Dana L. McMakin

Machine learning of neural representations of suicide and emotion concepts identifies suicidal youth

The clinical assessment of suicidal risk would be substantially complemented by a biologically based measure that assesses alterations in the neural representations of concepts related to death and life in people who engage in suicidal ideation. This study used machine-learning algorithms (Gaussian Naive Bayes) to identify such individuals (17 suicidal ideators versus 17 controls) with high (91%) accuracy, based on their altered functional magnetic resonance imaging neural signatures of death-related and life-related concepts. The most discriminating concepts were ‘death’, ‘cruelty’, ‘trouble’, ‘carefree’, ‘good’ and ‘praise’.xa0A similar classification accurately (94%) discriminated nine suicidal ideators who had made a suicide attempt from eight who had not. Moreover, a major facet of the concept alterations was the evoked emotion, whose neural signature served as an alternative basis for accurate (85%) group classification. This study establishes a biological, neurocognitive basis for altered concept representations in participants with suicidal ideation, which enables highly accurate group membership classification.Just et al. develop a highly accurate biological classification method for identifying suicidal ideators by applying machine learning to neural representations of death- and life-related concepts.

The impact of experimental sleep restriction on affective functioning in social and nonsocial contexts among adolescents

BACKGROUNDnShort sleep duration is highly prevalent in adolescence, and it prospectively predicts problems with emotional adjustment and psychiatric health. To move beyond epidemiological associations and inform models of developmental psychopathology, we experimentally restricted sleep to observe impacts on affective functioning. Based on the importance of social contexts to adolescent emotional experiences, we also examined the impact of restricted sleep on socioaffective functioning in an ecologically valid peer interaction task.nnnMETHODSnIn Study 1, adolescents (ages 11.5-15.0, nxa0=xa048) were randomly assigned to two nights of polysomnography-monitored sleep restriction (4xa0hr in bed) or extension (10xa0hr in bed). One week later, they completed the other sleep manipulation. Affective functioning was assessed by self-report and pupil response to standardized affective sounds. Study 2 used a similar protocol and invited adolescents (ages 12-15.0, nxa0=xa016) to the sleep laboratory along with 2-4 friends to observe affective behavior in a social context primed for peer conflict. Mixed effects models were used to evaluate the effect of sleep condition on affective outcomes.nnnRESULTSnStudy 1 demonstrated increased negative affect following sleep restriction, relative to extension, on self-report (pxa0=xa0.02) and pupil measures (pxa0=xa0.01). Study 2 replicated these effects (both pxa0=xa0.04) and demonstrated greater negative affective behavior in a peer social context (pxa0=xa0.01). Exploratory analyses for positive affect showed reductions as assessed by self-report (pxa0=xa0.005), but not pupil (pxa0=xa0.81), in Study 1; and no significant effects in Study 2 (self-report, pxa0=xa0.14; pupil, pxa0=xa0.29; positive affective behavior, pxa0=xa0.43).nnnCONCLUSIONSnExperimental sleep restriction in adolescence impacts negative affective functioning as evidenced by self-report and pupil reactivity, as well as observed behavior in a social context primed for peer conflict. Implications for the impact of short sleep on developmental trajectories of emotional adjustment and psychiatric health, and opportunities for early intervention, are briefly discussed.

The SENSE Study: Treatment Mechanisms of a Cognitive Behavioral and Mindfulness-Based Group Sleep Improvement Intervention for At-Risk Adolescents

ObjectivesnThe aim of this study was to test whether a cognitive behavioral and mindfulness-based group sleep intervention would improve sleep and anxiety on school nights in a sample of at-risk adolescents. We also examined whether benefits to sleep and anxiety would be mediated by improvements in sleep hygiene awareness and presleep hyperarousal.nnnMethodsnSecondary analysis of a randomized controlled trial conducted with 123 adolescent participants (female = 60%; mean age = 14.48) who had high levels of sleep problems and anxiety symptoms. Participants were randomized into a sleep improvement intervention (n = 63) or active control study skills intervention (n = 60). Preintervention and postintervention, participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Childrens Anxiety Scale (SCAS), Sleep Beliefs Scale (SBS), and Presleep Hyperarousal Scale (PSAS) and wore an actiwatch and completed a sleep diary for five school nights.nnnResultsnThe sleep intervention condition was associated with significantly greater improvements in actigraphy-measured sleep onset latency (SOLobj), sleep diary measured sleep efficiency (SEsubj), PSQI, SCAS, SBS, and PSAS, with medium to large effect sizes. Improvements in the PSQI and SCAS were specifically mediated by the measured improvements in the PSAS that resulted from the intervention. Improvements in SOLobj and SEsubj were not specifically related to improvements in any of the putative treatment mechanisms.nnnConclusionsnThis study provides evidence that presleep arousal but not sleep hygiene awareness is important for adolescents perceived sleep quality and could be a target for new treatments of adolescent sleep problems.

Targeted Reactivation during Sleep Differentially Affects Negative Memories in Socially Anxious and Healthy Children and Adolescents

Cognitive models propose a negative memory bias as one key factor contributing to the emergence and maintenance of social anxiety disorder (SAD). The long-term consolidation of memories relies on memory reactivations during sleep. We investigated in SAD patients and healthy controls the role of memory reactivations during sleep in the long-term consolidation of positive and negative information. Socially anxious and healthy children and adolescents learnt associations between pictures showing ambiguous situations and positive or negative words defining the situations outcome. Half of the words were re-presented during postlearning sleep (i.e., they were cued). Recall of picture–word associations and subjective ratings of pleasantness and arousal in response to the pictures was tested for cued and uncued stimuli. In the morning after cueing, cueing facilitated retention of positive and negative memories equally well in SAD patients and healthy controls. One week later, cueing led to reduced ratings of pleasantness of negative information in SAD but not in healthy controls. Coincidental to these findings was more pronounced EEG theta activity over frontal, temporal and parietal regions in response to negative stimuli in SAD patients. Our findings suggest that the preferential abstraction of negative emotional information during sleep might represent one factor underlying the negative memory bias in SAD. SIGNIFICANCE STATEMENT We aim to uncover mechanisms underlying the characteristic negative memory bias in social anxiety disorder (SAD). The formation of long-lasting memories—a process referred to as memory consolidation—depends on the reactivation of newly acquired memories during sleep. We demonstrated that experimentally induced memory reactivation during sleep renders long-term memories of negative experiences more negative in SAD patients but not in healthy controls. We also found in SAD patients that the reactivation of negative experiences coincided with more pronounced oscillatory theta activity. These results provide first evidence that memory reactivation during sleep might contribute to the negative memory bias in SAD.

The role of day-to-day emotions, sleep, and social interactions in pediatric anxiety treatment

Do day-to-day emotions, social interactions, and sleep play a role in determining which anxious youth respond to supportive child-centered therapy (CCT) versus cognitive behavioral therapy (CBT)? We explored whether measures of day-to-day functioning (captured through ecological momentary assessment, sleep diary, and actigraphy), along with clinical and demographic measures, were predictors or moderators of treatment outcome in 114 anxious youth randomized to CCT or CBT. We statistically combined individual moderators into a single, optimal composite moderator to characterize subgroups for which CCT or CBT may be preferable. The strongest predictors of better outcome included: (a) experiencing higher positive affect when with ones mother and (b) fewer self-reported problems with sleep duration. The composite moderator indicated that youth for whom CBT was indicated had: (a) more day-to-day sleep problems related to sleep quality, efficiency, and waking, (b) day-to-day negative events related to interpersonal concerns, (c) more DSM-IV anxiety diagnoses, and (d) college-educated parents. These findings illustrate the value of both day-to-day functioning characteristics and more traditional sociodemographic and clinical characteristics in identifying optimal anxiety treatment assignment. Future studies will need to enhance the practicality of real-time measures for use in clinical decision making and evaluate additional anxiety treatments.

Altered Positive Affect in Clinically Anxious Youth: the Role of Social Context and Anxiety Subtype

Anxious youth may experience altered positive affect (PA) relative to healthy youth, perhaps because of greater sensitivity to social experiences. Altered PA may be especially evident during the transition to adolescence, a period in which positive social events increase in salience and value. The current study evaluated whether anxious youth show differences in baseline PA, rate of return to baseline, and variability around baseline PA and tested whether these differences would depend on social context and anxiety subtype. Participants were 176 9- to 14-year-old youth, including 130 clinically anxious (with Social Anxiety Disorder, Generalized Anxiety Disorder, and/or Separation Anxiety Disorder) and 46 healthy youth. Youth reported their current PA, peak PA in the past hour, and social context in natural settings using ecological momentary assessment. Hierarchical linear models showed that both socially anxious and other anxious youth showed greater variability of PA relative to healthy youth. Youth with other anxiety disorders showed higher peak PA to a positive event relative to healthy youth. Feeling close to a friend was associated with higher peak PA, especially for socially anxious youth. Socially anxious youth showed significantly lower peak PA relative to both healthy and other anxious youth when interacting with a less close peer, but similar levels to these youth when interacting with a close friend. These findings suggest that clinically anxious youth may more sensitive to positive events and social interactions than healthy youth. Findings provide potential treatment targets for anxious youth, including applying regulatory strategies to positive events.

Who benefits from adolescent sleep interventions? Moderators of treatment efficacy in a randomized controlled trial of a cognitive-behavioral and mindfulness-based group sleep intervention for at-risk adolescents

BACKGROUNDnThe aim of this study was to test moderators of therapeutic improvement in an adolescent cognitive-behavioral and mindfulness-based group sleep intervention. Specifically, we examined whether the effects of the program on postintervention sleep outcomes were dependent on participant gender and/or measures of sleep duration, anxiety, depression, and self-efficacy prior to the interventions.nnnMETHODnSecondary analysis of a randomized controlled trial conducted with 123 adolescent participants (femalexa0=xa059.34%; mean agexa0=xa014.48xa0years, range 12.04-16.31xa0years) who had elevated levels of sleep problems and anxiety symptoms. Participants were randomized into either a group sleep improvement intervention (nxa0=xa063) or group active control study skills intervention (nxa0=xa060). The sleep intervention (Sleep SENSE) was cognitive behavioral in approach, incorporating sleep education, sleep hygiene, stimulus control, and cognitive restructuring, but also had added anxiety-reducing, mindfulness, and motivational interviewing elements. Components of the active control intervention (Study SENSE) included personal organization, persuasive writing, critical reading, referencing, memorization, and note taking. Participants completed the Pittsburgh Sleep Quality Index (PSQI), Spence Childrens Anxiety Scale (SCAS), Center for Epidemiologic Studies Depression Scale (CES-D), and General Self-Efficacy Scale (GSE) and wore an actigraph and completed a sleep diary for five school nights prior to the interventions. Sleep assessments were repeated at postintervention. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12612001177842; http://www.anzctr.org.au/TrialSearch.aspx?searchTxt=ACTRN12612001177842&isBasic=True).nnnRESULTSnThe results showed that compared with the active control intervention, the effect of the sleep intervention on self-reported sleep quality (PSQI global score) at postintervention was statistically significant among adolescents with relatively moderate to high SCAS, CES-D, and GSE prior to the intervention, but not among adolescents with relatively low SCAS, CES-D, and GSE prior to the intervention. The results were consistent across genders. However, the effects of the sleep intervention on actigraphy-measured sleep onset latency and sleep diary-measured sleep efficiency at postintervention were not dependent on actigraphy-measured total sleep time, SCAS, CES-D, or GSE prior to the intervention.nnnCONCLUSIONSnThis study provides evidence that some sleep benefits of adolescent cognitive-behavioral sleep interventions are greatest among those with higher levels of anxiety and depressive symptoms, suggesting that this may be an especially propitious group to whom intervention efforts could be targeted. Furthermore, adolescents with lower levels of self-efficacy may need further targeted support (e.g. additional motivational interviewing) to help them reach treatment goals.

Reply to ‘Neural signatures to emotion-related word stimuli may vary’

Just et al. reply — Dawson and Guberman’s1 thoughtful comments raise interesting issues. We concur with two of their prescriptive suggestions, namely that our study should be extended to a larger sample and that it should include other psychiatric groups. A larger study that includes these two goals is now underway. However, their speculation concerning the reason for inaccurate classification of concepts in the initially excluded participants (both controls and suicidal ideators) is incorrect. They “question whether the inaccurate concept identification is indeed inaccurate or simply different for those [excluded] subjects.” The accuracy measure utilized only the participant’s own data, a measure completely indifferent to the similarity of the participant’s neural representations to other participants’ representations. By contrast, as we suggested, the ability to attend to the task, thinking consistently about a concept as it was presented on six different occasions, affects this accuracy. We also disagree that the classifier was arrived at by trial and error. The choices of stimuli (generalized from Cha et al.2), the Gaussian Naïve Bayes classifier and analysis parameters (adopted from previous studies) were all specified a priori. However, the determination of the most discriminating word concepts was made a posteriori, as described. Dawson and Guberman1 question the assumption that there is considerable commonality in the neural representations of concepts across people. But several previous studies have found that a classifier trained on the data of a set of neurotypical participants can classify the concepts of a participant on which it has not been trained, and withinand between-subject accuracies are typically comparable. This finding applies to different types of concepts, such as concrete objects3, abstract physics concepts4, numbers5, social interactions6 and concepts in a sentence7. Furthermore, the commonality occurs across monolingual members of different language groups/ cultures (English, Portuguese and Mandarin)8, which speaks to the issue of cultural diversity. The commonality also occurs across participants experiencing various emotions9. A commonality of neural representations of social interactions was also found among participants with autism spectrum disorder (ASD)6, despite these representations being reliably discriminable between an ASD group and a control group. In summary, there is a considerable amount of evidence indicating commonality of neural representations among neurotypical participants, among participants with ASD and among those with suicidal ideation, as well as a difference between neurotypical and psychiatric samples for concepts related to the psychiatric disorder. Of course there is some likelihood that the neural representation of a concept such as ‘death’ (including the emotion component) differs across cultures, and perhaps across age and socio-economic groups. In fact, we demonstrated one aspect of diversity measurable by our methods by reporting detectable neurosemantic differences between ideators who had made an attempt and those who had not. Another type of variation we reported demonstrated a correlation between degree of suicidal ideation (Adult Suicidal Ideation Questionnaire) and the degree of alteration of the neurosemantic signatures. The variation of neural representations in suicidal ideation is an interesting issue for further study, and we are optimistic that our methods will be useful in assessing variation and providing diagnostic, therapeutic and biological insights into numerous psychiatric disorders. ❐

Error-related brain activity in pediatric anxiety disorders remains elevated following individual therapy: A randomized clinical trial

BACKGROUNDnAnxiety disorders are associated with an overactive action monitoring system as indexed by a larger error-related negativity (ERN). This study tests whether ERN magnitude changes following treatment, predicts response to treatment, and varies by treatment type.nnnMETHODSnThe sample included 130 youth (9-14xa0years): youth with an anxiety disorder (ANX; nxa0=xa0100) and healthy control (HC; nxa0=xa030) youth with no lifetime DSM-IV disorders. ANX youth were randomized to either a manualized cognitive-behavior therapy (CBT) or a comparison child-centered therapy (CCT). The ERN was assessed before and after 16 sessions of treatment and within a comparable interval for HC. Subjective ratings about making errors on the task were obtained following each testing session. The ClinicalTrials.gov identifier is NCT00774150.nnnRESULTSnThe ERN was larger in ANX than HC youth but ERN magnitude did not significantly change following treatment in the ANX youth, regardless of treatment type, and baseline ERN did not predict treatment response. Post-task ratings revealed that ANX youth worried more about task performance feedback than HC. Like the ERN, mean ratings did not significantly change following treatment. However, these ratings were not correlated with ERN amplitude.nnnCONCLUSIONSnFindings of greater ERN in pediatric anxiety disorders are replicated in a larger sample. More importantly, findings from this randomized control trial show that a larger ERN and feeling worried about performance feedback remain unchanged following treatment and are unrelated to treatment response. Such findings suggest that action monitoring systems remain overactive in anxious youth treated with psychotherapy, suggesting the need for future investigation of whether novel complimentary cognitive and emotional training programs can modify these systems would be warranted.

The Link Between Anxiety Severity and Irritability Among Anxious Youth: Evaluating the Mediating Role of Sleep Problems

Although recent studies have linked pediatric anxiety to irritability, research has yet to examine the mechanisms through which youth anxiety may be associated with irritability. Importantly, sleep related problems (SRPs) have been associated with both child anxiety and irritability, but research has not considered whether the link between youth anxiety and irritability may be accounted for by SRPs. The present study investigated whether SRPs mediated the relationship between anxiety severity and irritability in a large sample of treatment-seeking anxious youth (Nu2009=u2009435; ages 7–19 years, Mu2009=u200912.7; 55.1% female). Anxiety severity, SRPs and irritability showed significant pairwise associations, and the indirect effect of youth anxiety severity on irritability, via SRPs, was positive and significant. The present analysis is the first to examine youth anxiety, irritability, and SPRs in a single model in a sample of anxious youth, and provides preliminary evidence that SRPs partially mediate links between child anxiety and irritability.