Trying to name what doesn't change: Neural nonresponse to Cognitive Therapy for depression.

BACKGROUND: Theoretical models of neural mechanisms underlying Cognitive Behavior Therapy (CBT) for major depressive disorder (MDD) propose that psychotherapy changes neural functioning of prefrontal cortical structures associated with cognitive-control processes (DeRubeis, Siegle, & Hollon, ); however, MDD is persistent and characterized by long-lasting vulnerabilities to recurrence after intervention, suggesting that underlying neural mechanisms of MDD remain despite treatment. It follows that identification of treatment-resistant aberrant neural processes in MDD may inform clinical and research efforts targeting sustained remission. Thus, we sought to identify brain regions showing aberrant neural functioning in MDD that either (1) fail to exhibit substantive change (nonresponse) or (2) exhibit functional changes (response) following CBT. METHODS: To identify treatment-resistant neural processes (as well as neural processes exhibiting change after treatment), we collected functional magnetic resonance imaging (fMRI) data of MDD patients (n = 58) before and after CBT as well as never-depressed controls (n = 35) before and after a similar amount of time. We evaluated fMRI data using conjunction analyses, which utilized several contrast-based criteria to characterize brain regions showing both differences between patients and controls at baseline and nonresponse or response to CBT. RESULTS: Findings revealed nonresponse in a cerebellar region and response in prefrontal and parietal regions. CONCLUSIONS: Results are consistent with prior theoretical models of CBT's direct effect on cortical regulatory processes but expand on them with identification of additional regions (and associated neural systems) of response and nonresponse to CBT.

Cingulate prediction of response to antidepressant and cognitive behavioral therapies for depression: Meta-analysis and empirical application.

We sought to identify baseline (pre-treatment) neural markers associated with treatment response in major depressive disorder (MDD), specific to treatment type, Cognitive Behavioral Therapy (CBT) or pharmacotherapy (selective serotonin reuptake inhibitors; SSRI). We conducted a meta-analysis of functional magnetic resonance imaging (fMRI) studies to identify neural prognostic indicators of response to CBT or SSRI. To verify the regions derived from literature, the meta-analytic regions were used to predict clinical change in a verification sample of participants with MDD who received either CBT (n = 60) or an SSRI (n = 19) as part of prior clinical trials. The meta-analysis consisted of 21 fMRI studies that used emotion-related tasks. It yielded prognostic regions of the perigenual (meta pgACC) and subgenual anterior cingulate cortex (meta sgACC), associated with SSRI and CBT response, respectively. When applying the meta-analytic regions to predict treatment response in the verification sample, reactivity of the meta pgACC was prognostic for SSRI response, yet the effect direction was opposite of most prior studies. Meta sgACC reactivity failed to be prognostic for CBT response. Results confirm the prognostic potential of neural reactivity of ACC subregions in MDD but further research is necessary for clinical translation.

What does "staying well" after depression mean? Chronic low grade symptomatology after treatment for depression is common.

BACKGROUND: Persistent low grade depression symptoms are common and impairing in major depressive disorder (MDD) yet rarely reported in treatment follow-up studies (Judd et al., 1998a; Kennedy et al., 2004), suggesting that extant sustained remission rates may not reflect this important clinical feature. Furthermore, no long-term MDD treatment follow-up study has reported on quality of life ratings across functioning levels and years throughout the follow-up period, thus the severity, breadth, and persistence of functional impairment remain unclear. Accordingly, the current study evaluated the course of MDD with consideration of low grade depressive symptomatology and holistic features (e.g., quality of life). METHODS: We report long-term (9-14 years) follow-up data from individuals with MDD (N = 37) who underwent either Cognitive Therapy (CBT) or a course of selective serotonin reuptake inhibitor (SSRI) treatment. Patients provided retrospective reports of depression symptoms and quality of life in the years following treatment. RESULTS: Chronic depression symptoms (most often mild in severity) and decreased quality of life in multiple domains are frequent and suggest poorer sustained remission rates than previously observed in the literature. LIMITATIONS: Study limitations include small sample size recruited via convenience sampling methods. CONCLUSIONS: Findings support a conceptualization of depression recovery that entails persistent symptoms and vulnerabilities. Clinical recommendations are provided for discussing these features of depression recovery with patients.

Mindfulness-Based Interventions for Adolescent Social Anxiety: A Unique Convergence of Factors.

Social anxiety disorder (SAD) is a debilitating and often chronic psychiatric disorder that typically onsets during early adolescence. Cognitive behavior therapy (CBT), the current "gold-standard" treatment for SAD, tends to focus on threat- and fear-based systems hypothesized to maintain the disorder. Despite this targeted approach, SAD ranks among the least responsive anxiety disorders to CBT in adolescent samples, with a considerable proportion of individuals still reporting clinically significant symptoms following treatment, suggesting that the CBT-family of interventions may not fully target precipitating or maintaining factors of the disorder. This gap in efficacy highlights the need to consider new therapeutic modalities. Accordingly, this brief review critically evaluates the emergent literature supporting the use of mindfulness-based interventions (MBIs) for treating adolescent SAD. MBIs may be particularly relevant for addressing maintaining factors within this diagnosis, as they may target and interrupt cycles of avoidance and de-motivation. Despite limitations in the relative lack of randomized controlled trials (RCTs) on this topic, a unique convergence of factors emerge from the extant literature that support the notion that MBIs may hold particular promise for attenuating symptoms of SAD in adolescents. These factors include: (1) MBIs demonstrate the ability to directly engage symptoms of SAD; (2) MBIs also show consistent reduction of anxiety, including symptoms of social anxiety in adolescent populations; and (3) MBIs demonstrate high rates of feasibility and acceptability in anxious adolescent samples. We briefly review each topic and conclude that MBIs are an encouraging treatment approach for reducing symptoms of social anxiety in adolescents. However, given the lack of research within MBIs for adolescent SAD in particular, more research is needed to determine if MBIs are more advantageous than other current treatment approaches.

Maternal Affect During a Challenging Mother-Child Interaction: The Effects of Broad Autism Phenotype and Respiratory Sinus Arrhythmia Reactivity in Mothers of Children With and Without Autism Spectrum Disorder.

Respiratory sinus arrhythmia (RSA) is proposed to index cognitive and behavioral inflexibility. Broad autism phenotype (BAP) traits are prevalent in family members of children with autism spectrum disorder (ASD). The study investigated whether RSA and BAP traits in mothers of typically developing (TD) children and mothers of children with ASD influence maternal affect. It was hypothesized that these factors would interact to influence mother-child interactions. Twenty-three mother-child dyads participated in a challenging interaction while measuring mother's RSA. Results indicated that mothers of children with ASD show different RSA reactivity than mothers of TD children. Furthermore, preliminary analyses revealed RSA reactivity moderated the relationship between mothers' rigidity and maternal affect during this interaction. Implications for future research and interventions are discussed.

Sensitivity shift theory: A developmental model of positive affect and motivational deficits in social anxiety disorder.

Social anxiety disorder (SAD) is a common and impairing condition that emerges in early adolescence, confers significant interpersonal disability and often persists into adulthood. Prevailing interventions for socially anxious youth are largely based on cognitive-behavioral models originally developed in adult samples, but produce only modest rates of remission in adolescents. The purposes of this review are to examine plausible explanations for these modest rates of treatment response and to critically evaluate the relevance of developmental mechanisms related to reward circuitry function. In doing so, we propose Sensitivity Shift Theory (SST), an integrated theoretical model addressing the development of social anhedonia in a meaningful subset of adolescents and adults with SAD. The central prediction of SST involves a shift, or developmental transition from social sensitivity during the late childhood/early adolescent period into later-emerging social anhedonia that includes reductions in positive affect, infrequent social approach behaviors and social skills deficits. We further provide a complementary mechanistic account by which these newly identified processes may be addressed using available evidence-based treatments that influence positive affect, including mindfulness-based interventions (MBIs). Collectively, SST provides a mechanisms-focused framework for explaining relatively modest rates of response to current front-line treatments in socially anxious youth, as well as discrepant observations in SAD samples of both high- and low- levels of social motivation depending on developmental factors and learning history.

Attention Bias Modification Treatment for Adolescents With Social Anxiety Disorder.

Social anxiety disorder (SAD) tends to emerge during the early teenage years and is particularly refractory to change even when standard evidence-based CBT treatments are delivered. Efforts have been made to develop novel, mechanistic-driven interventions for this disorder. In the present study, we examined Attention Bias Modification Treatment (ABMT) for youth with SAD. Participants were 58 adolescents (mean age = 14.29 years) who met diagnostic criteria for SAD and who were randomized to ABMT or a placebo control condition, Attention Control Training (ACT). We predicted that ABMT would result in greater changes in both threat biases and social anxiety symptoms. We also explored potential moderators of change including the severity of social anxiety symptoms, the level of threat bias at pretreatment, and the degree of temperament-defined attention control. Contrary to our hypotheses, changes in attention bias were not observed in either condition, changes in social anxiety symptoms and diagnosis were small, and significant differences were not observed between the ABMT and ACT conditions. Little support for the proposed moderators was obtained. Reasons for our failure to find support for ABMT and its potential moderators are explored and recommendations for changes in the ABMT paradigm are suggested.

How Do Graduate Teaching Assistants Perceive and Understand Their Autistic College Students?

Background: As autistic college students increase in number, it is important to identify how to best support them. Beyond the increased academic demands of higher education, many autistic young adults struggle with social interactions, time management, emotion regulation, and routine changes. Having an accurate understanding of Graduate Teaching Assistants' (GTAs') knowledge of neurodiverse learners could inform improvements to GTA training programs. Methods: We explored GTAs' understanding of autism spectrum disorder (ASD) and any related pedagogical training. We used the Autism Awareness Survey by Tipton and Belcher and several supplemental questions to assess 92 GTAs' knowledge of ASD (65% female [n = 59], mean age = 27 years [standard deviation, SD = 4 years], 69% Caucasian [n = 62]). Results: Most GTAs (n = 76; 83%) had heard of ASD, primarily from a family member (n = 51; 66%). Out of 14 questions, 61% (n = 56) of GTAs answered at least 10 accurately. Eight questions were answered correctly by more than 75% of respondents, indicating some understanding of ASD, although room for improvement remained. GTAs with an autistic family member were not more knowledgeable about ASD, nor did they report feeling better-equipped to support autistic students. The majority of GTAs (n = 89; 97%) had not received any ASD-specific pedagogical training and only 15% of GTAs felt well-equipped to teach autistic students. Conclusions: While most GTAs answered basic knowledge questions about ASD correctly, they did not feel prepared to support autistic students. Increased understanding of neurodiverse learners could help GTAs foster a more supporting and inclusive environment and improve academic and social outcomes for autistic students. Further research is needed on what specific supports autistic learners need in the college classroom, how to train GTAs on how to provide these supports, and how to measure the effectiveness of such interventions.

Gender differences in restricted and repetitive behaviors and interests in youth with autism.

Previous work has found gender differences in restricted and repetitive behaviors and interests (RRBI) for autism spectrum disorder (ASD). Compared to girls, affected boys have increased stereotyped and restricted behaviors; however much less is known about gender differences in other areas of RRBI. This study aims to identify whether specific RRBI (i.e., stereotyped, self-injurious, compulsive, insistence on sameness, ritualistic, and restricted), as measured by item-level data on the Repetitive Behavior Scale-Revised (RBS-R), can distinguish girls from boys with ASD. Participants included 615 individuals with ASD (507 boys; 82.4%), ages 3-18 years of age (M = 10.26, SD = 4.20), who agreed to share data with the National Database for Autism Research (NDAR). Multivariate analysis of variance and discriminant function analysis (DFA) were used to determine whether item-level RBS-R data could correctly classify cases by gender. DFA results suggest that RBS-R items significantly differentiate gender. Strongly differentiating RBS-R items had greater success in correctly classifying affected boys (67.90%) than girls (61.00%). Items that best-discriminated gender were heightened stereotyped behaviors and restricted interests items in boys and compulsive, sameness, restricted, and self-injurious behavior items in girls. This study is the first to find that girls with ASD may have increased compulsive, sameness, and restricted RRBI compared to boys. Additionally, findings support heightened self-injurious behaviors in affected girls. Future research should disentangle whether elevated rates of RRBI in girls are central to the presentation of ASD in girls or an epiphenomenon of the high rates of co-occurring disorders (e.g., anxiety) noted in girls. Autism Res 2019, 12: 274-283 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study is the first to examine a comprehensive measure of repetitive behavior in children with autism, with findings of increased compulsive, insistence on sameness, and self-injurious behavior characterizing girls and increased stereotyped and restricted behavior characterizing boys. Future research should determine whether these elevated behaviors in girls are directly part of the autism presentation in girls or symptoms of co-occurring psychopathology. It is important for autism diagnostic measures to best capture the types of repetitive behavior girls may demonstrate.

A Pilot Study of the Effects of Mindfulness-Based Cognitive Therapy on Positive Affect and Social Anxiety Symptoms.

Randomized controlled trials have demonstrated that mindfulness-based cognitive therapy (MBCT) is efficacious in reducing residual depressive symptoms and preventing future depressive episodes (Kuyken et al., 2016). One potential treatment effect of MBCT may be improvement of positive affect (PA), due to improved awareness of daily positive events (Geschwind et al., 2011). Considering social anxiety disorder (SAD) is characterized by diminished PA (Brown et al., 1998; Kashdan, 2007), we sought to determine whether MBCT would reduce social anxiety symptoms, and whether this reduction would be associated with improvement of PA deficits. Adults (N = 22) who met criteria for varied anxiety disorders participated in a small, open-label trial of an 8-week manualized MBCT intervention. Most participants presented with either a diagnosis (primary, secondary, or tertiary) of generalized anxiety disorder (GAD) (N = 15) and/or SAD (N = 14) prior to treatment, with eight individuals meeting diagnostic criteria for both GAD and SAD. We hypothesized participants would demonstrate improvements in social anxiety symptoms, which would be predicted by improvements in PA, not reductions in negative affect (NA). Results of several hierarchical linear regression analyses (completed in both full and disorder-specific samples) indicated that improvements in PA but not reductions in NA predicted social anxiety improvement. This effect was not observed for symptoms of worry, which were instead predicted by decreased NA for individuals diagnosed with GAD and both decreased NA and increased PA in the entire sample. Results suggest that MBCT may be efficacious in mitigating social anxiety symptoms, and this therapeutic effect may be linked to improvements in PA. However, further work is necessary considering the small, heterogeneous sample, uncontrolled study design, and exploratory nature of the study.

Intolerance for approach of ambiguity in social anxiety disorder.

Previous research has utilised the approach-avoidance task (AAT) to measure approach and avoidance action tendencies in socially anxious individuals. "Neutral" social stimuli may be perceived as ambiguous and hence threatening to socially anxious individuals, however it is unclear whether this results in difficulty approaching ambiguous ("neutral") versus unambiguous threat (e.g. disgust) faces (i.e. intolerance of ambiguity). Thirty participants with social anxiety disorder (SADs) and 29 non-anxious controls completed an implicit AAT in which they were instructed to approach or avoid neutral and disgust faces (i.e. pull or push a joystick) based on colour of the picture border. Results indicated that SADs demonstrated greater difficulty approaching neutral relative to disgust faces. Moreover, intolerance for approach of ambiguity predicted social anxiety severity while controlling for the effects of trait anxiety and depression. Our results provide further support for the role of intolerance of ambiguity in SAD.

Spatiotemporal dissociation of brain activity underlying threat and reward in social anxiety disorder.

Social anxiety disorder (SAD) involves abnormalities in social motivation, which may be independent of well-documented differences in fear and arousal systems. Yet, the neurobiology underlying motivational difficulties in SAD is not well understood. The aim of the current study was to spatiotemporally dissociate reward circuitry dysfunction from alterations in fear and arousal-related neural activity during anticipation and notification of social and non-social reward and punishment. During fMRI acquisition, non-depressed adults with social anxiety disorder (SAD; N = 21) and age-, sex- and IQ-matched control subjects (N = 22) completed eight runs of an incentive delay task, alternating between social and monetary outcomes and interleaved in alternating order between gain and loss outcomes. Adults with SAD demonstrated significantly reduced neural activity in ventral striatum during the anticipation of positive but not negative social outcomes. No differences between the SAD and control groups were observed during anticipation of monetary gain or loss outcomes or during anticipation of negative social images. However, consistent with previous work, the SAD group demonstrated amygdala hyper-activity upon notification of negative social outcomes. Degraded anticipatory processing in bilateral ventral striatum in SAD was constrained exclusively to anticipation of positive social information and dissociable from the effects of negative social outcomes previously observed in the amygdala. Alterations in anticipation-related neural signals may represent a promising target for treatment that is not addressed by available evidence-based interventions, which focus primarily on fear extinction and habituation processes.

One session treatment for specific phobias in children: Comorbid anxiety disorders and treatment outcome.

BACKGROUND AND OBJECTIVES: One-Session Treatment (OST) for specific phobias has been shown to be effective in reducing phobia severity; however, the effect of different types of co-occurring anxiety disorders on OST outcomes is unknown. The present study examined (1) the effects of co-occurring generalized anxiety disorder (GAD), social anxiety disorder (SAD), or another non-targeted specific phobia (OSP) on the efficacy of OST for specific phobias, and (2) the effects of OST on these co-occurring disorders following treatment. METHODS: Three groups of 18 youth (7-15 years) with a specific phobia and comorbid GAD, SAD, or OSP were matched on age, gender, and phobia type. Outcome measures included diagnostic status and severity, and clinician rated improvement. RESULTS: All groups demonstrated an improvement in their specific phobia following treatment. Treatment was equally effective regardless of co-occurring anxiety disorder. In addition, comorbid anxiety disorders improved following OST; however, this effect was not equal across groups. The SAD group showed poorer improvement in their comorbid disorder than the GAD group post-treatment. However, the SAD group continued to improve and this differential effect was not evident six-months following treatment. LIMITATIONS: The current study sample was small, with insufficient power to detect small and medium effect sizes. Further, the sample only included a portion of individuals with primary GAD or SAD, which may have attenuated the findings. CONCLUSIONS: The current study demonstrated that co-occurring anxiety disorders did not interfere with phobia treatment. OST, despite targeting a single specific phobia type, significantly reduced comorbid symptomatology across multiple anxiety disorders.

A Pilot Study of an Adaptive, Idiographic, and Multi-Component Attention Bias Modification Program for Social Anxiety Disorder.

An attentional bias toward threat may be one mechanism underlying clinical anxiety. Attention bias modification (ABM) aims to reduce symptoms of anxiety disorders by directly modifying this deficit. However, existing ABM training programs have not consistently modified attentional bias and may not reflect optimal learning needs of participants (i.e., lack of explicit instruction, training goal unclear to participants, lack of feedback, non-adaptive, inability to differentiate or target different components of attentional bias). In the current study, we introduce a new adaptive ABM program (AABM) and test its feasibility in individuals with social anxiety disorder. We report task characteristics and preliminary evidence that this task consistently modifies attentional bias and that changes in attentional bias (but not number of trials) correlate with the level of symptom reduction. These results suggest that AABM may be a targeted method for the next generation of studies examining the utility of attention training.