Computer-based approaches, such as Attention Bias Modification (ABM), could help improve access to care for anxiety. Study-level meta-analyses of ABM have produced conflicting findings and leave critical questions unresolved regarding ABM’s mechanisms of action and clinical potential. We pooled patient-level datasets from randomized controlled trials of children and adults with high-anxiety. Attentional bias (AB) towards threat, the target mechanism of ABM, was tested as an outcome and a mechanistic mediator and moderator of anxiety reduction. Diagnostic remission and Liebowitz Social Anxiety Scale (LSAS) were clinical outcomes available in enough studies to enable pooling. Per-patient data were obtained on at least one outcome from 13/16 eligible studies [86% of eligible participants; n=778]. Significant main effects of ABM on diagnostic remission (ABM—22.6%, control—10.8%; OR=2.57; p=.006) and AB (β*(95%CI)=−.63(−.83, −.42); p<.00005) were observed. There was no main effect of ABM on LSAS. However, moderator analyses suggested ABM was effective for patients who were younger (≤37y), trained in the lab, and/or assessed by clinicians. Under the same conditions where ABM was effective, mechanistic links between AB and anxiety reduction were supported. Under these specific circumstances, ABM reduces anxiety and acts through its target mechanism, supporting ABM’s theoretical basis while simultaneously suggesting clinical indications and refinements to improve its currently limited clinical potential.

This study aimed to identify neuroimaging measures associated with risk for, or protection against, bipolar disorder by comparing youth offspring of parents with bipolar disorder versus youth offspring of non-bipolar parents versus offspring of healthy parents in (i) the magnitude of activation within emotional face processing circuitry; and (ii) functional connectivity between this circuitry and frontal emotion regulation regions. The study was conducted at the University of Pittsburgh Medical Centre. Participants included 29 offspring of parents with bipolar disorder (mean age = 13.8 years; 14 females), 29 offspring of non-bipolar parents (mean age = 13.8 years; 12 females) and 23 healthy controls (mean age = 13.7 years; 11 females). Participants were scanned during implicit processing of emerging happy, sad, fearful and angry faces and shapes. The activation analyses revealed greater right amygdala activation to emotional faces versus shapes in offspring of parents with bipolar disorder and offspring of non-bipolar parents than healthy controls. Given that abnormally increased amygdala activation during emotion processing characterized offspring of both patient groups, and that abnormally increased amygdala activation has often been reported in individuals with already developed bipolar disorder and those with major depressive disorder, these neuroimaging findings may represent markers of increased risk for affective disorders in general. The analysis of psychophysiological interaction revealed that offspring of parents with bipolar disorder showed significantly more negative right amygdala-anterior cingulate cortex functional connectivity to emotional faces versus shapes, but significantly more positive right amygdala-left ventrolateral prefrontal cortex functional connectivity to happy faces (all P-values corrected for multiple tests) than offspring of non-bipolar parents and healthy controls. Taken together with findings of increased amygdala-ventrolateral prefrontal cortex functional connectivity, and decreased amygdala-anterior cingulate cortex functional connectivity previously shown in individuals with bipolar disorder, these connectivity patterns in offspring of parents with bipolar disorder may be risk markers for, rather than markers conferring protection against, bipolar disorder in youth. The patterns of activation and functional connectivity remained unchanged after removing medicated participants and those with current psychopathology from analyses. This is the first study to demonstrate that abnormal functional connectivity patterns within face emotion processing circuitry distinguish offspring of parents with bipolar disorder from those of non-bipolar parents and healthy controls.

High trait impulsive sensation seeking (ISS) is common in 18–25-year olds, and is associated with risky decision-making and deleterious outcomes. We examined relationships among: activity in reward regions previously associated with ISS during an ISS-relevant context, uncertain reward expectancy (RE), using fMRI; ISS impulsivity and sensation-seeking subcomponents; and risky decision-making in 100, transdiagnostically recruited 18–25-year olds. ISS, anhedonia, anxiety, depression and mania were measured using self-report scales; clinician-administered scales also assessed the latter four. A post-scan risky decision-making task measured ‘risky' (possible win/loss/mixed/neutral) fMRI-task versus ‘sure thing' stimuli. ‘Bias' reflected risky over safe choices. Uncertain RE-related activity in left ventrolateral prefrontal cortex and bilateral ventral striatum was positively associated with an ISS composite score, comprising impulsivity and sensation-seeking–fun-seeking subcomponents (ISSc; P⩽0.001). Bias positively associated with sensation seeking–experience seeking (ES; P=0.003). This relationship was moderated by ISSc (P=0.009): it was evident only in high ISSc individuals. Whole-brain analyses showed a positive relationship between: uncertain RE-related left ventrolateral prefrontal cortical activity and ISSc; uncertain RE-related visual attention and motor preparation neural network activity and ES; and uncertain RE-related dorsal anterior cingulate cortical activity and bias, specifically in high ISSc participants (all ps<0.05, peak-level, family-wise error corrected). We identify an indirect pathway linking greater levels of uncertain RE-related activity in reward, visual attention and motor networks with greater risky decision-making, via positive relationships with impulsivity, fun seeking and ES. These objective neural markers of high ISS can guide new treatment developments for young adults with high levels of this debilitating personality trait.

Background Offspring of parents with BD (BO) are at higher risk of bipolar disorder (BD) than offspring of parents with non-BD psychopathology (NBO), although both groups are at higher risk than offspring of psychiatrically healthy parents (HC) for other affective and psychiatric disorders. Abnormal functioning in reward circuitry has been demonstrated previously in individuals with BD. We aimed to determine whether activation and functional connectivity in this circuitry during risky decision-making differentiated BO, NBO and HC. Methods BO (n=29;mean age=13.8 years;14 female), NBO (n=28;mean age=13.9 years;12 female) and HC (n=23;mean age=13.7 years;11 female) were scanned while performing a number guessing reward task. 11 BO and 12 NBO had current non-BD psychopathology; 5 BO and 4 NBO were taking psychotropic medications. Results A 3(Group) x 2(Conditions:Win-Control/Loss-Control) ANOVA revealed a main effect of Group on right frontal pole activation: BO showed significantly greater activation than HC. There was a significant main effect of Group on functional connectivity between bilateral ventral striatum (VS) and right ventrolateral prefrontal cortex (Z>3.09, cluster-p<0.05): BO showed significantly greater negative functional connectivity than other participants. These between-group differences remained after removing youth with psychiatric disorders and psychotropic medications from analyses. Conclusions This is the first study to demonstrate that reward circuitry activation and functional connectivity distinguish BO from NBO and HC. The fact that the pattern of findings remained when comparing healthy BO vs. healthy NBO vs. HC suggests that these neuroimaging measures may represent trait-level neurobiological markers conferring either risk for, or protection against, BD in youth.

Objective Clinical anxiety is prevalent, highly comorbid with other conditions, and associated with significant medical morbidity, disability, and public health burden. Excessive attentional deployment towards threat is a transdiagnostic dimension of anxiety seen at both initial and sustained stages of threat processing. However, group-level observations of these phenomena mask considerable within-group heterogeneity that has been linked to treatment outcomes, suggesting that a transdiagnostic, individual differences approach may capture critical, clinically relevant information. Methods 70 clinically anxious individuals were randomized to receive 8 sessions of Attention Bias Modification (ABM; n=41 included in analysis), a computer-based mechanistic intervention that specifically targets initial stages of threat processing, or a sham control (n=21). Participants completed a mixed block/event-related fMRI task optimized to discriminate transient from sustained neural responses to threat. Results Larger transient responses across a wide range of cognitive-affective regions (e.g., ventrolateral prefrontal cortex, anterior cingulate cortex, amygdala) predicted better clinical outcomes following ABM, in both a priori anatomical regions and whole-brain analyses; sustained responses did not. A spatial pattern recognition algorithm using transient threat responses successfully discriminated the top quartile of ABM responders with 68% accuracy. Conclusions Neural alterations occurring on the relatively transient timescale that is specifically targeted by ABM predict favorable clinical outcomes. Results inform how to expand on the initial promise of neurocognitive treatments like ABM by fine-tuning their clinical indications (e.g., through personalized mechanistic intervention relevant across diagnoses) and by increasing the range of mechanisms that can be targeted (e.g., through synergistic treatment combinations and/or novel neurocognitive training protocols designed to tackle identified predictors of nonresponse).