Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

BACKGROUND: Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. METHODS: Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. RESULTS: The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. CONCLUSION: We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Testing the reciprocal relationship between depressive symptoms and insomnia.

BACKGROUND: Although the importance of sleep difficulties in emotional disorders has long been acknowledged, the nature of the potential reciprocal relationship between sleep and depressive symptoms is not yet well understood. The coronavirus disease 19 pandemic provided a unique opportunity to study the interrelation of these symptoms over a period marked by increases in sleep and psychological difficulties. METHODS: Using online data collection, we followed 1200 adults (59% male) through 1 year of the pandemic. Measures of sleep disturbance and depressive symptoms were assessed at eight time points. Factor analysis of the items from these two measures suggested separate insomnia and depressive symptom factors. A random intercept cross-lagged panel model was used to assess within-person relationships between factor analysis-informed subscales of insomnia and depressive symptoms. RESULTS: Depressive symptoms predicted subsequent changes in insomnia symptoms; however, insomnia did not predict changes in depressive symptoms. CONCLUSIONS: Our findings suggest the impact of depressive symptoms on insomnia is evident, but the reverse is not. Implications of this finding along with the need for research addressing depressive symptoms and insomnia as treatment targets are discussed.

Promoting skill use in skill enhanced cognitive behavioral therapy: A case example.

Cognitive behavioral therapy (CBT) appears to achieve its effects at least in part by fostering the development of CBT skills. In an effort to leverage CBT skill development, our group developed and tested a skill-enhanced version of CBT (CBT-SE) in a recent trial. In this paper, we describe our work with a client who participated in a 12-week course of CBT-SE as part of that trial. Although homework is a critical aspect of CBT, the greater emphasis on skill development in CBT-SE means that homework is even more central. This client's course of treatment illustrates the potential benefits of a strong focus on skill development and the use of specific homework assignments to foster mastery and ongoing use of CBT skills. The client developed CBT skills at a rapid pace early in treatment and exhibited enduring symptom reductions. The experience of this client reinforces the value of a focus on CBT skills and highlights strategies for fostering skill development. Given the evidence in support of the therapeutic value of CBT skills and the well-established benefits of homework assignment, we encourage use of skill enhancing procedures, including in-session procedures and assignments that help clients develop and maintain ongoing skill use.

Seeing is believing: The effect of subtle communication in social media on viewers' beliefs about depression and anxiety symptom trajectories.

OBJECTIVE: One barrier to treatment seeking, uptake, and engagement is the belief that nothing can be done to reduce symptoms. Given the widespread use of social media to disseminate information about important issues, including psychological health, we sought to understand how the influence of social media communication regarding mental health impacts viewers' beliefs about psychopathology recovery. METHOD: Undergraduate participants from a large Midwestern university (N = 322) were randomized to view a series of Tweets characterizing psychopathology from a fixed mindset perspective, a growth mindset perspective, or, in the control condition, Tweets unrelated to psychopathology. Afterward, they completed a series of questionnaires designed to assess beliefs about recovery from depression and anxiety. RESULTS: Participants in the growth mindset condition endorsed less pessimistic beliefs about their ability (i.e., self-efficacy) to alleviate symptoms of depression and anxiety, and they believed these symptoms to be less stable and innate relative to those in the fixed mindset condition. CONCLUSION: Social media communication that characterizes psychopathology from a growth mindset perspective may be a viable intervention for improving beliefs around mental health self-efficacy and the malleable nature of mental illness, particularly depression and anxiety. Clinicians may be able to use social media platforms to promote functional beliefs around mental illness.

How relevant are cerebral white matter lesions in the D313Y variant of the α-galactosidase A gene? Neurological, cardiological, laboratory, and MRI data of 21 patients within a follow-up of 3 years.

BACKGROUND: Fabry disease is an inherited metabolic disorder with various symptoms. Neurological manifestations are small fiber neuropathy, cerebral white matter lesions (WML), megadolicho basilar artery, and stroke. The relevance of the D313Y variant in the galactosidase alpha gene is controversially discussed. OBJECTIVES: We aimed at elucidating the implications of this differential diagnosis of multiple sclerosis (MS), focussing on the analysis of WML over time and correlations with other markers. METHODS: We reviewed retrospectively the clinical, laboratory, and magnetic resonance imaging data of 21 carriers of the D313Y variant at a single German outpatient clinic for MS between 2004 and 2021. RESULTS: In our cohort (15 females, 6 males), mean age at diagnosis was 44.1 ± 16.3 years, and mean follow-up duration was 3.1 ± 3.9 years. WML were rated on both, the Fazekas scale and the age-related white matter changes rating scale, and were of variable interindividual extent. Follow-up imaging showed virtually no progress. WML did not correlate with the severity of clinical findings or lysoGb3 levels. Symptomatic carriers of the variant are characterized by an almost complete lack of internal organ manifestations and laboratory findings, usually associated with Fabry disease. CONCLUSION: WML in carriers of the D313Y variant do not seem to be suitable for assessing or predicting the (para-) clinical status. Concerning MS patients, the variant and its clinical signs can be a differential diagnosis, but also a co-factor. Imaging and cerebrospinal fluid findings facilitate the distinction between both entities.

Impact of messaging on views of depression treatment options: Examining credibility and expectations.

OBJECTIVE: Understanding how people respond to information about treatment options is important for informing efforts that promote treatment initiation and adherence. We examined the impact of informational treatment videos on treatment naive participants' views regarding the credibility of and their expectations for three treatment options. MATERIALS AND METHODS: Adults (N = 300) who had experienced elevated depressive symptoms but had not participated in a treatment for depression were randomly assigned to one of four conditions. Three of the conditions were shown videos, providing information about (1) cognitive behavioral therapy (CBT), (2) antidepressant medication (ADM), or (3) the combination of CBT and ADM. The fourth condition was not shown a video. Participants' self-reported views of the credibility of and expectations for treatment served as primary outcome variables. RESULTS: Compared with the control condition, videos about active treatments enhanced credibility and expectations for those treatments. When comparing CBT and ADM alone, messaging about either treatment enhanced credibility of and expectations for that treatment. The CBT only video produced the most positive expectations and highest credibility for CBT. Likewise, the ADM only video led to the most positive expectations and credibility for ADM. The video focused on combined treatment did not lead to particularly positive views of the combined treatment option. CONCLUSION: These findings demonstrate the importance of providing focused messaging to enhance the credibility of and expectations for treatment. Future research is needed to examine the impact of messaging in different contexts, as well as the impact of such messaging on treatment seeking, adherence, and outcomes.

Predicting anxiety and depression over 12 months of the COVID-19 pandemic: A machine learning study.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic was associated with substantial increases in anxiety and depressive symptoms. To understand individual risk, we examined a large set of potential risk factors for anxiety and depression in the pandemic context. METHODS: Adults in the United States (N = 1200) completed eight online self-report assessments over 12 months of the COVID-19 pandemic. Area under the curve scores summarized cumulative experiences of anxiety and depression over the assessment period. A machine learning approach to elastic net regularized regression was used to select predictors of cumulative anxiety and depression severity from a set of 68 sociodemographic, psychological, and pandemic-related baseline variables. RESULTS: Cumulative anxiety severity was most strongly explained by stress and depression-related variables (such as perceived stress) and select sociodemographic characteristics. Cumulative depression severity was predicted by psychological variables, including generalized anxiety and depressive symptom reactivity. Being immunocompromised or having a medical condition were also important. CONCLUSIONS: By considering many predictors, findings provide a more complete view than previous studies focused on specific predictors. Important predictors included psychological variables suggested by prior research and variables more specific to the pandemic context. We discuss how such findings can be used in understanding risk and planning interventions.

Congruence in patient and therapist-rated alliance predicts subsequent depressive symptoms in cognitive behavioral therapy for depression.

OBJECTIVE: The therapeutic alliance is a dyadic process involving both patient and therapist perspectives. We investigated the effect of patient and therapist agreement on the alliance in cognitive behavioral therapy for depression. METHOD: Patients (N = 191) were drawn from two studies of cognitive behavioral therapy for depression provided over 16 weeks. Alliance data were collected from patients and therapists at the first four sessions. Patients provided symptom data at each session. We used multilevel polynomial regression with response surface analysis to investigate the effect of alliance agreement and disagreement on symptoms. RESULTS: The within-person strength of patient and therapist-rated alliance (given agreement) predicted lower within-person symptoms. The nature and degree of the discrepancy in patient and therapist alliance scores was not a significant predictor. CONCLUSION: Patients and therapist alliance strength in early sessions (given agreement) predicted greater symptom change. Future research is needed to examine whether specific patient characteristics can be used to identify for whom the alliance plays a more or less important role.

Vindicating pollyanna? An experimental test of cognitive restructuring and positive thinking interventions.

OBJECTIVE: Despite its considerable potential, psychotherapy research has made limited use of small-scale experimental study designs to test intervention components. This study employs such a design to test the immediate effects on emotional experience of two approaches to changing negative thoughts, cognitive restructuring and fostering positive thinking. Cognitive restructuring draws on the strategies core to cognitive behavioral therapies. Fostering positive thinking has also received attention, though less so as a psychological intervention. METHOD: We tested the benefits of these strategies over a brief interval by randomizing 230 participants to complete a worksheet introducing one of the two strategies. Participants reported their skills prior to exposure to these worksheets and affect was assessed immediately prior to and following use of worksheets. RESULTS: Participants' negative affect reduced following both strategies. Conditions did not differ significantly in affect change. Analysis of potential moderators showed that, among those with higher levels of cognitive behavioral therapy skills, the positive thinking condition produced greater gains in positive affect than the cognitive restructuring condition. CONCLUSIONS: These results indicate that both forms of brief interventions promote reductions in negative affect. Positive thinking interventions, which are not focused on the accuracy of one's thinking, appear to be particularly effective in promoting positive affect.

Working with Black vs. White patients: an experimental test of therapist decision-making in cognitive behavioral therapy for depression.

Whether and how therapists' delivery of cognitive behavioral therapy (CBT) for depression differs by patients' ethnicity or race remains unclear. In this study, 218 therapists were randomized to clinical vignettes that involved the same text but varied in whether the accompanying image depicted a Black or White patient. Therapists exhibited three key differences in their views of clinical strategies for working with Black as compared to White patients. They viewed cognitive change strategies as less therapeutic and validation strategies as more therapeutic for Black patients. They reported similar differences for the time they would spend on each kind of strategy. When asked to compare the relative importance of cognitive change vs. validation strategies specifically, therapists rated validation as more important for Black than White patients. Among therapists presented with Black patients, positive racial attitudes were associated with viewing cognitive change and validation strategies as more therapeutic. These results suggest therapists tend to believe it is desirable to incorporate cognitive methods more limitedly when working with Black patients. Whether such adaptations enhance or detract from the care of Black patients is an important issue that merits future investigation.

Framing an intervention as focused on one's strength: Does framing enhance therapeutic benefit?

INTRODUCTION: A capitalization approach to enhancing client skills in cognitive behavioral interventions is focused on enhancing skills that represent relative strengths. This approach may bolster outcomes because the targeted skills are those that clients can most effectively use to recover from negative moods. Alternatively, the benefits might be due to client attitudes about these skills, such as their confidence that they can use these skills effectively. METHODS: In an unselected sample of 616 undergraduates, we randomized to one of two brief interventions (a cognitive or mindfulness intervention) and one of two framing conditions (framing the intervention as focusing on a relative strength or a weakness), resulting in four conditions. Participants were then asked to use the skill targeted in their intervention to recover from a sad mood induction. RESULTS: Framing conditions did not differ on expectations of benefit from sustained use of an intervention but did differ on mood recovery. Participants told that the intervention focused on a strength recovered more quickly following the mood induction. There was no difference between the skill interventions. DISCUSSION: Our finding suggests intervention framing positively contributes to the effects of strengths focused treatments, though perhaps not by enhancing treatment expectations.

Assessing the disproportionality of depressive reactions to life stress.

BACKGROUND: Prior to DSM-5, depression had long been conceptualized as symptoms without cause or disproportionate to one's circumstances. A central challenge to considering whether a depressive reaction is disproportionate is the lack of measures assessing disproportionality. Drawing on a study of patients participating in cognitive behavioural therapy for depression, we evaluate two new measures of the disproportionality of one's depressive symptoms to their recent life circumstances. METHODS: To assess the disproportionality of depressive symptoms, we developed an interview-based assessment and a brief self-report measure. We employed both assessments in a sample of 126 patients who participated in cognitive behavioural therapy for depression. RESULTS: Initial evidence for the reliability and validity of both self-report and interview-based approaches appeared promising. Interview judges demonstrated strong inter-rater reliability on life stress ratings, and both forms of disproportionality showed a pattern of correlations with variables reflecting greater clinical complexity, including self-reported personality dysfunction and symptom severity. Comorbid generalized anxiety disorder (GAD) was the only previously proposed marker of complicated depression to significantly predict both disproportionality scores. LIMITATIONS: The sample had limited ethnic diversity and tended to be highly educated. Participants all met criteria for major depressive disorder and sought treatment. CONCLUSIONS: Two assessments of the disproportionality of depressive reactions demonstrated evidence of reliability and validity. Despite limited efforts at assessment to date, these results suggest these measures may be able to reliably distinguish the disproportionality of depressive reactions and allow clinicians to better assess contextual life stress depressive disorders.

The therapeutic alliance and dropout in cognitive behavioral therapy of depression.

Identifying predictors of dropout is an important step in improving treatment outcomes. The alliance is the most frequently studied psychotherapy process variable, but its relation to dropout in cognitive behavioral therapy (CBT) of depression is not well understood.We evaluated the alliance at session one as reported by clients and therapists as predictors of dropout among 126 clients with major depressive disorder participating in CBT for depression.Over a similar time period, those who dropped out experienced less symptom change than those who did not. Client, but not therapist reported alliance was related to reduced risk for dropout. This relation remained significant even when clients' pre-treatment predictions of the alliance were included as a covariate. Concurrent use of medication did not moderate the alliance-dropout relation.Our findings are consistent with alliance being an important contributor to risk of dropout in CBT for depression. Future research should investigate intervention strategies that might promote the alliance as a means of reducing dropout.

Getting down to business: an examination of occupational outcomes in cognitive behavioral therapy for depression.

Depression is associated with unemployment and poor occupational functioning. Although cognitive behavioral therapy (CBT) has been shown to reduce depressive symptoms, the degree to which it improves occupational outcomes has received little attention. We investigated change in job status and presenteeism (i.e., the inability to focus on and accomplish work) over the course of CBT. We assessed employment status, presenteeism, depressive symptoms, cognitive style, and CBT skills at intake and posttreatment in a sample of 126 participants enrolled in a 16-week course of CBT for depression. Employment status significantly improved from pre to posttreatment, with 11 of the 27 patients (41%) seeking to improve their employment status achieving this goal. Among the 59 consistently employed patients, presenteeism decreased significantly over the course of treatment (dz = 1.13). We also found, even after controlling for changes in symptoms, reductions in negative cognitive style (but not changes in CBT skills) were associated with reductions in presenteeism. Our findings suggest CBT patients experience positive changes in occupational outcomes, both in finding work and being more focused and productive at work. Changes in negative cognitive styles appeared to partly explain this latter change. We encourage future work examining CBT's impact on occupational outcomes.

Pay no attention to the man behind the curtain: The overlooked issue of rater selection in psychotherapy observer ratings.

Objective: Psychotherapy process research relies heavily upon trained raters to identify and code therapist and client behaviors. Raters are often selected out of convenience or availability with little research to inform what qualities are desirable for this role. In this study, we evaluated several rater characteristics as potential predictors of raters' performance. Method: We provided training to 39 undergraduate students to serve as raters in a psychotherapy process study. We assessed baseline characteristics, personality characteristics, executive functioning, and interviewers' assessment of students' rating potential as predictors of rater agreement with gold standard ratings (i.e., consensus judgements from a panel of CBT-trained clinicians). We also assessed these variables as predictors of the risk of raters dropping out prior to completing assigned ratings. Results: Higher conscientiousness, higher neuroticism, and a lower year in college predicted greater agreement with the gold standard ratings. Lower year in college also predicted lower risk of dropout. Conclusion: These findings provide empirical support for key characteristics as predictors of rater performance. Such evidence raises the possibility of using these characteristics to select raters and thereby enhance the psychometric properties of psychotherapy ratings.

Initial experience with [18F]DPA-714 TSPO-PET to image inflammation in primary angiitis of the central nervous system.

PURPOSE: Primary angiitis of the central nervous system (PACNS) is a heterogeneous, rare, and poorly understood inflammatory disease. We aimed at non-invasive imaging of activated microglia/macrophages in patients with PACNS by PET-MRI targeting the translocator protein (TSPO) with [18F]DPA-714 to potentially assist differential diagnosis, therapy monitoring, and biopsy planning. METHODS: In total, nine patients with ischemic stroke and diagnosed or suspected PACNS underwent [18F]DPA-714-PET-MRI. Dynamic PET scanning was performed for 60 min after injection of 233 ± 19 MBq [18F]DPA-714, and MRI was simultaneously acquired. RESULTS: In two PACNS patients, [18F]DPA-714 uptake patterns exceeded MRI correlates of infarction, whereas uptake was confined to the infarct in four patients where initial suspicion of PACNS could not be confirmed. About three patients with PACNS or cerebral predominant lymphocytic vasculitis showed no or only faintly increased uptake. Short-term [18F]DPA-714-PET follow-up in a patient with PACNS showed reduced lesional [18F]DPA-714 uptake after anti-inflammatory treatment. Biopsy in the same patient pinpointed the source of tracer uptake to TSPO-expressing immune cells. CONCLUSIONS: [18F]DPA-714-PET imaging may facilitate the diagnosis and treatment monitoring of PACNS. Further studies are needed to fully understand the potential of TSPO-PET in deciphering the heterogeneity of the disease.

An examination of dysfunctional attitudes and extreme response styles as predictors of relapse in guided internet-based cognitive behavioral therapy for depression.

OBJECTIVES: Internet-based cognitive behavioral therapy (iCBT) is an effective treatment option for depression, but its long-term effects are not well understood. We investigate for whom iCBT may have more enduring effects by evaluating dysfunctional attitudes as predictors of relapse. METHODS: The sample consists of 31 iCBT responders (20 women, average age 31.6) who were followed for 1 year. RESULTS: Higher Dysfunctional Attitudes Scale scores predicted higher risk of relapse (hazard ratio = 1.98). This relation remained significant when controlling for high style (dysfunctional) or content (functional) responses. Having relatively more positive extreme responses on style rather than content items did not predict risk of relapse. CONCLUSIONS: Our results were consistent with the value of differentiating an extreme style of responding from otherwise endorsing belief in dysfunctional attitudes. Research that refines our understanding of patients' individual risk for relapse has the potential to inform how treatment might be individually tailored.

Guided internet CBT versus "gold standard" depression treatments: An individual patient analysis.

OBJECTIVE: Guided, computerized cognitive behavioral therapy delivered over the internet (iCBT) is a promising treatment for depression. However, comparisons to "gold standard" treatments and comparators, such as structured psychotherapy, medications, or pill placebo are rare. We compare the results of an 8-week trial of guided iCBT to outcomes from two trials of depression treatment, Penn-Vandy and U. Washington, using individual patient data. METHOD: We adjusted for sample differences by restricting the iCBT sample to randomised controlled trial (RCT) inclusion criteria and using propensity scores. Three separate samples were included in analyses: iCBT trial (N = 89), Penn-Vandy (N = 240), and U. Washington (N = 241). Continuous outcomes were analyzed with linear-mixed models and noninferiority analyses were conducted for iCBT versus the psychotherapy conditions. The primary outcomes were attrition, remission, and the Hamilton Rating Scale for Depression. RESULTS: Dropout was greater in iCBT than in CT, medications, placebo (Penn-Vandy), and CT and BA (U. Washington), but the rates of remission were similar. In continuous analyses, iCBT was superior to placebo in both RCTs and most analyses indicated no difference between iCBT and the active treatments. CONCLUSIONS: Guided iCBT appears not inferior to "gold standard" treatments for depression and is superior to placebo. Weaknesses include a lack of randomization, unblinded assessments, and a shorter "frame of treatment" in the iCBT sample.

Measuring Patients' Acquisition of Therapy Skills in Psychotherapy for Depression: Assessing the CCTS-SR and the IPSS-SR.

Using data from 202 patients with depression, the authors conducted a psychometric evaluation of the Dutch translation of the Competencies of Cognitive Therapy Scale-Self-Report and an initial psychometric evaluation of the newly developed Interpersonal Psychotherapy Skills Scale-Self-Report.