Altered fronto-amygdalar functional connectivity predicts response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Based on findings from adults with obsessive-compulsive disorder (OCD), this study examined alterations in resting-state functional connectivity (rs-fc) between the basolateral amygdala (BLA) and the ventromedial prefrontal cortex (vmPFC) in children and adolescents with OCD. We also assessed whether such BLA-vmPFC connectivity changed with or predicted response to exposure and response prevention (E/RP), the first-line treatment for pediatric OCD, given the involvement of these regions in fear processing, regulation, and extinction learning-a probable mechanism of action of E/RP. METHODS: Resting state functional magnetic resonance imaging scans were acquired from 25 unmedicated, treatment-naïve pediatric patients with OCD (12.8 ± 2.9 years) and 23 age- and sex-matched healthy controls (HCs; 11.0 ± 3.3 years). Patients completed a 12-16-week E/RP intervention for OCD. Participants were rescanned after the 12-16-week period. ANCOVAs tested group differences in baseline rs-fc. Cross-lagged panel models examined relationships between BLA-vmPFC rs-fc and OCD symptoms pre- and posttreatment. All tests were adjusted for participants' age, sex, and head motion. RESULTS: Right BLA-vmPFC rs-fc was significantly reduced (more negative) in patients with OCD relative to HCs at baseline, and increased following treatment. In patients, more positive (less negative) right BLA-vmPFC rs-fc pretreatment predicted greater OCD symptoms reduction posttreatment. Changes in BLA-vmPFC rs-fc was unassociated with change in OCD symptoms pre- to posttreatment. CONCLUSIONS: These results provide further evidence of the BLA-vmPFC pathway as a potential target for novel treatments or prevention strategies aimed at facilitating adaptive learning and fear extinction in children with OCD or subclinical OCD symptoms.

Thematic content of obsessive and compulsive symptoms and conversion to psychosis in a clinical high-risk cohort.

AIM: We sought to explore the complex phenomenological overlap between obsessive and compulsive symptoms (OCS), and attenuated positive symptoms among 156 young people at clinical high-risk (CHR) for psychosis. METHODS: In order to explore the hypothesis that OCS of an implausible nature might optimally predict future transition to syndromal psychosis, ideas associated with obsessive and compulsive experiences elicited by clinical measures were thematically categorized as "plausible" or "implausible." RESULTS: While OCS were found to be common in our CHR sample, we did not find that implausible OCS themes were predictive of conversion. CONCLUSION: Given the absence of qualitative differences between OCS and early psychotic symptoms, we propose that clinicians encountering adolescent or young adult patients with new-onset OCD or OCS in the past year should monitor such symptoms for a minimum of 2 years to assess for the possible emergence of psychosis.

Structural neural markers of response to cognitive behavioral therapy in pediatric obsessive-compulsive disorder.

BACKGROUND: Cognitive behavioral therapy (CBT) is an effective, first-line treatment for pediatric obsessive-compulsive disorder (OCD). While neural predictors of treatment outcomes have been identified in adults with OCD, robust predictors are lacking for pediatric patients. Herein, we sought to identify brain structural markers of CBT response in youth with OCD. METHODS: Twenty-eight children/adolescents with OCD and 27 matched healthy participants (7- to 18-year-olds, M = 11.71 years, SD = 3.29) completed high-resolution structural and diffusion MRI (all unmedicated at time of scanning). Patients with OCD then completed 12-16 sessions of CBT. Subcortical volume and cortical thickness were estimated using FreeSurfer. Structural connectivity (streamline counts) was estimated using MRtrix. RESULTS: Thinner cortex in nine frontoparietal regions significantly predicted improvement in Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) scores (all ts > 3.4, FDR-corrected ps < .05). These included middle and superior frontal, angular, lingual, precentral, superior temporal, and supramarginal gyri (SMG). Vertex-wise analyses confirmed a significant left SMG cluster, showing large effect size (Cohen's d = 1.42) with 72.22% specificity and 90.00% sensitivity in predicting CBT response. Ten structural connections between cingulo-opercular regions exhibited fewer streamline counts in OCD (all ts > 3.12, Cohen's ds > 0.92) compared with healthy participants. These connections predicted post-treatment CY-BOCS scores, beyond pretreatment severity and demographics, though not above and beyond cortical thickness. CONCLUSIONS: The current study identified group differences in structural connectivity (reduced among cingulo-opercular regions) and cortical thickness predictors of CBT response (thinner frontoparietal cortices) in unmedicated children/adolescents with OCD. These data suggest, for the first time, that cortical and white matter features of task control circuits may be useful in identifying which pediatric patients respond best to individual CBT.

Ablation of supraventricular tachycardia allows more liberal therapy in some children with attention-deficit-hyperactivity disorder.

BACKGROUND: First-line therapy for children with attention-deficit-hyperactivity disorder (ADHD) is stimulant medication, which may have potential cardiovascular side-effects. In patients with supraventricular tachycardia or Wolf-Parkinson-White syndrome (WPW), therapy for ADHD could become challenging. The purpose of the present study was to review the authors' experience of performing electrophysiologic study (EPS) with or without ablation to determine how it affected ADHD therapy. METHODS: Retrospective chart review of patients who underwent EPS between 2002 and 2009 was carried out. All patients under 21 years of age who had prior diagnosis of ADHD were included. RESULTS: Twenty patients met the inclusion criteria. The mean age was 12.1 ± 2.7 years (range: 5.6-16.8 years). The patients were diagnosed with ADHD on average 3.9 ± 2.7 years (range: 6 months-9 years) prior to the EPS. All patients had a structurally normal heart. Sixteen patients had cardiac symptoms. Seventeen patients underwent ablation of the arrhythmia substrate (16/17, 94% successful). Three patients with asymptomatic WPW were at low risk for life-threatening arrhythmias and did not have ablation. After the EPS, two patients had increased doses of their ADHD medications, and two patients whose health-care providers stopped the stimulant medication prior to EPS because of recurrent tachycardia were restarted on medications. All other patients on ADHD medications continued therapy. CONCLUSIONS: EPS for risk stratification and ablation of arrhythmia substrate is safe and effective, allowing more liberal therapy in patients with ADHD and supraventricular tachycardia or WPW.

Psychotropic medications and substances of abuse interactions in youth.

The majority of youth with substance use disorders (SUDs) manifest one or more co-occurring psychiatric disorders. Consequently, many of these youths are being prescribed with psychotropic medications. As prescribing rates continue to increase for early-onset psychiatric disorders, potential risk for substance of abuse-psychiatric medication interactions may be enhanced. Because this type of drug-drug interaction has received little attention in the scientific literature, the authors conducted a systematic literature search examining the potential interactive adverse effects between psychotropic medications and substances of abuse in youth. Regardless of the scarcity of psychotropic medications-substance of abuse interactions found, it is important to stay vigilant due to the continued introduction of new classes of medications as well as the ever-changing map of street drugs.

Comparing impulsiveness, hostility, and depression in borderline personality disorder and bipolar II disorder.

OBJECTIVE: To determine whether borderline personality disorder (BPD) and bipolar II disorder can be differentiated from each other and from major depressive disorder (MDD) by comparing depression severity, impulsiveness, and hostility in mood disorder patients with and without BPD. METHOD: One hundred seventy-three patients with either MDD or bipolar II disorder were enrolled from a larger sample admitted to a multisite project on mood disorders and suicidal behavior conducted from June 1996 through June 2006. Patients were divided into 4 groups: MDD with BPD, MDD without an Axis II diagnosis, bipolar II disorder with BPD, and bipolar II disorder without an Axis II diagnosis. All diagnoses were based on DSM-IV criteria. Depression was assessed using the 17-item Hamilton Rating Scale for Depression (HAM-D) and the self-rated Beck Depression Inventory (BDI). Impulsiveness was assessed using the Barratt Impulsiveness Scale, and hostility was assessed using the Buss-Durkee Hostility Inventory. RESULTS: Patients with BPD reported higher levels of impulsiveness (p = .004) and hostility (p = .001), independent of Axis I diagnosis. Bipolar II patients reported greater attentional impulsiveness (p = .008) than MDD patients, independent of BPD status, while BPD patients reported greater nonplanning impulsiveness than patients without BPD, independent of Axis I diagnosis (p = .02). For motor impulsiveness, there was a main effect for Axis I diagnosis (p = .05) and Axis II diagnosis (p = .002). The bipolar II + BPD group scored the highest, suggesting a compound effect of comorbidity. There were no differences in depression severity when measured with the HAM-D, although the BPD groups reported more severe depression on the BDI, independent of their Axis I diagnosis (p = .05). The BPD groups scored higher on the cognitive factor (p = .01) and anxiety factor (p = .03) of the HAM-D. CONCLUSION: Results suggest that there is a unique symptom and trait profile associated with BPD that distinguishes the diagnosis from bipolar II disorder. Results also suggest that impulsiveness is an important aspect of both disorders and that there is a compounding effect associated with a diagnosis of bipolar II disorder with comorbid BPD.

Sex differences in clinical predictors of suicidal acts after major depression: a prospective study.

OBJECTIVE: Whether sex differences exist in clinical risk factors associated with suicidal behavior is unknown. The authors postulated that among men with a major depressive episode, aggression, hostility, and history of substance misuse increase risk for future suicidal behavior, while depressive symptoms, childhood history of abuse, fewer reasons for living, and borderline personality disorder do so in depressed women. METHOD: Patients with DSM-III-R major depression or bipolar disorder seeking treatment for a major depressive episode (N=314) were followed for 2 years. Putative predictors were tested with Cox proportional hazards regression analysis. RESULTS: During follow-up, 16.6% of the patients attempted or committed suicide. Family history of suicidal acts, past drug use, cigarette smoking, borderline personality disorder, and early parental separation each more than tripled the risk of future suicidal acts in men. For women, the risk for future suicidal acts was sixfold greater for prior suicide attempters; each past attempt increased future risk threefold. Suicidal ideation, lethality of past attempts, hostility, subjective depressive symptoms, fewer reasons for living, comorbid borderline personality disorder, and cigarette smoking also increased the risk of future suicidal acts for women. CONCLUSIONS: These findings suggest that the importance of risk factors for suicidal acts differs in depressed men and women. This knowledge may improve suicide risk evaluation and guide future research on suicide assessment and prevention.

Neurobiology of depression in children and adolescents.

This article reviews classical and updated studies of the neurobiology of depressive disorders in children and adolescents. Most studies of childhood and adolescent depression and suicide have followed up the observations and methods used in studies in adults. These studies include neuroendocrine studies, which particularly look at the hypothalamic-pituitary-adrenal axis, the serotonergic system, peripheral blood and cerebrospinal fluid biologic markers, genetics, gene-environment interactions and sleep studies, and neuroimaging and postmortem studies, although in these areas the number of studies is limited.

Prevalence of alcohol misuse among adolescents and young adults evaluated in a primary care setting.

OBJECTIVE: To determine the prevalence of alcohol misuse among older adolescents and young adults evaluated in a primary care setting using the CAGE questionnaire. METHODS: In this crossover descriptive study, a general practitioner, using the CAGE questionnaire, interviewed consecutive primary care patients aged 18-30 years. RESULTS: 29.5% of adolescents and young adults answered "yes" to at least one question of the CAGE questionnaire. However, only 7.4% of study participants gave an affirmative answer to at least two CAGE questions. There were more males than females among subjects who answered "yes" to at least one question. Furthermore, males more commonly gave an affirmative answer to at least two CAGE questions. CONCLUSIONS: A substantial number of older adolescents and young adults evaluated at a primary care center may have alcohol misuse. Instruments with higher sensitivity may be preferable in screening procedures for alcohol misuse. Responses suggestive of problematic drinking should be confirmed during the second post-screening stage with a more detailed discussion about patterns of use, problems related to drinking, and symptoms of alcohol use disorder. Further studies of prevention interventions in adolescents and young adults are needed.

Family-based association study of 5-HT(2A) receptor T102C polymorphism and suicidal behavior in Ashkenazi inpatient adolescents.

UNLABELLED: Suicidal behavior runs in families and is partially genetically determined. Since greater serotonin 5-HT(2A) receptor binding has been reported in postmortem brain and platelets of suicide victims, the 5-HT(2A) receptor gene polymorphism T102C became one of the candidate sites in the study of suicide and impulsive-aggressive traits. However, studies that examined the association of this polymorphism with suicidality have contradictory results. This study used a family-based method and one homogenous ethnic group to overcome ethnic stratification in order to test this association. METHODS: Thirty families of inpatient adolescents from Jewish Ashkenazi origin, with a recent suicide attempt, were genotyped. All subjects were interviewed for clinical diagnosis, depressive and impulsive-aggressive traits and demographic data. Allele frequencies were assessed using the Haplotype Relative Risk method for trios. RESULTS: No difference was found in allelic distribution between transmitted and non-transmitted alleles. There was no significant association of genotype with any of the clinical traits CONCLUSIONS: These preliminary results suggest that the 5-HT(2A) T102C polymorphism is unlikely to be associated with suicidal behavior and related traits in adolescent suicide attempters.

Supportive short-term family therapy by nursing staff in the inpatient unit: preventing dependence and rehospitalization in the acutely ill and suicidal adolescent.

Adolescents with acute mental illness or suicidal behavior are almost always hospitalized for safety and evaluation purposes. The tendency towards long-term or repeated hospitalizations has many adverse effects such as dependency on the mental health care system and increased chronicity of illness. The causes for these phenomena may be prevented in the early stages of hospitalization. We suggest a therapeutic model of supportive short-term family therapy. The family therapy component aims to enhance the quality of interaction and the level of support among family members. The therapy component dealing with the individual targets the patient's anxiety symptoms and coping strategies, and focuses on return to a healthy state. The child is encouraged to return home to a supportive family as soon as the treatment team feels this to be advisable. This paper discusses a case which highlights how a patient reacts in crisis, and ways in which a supportive environment can help bring about therapeutic success with reduced hospitalization.

Atypical neuroleptic malignant syndrome associated with risperidone treatment in two adolescents.

Neuroleptic Malignant Syndrome (NMS) is a known, life threatening, side effect of classical antipsychotic drugs. We report two cases of 16 and 17 year old males, who suffered life-threatening "NMS-Like" syndromes in association with Risperidone treatment. Further controlled studies are needed.

Attention patterns in children with attention deficit disorder with or without hyperactivity.

The objective of this study was to differentiate the attention patterns associated with attention deficit disorder with or without hyperactivity using continuous performance test (CPT). The diagnoses were based on the DSM-III, III-R, and IV criteria and of the 39 children who participated in the study, 14 had attention deficit disorder with hyperactivity (ADDH) and 11 had attention deficit disorder without hyperactivity (ADDWO), while 14 normal children served as a control group. Attention patterns were examined according to the performance of subjects on the CPT and parental scores on the ADHD Rating Scale, the Child Attention Profile, and the Conners Rating Scale. CPT performances were assessed before and after administration of 10 mg methylphenidate. We found as hypothesized that the CPT differentiated between the ADDH and ADDWO groups. However, contrary to our expectations, the ADDH children made more omission errors than the ADDWO children; they also showed more hyperactivity and impulsivity. The performance of both groups improved to an equal degree after the administration of methylphenidate. It is concluded that different subtypes of the attention deficit disorders are characterized by different attention profiles and that methylphenidate improves scores on test of continuous performance.