Pharmacogenetic Factors Influence Escitalopram Pharmacokinetics and Adverse Events in Youth with a Family History of Bipolar Disorder: A Preliminary Study.

Introduction: Escitalopram is an effective and generally well-tolerated antidepressant, but children of parents with bipolar disorder (BD) may be at increased risk for adverse events associated with antidepressants, including increased irritability, restlessness, impulsivity, and manic symptoms. This risk may be influenced by polymorphisms in genes encoding cytochrome P450 enzymes (CYP2C19 or CYP2D6), the serotonin transporter (SLC6A4), and the serotonin receptor 2A subtype (HTR2A). We explored whether gene-drug interactions influence the emergence of adverse events in depressed and/or anxious youth with a family history of BD. Materials and Methods: Children and adolescents aged 12-17 years with a first-degree relative with bipolar I disorder were treated with escitalopram and monitored for adverse effects, underwent pharmacogenetic testing, and provided serum escitalopram levels. Emergence of adverse events was determined by study clinicians, and symptoms were tracked using the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) and Pediatric Adverse Events Rating Scale. Clinical Pharmacogenetics Implementation Consortium guidelines were used to determine CYP2C19 and CYP2D6 phenotypes. Results: Slower CYP2C19 metabolizers had greater dose-normalized 24-hour area under the curve (AUC0-24; p = 0.025), trough concentrations (Ctrough; p = 0.013), and elimination half-lives (t1/2; p < 0.001). CYP2D6 phenotype was not significantly associated with any pharmacokinetic parameter. Slower CYP2D6 metabolizers had increased TEASAP akathisia (p = 0.015) scores. HTR2A A/A and A/G genotypes were associated with increased TEASAP "self-injury, suicidality, and harm to others" subscale scores (p = 0.017). Escitalopram maximum concentration, AUC0-24, CYP2C19 phenotype, and SLC6A4 genotype were not associated with adverse events. Conclusions: CYP2C19 phenotype influences escitalopram pharmacokinetics whereas CYP2D6 phenotype does not. Slower CYP2D6 metabolism was associated with increased akathisia, and HTR2A A/A or A/G genotypes were associated with increased risk of self-harm or harm to others. Larger cohorts are needed to identify associations between genetic test results and antidepressant-associated adverse events. Trial Registration: ClinicalTrials.gov identifier: NCT02553161.

Aberrant brain network topology in youth with a familial risk for bipolar disorder: a task-based fMRI connectome study.

BACKGROUND: Youth with a family history of bipolar disorder (BD) may be at increased risk for mood disorders and for developing side effects after antidepressant exposure. The neurobiological basis of these risks remains poorly understood. We aimed to identify biomarkers underlying risk by characterizing abnormalities in the brain connectome of symptomatic youth at familial risk for BD. METHODS: Depressed and/or anxious youth (n = 119, age = 14.9 ± 1.6 years) with a family history of BD but no prior antidepressant exposure and typically developing controls (n = 57, age = 14.8 ± 1.7 years) received functional magnetic resonance imaging (fMRI) during an emotional continuous performance task. A generalized psychophysiological interaction (gPPI) analysis was performed to compare their brain connectome patterns, followed by machine learning of topological metrics. RESULTS: High-risk youth showed weaker connectivity patterns that were mainly located in the default mode network (DMN) (network weight = 50.1%) relative to controls, and connectivity patterns derived from the visual network (VN) constituted the largest proportion of aberrant stronger pairs (network weight = 54.9%). Global local efficiency (Elocal, p = .022) and clustering coefficient (Cp, p = .029) and nodal metrics of the right superior frontal gyrus (SFG) (Elocal: p < .001; Cp: p = .001) in the high-risk group were significantly higher than those in healthy subjects, and similar patterns were also found in the left insula (degree: p = .004; betweenness: p = .005; age-by-group interaction, p = .038) and right hippocampus (degree: p = .003; betweenness: p = .003). The case-control classifier achieved a cross-validation accuracy of 78.4%. CONCLUSIONS: Our findings of abnormal connectome organization in the DMN and VN may advance mechanistic understanding of risk for BD. Neuroimaging biomarkers of increased network segregation in the SFG and altered topological centrality in the insula and hippocampus in broader limbic systems may be used to target interventions tailored to mitigate the underlying risk of brain abnormalities in these at-risk youth.

Effect of non-invasive spinal cord stimulation in unmedicated adults with major depressive disorder: a pilot randomized controlled trial and induced current flow pattern.

Converging theoretical frameworks suggest a role and a therapeutic potential for spinal interoceptive pathways in major depressive disorder (MDD). Here, we aimed to evaluate the antidepressant effects and tolerability of transcutaneous spinal direct current stimulation (tsDCS) in MDD. This was a double-blind, randomized, sham-controlled, parallel group, pilot clinical trial in unmedicated adults with moderate MDD. Twenty participants were randomly allocated (1:1 ratio) to receive "active" 2.5 mA or "sham" anodal tsDCS sessions with a thoracic (anode; T10)/right shoulder (cathode) electrode montage 3 times/week for 8 weeks. Change in depression severity (MADRS) scores (prespecified primary outcome) and secondary clinical outcomes were analyzed with ANOVA models. An E-Field model was generated using the active tsDCS parameters. Compared to sham (n = 9), the active tsDCS group (n = 10) showed a greater baseline to endpoint decrease in MADRS score with a large effect size (-14.6 ± 2.5 vs. -21.7 ± 2.3, p = 0.040, d = 0.86). Additionally, compared to sham, active tsDCS induced a greater decrease in MADRS "reported sadness" item (-1.8 ± 0.4 vs. -3.2 ± 0.4, p = 0.012), and a greater cumulative decrease in pre/post tsDCS session diastolic blood pressure change from baseline to endpoint (group difference: 7.9 ± 3.7 mmHg, p = 0.039). Statistical trends in the same direction were observed for MADRS "pessimistic thoughts" item and week-8 CGI-I scores. No group differences were observed in adverse events (AEs) and no serious AEs occurred. The current flow simulation showed electric field at strength within the neuromodulation range (max. ~0.45 V/m) reaching the thoracic spinal gray matter. The results from this pilot study suggest that tsDCS is feasible, well-tolerated, and shows therapeutic potential in MDD. This work also provides the initial framework for the cautious exploration of non-invasive spinal cord neuromodulation in the context of mental health research and therapeutics. The underlying mechanisms warrant further investigation. Clinicaltrials.gov registration: NCT03433339 URL: https://clinicaltrials.gov/ct2/show/NCT03433339 .

Cognitive, Family, and Quality-of-Life Characteristics of Youth with Depression Associated with Bipolar Disorder.

Background: Depression associated with bipolar disorder (BD) is more common compared to mania. Cognitive, family, and quality-of-life (QOL) factors associated with pediatric bipolar depression are understudied. The goal of this study was to evaluate cognitive, family environmental, and QOL characteristics of youth with bipolar depression. Methods: Thirty-two youth (12-18 years of age) with BD type I currently depressed were recruited from inpatient and outpatient setting. Subjects were assessed using the Behavior Rating Inventory of Executive Function (BRIEF), the Family Environment Scale (FES), and the Child Health Questionnaire-Parental-Form 50 (CHQ-PF50). Results were compared with population norms and the relationship between these domains was calculated. Results: Youth with depression associated with BD did not show significant impairment in executive functions. They displayed impaired family environment in the domains of cohesion, independence, achievement orientation, and organization. Youth also displayed impairments in the psychosocial health domains compared with the population normative data. The CHQ-Psychosocial health significantly negatively correlated with the BRIEF-Global Executive Control score (r = -0.76, p < 0.0001). Conclusion: Depression in youth with BD is associated with impairments in family functioning and QOL. Impairments in psychosocial QOL are associated with cognitive functioning. Further intervention studies examining executive functioning and family environment as treatment targets are needed. ClinicalTrials.gov identifier:NCT00232414.

Deficits in sustained attention in adolescents with bipolar disorder during their first manic episode.

OBJECTIVES: Evaluate differences in sustained attention (SAT) and associated neurofunctional profiles between bipolar disorder type I (BD), attention-deficit/hyperactivity disorder (ADHD), and healthy comparison (HC) youth. METHODS: Adolescent participants, aged 12-17 years, with BD (n = 30) and ADHD (n = 28) and HC adolescents (n = 26) underwent structural and functional magnetic resonance imaging (fMRI) while completing a modified Continuous Performance Task-Identical Pairs task. Attentional load was modifying in this task using three levels of image distortion (0 %, 25 % and 50 % image distortion). Task related fMRI activation and performance measures: perceptual sensitivity index (PSI); response bias (RB) and response time (RT); were calculated and compared between groups. RESULTS: BD participants displayed lower perceptual sensitivity index (0 % p = 0.012; 25 % p = 0.015; 50 % p = 0.036) and higher values of response bias across levels of distortion (0 % p = 0.002, 25 % p = 0.001, and 50 % p = 0.008) as compared to HC. No statistically significant differences were observed for PSI and RB between BD and ADHD groups. No difference in RT were detected. Between-group and within-group differences in task related fMRI measures were detected in several clusters. In a region of interest (ROI) analysis of these clusters comparing BD and ADHD confirmed differences between these two groups. CONCLUSIONS: Compared with HC, BD participants displayed SAT deficits. Increased attentional load revealed that BD participants had lower activation in brain regions associated with performance and integration of neural processes in SAT. ROI analysis between BD and ADHD participants shows that the differences were likely not attributable to ADHD comorbidity, suggesting SAT deficits were distinct to the BD group.

Fusion of Heterogenous Sensor Data in Border Surveillance.

Wide area surveillance has become of critical importance, particularly for border control between countries where vast forested land border areas are to be monitored. In this paper, we address the problem of the automatic detection of activity in forbidden areas, namely forested land border areas. In order to avoid false detections, often triggered in dense vegetation with single sensors such as radar, we present a multi sensor fusion and tracking system using passive infrared detectors in combination with automatic person detection from thermal and visual video camera images. The approach combines weighted maps with a rule engine that associates data from multiple weighted maps. The proposed approach is tested on real data collected by the EU FOLDOUT project in a location representative of a range of forested EU borders. The results show that the proposed approach can eliminate single sensor false detections and enhance accuracy by up to 50%.

Symptom Profiles, But Not Prefrontal Neurochemistry, Differentiate ADHD Youth With and Without a Family History of Bipolar I Disorder.

Objective: To identify clinical and central features that differentiate ADHD youth with and without familial risk for bipolar I disorder (BD). Methods: Psychostimulant-free ADHD youth (10-18 years) with and without a first-degree relative with BD and healthy controls were enrolled. Bilateral ventrolateral prefrontal cortex (VLPFC) proton magnetic resonance spectroscopy (1H MRS) scans and a range of symptom ratings were performed. Results: A total of n = 145 youth were enrolled. ADHD youth with a family history of BD exhibited greater manic and depressive symptom severity, ADHD hyperactivity/impulsive symptom severity, and higher parent-reported ratings of dysregulation compared with ADHD youth without a BD family history. Although VLPFC metabolite levels did not differ across groups, choline levels in the left VLPFC correlated with different symptom ratings. Conclusion: Symptom profiles including more severe mood and externalizing symptoms, but not VLPFC neurochemistry, differentiate psychostimulant-free ADHD youth with and without a family history of BD.

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder.

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

Adaptación de la escala Dragones de Inacción Barreras Psicológicas (DIPB) en población colombiana / Adaptation of the Dragons of Inaction Psychological Barriers (DIPB) scale in a Colombian population

Resumen El daño ambiental que se ha venido provocando a causa de la actividad humana es preocupante, razón por la cual se ha identificado como una de las posibles soluciones tener un comportamiento proambiental. Sin embargo, se ha visto que hay barreras psicológicas que impiden o dificultan esta conducta. Por este motivo, con el fin de tener un instrumento que permita evaluar estas barreras psicológicas en nuestro contexto, el objetivo de la presente investigación fue realizar la adaptación de la escala Dragons of Inaction Psychological Barriers (DIPB) en población colombiana. La muestra estuvo compuesta por 810 estudiantes universitarios de Bogotá y Chía, Colombia; 367 hombres y 443 mujeres con edades entre los 15 y los 48 años (M = 19.67, DE = 2.414). En general, se realizó un análisis factorial exploratorio y un análisis factorial confirmatorio, con los cuales se comprobó la existencia de una estructura de cinco factores con 20 ítems; se realizaron análisis de reactivos y fiabilidad que demostraron que el instrumento tiene una alta consistencia interna; y se llevaron a cabo dos estudios de invarianza, con los que se demostró que la estructura factorial es invariante para todos los grupos de estudio. Además, se realizó la baremación del instrumento total. En conclusión, esta adaptación del DIPB presenta adecuada validez y fiabilidad, y permite guiar futuras investigaciones acerca de las barreras de inacción en el contexto latinoamericano, a la vez que aporta un insumo para realizar un primer diagnóstico de este constructo en Colombia.

Abstract The environmental damage that has been generated by human activity is a cause for concern, so pro-environmental behavior has been identified as one of the possible solutions. However, it has been seen that there are psychological barriers that prevent or hinder this behavior. For this reason, in order to have an instrument to evaluate these psychological barriers in our context, the objective of this research was to adapt the Dragons of Inaction Psychological Barriers (DIPB) scale to the Colombian population. The sample was made up of 810 university students from Bogotá and Chía, Colombia; 367 males and 443 females between 15 and 48 years of age (M = 19.67, SD = 2.414). In general, an exploratory factor analysis and a confirmatory factor analysis were carried out, which demonstrated the existence of a five-factor structure with 20 items. Item and reliability analyses were performed, which demonstrated that the instrument has a high internal consistency; and two invariance studies were carried out, which showed that the factor structure is invariant for all study groups. In addition, the total instrument was scored. In conclusion, this adaptation of the DIPB presents adequate validity and reliability, and allows guiding future research on inaction barriers in the Latin American context, while providing an input for a first diagnosis of this construct in Colombia.

Pretreatment Alterations and Acute Medication Treatment Effects on Brain Task-Related Functional Connectivity in Youth With Bipolar Disorder: A Neuroimaging Randomized Clinical Trial.

OBJECTIVE: Disruptions in cognition are a clinically significant feature of bipolar disorder (BD). The effects of different treatments on these deficits and the brain systems that support them remain to be established. METHOD: A continuous performance test was administered to 55 healthy controls and 71 acutely ill youths with mixed/manic BD to assess vigilance and working memory during task-based functional magnetic resonance imaging studies. Patients, who were untreated for at least 7 days at baseline, and controls were scanned at pretreatment baseline and at weeks 1 and 6. After baseline testing, patients (n = 71) were randomly assigned to 6-week double-blind treatment with lithium (n = 26; 1.0-1.2 mEq/L) or quetiapine (n = 45; 400-600 mg). Weighted seed-based connectivity (wSBC) was used to assess regional brain interactions during the attention task compared with the control condition. RESULTS: At baseline, youths with BD showed reduced connectivity between bilateral anterior cingulate cortex and both left ventral lateral prefrontal cortex and left insula and increased connectivity between left ventral lateral prefrontal cortex and left temporal pole, left orbital frontal cortex and right postcentral gyrus, and right amygdala and right occipital pole compared with controls. At 1-week follow-up, quetiapine, but not lithium, treatment led to a significant shift of connectivity patterns toward those of the controls. At week 6, compared with baseline, there was no difference between treatment conditions, at which time both patient groups showed significant normalization of brain connectivity toward that of controls. CONCLUSION: Functional alterations in several brain regions associated with cognitive processing and the integration of cognitive and affective processing were demonstrated in untreated youths with BD before treatment. Treatment reduced several of these alterations, with significant effects at week 1 only in the quetiapine treatment group. Normalization of functional connectivity might represent a promising biomarker for early target engagement in youth with BD. CLINICAL TRIAL REGISTRATION INFORMATION: Multimodal Neuroimaging of Treatment Effects in Adolescent Mania; https://clinicaltrials.gov/; NCT00893581.

N-acetylcysteine for depression and glutamate changes in the left prefrontal cortex in adolescents and young adults at risk for bipolar disorder: A pilot study.

AIMS: To investigate the mechanism of action of N-acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder. METHODS: We conducted an 8-week open label clinical trial of NAC 2400 mg/days in 15-24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC). RESULTS: Nine participants were enrolled and finished the study. NAC significantly improved depressive and anxiety symptom scores, and clinical global impression (all p < .001). There was a non-significant reduction in glutamate levels in the left VLPFC. Reduction in depressive symptom scores was positively associated with reduction in glutamate levels in the left VLPFC (p = .007). CONCLUSIONS: This pilot study suggests that NAC might be efficacious for depressive symptoms in at-risk youth, and that its mechanism of action involves the modulation of glutamate in the left VLPFC.

Fish oil supplementation alters emotion-generated corticolimbic functional connectivity in depressed adolescents at high-risk for bipolar I disorder: A 12-week placebo-controlled fMRI trial.

OBJECTIVE: To evaluate the effects of fish oil (FO), a source of the omega-3 polyunsaturated fatty acids (n-3 PUFA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on emotion-generated corticolimbic functional connectivity in depressed youth at high risk for developing bipolar I disorder. METHODS: Thirty-nine antidepressant-free youth with a current depressive disorder diagnosis and a biological parent with bipolar I disorder were randomized to 12-week double-blind treatment with FO or placebo. At baseline and endpoint, fMRI (4 Tesla) scans were obtained while performing a continuous performance task with emotional and neutral distractors (CPT-END). Seed-to-voxel functional connectivity analyses were performed using bilateral orbitofrontal cortex (OFC) and amygdala (AMY) seeds. Measures of depression, mania, global symptom severity, and erythrocyte fatty acids were obtained. RESULTS: Erythrocyte EPA+DHA composition increased significantly in the FO group (+47%, p ≤ 0.0001) but not in the placebo group (-10%, p = 0.11). Significant group by time interactions were found for functional connectivity between the left OFC and the left superior temporal gyrus (STG) and between the right AMY and right inferior temporal gyrus (ITG). OFC-STG connectivity increased in the FO group (p = 0.0001) and decreased in the placebo group (p = 0.0019), and AMY-ITG connectivity decreased in the FO group (p = 0.0014) and increased in the placebo group (p < 0.0001). In the FO group, but not placebo group, the decrease in AMY-ITG functional connectivity correlated with decreases in Childhood Depression Rating Scale-Revised and Clinical Global Impression-Severity Scale scores. CONCLUSIONS: In depressed high-risk youth FO supplementation alters emotion-generated corticolimbic functional connectivity which correlates with changes in symptom severity ratings.

A Randomized, Double-Blind, Controlled Trial of Lithium Versus Quetiapine for the Treatment of Acute Mania in Youth with Early Course Bipolar Disorder.

Objective: To compare the efficacy and tolerability of lithium versus quetiapine for the treatment of manic or mixed episodes in youths with early course bipolar I disorder. Methods: Six-week, randomized, double-blind clinical trial of lithium versus quetiapine for the treatment of adolescents with acute manic/mixed episode. Target dose of quetiapine dose was adjusted to a target dose of 400-600 mg and target serum level for lithium was 1.0-1.2 mEq/L. Primary outcome measure was baseline-to-endpoint change in the Young Mania Rating Scale (YMRS). Secondary outcomes were treatment response (50% or more decrease from baseline in YMRS score) and remission (YMRS score ≤12, Children's Depression Rating Scale-Revised [CDRS-R] total score ≤28 and Clinical Global Impression Bipolar Severity Scale [CGI-BP-S] overall score of ≤3, respectively). Results: A total of 109 patients were randomized (quetiapine = 58 and lithium = 51). Participants in the quetiapine treatment group showed a significantly greater reduction in YMRS score than those in the lithium group (-11.0 vs. -13.2; p < 0.001; effect size 0.39). Response rate was 72% in the quetiapine group and 49% in the lithium group (p = 0.012); no differences in remission rates between groups were observed. Most frequent side effects for lithium were headaches (60.8%), nausea (39.2%), somnolence (27.5%), and tremor (27.5%); for quetiapine somnolence (63.8%), headaches (55.2%), tremor (36.2%), and dizziness (36.2%) were evidenced. Participants receiving quetiapine experienced more somnolence (p < 0.001), dizziness (p < 0.05), and weight gain (p < 0.05). Conclusions: Treatment with both lithium and quetiapine led to clinical improvement. Most study participants in this study experienced a clinical response; however, less than half of the participants in this study achieved symptomatic remission. The head-to-head comparison of both treatment groups showed quetiapine was associated with a statistically significant greater rate of response and overall symptom reduction compared with lithium. Trial registration: clinicaltrials.gov NCT00893581.

Propiedades Psicométricas del Cuestionario de Regulación Emocional (ERQ-CA) en Estudiantes Universitarios Colombianos / Psychometric properties of the Emotional Regulation Questionnaire (ERQ-CA) in Colombian University Students

El propósito de esta investigación fue analizar las propiedades psicométricas del cuestionario de regulación emocional (ERQ-CA) en población colombiana. Se utilizó una muestra de 798 estudiantes universitarios de Bogotá y sus alrededores, con edades entre 15 y 25 años (M = 19.59, DE = 1.78). La muestra se dividió en dos grupos proporcionales. La primera parte de la muestra estuvo conformada por el 25% (n = 200). Con ella se realizó el análisis factorial exploratorio, χ² (13) = 16.38, p < 0.23, encontrando una estructura bidimensional, de acuerdo con los índices de bondad de ajuste: TLI = .951, RMSEA = .057, SRMR = .04. Con la segunda submuestra (n = 598) se realizó el análisis factorial confirmatorio. Se encontraron excelentes índices de ajuste: S-Bχ² (20) = 45.812; χ²/gl = 2.29; CFI = .962; NNFI = .940; TLI = .947; IFI= .958; RMSEA = .051; SRMR = .048. Se obtuvieron las estimaciones y errores del modelo a través de métodos robustos, se realizó el análisis de consistencia interna, se estudió la invarianza del modelo por género y se hallaron las diferencias por género. Se puede concluir que el ERQ-CA es un cuestionario con propiedades psicométricas muy favorables para su uso en el contexto colombiano. (AU)

The purpose of this research was to analyze the psychometric properties of the emotional regulation questionnaire (ERQ-CA) in the Colombian population. A sample of 798university students from Bogotá and its surroundings, with ages between 15 and 25 years old (M = 19.59, SD = 1.78) was used. The sample was divided into two proportional groups. The first part of the sample was composed by 25% (n = 200), with it the exploratory factorial analysis was made, χ² (13) = 16.38, p < 0.23, finding a two-dimensional structure, according to the indexes of goodness of fit: TLI = .951, RMSEA = .057. SRMR = .04. Then with 70% of the sample (n = 598) the confirmatory factorial analysis was performed. Excellent fit rates were found: S-Bχ² (20) = 45,812; χ²/gl = 2.29; IFC = .962; NNFI = .940; TLI = .947; IFI= .958; RMSEA = .051; SRMR = .048. Estimates and errors of the model were obtained through robust methods, internal consistency analysis was performed, the invariance of the model by gender was studied and differences by gender were found. It can be concluded that the ERQ-CA is a questionnaire with psychometric properties that are very favorable to be used in the Colombian context. (AU)

Validation of the Multidimensional Inventory of Infidelity (IMIN) in Colombian Population.

Infidelity is a problem that entails psychological and physical consequences in humankind (Buss, 2016; González et al., 2009; Shackelford et al., 2003); thus, indicating the importance of measuring infidelity construct. The objective of the study was to determine the validity and reliability of the Multidimensional Infidelity Inventory (IMIN) for Colombian samples. For this, the instrument was applied to 674 Colombian participants, 224 men (33.28%) and 449 women (66.71%), with ages between 18 and 81 years (M = 25.11; SD = 10.56), carrying out exploratory factor analysis, confirmatory, and internal consistency for each subscale. In general, in the Motives to infidelity scale, three factors were found that explained 66.74% of the total accumulated variance; three factors were found in the Trend to Infidelity scale, explaining 65.02% of the total variance; in the sub-scale of Beliefs to infidelity, five factors were obtained, explaining 58.33% of the accumulated variance; and in the sub-scale of Consequences of infidelity, two clearly constituted factors were found, which explain 57.58% of the accumulated variance. All of them had confirmatory models with adequate levels of goodness of fit, adequate Cronbach alpha indicators, item-item, and item-test correlations, in addition to concordance with the original proposal of the instrument.

La infidelidad es un importante constructo a medir, al ser una problemática que conlleva consecuencias psicológicas y físicas (Buss, 2016; González et al., 2009; Shackelford et al., 2003). Se buscó determinar la validez y la confiabilidad del Inventario Multidimensional de Infidelidad (IMIN) para muestras colombianas. Se aplicó el instrumento a 674 participantes colombianos, 224 hombres (33.28%) y 449 mujeres (66.71%), con edades comprendidas entre los 18 y 81 años (M = 25.11; DE = 10.56), llevando a cabo análisis factoriales exploratorios, confirmatorios y de consistencia interna para cada subescala. En la escala de Tendencia a la infidelidad, se identificaron 3 factores que explicaron el 66.74% de la varianza total acumulada; en la escala de Motivos a la infidelidad, se hallaron siete factores, explicando el 65.02% de la varianza total; en la subescala de Creencias a la infidelidad, se obtuvieron cinco factores, explicando el 58.33% de la varianza acumulada; y en la subescala de Consecuencias de la infidelidad se hallaron dos factores claramente constituidos, que explican el 57.58% de la varianza acumulada. Todos los anteriores tenían modelos confirmatorios con adecuados niveles de bondad de ajuste y adecuados indicadores alfas de Cronbach, correlaciones ítem-ítem e ítem-prueba, además de concordancia con la propuesta original del instrumento.

Irritability, Anger, and Aggression in the Context of Pediatric Bipolar Disorder.

Irritability, anger, and aggression, although not specific for pediatric bipolar disorder (BD), can be a common finding and an important source of distress and impairment in these patients. Over the past 2 decades the diagnostic significance of irritability in pediatric BD has been highly debated. Beyond the debate of its diagnostic significance, the clinical importance of irritability, anger, and aggression in youth with BD has been well established. In this review, the authors discuss evaluation and management strategies of irritability, anger, and aggression in youth with BD.

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study

Objectives: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. Methods: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). Results: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. Conclusions: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

Medication exposure and predictors of first mood episode in offspring of parents with bipolar disorder: a prospective study.

OBJECTIVES: To prospectively investigate whether baseline clinical characteristics and medication exposure predict development of major depressive disorder or bipolar disorder in offspring of parents with bipolar disorder. METHODS: Youth aged 9-20 years with at least one biological parent with bipolar disorder and no prior history of mood or psychotic episodes (n=93) were prospectively evaluated and treated naturalistically during the study. Participants were divided into two groups: converters, defined as those who met DSM-IV criteria for a mood episode during follow-up (n=19); or non-converters (n=74). Logistic regression models were used to investigate associations between baseline clinical variables and medication exposure during follow-up and risk of developing a first mood episode (conversion). RESULTS: Multivariate regression analyses showed that baseline anxiety disorders and subsyndromal mood disorders were associated with increased risk of conversion during follow-up. Adding medication exposure to the multivariate model showed that exposure to antidepressants during follow-up was associated with increased risk of conversion. CONCLUSIONS: Caution should be used when treating bipolar offspring with anxiety and/or emerging depressive symptoms using antidepressant agents, given the increased risk of developing a major mood disorder.

Cariprazine in Youth with Bipolar and Psychotic Disorders: A Retrospective Chart Review.

Objective: To examine the potential effectiveness and tolerability of cariprazine in pediatric bipolar and psychotic disorders. Methods: We retrospectively reviewed the electronic health records of patients <21 years of age prescribed cariprazine to treat bipolar and psychotic disorders. Adverse effects, tolerability, therapeutic response (Clinical Global Impression-Improvement [CGI-I]), and severity of illness (Clinical Global Impression-Severity [CGI-S]) were determined through manual chart review. Results: We identified 16 patients aged 6-20 years who were treated with cariprazine (initial dose: 1.5 mg/day, interquartile range [IQR], 1.5-1.5; endpoint dose: 3 mg/day, IQR, 1.5-4.5). No serious adverse events were reported, but the most commonly reported side effect was weight gain (n = 3, 19%). Of the 14 patients for whom baseline and endpoint body mass index (BMI) data were available, neither changes in BMI (p = 0.391; 0.54 kg/m2, IQR, -0.33 to 1.38) nor BMI percentile (p = 0.71; 0.36%, IQR, -0.49 to 3.97) significantly differed between baseline and endpoint. However, patients receiving ≥4.5 mg/day had a significantly greater BMI increases during the course of treatment compared with those receiving ≤3 mg/day (p = 0.034; -1.14 kg/m2, IQR, -3.65 to 0.53 vs. 1.01 kg/m2, IQR, 0.17-4.88). CGI-S scores (p = 0.016; 4.5, IQR, 4-5 vs. 4, IQR, 3-4) significantly differed from baseline to endpoint. The response rate was 44% (n = 7/16), with responders being prescribed higher doses (p = 0.005; 6 mg/day, IQR, 4.875-6 vs. 3 mg/day, IQR, 3-4.125). Conclusions: Cariprazine may be well tolerated and effective for pediatric bipolar and psychotic disorders; however, compared with higher doses, total daily doses ≤3 mg/day appear to be more tolerable. Prospective controlled studies to further evaluate cariprazine in youth are needed.

Longitudinal proton spectroscopy study of the prefrontal cortex in youth at risk for bipolar disorder before and after their first mood episode.

OBJECTIVES: To investigate neurochemical abnormalities in the left and right ventrolateral prefrontal cortex (VLPFC) and anterior cingulate cortex (ACC) of youth at risk for bipolar disorder using proton magnetic resonance spectroscopy before and after their first mood episode. METHODS: Children and adolescents offspring of parents with bipolar I disorder (at-risk group, n = 117) and matched healthy controls (HC group, n = 61) were recruited at the University of Cincinnati. At-risk subjects had no lifetime major mood and psychotic disorders at baseline, and were followed up every 4 months to monitor for development of a major depressive, manic, hypomanic, or mixed mood episode. Levels of N-acetyl-aspartate (NAA), phosphocreatine plus creatine (PCr + Cr), choline-containing compounds, myo-inositol, and glutamate were determined using LCModel and corrected for partial volume effects. RESULTS: There were no baseline differences in metabolite levels for any of the brain regions between at-risk and HC youth. Nineteen at-risk subjects developed a first mood episode during follow-up. Survival analyses showed that baseline PCr + Cr levels in the left VLPFC significantly predicted a mood episode during follow-up in the at-risk group (HR: 0.47, 95% CI: 0.27-0.82, P = 0.008). There were no longitudinal changes in metabolites levels in the VLPFC and ACC before and after a mood episode in at-risk subjects. CONCLUSIONS: We found no evidence for abnormal proton spectroscopy metabolite levels in the VLPFC and ACC of at-risk youth, prior and after the development of their first mood episode. Preliminary findings of association between baseline PCr + Cr levels in the left VLPFC and risk to develop a mood episode warrant further investigation.