Brain volumes, behavioral inhibition, and anxiety disorders in children: results from the adolescent brain cognitive development study.

BACKGROUND: Magnetic resonance imaging (MRI) studies have identified brain changes associated with anxiety disorders (ADs), but the results remain mixed, particularly at a younger age. One key predictor of ADs is behavioral inhibition (BI), a childhood tendency for high avoidance of novel stimuli. This study aimed to evaluate the relationships between candidate brain regions, BI, and ADs among children using baseline data from the Adolescent Brain Cognitive Development (ABCD) study. METHODS: We analyzed global and regional brain volumes of 9,353 children (9-10 years old) in relation to BI and current ADs, using linear mixed models accounting for family clustering and important demographic and socioeconomic covariates. We further investigated whether and how past anxiety was related to brain volumes. RESULTS: Among included participants, 249 (2.66%) had a current AD. Larger total white matter (Beta = -0.152; 95% CI [-0.281, -0.023]), thalamus (Beta = -0.168; 95% CI [-0.291, -0.044]), and smaller hippocampus volumes (Beta = 0.094; 95% CI [-0.008, 0.196]) were associated with lower BI scores. Amygdala volume was not related to BI. Larger total cortical (OR = 0.751; 95% CI [0.580;0.970]), amygdala (OR = 0.798; 95%CI [0.666;0.956]), and precentral gyrus (OR = 0.802; 95% CI [0.661;0.973]) volumes were associated with lower odds of currently having ADs. Children with past ADs had smaller total white matter and amygdala volumes. CONCLUSIONS: The results show associations between brain volumes and both BI and ADs at an early age. Importantly, results suggest that ADs and BI have different neurobiological correlates and that earlier occurrences of ADs may influence brain structures related to BI and ADs, motivating research that can better delineate the similarities and divergence in the neurobiological underpinnings and building blocks of BI and ADs across their development in early life.

Impact of Emotions on Test of Variables of Attention(TOVA) Performance in a Pediatric Clinical Population: A Retrospective Study.

BACKGROUND: Continuous Performance Tests, like the Test of Variables of Attention (TOVA), are commonly used to assess attention processes in clinical settings. Although a few previous studies have explored the effects of emotions on the outcome of such tests, the results are scarce and contradictory at times. OBJECTIVE: Through this retrospective study, we  aimed to explore the correlation between performance on the TOVA and parent-reported emotional symptoms in youth. METHODS: We used preexisting datasets of Mood and Feelings Questionnaire, Screen for Child Anxiety Related Disorders, and Vanderbilt Attention-Deficit/Hyperactivity Disorder Diagnostic Rating Scale as well as preexisting results from the TOVA test from 216 patients aged between 8 and 18 years. Pearson's correlation coefficients, as well as linear regression models, were computed to examine the association between depressive and anxiety symptoms and the four indices of TOVA (response time variability, response time, commission errors, and omission errors). Additionally, we used generalized estimating equations to determine whether the reported emotional symptoms affect the TOVA outcome differently as the test progresses. RESULTS: Our results showed no significant effect of the reported emotional symptoms on the TOVA results even when controlling for sex or reported inattention and hyperactivity. CONCLUSION: TOVA results do not seem to be affected by emotional symptoms in youth. This being said, future studies should also explore other factors that can affect the performance on the TOVA, like motor disability, sleepiness, or neurodevelopmental disorders affecting cognitive abilities.

Psychopathology in Children and Adolescents in Lebanon Study (PALS): a national household survey.

INTRODUCTION: Psychiatric disorders are among the leading causes of disability in children and adolescents globally. In Lebanon, a country that has endured a prolonged history of conflict and economic and political uncertainty, mental health surveys in children and adolescents have been limited to specific disorders or specific settings or cities. PALS (Psychopathology in Children and Adolescents in Lebanon Study) is the first study to screen a nationally representative sample of children and adolescents for psychiatric disorders and estimate the national prevalence of children and adolescents at risk of having a psychiatric disorder. METHODS: A nationally representative household sample of 1517 children and adolescents (aged 5 years 0 months to 17 years 11 months) was recruited through a multi-stage stratified proportionate sampling technique between February 2018 and November 2018. Parents and adolescents completed a battery of self-reported scales including the Strengths and Feelings Questionnaire (SDQ), Mood and Feelings Questionnaire (MFQ), Screen for Child Anxiety and Emotional Related Disorders (SCARED), the Peer Relations Questionnaire (PRQ), General Health Questionnaire (GHQ), and Conflict Behavior Questionnaire (CBQ), Child Revised Impact of Events Scale (CRIES), and a demographic/clinical information questionnaire. Logistic regression models were used to examine the correlates of screening positive for psychiatric disorders. RESULTS: About a third of children and adolescents (32.7%, n = 497) screened positive for at least one psychiatric disorder, of whom only 5% (n = 25) reported ever seeking professional mental health help. Academic performance, having a chronic physical illness, higher parental GHQ scores, and involvement in bullying were associated with a higher odds of screening positive for a psychiatric disorder. Higher family income was negatively associated with screening positive for a psychiatric disorder. CONCLUSION: This first national study shows a high prevalence of psychiatric symptoms in Lebanese children and adolescents and an alarming treatment gap. School-based primary prevention programs or screening in primary care settings are key for early detection and management of psychiatric symptoms, and prevention of psychiatric disorders.

Effectiveness of a Preventive Parenting Program Combining Attachment and Behavioral Approaches in an Arab Context: a Cluster-Based Randomized Control Trial.

Parenting programs aim to help parents and carers enhance their skills and ameliorate infants' and toddlers' wellbeing. In Lebanon and other Arab countries, contextualized group-based parenting programs addressing parents' mental wellbeing, parenting styles, and child development are quite rare. Therefore, a Preventive Parenting Program consisting of 7 sessions has been designed by local experts for the local cultural context. This study aims to assess its effectiveness. Thirty-three sites were identified in Great Beirut: private firms, primary healthcare centers, and child daycares. Sixteen agreed to take part in the study and were randomly assigned to intervention and control arms. From these clusters, 191 mothers of typically developed children younger than three years were recruited to intervention (106) or control (85) groups. The Mental Health Inventory, Caregiver Knowledge about Child Development Inventory, Parent Authority Questionnaire, and a Demographic questionnaire were completed at pre-intervention and post-intervention and 3 months later by both groups of mothers. There were no significant differences between clusters with respect to all scales' scores at baseline as well as the 2 other data collection points. Despite the positive feedback collected from mothers who attended the sessions, no significant effects were detected. The design of the program, the expected outcomes, and the characteristics of the participants may have contributed to the limited results, hence the need for further research.

Maintenance Electroconvulsive Therapy Is an Essential Medical Treatment for Patients With Catatonia: A COVID-19 Related Experience.

Aim: Describe naturalistic clinical course over 14 weeks in a mixed adolescent and a young-adult patient group diagnosed with developmental delays and catatonia, when the frequency of maintenance electroconvulsive therapy (M-ECT) was reduced secondary to 2020 COVID-19 pandemic restrictions. Methods: Participants were diagnosed with catatonia, and were receiving care in a specialized clinic. They (n = 9), F = 5, and M = 4, ranged in age from 16 to 21 years; ECT frequency was reduced at end of March 2020 due to institutional restrictions. Two parents/caregivers elected to discontinue ECT due to concern for COVID-19 transmission. Majority (n = 8) were developmentally delayed with some degree of intellectual disability (ID). Observable symptoms were rated on a three point scale during virtual visits. Results: All cases experienced clinically significant decline. Worsening of motor symptoms (agitation, aggression, slowness, repetitive self-injury, stereotypies, speech deficits) emerged within the first 3 weeks, persisted over the 14 week observation period and were more frequent than neurovegetative symptoms (appetite, incontinence, sleep). Four participants deteriorated requiring rehospitalization, and 2 among these 4 needed a gastrostomy feeding tube. Conclusion: Moderate and severe symptoms became apparent in all 9 cases during the observation period; medication adjustments were ineffective; resuming M-ECT at each participant's baseline schedule, usually by week 7, resulted in progressive improvement in some cases but the improvement was insufficient to prevent re-hospitalization in 4 cases. In summary, rapid deterioration was noted when M-ECT was acutely reduced in the setting of COVID-19 related restrictions.

Episode of mixed mood with psychotic features secondary to Binswanger disease: a case report with a literature review.

Neurodegenerative and mood disorders in the geriatric population might exhibit interchangeable cognitive and behavioural symptoms. This overlap in presentation might raise a diagnostic challenge for psychiatrists evaluating elderly patients who are presenting with such symptoms. Additionally, there is limited data published about early psychiatric manifestations of neurodegenerative disorders in the elderly. We report a case of a 71-year-old with a history of refractory depressive disorder and multiple cardiovascular risk factors presenting with verbalisation of suicidal and homicidal intent as well as mixed mood and psychotic symptoms. The patient was diagnosed with Binswanger's disease (BD). We also provide a literature review of challenging early psychiatric presentations of neurocognitive disorders and a summary of similar cases to help facilitate diagnosis of BD cases in future.

A retrospective investigation of the added clinical value of SCT symptoms on neuropsychological assessments in youth with ADHD.

Some researchers believe that Sluggish Cognitive Tempo (SCT) should be its own psychiatric disorder. However, despite the abundance of literature describing its possible symptoms, evidence of its clinical impact on cognitive tests and some clinical comorbidities is still weak. This retrospective study aimed to analyze the added clinical value of exploring SCT symptoms prior to a neuropsychological assessment in a youth population diagnosed with an Attention-Deficit/Hyperactivity Disorder (ADHD). For this purpose, we used linear regressions to examine the association between different test results and SCT, as well as logistic regressions to examine the association between the existence of different diagnoses and SCT in a group of 295 ADHD patients [73 females, 24.7%], aged between 6 and 18 years [Mean (SD): 9.91 (3.12)]. Our results showed that parent-reported SCT symptoms did not help predict neuropsychological test outcomes. In addition, they did not predict Specific Learning Disorder (SLD) or Developmental Coordination Disorder (DCD), nor anxiety and depression when we controlled for age, Vanderbilt inattention and hyperactivity subscales, autism spectrum disorder, and intellectual disability. These results requestion the added-value of screening for SCT in similar clinical neuropsychological settings.

Building Emotional Resilience in Youth in Lebanon: a School-Based Randomized Controlled Trial of the FRIENDS Intervention.

In Lebanon, approximately one in four adolescents suffers from a psychiatric disorder. Alarmingly, 94% of adolescents with a mental disorder have not sought any treatment. This study assessed the effectiveness of an evidence-based school-based universal mental health intervention (the FRIENDS program) in reducing depression and anxiety symptoms in middle school students in Lebanon. A total of 280 6th graders aged 11-13 years were recruited from 10 schools in Beirut. Schools were matched on size and tuition and randomly assigned to intervention or control groups. The FRIENDS program was translated into Arabic, adapted, and then implemented by trained mental health professionals during 10 classroom sessions over 3 months. We assessed sociodemographic and relevant psychological symptoms by self-report, using the Scale for Childhood Anxiety and Related Disorders (SCARED), Mood and Feelings Questionnaire (MFQ), and Strengths and Difficulties Questionnaire (SDQ), at baseline. We re-administered these scales at 3 months post-intervention. There was a significant time × group interaction for the SDQ emotional score (p = 0.011) and total MFQ score (p = 0.039) indicating significant improvement in depressive and emotional symptoms in the intervention group. Subgroup analysis by gender showed a significant time × group interaction for the total SCARED score (p = 0.025) in females but not in males (p = 0.137), consistent with a reduction of anxiety symptoms in this stratum of the intervention group as compared with the control group. The FRIENDS program was effective in reducing general emotional and depressive symptoms among middle school students in this Lebanese study population. This intervention provides an opportunity for promoting mental health in Lebanese schools and reducing the treatment gap in mental health care.

Electroconvulsive Therapy for the Treatment of Severe Mood Disorders During Adolescence: A Retrospective Chart Review.

Objective: Electroconvulsive therapy (ECT) is a well-recognized treatment of refractory mood disorders in adults. However, relatively little is known about its use for similar conditions in adolescents. Based on a chart review, we describe its use and outcome in a sample of adolescents with severe, refractory mood disorders (unipolar or bipolar disorder) hospitalized in an academic medical center. Methods: The sample was drawn from referrals to an adolescent psychiatry service. After obtaining approval from the ethics board, medical records of 54 adolescents with refractory mood disorder were examined. Participants (males 24, females 30; mean age 15.8 ± 1.5 years) had received their first course of ECT before the age of 18 years during the period 1996-2010. Response to treatment was examined after the initial treatment and during a 1-year follow-up. Results: Following the index course of ECT (mean number of treatments = 13.7 ± 6.3), a 52.8% response rate (defined as a Clinical Global Impressions [CGI] score ≤2) was noted, while 15.1% achieved remission (CGI = 1). The response rate was 82.4% after a 1-year follow-up with a remission rate of 23.5%. The Children's Depression Rating scores declined significantly from pre-ECT to the end of the index course (70.7 ± 16.4 to 52.5 ± 18; p ≤ 0.00). A reduction in suicidal ideation and self-injurious behaviors along with increased school attendance was noted. Cognition, monitored by the Mini-Mental State Examination, did not decline significantly. Minor side effects were limited to the day of the treatment. Prolonged seizures (>2 minutes) were common during ECT (74% of subjects experienced one or more). The only side effect noted at the 1-year follow-up was self-reported memory loss involving events during and around the index treatment course. Conclusions: In this severely impaired sample of adolescents, ECT was found to decrease suicidal behavior, reduce depressive symptoms, and improve overall functioning, as indexed by school attendance at follow-up after 1 year. Prospective studies using large samples are needed to determine its effectiveness and safety in refractory mood disorders in adolescents.

The Role of Epigenetics in Addiction: Clinical Overview and Recent Updates.

Addiction is an international public health problem. It is a polygenic disorder best understood by accounting for the interplay between genetic and environmental factors. A recent way of perceiving this interaction is through epigenetics, which help grasp the neurobiological changes that occur in addiction and explain its relapsing-remitting nature. It is now known that every cell has a different way of expressing its phenotype, despite a universal DNA sequence. This is particularly true in the central nervous system where environmental factors influence this expression. Three major epigenetic processes have been found to participate in the perpetuation of addiction by changing the state of the chromatin and the degree of gene transcription: histone acetylation and methylation, DNA methylation, and noncoding RNAs. In the animal model literature, substantial evidence exists about the role of these epigenetic changes in the different phases of substance use disorders. This book chapter is a non-systematic literature review of the recent publications tackling the topic of epigenetics in addiction. Even though this evidence remains scarce and relatively poorly systematized, it is a promising foundation for future research of molecules that target specific brain regions and their functions to address core behavioral changes seen in addiction.

Salivary melatonin onset in youth at familial risk for bipolar disorder.

Melatonin secretion and polysomnography (PSG) were compared among a group of healthy adolescents who were at high familial risk for bipolar disorder (HR) and a second group at low familial risk (LR). Adolescent participants (n = 12) were a mean age 14 ± 2.3 years and included 8 females and 4 males. Saliva samples were collected under standardized condition light (red light) and following a 200 lux light exposure over two consecutive nights in a sleep laboratory. Red Light Melatonin onset (RLMO) was defined as saliva melatonin level exceeding the mean of the first 3 readings plus 2 standard deviations. Polysomnography was also completed during each night. HR youth, relative to LR, experienced a significantly earlier melatonin onset following 200 lux light exposure. Polysomnography revealed that LR youth, relative to HR, spent significantly more time in combined stages 3 and 4 (deep sleep) following red light exposure. Additionally, regardless of the group status (HR or LR), there was no significant difference in Red Light Melatonin Onset recorded at home or in the laboratory, implying its feasibility and reliability.

Prevention of Depression in At-Risk Adolescents: Predictors and Moderators of Acute Effects.

OBJECTIVE: To assess predictors and moderators of a cognitive-behavioral prevention (CBP) program for adolescent offspring of parents with depression. METHOD: This 4-site randomized trial evaluated CBP compared to usual community care (UC) in 310 adolescents with familial (parental depression) and individual (youth history of depression or current subsyndromal symptoms) risk for depression. As previously reported by Garber and colleagues, a significant prevention effect favored CBP through 9 months; however, outcomes of CBP and UC did not significantly differ when parents were depressed at baseline. The current study expanded on these analyses and examined a range of demographic, clinical, and contextual characteristics of families as predictors and moderators and used recursive partitioning to construct a classification tree to organize clinical response subgroups. RESULTS: Depression onset was predicted by lower functioning (hazard ratio [HR] = 0.95, 95% CI = 0.92-0.98) and higher hopelessness (HR = 1.06, 95% CI = 1.01-1.11) in adolescents. The superior effect of CBP was diminished when parents were currently depressed at baseline (HR = 6.38, 95% CI = 2.38-17.1) or had a history of hypomania (HR = 67.5, 95% CI = 10.9-417.1), or when adolescents reported higher depressive symptoms (HR = 1.04, 95% CI = 1.00-1.08), higher anxiety (HR = 1.05, 95% CI = 1.01-1.08), higher hopelessness (HR = 1.10, 95% CI = 1.01-1.20), or lower functioning (HR = 0.94, 95% CI = 0.89-1.00) at baseline. Onset rates varied significantly by clinical response cluster (0%-57%). CONCLUSION: Depression in adolescents can be prevented, but programs may produce superior effects when timed at moments of relative wellness in high-risk families. Future programs may be enhanced by targeting modifiable negative clinical indicators of response. CLINICAL TRIAL REGISTRATION INFORMATION: Prevention of Depression in At-Risk Adolescents; http://clinicaltrials.gov/; NCT00073671.

The bidirectional relationship between body mass index and treatment outcome in adolescents with treatment-resistant depression.

OBJECTIVE: Depression and obesity are associated, but the impact of obesity on depression treatment outcome, or, conversely, the impact of treatment on body mass index (BMI) in depressed adolescents has not been reported. In this article, we examine the bidirectional relationships between BMI and treatment response in adolescents with treatment-resistant depression. METHOD: Participants in the Treatment of Selective Serotonin Reuptake Inhibitor (SSRI) Resistant Depression in Adolescents (TORDIA) study had height and weight assessed at baseline, weekly for the first 6 weeks, biweekly for the next 6 weeks, and monthly from weeks 12 through 24. The impact of baseline BMI as a predictor and moderator of treatment response was assessed. In addition, participants' changes in BMI were assessed as a function of specific treatment assignment and treatment response. RESULTS: Participants assigned to SSRIs had a greater increase in BMI-for-age-sex z-score and weight than did those assigned to venlafaxine. Post-hoc, those treated with paroxetine or citalopram had the biggest increases in BMI, relative to fluoxetine or venlafaxine. Overweight or obesity was neither a predictor nor a moderator of treatment outcome, nor of subsequent BMI change. CONCLUSIONS: Overweight status does not appear to affect treatment response in adolescents with resistant depression. The successful treatment of depression does not appear to favorably affect weight or BMI. Fluoxetine and venlafaxine are less likely to cause an increase in BMI than paroxetine or citalopram.

The bi-directional relationship between parent-child conflict and treatment outcome in treatment-resistant adolescent depression.

OBJECTIVE: To examine the bidirectional relationship between parent-child discord and treatment outcome for adolescent treatment-resistant depression. METHOD: Depressed youth who had not responded to an adequate course of a selective serotonin reuptake inhibitor (SSRI) were randomized to either a switch to another SSRI or venlafaxine, with or without the addition of cognitive behavior therapy (CBT) in the Treatment of SSRI-Resistant Depression in Adolescents (TORDIA) study. The Conflict Behavior Questionnaire was used to assess adolescent (CBQ-A) and parent-reported (CBQ-P) parent-child discord. The impact of remission on parent-child conflict, and the differential impact of medication and CBT on the CBQ-A and CBQ-P, were assessed using generalized linear models. RESULTS: Although there were no differential treatment effects on parent or adolescent-report of conflict, remission was associated with improvement in the CBQ-P. In general, intake family conflict did not predict remission, except in the sub-group of participants whose parents reported clinically significant parent-child conflict at intake, for whom high levels of parent-reported conflict predicted a lower likelihood of remission. Conflict also did not moderate treatment response. CONCLUSIONS: Remission of depression may be sufficient to reduce parent-reported parent-child conflict. However, higher parent-reported conflict, in the clinically significant range, predicts a lower likelihood of remission from depression. Clinical trial registration information-Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.

Impact of treatments for depression on comorbid anxiety, attentional, and behavioral symptoms in adolescents with selective serotonin reuptake inhibitor-resistant depression.

OBJECTIVE: To assess the relative efficacy of antidepressant medication, alone and in combination with cognitive behavioral therapy (CBT), on comorbid symptoms of anxiety, attention, and disruptive behavior disorders in participants in the Treatment of Resistant Depression in Adolescents (TORDIA) trial. METHOD: Adolescents with selective serotonin reuptake inhibitor (SSRI)-resistant depression (N = 334) were randomly assigned to a medication switch alone (to another SSRI or to venlafaxine) or to a medication switch plus CBT. Anxiety, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorder (DBD) symptoms were assessed by psychiatric interview and self-report at regular intervals between baseline and 24 weeks. The differential effects of medication and of CBT, and the impact of remission on the course of comorbid symptoms and diagnoses, were assessed using generalized linear mixed models. RESULTS: Remission was associated with a greater reduction in scalar measures of anxiety, ADHD, and DBDs, and a greater decrease in the rate of diagnosed anxiety disorders. The correlations between the changes in symptoms of depression on the CDRS-R and anxiety, ADHD, and oppositional symptoms were modest, ranging from r = 0.12 to r = 0.28. There were no significant differential treatment effects on diagnoses, or corresponding symptoms. CONCLUSION: The achievement of remission had a beneficial effect on anxiety, ADHD, and DBD symptoms, regardless of the type of treatment received. There were no differential effects of medication or CBT on outcome, except for a nonsignificant trend that those adolescents treated with SSRIs showed a greater decrease in rates of comorbid DBDs relative to those treated with venlafaxine. Clinical trial registration information-Treatment of SSRI-Resistant Depression In Adolescents (TORDIA); http://clinicaltrials.gov/; NCT00018902.

Anhedonia predicts poorer recovery among youth with selective serotonin reuptake inhibitor treatment-resistant depression.

OBJECTIVE: To identify symptom dimensions of depression that predict recovery among selective serotonin reuptake inhibitor (SSRI) treatment-resistant adolescents undergoing second-step treatment. METHOD: The Treatment of Resistant Depression in Adolescents (TORDIA) trial included 334 SSRI treatment-resistant youth randomized to a medication switch, or a medication switch plus CBT. This study examined five established symptom dimensions (Child Depression Rating Scale-Revised) at baseline as they predicted recovery over 24 weeks of acute and continuation treatment. The two indices of recovery that were evaluated were time to remission and number of depression-free days. RESULTS: Multivariate analyses examining all five depression symptom dimensions simultaneously indicated that anhedonia was the only dimension to predict a longer time to remission, and also the only dimension to predict fewer depression-free days. In addition, when anhedonia and CDRS-total score were evaluated simultaneously, anhedonia continued to uniquely predict longer time to remission and fewer depression-free days. CONCLUSIONS: Anhedonia may represent an important negative prognostic indicator among treatment-resistant depressed adolescents. Further research is needed to elucidate neurobehavioral underpinnings of anhedonia, and to test treatments that target anhedonia in the context of overall treatment of depression.

Adjunctive sleep medications and depression outcome in the treatment of serotonin-selective reuptake inhibitor resistant depression in adolescents study.

OBJECTIVE: In the Treatment of Resistant Depression in Adolescents, study participants who received medication for sleep had a lower response rate. This report sought to clarify this finding. METHOD: Depressed adolescents who had not responded to a previous adequate serotonin-selective reuptake inhibitor (SSRI) trial were randomly assigned to another SSRI, venlafaxine, another SSRI+cognitive behavior therapy (CBT), or venlafaxine+CBT. Augmentation with sleep medication was permitted as clinically indicated. RESULTS: Youth who received trazodone were six times less likely to respond than those with no sleep medication (adjusted odds ratio [OR]=0.16, 95% confidence interval [CI]: 0.05-0.50, p=0.001) and were three times more likely to experience self-harm (OR=3.0, 95% CI: 1.1-7.9, p=0.03), even after adjusting for baseline differences associated with trazodone use. None (0/13) of those cotreated with trazodone and either paroxetine or fluoxetine responded. In contrast, those treated with other sleep medications had similar rates of response (60.0% vs. 50.4%, χ(2)=0.85, p=0.36) and of self-harm events (OR=0.5, 95% CI: 0.1-2.6, p=0.53) as those who received no sleep medication. CONCLUSIONS: These findings should be interpreted cautiously because these sleep agents were not assigned randomly, but at clinician discretion. Nevertheless, they suggest that the use of trazodone for the management of sleep difficulties in adolescent depression should be re-evaluated and that future research on the management of sleep disturbance in adolescent depression is needed. The very low response rate of participants cotreated with trazodone and either fluoxetine or paroxetine could be due to inhibition of CYP 2D6 by these antidepressants.

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

BACKGROUND: To identify distinct depressive symptom trajectories in the TORDIA study and determine their correlates. METHODS: Latent Class Growth Analysis (LCGA) using the Children's Depression Rating Scale-Revised (CDRS-R) through 72 weeks from intake. RESULTS: 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). LIMITATIONS: 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. CONCLUSION: 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.

Treatment-resistant depressed youth show a higher response rate if treatment ends during summer school break.

OBJECTIVE: There is little work on the effect of school on response to treatment of depression, with available research suggesting that children and adolescents with school difficulties are less likely to respond to fluoxetine compared with those with no school difficulties. METHOD: Depressed adolescents in the Treatment of Resistant Depression in Adolescents study, who had not responded to a previous adequate selective serotonin reuptake inhibitor (SSRI) trial, were randomly assigned to one of the following: another SSRI, venlafaxine, another SSRI + cognitive behavior therapy (CBT), or venlafaxine + CBT. Participants were classified into four groups depending on whether their enrollment in the study and end of treatment was during school or summer vacation. RESULTS: Controlling for baseline differences, adolescents ending their 12-week treatment during summer vacation had odds 1.7 times (95% confidence interval = 1.02-2.8, p = .04) greater to have an adequate response as those ending their treatment while being in school. In addition, adequate depression response was associated with fewer school problems at week 12 (scores <5 versus scores ≥5: odds ratio = 3.3, 95% confidence interval = 1.9-5.8, p < .001). There was a significant interaction between school difficulties and timing of treatment, with the lowest rates of response being among adolescents having school difficulties and ending their treatment during the active school year. CONCLUSION: School problems are relevant to treatment response in depressed adolescents and should be incorporated into the treatment plan. These findings also suggest that the time of the year might need to be taken into consideration for analysis of clinical trials in school-aged youth. CLINICAL TRIAL REGISTRATION INFORMATION: Treatment of SSRI-Resistant Depression in Adolescents (TORDIA); http://www.clinicaltrials.gov; NCT00018902.