale (MRS) (p=0.01) were the strongest discriminators between SLOW and GO. Other variables differentiating GO from both NO and from SLOW, were better baseline functioning, lower hopelessness, and lower family conflict. Both NO and SLOW showed increases on the MRS over time compared to GO (ps ≤ 0.04), and increasing MRS was strongly associated with lack of remission by 72 weeks (p=0.02). High rate of open treatment by the end of the follow-up period creates difficulty in drawing clear inferences about the long-term impact of initial randomization. Along with depressive severity, sub-syndromal manic symptoms, at baseline, and over time emerged as important predictors and correlates of poor outcome in this sample. Further research is needed on the treatment of severe depression, and on the assessment and management of sub-syndromal manic symptoms in treatment resistant depression.

Study Implicates Neurotransmitter in Adolescent Depression

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessStudy Implicates Neurotransmitter in Adolescent DepressionLeslie SinclairLeslie SinclairSearch for more papers by this authorPublished Online:16 Dec 2011https://doi.org/10.1176/pn.46.24.psychnews_46_24_27-bAbstractTeenagers are the masters of indifference. They invented rolled eyes, shrugged shoulders, and “whatever.” But when typical teen apathy crosses the line into anhedonia, the reduced capacity to experience pleasure that is a core symptom of major depressive disorder (MDD), are there neurobiological abnormalities present?Researchers at the New York University Child Study Center and the Nathan S. Kline Institute for Psychiatric Research recently sought to determine whether the presence of anhedonia may involve alterations in the major inhibitory neurotransmitter system of gamma-aminobutyric acid (GABA). Studies in adults have documented decreases of cortical GABA in melancholic MDD and decreases of glutamine (the molecular precursor of GABA and glutamate) in anhedonic depressed patients, but no studies have yet investigated brain GABA alterations in adolescents with MDD, said the researchers in the online October 3 Archives of General Psychiatry.Vilma Gabbay, M.D., the medical director of the Anita Saltz Institute for Anxiety and Mood Disorders and Leon Levy assistant professor of child and adolescent psychiatry at the New York University School of Medicine, and her colleagues studied 20 psychotropic medication–free adolescents with a current episode of MDD lasting eight weeks or more; 10 of them were anhedonic, 12 were female, and all were aged 12 to 19. They all met the DSM-IV-TR diagnosis of MDD and displayed a severity score of 38 or more on the Children’s Depression Rating Scale-Revised (CDRS-R). Potential participants were excluded if they had a significant medical or neurological disorder, an IQ under 80, claustrophobia, an MRI contraindication as assessed by a standard safety-screening form, positive urine toxicology test results, or a positive pregnancy test result. A group of 21 control subjects matched for sex and age were also studied.Using an approach that had already been demonstrated in several investigations to assess anhedonia severity, the investigators required the presence of both anhedonia and lack of mood reactivity based on semistructured interviews conducted by two child and adolescent psychiatrists (members of the research team); parents were included in the interview for participants under age 18. Anhedonia scores were computed by summing the responses associated with anhedonia on the self-rated Beck Depression Inventory and the clinician-rated CDRS-R.The anterior cingulate cortex (ACC) region of the brain has been strongly implicated in MDD, and the region appears to be highly relevant in anhedonia, according to Gabbay and colleagues, who assessed ACC GABA levels in their study participants. “We used an imaging method called magnetic resonance spectroscopy, or MRS, which allows the noninvasive assessment of metabolite and chemical concentrations within the brain, to evaluate the ACC region in the study subjects and in the control group,” Gabbay explained to Psychiatric News. “Since GABA concentrations are considerably lower than concentrations of other neuro-chemicals, we used J-Editing MRS methodology to assess GABA.”Compared with the controls, adolescents with MDD had significantly less GABA in their ACC regions. When Gabbay and her colleagues looked more closely at the two groups, they realized there was no difference in GABA levels between adolescents with MDD but no anhedonia and the control group: GABA appeared to be specifically implicated in anhedonia.These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescents with MDD accompanied by anhedonia, according to Gabbay and colleagues, who cautioned that future larger studies replicating these findings as well as building on them are warranted.Gabbay described the direction she and her colleagues have plotted to advance their findings: “We have initiated the assessment of glutamate concentrations in depressed adolescents using a newly developed MRS imaging technique. Numerous animal studies have linked glutamatergic alterations with anhedonia and depression models; moreover, the syntheses of gluta-mate and GABA are closely linked. As such, assessment of glutamate is a key to further enhancing our understanding of the neuro-biology of MDD and anhedonia.”This study was supported by multiple grants from the National Institutes of Health, the Chrissy Rossi National Alliance for Research on Schizophrenia and Depression Award, and by gifts from the Leon Levy and Anita Saltz foundations.An abstract of “Anterior Cingulate Cortex Gamma-Aminobutyric Acid in Depressed Adolescents: Relationship to Anhedonia” is posted at <www.ncbi.nlm.nih.gov/pubmed/21969419>. ISSUES NewArchived

A Pragmatic Randomized Controlled Trial of Computerized CBT (SPARX) for Symptoms of Depression among Adolescents Excluded from Mainstream Education

Adolescents excluded from mainstream education have high mental health needs. The use of computerized Cognitive Behavioural Therapy (cCBT) has not been investigated with this group. To test the efficacy of the SPARX cCBT programme for symptoms of depression among adolescents in programmes for students excluded or alienated from mainstream education. Adolescents (32; 34% Maori, 38% Pacific Island, 56% male) aged 13-16 with Child Depression Rating Scale Revised (CDRS-R) scores indicating possible through to almost certain depressive disorder were randomized to SPARX to be completed over the following 5 weeks (n = 20) or to waitlist control (n = 12). Assessments were at baseline, 5 weeks and 10 weeks. Those in the wait condition were invited to complete SPARX after the 5 week assessment. Most participants (n = 26, 81%) completed at least 4 levels of SPARX and 22 (69%) completed all 7 levels. Among the 30 (94%) participants who began treatment as randomized and provided 5-week data, significant differences were found between cCBT and wait groups on the CDRS-R (baseline to 5-week mean change -14.7 versus -1.1, p<.001), remission (78% vs. 36%, p = .047) and on the Reynolds Adolescent Depression Scale (-4.6 vs. +3.2 p = .05) but not on other self-rating psychological functioning scales. In intent-to-treat analyses CDRS-R changes and remission remained significant. Gains were maintained at 10-week follow-up. SPARX appears to be a promising treatment for students with symptoms of depression who are in alternative schooling programmes for those excluded from mainstream education.

Decreased Levels of Serum Brain-Derived Neurotrophic Factor in Male Pediatric Patients with Depression

Background: Brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of ma- jor depressive disorder (MDD). Several meta-analyses have shown decreased serum levels of BDNF in adult patients with MDD, but there has been no report on the serum levels of BDNF in pediatric patients with depression. In this study, we investigated whether serum levels of BDNF are altered in pediatric patients with depression. Methods: We measured serum BDNF levels in the following four groups: male pediatric patients with depression (n = 13), female pediatric patients with depression (n = 17), and age-matched normal control subjects (n = 10 for Male, n=12 for Female). Patients were evaluated using the Children's Depression Rating Scale Revised (CDRS-R). Serum levels of BDNF were measured with the sandwich ELISA method. Results: Serum levels (6.97 ± 3.69 ng/mL (mean ± SD)) of BDNF in male pediatric patients with depression were signifi- cantly (p=0.019) lower than those (10.67 ± 3.11 ng/mL) in the male control group. However, there was no difference be- tween the female pediatric patients with depression (9.29 ± 4.61 ng/mL) and the female control group (10.21 ± 4.79 ng/mL). Furthermore, there was no correlation between serum levels of BDNF and CDRS-R scores in the pediatric pa- tients with depression. Interestingly, there was a significant negative correlation (r = -0.683, p=0.010) between the serum BDNF levels and the duration of illness in male, but not female, pediatric patients with depression. Conclusions: This study suggests that low BDNF levels may play a role in the pathophysiology of male pediatric patients with depression.

Adjunctive Use of Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents

Depression is often a serious and debilitating illness in adolescents. Unfortunately, a significant number of adolescents do not respond to antidepressant medications or psychotherapy. Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment intervention shown to benefit depression in adults. This study considered rTMS as an adjunctive treatment in adolescents with major depressive disorder. This prospective, open, multicenter trial of active adjunctive rTMS was conducted with 8 adolescents with DSM-IV-TR major depressive disorder (MDD) that had not responded sufficiently to 2 adequate antidepressant medication trials. All subjects were maintained on a stable dose of a selective serotonin reuptake inhibitor during the trial. Thirty daily rTMS treatments were given 5 days per week over 6 to 8 weeks. rTMS was applied to the left dorsolateral prefrontal cortex (120% of motor threshold; 10 Hz; 4-second trains; 26-second intertrain interval; 75 trains) for a total of 3,000 stimulations per treatment session. Seven of 8 adolescents completed all 30 treatments. rTMS was well tolerated, and no significant safety issues were identified. Suicidal ideation was present at baseline in 3 of the adolescents, and it improved during treatment. The primary outcome measure was the Children's Depression Rating Scale-Revised (CDRS-R); results improved significantly from baseline (mean [SD]) (65.9 [6.6]) to treatment 10 (50.9 [12]), P < .02. The CDRS-R scores continued to improve through the rTMS treatment series at treatment 20 (40.1 [14]), P < .01; treatment 30 (32.6 [7.3]), P < .0001; and at 6-month follow-up (32.7 [3.8]), P < .0001. This prospective open trial suggests that rTMS is a safe, feasible, and potentially effective adjunctive therapy for treatment-resistant MDD in adolescents. clinicaltrials.gov Identifier: NCT00587639.

Anxiety in children with mood disorders: a treatment help or hindrance?

This study examined the role of comorbid anxiety in treatment outcome for children with mood disorders (N = 165; age 8-11) participating in Multi-Family Psychoeducational Psychotherapy (MF-PEP). Assessments occurred at baseline, 6, 12, and 18 months for two randomly assigned groups: immediate treatment and 1-year wait-list. Most children (69%) had comorbid anxiety disorders. Baseline comorbid anxiety, as reported on the Children's Interview for Psychiatric Syndromes (ChIPS), was associated with higher Children's Depression Rating Scale- Revised (CDRS-R) scores but not Young Mania Rating Scale (YMRS) scores. Higher levels of anxiety symptoms were associated with lower Children's Global Assessment Scale (C-GAS) scores. Participation in MF-PEP did not significantly reduce anxiety symptoms (p = 0.62). However, presence of comorbid anxiety did not impede reduction in depressive (CDRS-R, p = 0.74) or manic (YMRS scores, p = 0.94) symptoms following MF-PEP. More baseline anxiety symptoms were associated with greater improvement in C-GAS scores post-treatment (p = 0.02). Implications are discussed.