A Randomized Comparison of Two Psychosocial Interventions on Family Functioning in Adolescents with Bipolar Disorder.

Impairments in family functioning are associated with more severe depressive and manic symptoms, earlier recurrences, and more suicidal behaviors in early-onset bipolar disorder. This study examined whether family-focused treatment for adolescents (FFT-A) with BD I or II disorder led to greater increases in family cohesion and adaptability and decreases in conflict over 2 years compared to a briefer psychoeducational treatment (enhanced care, EC). Participants were 144 adolescents (mean age: 15.6 ± 1.4 years) with BD I or II with a mood episode in the previous 3 months. Adolescents and parents were randomized to either FFT-A (21 sessions) or EC (three sessions). Patients received guideline-based pharmacotherapy throughout the 2-year study. Trajectories of adolescent- and parent-rated family cohesion, adaptability, and conflict were analyzed over 2 years. FFT-A had greater effects on adolescent-rated family cohesion compared to EC over 2 years. Participants in FFT-A and EC reported similar improvements in family conflict across the 2 years. In the FFT-A group, low-conflict families had greater adolescent-rated family cohesion throughout the study compared to high-conflict families. High-conflict families in both treatment groups tended to show larger reductions in conflict over 2 years than low-conflict families. Family psychoeducation and skills training may improve family cohesion in the early stages of BD. Measuring levels of family conflict at the start of treatment may inform treatment responsiveness among those receiving FFT-A.

Los problemas en el funcionamiento familiar están asociados con síntomas depresivos y maníacos más graves, recidivas en periodos más breves y más conductas suicidas en el trastorno bipolar de inicio precoz. Este estudio analizó si el "Tratamiento centrado en la familia para adolescentes" (Family-Focused Treatment for Adolescents, FFT-A) con trastorno bipolar tipo I y tipo II condujo a mayores aumentos en la cohesión familiar y en la adaptabilidad y a disminuciones en el conflicto durante dos años en comparación con un tratamiento psicoeducativo más breve (atención optimizada; Enhanced Care: EC). Los participantes fueron 144 adolescentes (edad promedio: 15.6±1.4 años) con trastorno bipolar tipo I o tipo II con un episodio de alteración del humor en los tres meses previos. Los adolescentes y los padres fueron asignados aleatoriamente al FFT-A (21 sesiones) o a la EC (3 sesiones). Los pacientes recibieron farmacoterapia pautada durante todo el estudio de dos años. Las trayectorias de la cohesión familiar evaluada por los adolescentes y los padres, la adaptabilidad y el conflicto se analizaron durante dos años. El FFT-A tuvo mayores efectos en la cohesión familiar evaluada por los adolescentes en comparación con la EC durante dos años. Los participantes del FFT-A y de la EC informaron mejoras similares en el conflicto familiar durante los dos años. Las familias con un alto nivel de conflicto en el FFT-A tuvieron una menor cohesión evaluada por los adolescentes y una menor adaptabilidad durante dos años en comparación con las familias con un bajo nivel de conflicto en el FFT-A. Las familias con un alto nivel de conflicto en ambos grupos de tratamiento tendieron a mostrar reducciones más grandes en el conflicto durante dos años que las familias con un bajo nivel de conflicto. La psicoeducación familiar y la capacitación en habilidades pueden mejorar la cohesión familiar en las etapas iniciales del trastorno bipolar. La medición de los niveles de conflicto familiar al comienzo del tratamiento puede respaldar la capacidad de respuesta al tratamiento entre aquellos que reciben el FFT-A.

The role of avoidance motivation in the relationship between reward sensitivity and depression symptoms in adolescents: An ERP study.

Blunted neural responses to reward in an EEG paradigm (RewP) are associated with vulnerability to depression, but the pathways linking this biomarker to depressive symptoms are unclear. We examined whether the relationship between reward response (RewP mean amplitude and latency) and depression was in part explained by approach-motivated behaviors in adolescents with varying levels of depression. EEG was collected during a game rigged to provide win/loss trials. Longer RewP latency was associated with depression symptoms only when scores on a measure of avoidance motivation were included. These results suggest that treatments targeting avoidance may decrease vulnerability to depressive episodes.

Is distress tolerance an approach behavior? An examination of frontal alpha asymmetry and distress tolerance in adolescents.

Frontal EEG asymmetry, relatively greater left-than-right frontal activity (rLFA), has been associated with mood symptoms and approach versus withdrawal behaviors. Distress tolerance (DT), a transdiagnostic behavior, has yet to be examined as an approach behavior using rLFA. Adolescents (N = 20; M age = 14.53, SD = 2.09) completed a frustrating mirror-tracing task which provided an index of DT. Higher resting rLFA was associated with lower DT. The results are the first to identify a relationship between cortical activation and distress tolerance in adolescents. rLFA appears to be a neurophysiological index of behaviors associated with approach motivation and escape from punishment or aversive situations.

Mood instability as a predictor of clinical and functional outcomes in adolescents with bipolar I and bipolar II disorder.

BACKGROUND: Traditional assessment and treatment of bipolar disorder (BD) often overlooks an important feature of the illness, mood instability (MI). MI - the presence of intense, rapidly shifting emotional states - is associated with a number of poor prognostic outcomes. This study examined whether MI among adolescents with BD was cross-sectionally related to bipolar subtype (I vs. II) and prognostically associated with symptoms and functioning over 3 months. METHODS: Participants included 145 adolescents (mean age: 15.6 years ±â€¯1.4) with BD I or II with a mood episode in the previous 3 months. Depression and (hypo)mania instability were computed using the root mean square successive difference (rMSSD) score, reflecting both the size and temporal order of changes in weekly depression and (hypo)mania scores (over 12 weeks) from the Adolescent Longitudinal Interval Follow-Up Evaluation. RESULTS: Greater depression instability was associated with BD II, whereas greater (hypo)mania instability was associated with BD I. Baseline MI, particularly depression, predicted more instability, a higher percentage of weeks in a clinical mood state, and poorer global functioning over 3 months, even when covarying concurrent mood severity scores. LIMITATIONS: The clinical measure of symptoms used retrospective reports of clinically significant symptoms only. We were unable to standardize medication use or adherence. CONCLUSIONS: MI differs by diagnostic subtype, is relatively stable over time, and predicts clinical and functional outcomes. Targeting MI should be considered a clinical focus to augment traditional methods of assessing and treating BD during adolescence to enhance clinical and functional outcomes.

Frontal alpha asymmetry predicts inhibitory processing in youth with attention deficit/hyperactivity disorder.

INTRODUCTION: Atypical asymmetry in brain activity has been implicated in the behavioral and attentional dysregulation observed in ADHD. Specifically, asymmetry in neural activity in the right versus left frontal regions has been linked to ADHD, as well as to symptoms often associated with ADHD such as heightened approach behaviors, impulsivity and difficulties with inhibition. Clarifying the role of frontal asymmetry in ADHD-like traits, such as disinhibition, may provide information on the neurophysiological processes underlying these behaviors. METHOD: ADHD youth (ADHD: n = 25) and healthy, typically developing controls (TD: n = 25) underwent an electroencephalography (EEG) recording while completing a go/no-go task-a commonly used test measuring behavioral inhibition. In addition, advanced signal processing for source localization estimated the location of signal generators underlying frontal alpha asymmetry (FA) during correct and incorrect trials. RESULTS: This is the first study in ADHD to demonstrate that the dorsal-lateral prefrontal cortex (DLPFC) may be responsible for generating frontal alpha. During failed inhibition trials, ADHD youth displayed greater FA than TD youth. In addition, within the ADHD group, frontal asymmetry during later processing stages (i.e., 400-800ms after stimulus) predicted a higher number of commission errors throughout the task. CONCLUSIONS: These results suggest that frontal alpha asymmetry may be a specific biomarker of cognitive disinhibition among youth with ADHD.

The effects of respiratory sinus arrhythmia on anger reactivity and persistence in major depression.

The experience of anger during a depressive episode has recently been identified as a poor prognostic indicator of illness course. Given the clinical implications of anger in major depressive disorder (MDD), understanding the mechanisms involved in anger reactivity and persistence is critical for improved intervention. Biological processes involved in emotion regulation during stress, such as respiratory sinus arrhythmia (RSA), may play a role in maintaining negative moods. Clinically depressed (MDD; n = 49) and nondepressed (non-MDD; n = 50) individuals were challenged with a stressful computer task shown to increase anger, while RSA (high frequency range 0.15-0.4 Hz) was collected. RSA predicted future anger, but was unrelated to current anger. That is, across participants, low baseline RSA predicted anger reactivity during the task, and in depressed individuals, those with low RSA during the task had a greater likelihood of anger persistence during a recovery period. These results suggest that low RSA may be a psychophysiological process involved in anger regulation in depression. Low RSA may contribute to sustained illness course by diminishing the repair of angry moods.

Inhibition of Attention for Affective Material: Contributions by HOMER1 Gene Variation.

Failure to inhibit attention to irrelevant affective information has been linked to depression and rumination. However, few studies have investigated the biological bases of this process. Variation in the HOMER1 gene was identified in a genome-wide association study as associated with major depressive disorder and is associated with executive functioning inefficiency. Several studies have linked variation in the BDNF gene with emotional and cognitive processes such as rumination. The current study examined the association between these two auspicious genetic variants and inhibition of attention for affective information. In Study 1, 60 psychiatrically healthy community participants completed a negative affective priming task with positive and negative words. HOMER1 variation, but not BDNF variation, was associated with difficulty inhibiting irrelevant negative information. These results were replicated in a second study utilizing a sample of 97 psychiatrically healthy young adults. Implications for the current literature and future directions are discussed.

Parental expressed emotion and suicidal ideation in adolescents with bipolar disorder.

Family environmental variables are risk factors for recurrent courses of mood disorder in adolescents. The present study examined the association between parental expressed emotion (EE)-critical, hostile and/or emotionally overinvolved attitudes toward a concurrently ill offspring-and suicidal ideation in adolescents with bipolar disorder. The sample consisted of 95 adolescents with a bipolar I or II diagnosis who had experienced a mood episode in the prior 3 months. Participants (mean age=15.54 years, S.D.=1.4) were interviewed and completed questionnaires regarding current and past suicidal ideation prior to their participation in a treatment trial. Parents completed five-minute speech samples from which levels of EE were assessed. High EE attitudes in parents were associated with current suicidal ideation in adolescents. This relationship was independent of the effects of age, gender, current depressive or manic symptoms, comorbid diagnoses, bipolar I/II subtypes, family adaptability, and family cohesion. These results underscore the importance of addressing the emotional reactivity of caregivers in treating adolescents with bipolar disorder who have suicidal ideation.

5-HTTLPR, HTR1A, and HTR2A cumulative genetic score interacts with mood reactivity to predict mood-congruent gaze bias.

Genetic variation within the serotonin system has been associated with biased attention for affective stimuli and, less consistently, with vulnerability for major depressive disorder. In particular, 5-HTTLPR, HTR1A (rs6295), and HTR2A (rs6311) polymorphisms have been linked with biased cognition. The present study developed a serotonergic cumulative genetic score (CGS) that quantified the number of risk alleles associated with these candidate polymorphisms to yield a single CGS. The CGS was then used to model genetic influence on the relationship between reactivity to a negative mood induction and negatively biased cognition. A passive-viewing eye-tracking task was administered to 170 healthy volunteers to assess sustained attention for positive, dysphoric, neutral, and threatening scenes. Participants were then induced into a sad mood and readministered the passive-viewing task. Change in gaze bias, as a function of reactivity to mood induction, was the primary measure of cognitive vulnerability. Results suggest that, although none of the individual genes interacted with mood reactivity to predict change in gaze bias, individuals with higher serotonin CGS were significantly more likely to look toward dysphoric images and away from positive images as mood reactivity increased. These findings suggest that a CGS approach may better capture genetic influences on cognitive vulnerability and reaffirm the need to examine multilocus approaches in genomic research.

Effect of antidepressant medication use on emotional information processing in major depression.

OBJECTIVE: Acute administration of antidepressant medication increases emotional information processing for positive information in both depressed and healthy persons. This effect is likely relevant to the therapeutic actions of these medications, but it has not been studied in patients with major depressive disorder taking antidepressants as typically prescribed in the community. METHOD: The authors used eye tracking to examine the effects of antidepressant medication on selective attention for emotional stimuli in a sample of 47 patients with major depressive disorder (21 medicated and 26 unmedicated) and 47 matched comparison subjects without depression. Participants completed a passive-viewing eye-tracking task assessing selective attention for positive, dysphoric, threatening, and neutral stimuli in addition to providing medication information and self-report measures of depression and anxiety severity. RESULTS: Depressed participants currently taking antidepressants and nondepressed comparison subjects demonstrated greater total gaze duration and more fixations for positive stimuli compared with unmedicated depressed participants. Depressed participants on medication also had fewer fixations for dysphoric stimuli compared with depressed participants not on medication. CONCLUSIONS: Antidepressants, as prescribed in the community to patients with depression, appear to modify emotional information processing in the absence of differences in depression severity. These results are consistent with previous work and indicate a robust effect for antidepressants on positive information processing. They also provide further evidence for modification of information processing as a potential mechanism of action for antidepressant medication.

The role of controlled attention on recall in major depression.

Information processing biases are hallmark features of major depressive disorder (MDD). Depressed individuals display biased memory and attention for negative material. Given that memory is highly dependent on attention for initial encoding, understanding the interplay of these processes may provide important insight into mechanisms that produce memory biases in depression. In particular, attentional control-the ability to selectively attend to task-relevant information by both inhibiting the processing of irrelevant information and disengaging attention from irrelevant material-may be one area of impairment in MDD. In the current study, clinically depressed (MDD: n = 15) and never depressed (non-MDD: n = 22) participants' line of visual gaze was assessed while participants viewed positive and negative word pairs. For each word pair, participants were instructed to attend to one word (target) and ignore one word (distracter). Free recall of study stimuli was then assessed. Depressed individuals displayed greater recall of negatively valenced target words following the task. Although there were no group differences in attentional control in the context of negative words, attention to negative targets mediated the relationship between depression status and recall of negative words. Results suggest a stronger link between attention and memory for negative material in MDD.

Attentional biases and the persistence of sad mood in major depressive disorder.

This study examined whether attentional biases for emotional information are associated with impaired mood recovery following a sad mood induction among individuals with and without major depressive disorder (MDD). Attentional biases were assessed with an exogenous cuing task using emotional facial expressions as cues among adults with (n = 48) and without (n = 224) current MDD. Mood reactivity and recovery were measured following a sad mood induction. Mood reactivity strongly predicted mood recovery; however, this relationship was moderated by attentional biases for negative emotional stimuli. Biases for sad and fear stimuli were associated with diminished mood recovery following mood induction across the sample. However, biases for sad stimuli were associated with significantly greater impairments in mood recovery among individuals with MDD than healthy controls. Furthermore, within the MDD group, impaired mood recovery was positively associated with depression severity. These results suggest that attentional biases maintain depression, in part, by facilitating the persistence of sad mood.

Serotonin transporter promoter region (5-HTTLPR) polymorphism predicts resting respiratory sinus arrhythmia.

Respiratory sinus arrhythmia (RSA) is often conceptualized as an index of physiological flexibility that has been related to emotion regulatory capacity. Although behavioral genetics research indicates that RSA is partly heritable, relatively few molecular genetics studies have been conducted. We examined whether the serotonin transporter promoter region (5-HTTLPR) polymorphism was associated with resting RSA among healthy young adults (N=71). Short 5-HTTLPR allele carriers had significantly lower resting RSA than long 5-HTTLPR homozygotes. Genotype explained 5% of the variance in resting RSA. Although firm conclusions depend on further study, the short allele of the 5-HTTLPR polymorphism may contribute to individual differences in RSA and its behavioral correlates.

Association of predeployment gaze bias for emotion stimuli with later symptoms of PTSD and depression in soldiers deployed in Iraq.

OBJECTIVE: Biased processing of emotion stimuli is thought to confer vulnerability to psychopathology, but few longitudinal studies of this link have been conducted. The authors examined the relationship between predeployment gaze bias for emotion stimuli and later symptoms of posttraumatic stress disorder (PTSD) and depression in soldiers deployed to Iraq. METHOD: An eye-tracking paradigm was used to assess line of gaze in 139 soldiers while they viewed a two-by-two matrix of fearful, sad, happy, and neutral facial expressions before they were deployed to Iraq. Once they were deployed, the soldiers periodically reported on their levels of war zone stress exposure and symptoms of PTSD and depression. RESULTS: War zone stress exposure predicted higher scores on PTSD and depression symptom measures; however, eye gaze bias moderated this relationship. In soldiers with war zone stress exposure, shorter mean fixation time when viewing fearful faces predicted higher PTSD symptom scores, and greater total fixation time and longer mean fixation time for sad faces predicted higher depressive symptom scores. CONCLUSIONS: Biased processing of emotion stimuli, as measured by gaze bias, appears to confer vulnerability to symptoms of PTSD and depression in soldiers who experience war zone stress.

Gaze behavior predicts memory bias for angry facial expressions in stable dysphoria.

Interpersonal theories suggest that depressed individuals are sensitive to signs of interpersonal rejection, such as angry facial expressions. The present study examined memory bias for happy, sad, angry, and neutral facial expressions in stably dysphoric and stably nondysphoric young adults. Participants' gaze behavior (i.e., fixation duration, number of fixations, and distance between fixations) while viewing these facial expressions was also assessed. Using signal detection analyses, the dysphoric group had better accuracy on a surprise recognition task for angry faces than the nondysphoric group. Further, mediation analyses indicated that greater breadth of attentional focus (i.e., distance between fixations) accounted for enhanced recall of angry faces among the dysphoric group. There were no differences between dysphoria groups in gaze behavior or memory for sad, happy, or neutral facial expressions. Findings from this study identify a specific cognitive mechanism (i.e., breadth of attentional focus) that accounts for biased recall of angry facial expressions in dysphoria. This work also highlights the potential for integrating cognitive and interpersonal theories of depression.

Serotonin transporter gene promoter region polymorphism and selective processing of emotional images.

Several studies have now documented that the serotonin transporter promoter region (5-HTTLPR) polymorphism predicts neural response to affective images in brain regions involved in the experience of emotion. However, the behavioral consequences of this genetic effect are less well known. The current study used eye-tracking methodology to examine how individuals genotyped for the 5-HTTLPR allocated their attention when simultaneously presented an array of positive and negative emotional scenes. Short 5-HTTLPR allele homozygotes displayed a bias to focus on positive images, particularly in the first half of the 30s trial. In contrast, long 5-HTTLPR allele homozygotes viewed the stimuli in a more evenhanded fashion. Thus, short 5-HTTLPR allele homozygotes may be attempting to regulate greater reactivity to negative stimuli by purposefully turning their attention towards positive stimuli. Although this sensitivity may have benefits under benign conditions, it may also increase vulnerability to affective disorders when cognitive resources needed to turn attention away from negative stimuli are compromised.

Association of the serotonin transporter gene promoter region (5-HTTLPR) polymorphism with biased attention for emotional stimuli.

A deletion polymorphism in the serotonin transporter-linked polymorphic region (5-HTTLPR) has been associated with vulnerability to affective disorders, yet the mechanism by which this gene confers vulnerability remains unclear. Two studies examined associations between the 5-HTTLPR polymorphism and attentional bias for emotional stimuli among nondepressed adults. Biased attention, attention engagement, and difficulty with attention disengagement were assessed with a spatial cuing task using emotional stimuli. Results from Study 1 (N = 38) indicated that short 5-HTTLPR allele carriers experienced greater difficulty disengaging their attention from sad and happy stimuli compared with long allele homozygotes. Study 2 participants (N = 144) were genotyped for the 5-HTTLPR polymorphism, including single nucleotide polymorphism rs25531 in the long allele of the 5-HTTLPR. Consistent with Study 1, individuals homozygous for the low-expressing 5-HTTLPR alleles (i.e., S and LG) experienced greater difficulty disengaging attention from sad, happy, and fear stimuli than high-expressing 5-HTTLPR homozygotes. Because this association exists in healthy adults, it may represent a susceptibility factor for affective disorders that becomes problematic during stressful life experiences.

Emotional dysregulation in dysphoria: support for Emotion Context Insensitivity in response to performance-based feedback.

The Emotion Context Insensitivity (ECI) hypothesis predicts that individuals experiencing a sad mood will show diminished reactivity to emotionally evocative stimuli and will not differentiate emotional responses across contexts. Previous work has primarily been limited to studying depressed individuals' emotional responses to film clips, images, and autobiographical memories. The current study builds upon this work by examining emotional reactivity of dysphoric (n=47) and non-dysphoric (n=54) individuals to positive and negative feedback about their performance on a task they were led to believe measured social intelligence. Overall, dysphoric individuals reported higher negative emotion and lower positive emotion than non-dysphoric individuals before, during, and after feedback. However, consistent with ECI, dysphoric individuals displayed attenuated emotional reactivity to negative feedback compared to controls. Further, dysphoric individuals' emotional response did not differ to positive and negative feedback, whereas the non-dysphoric group appropriately differentiated their emotional response across these contexts. Findings support the ECI hypothesis and broaden its scope to include emotional reactivity to self-relevant performance feedback.

Identification of emotionally ambiguous interpersonal stimuli among dysphoric and nondysphoric individuals.

This study examined whether dysphoria influences the identification of non-ambiguous and ambiguous facial expressions of emotion. Dysphoric and non-dysphoric college students viewed a series of human faces expressing sadness, happiness, anger, and fear that were morphed with each other to varying degrees. Dysphoric and non-dysphoric individuals identified prototypical emotional expressions similarly. However, when viewing ambiguous faces, dysphoric individuals were more likely to identify sadness when mixed with happiness than non-dysphoric individuals. A similar but less robust pattern was observed for facial expressions that combined fear and happiness. No group differences in emotion identification were observed for faces that combined sadness and anger or fear and anger. Dysphoria appears to enhance the identification of negative emotion in others when positive emotion is also present. This tendency may contribute to some of the interpersonal difficulties often experienced by dysphoric individuals.

Time course of selective attention in clinically depressed young adults: an eye tracking study.

Depressed individuals display biased attention for emotional information when stimuli are presented for relatively "long" (e.g., 1s) durations. The current study examined whether attentional biases are sustained over a much longer period. Specifically, clinically depressed and never depressed young adults simultaneously viewed images from four emotion categories (sad, threat, positive, neutral) for 30s while line of visual gaze was assessed. Depressed individuals spent significantly more time viewing dysphoric images and less time viewing positive images than their never depressed counterparts. Time course analyses indicated that these biases were maintained over the course of the trial. Results suggest that depressed participants' attentional biases for dysphoric information are sustained for relatively long periods even when other emotional stimuli are present. Mood congruent information-processing biases appear to be a robust feature of depression and may have an important role in the maintenance of the disorder.