Treatment Non-responders Research Articles

Association between Sex Hormones and Mood, Cravings and Urges in Males and Females Who Smoke Tobacco.

Mood influences smoking behavior, with sex and sex hormones potentially complicating these relationships. We explored associations between Profile of Mood States (POMS) and Questionnaire on Smoking Urges (QSU) - Brief with sex hormones in men and women who smoke. This is a secondary analysis of treatment non-responders from a smoking cessation randomized trial investigating exogenous progesterone's efficacy. We considered the sex-specific associations between absolute serum progesterone (PRO) level and progesterone-to-estradiol ratio (P/E2), as well as the relative change in serum PRO and P/E2 with POMS and QSU subscale scores. Poisson generalized estimating equations models were used to estimate the associations. The analysis included 127 participants (62 women: median age of 38, 61% white; 65 men: median age of 36, 54% white). There were sex-specific associations between POMS negative mood factors and relative PRO levels (e.g., fatigue-inertia: women: 19% increase for a 10-fold increase in relative PRO, p=0.03 versus men: 10% decrease, p=0.19) and relative P/E2 (e.g., lonely: women: 7% increase for a 10-fold increase in relative P/E2, p=0.63 versus men: 27% decrease, p=0.01). Generally, larger relative PRO and P/E2 were associated with increased POMS negative mood factors in women, while larger relative PRO and P/E2 in men were associated with decreased POMS negative mood factors. Similar trends between POMS negative mood factors and the absolute PRO and P/E2 were observed. No significant associations were observed with POMS positive mood factors or QSU subscales. These findings suggest that the change in PRO and P/E2 may influence negative mood factors differently in men and women who smoke. Additional research is needed to understand how these sex-specific associations may contribute to smoking cessation. Progesterone and estrogen were linked to increased negative mood factors in women, whereas in men they were linked to a decrease in negative mood factors. These observations shed light on potential sex-specific intervention targets for mood management in adults who smoke.

Appetite Regulation in Response to Acute Exercise among Weight-Loss Treatment Responders vs Nonresponders: A Pilot Study

ABSTRACT Introduction The reason for weight-loss heterogeneity in response to lifestyle interventions is not clear. Important regulators of food intake and energy expenditure include peripheral hormonal signals from insulin, glucagon-like peptide 1 (GLP-1), leptin, and ghrelin. Herein, we examine the hormonal regulators of appetite and satiety following a high-volume bout of moderate-to-vigorous intensity exercise in responders and nonresponders to a 6-month, digitally delivered, weight-loss lifestyle intervention. Methods Young adults (27.7 ± 3.7 yr; 11 female, 1 male) characterized as responders (n = 7; lost 3% of their initial body weight) and nonresponders (n = 5) participated in a 60-min treadmill exercise challenge, consisting of three 15-min intervals at 80% of peak oxygen consumption (V̇O2peak), with 5 min of walking at 50% V̇O2peak between intervals. Blood samples were obtained prior to and immediately after exercise and 30 and 60 min after exercise during seated recovery for determination of plasma glucose, insulin, GLP-1active, leptin, and acylated ghrelin. Univariate analyses (mean ± standard deviation) and Cohen’s d described between-group differences in hormone responses to exercise. Results Glucose and leptin responses during the exercise challenge and recovery were similar for nonresponders and responders; however, nonresponders had higher insulin concentrations post-exercise compared to responders (9.8 ± 3.5 μU·mL−1 vs 6.2 ± 2.2 μU·mL−1 at 30 min (d = 1.23); 9.4 ± 1.8 μU·mL−1 vs 6.3 ± 2.1 μU·mL−1 at 60 min (d = 1.54)). Concentrations of GLP-1active also appeared higher in nonresponders compared to responders following exercise (12.2 ± 2.8 pmol·L−1 vs 9.3 ± 1.1 pmol·L−1 (d = 1.36)), but this difference disappeared after 30 min of recovery. Ghrelin levels were lower in the nonresponders following exercise (308 ± 27 pg·mL−1 vs 494 ± 98 pg·mL−1 (d = −2.58)) and remained so over the recovery period (287.4 ± 12.3 pg·mL−1 vs 392.1 ± 47.2 pg·mL−1 at 30 min (d = −3.08); 313.0 ± 39.8 pg·mL−1 vs 393.9 ± 60.8 pg·mL−1 at 60 min (d = −1.21)). Conclusions These findings support potential appetite hormonal differences in the heterogenous weight-loss response to lifestyle therapy. A better understanding of how exercise affects appetite regulation in young adults with overweight and obesity could help with precision care.

Persistent pro-inflammatory trait in elderly patients following treatment-resistant major depressive disorder: a longitudinal exploratory study

Objectives Considering that the remission rate for major depressive disorder (MDD) in elderly patients is below 50%, there is a compelling requirement for an enhanced comprehension of the underlying mechanisms. Chronic low-grade inflammation has been posited as one potential contributor to treatment-resistant MDD in the elderly. Accordingly, the objective of our study was to explore the longitudinal trends of systemic immune markers in elderly inpatients referred to electroconvulsive therapy due to an episode of treatment resistant unipolar MDD. Methods The study encompassed 64 elderly inpatients with unipolar MDD that had failed to respond to therapy in primary health care, and 18 non-depressed controls. Blood samples were collected at pre-treatment, mid-treatment, post-treatment and 12 weeks follow-up. We assessed 27 immune markers via multiplex assays. Depressive symptoms were evaluated using the Hamilton Rating Scale of Depression at these timepoints. For controls, the immune markers and depressive symptoms, were measured at baseline and eight weeks follow-up using identical methods. Results At follow-up, patients showed higher concentrations of 23 immune markers compared to controls, although the concentration of 19 immune markers decreased significantly from pre-treatment to follow-up. No differences in immune marker concentrations between treatment responders and non-responders were observed pre- and post-treatment in the patient group. Conclusion Our findings suggest that a pro-inflammatory trait persists in elderly after an episode of treatment resistant unipolar MDD. Thus, our study supports that chronic low-grade inflammation may characterise elderly with treatment-resistant unipolar MDD.

Plasma essential amino acid levels in first episode psychosis at baseline and after antipsychotic treatment

This study assessed plasma levels of essential amino acids (EAA) in drug-naïve first episode psychosis (FEP) patients at diagnosis and after 10 weeks of antipsychotic treatment. Forty FEP patients were enrolled at baseline, with blood samples collected before and after a 10-week antipsychotic treatment period. Plasma EAA levels were measured using an LC/MS/MS method. Psychotic symptoms were evaluated using standardized inventories before and after treatment. A decrease in BPRS score of more than 40% was used to indicate treatment response. Thirty-five healthy volunteers served as the control group. Baseline plasma levels of Thr, Met, Leu, Lys, His, and Tyr were higher in FEP patients than in healthy controls. After 10 weeks of treatment, Leu, His, and Tyr increased further, primarily in treatment-responsive patients. Conversely, Val level was lower than controls in patients at baseline and remained unchanged after treatment. Increased EAA levels were correlated with lower (less severe) scores in positive symptom scales. Treatment non-responders had persistently low Tyr/large neutral amino acid (LNAA) ratio. Tyr/LNAA ratio increased after treatment, specifically in treatment-responders. Phe/Tyr ratio decreased post-treatment in both responder and non-responder groups. Elevated EAA levels in FEP patients may signify compensatory responses to increased physiological demand for neurotransmitters or energy. Combining specific EAA supplementation with antipsychotic treatment may enhance treatment response in these patients.

Fecal and Sputum Microbiota and Treatment Response in Patients with Mycobacterium abscessus Pulmonary Disease.

The microbiota is a potential source of biomarkers for clinical outcomes in chronic respiratory conditions, but its role in Mycobacterium abscessus pulmonary disease (PD) remains unexplored. We aimed to identify microbial signatures in fecal and sputum microbiotas associated with treatment response in patients with M. abscessus PD. We conducted a cohort study prospectively enrolling patients undergoing antibiotic treatment for M. abscessus PD. Fecal and sputum samples were collected before, and 2 weeks and 6 months after, treatment initiation. 16S rRNA amplicon sequencing approach was used to characterize the microbiotas. After categorizing patients as early treatment responders and non-responders based on sputum culture results at 2 weeks, we elucidated the differences in their diversity and composition of microbiotas. Among 32 patients enrolled, 27 patients (median 66 years, 85.2% women, 48.1% with subspecies abscessus) were included for microbiota analysis. Fifteen patients (55.6%) achieved negative conversion at 2 weeks, which was maintained in 14 (93.3%) after 6 months. Alpha-diversity of the fecal microbiota after 2 weeks of treatment decreased significantly in responders, but not in non-responders (P=0.029). Increased abundance of Eubacterium hallii group in baseline fecal microbiota was indicative of unresponsiveness to antibiotics, whereas an increase in Enterococcus in fecal microbiota at week 2 was linked with favorable response. Increased abundance of Burkholderia-Caballeronia-Paraburkholderia and Porphyromonas in baseline, and decreased abundance of Rothia in week 2 sputum microbiota were also associated with good treatment response. In M. abscessus PD, changes in microbial diversity and compositional signatures vary with treatment response.

Defining immune cell phenotypes that distinguish treatment responders and non-responders in RA

.

Prize-based Incentives for Smoking Cessation Among People with HIV: A Sequential Multiple Assignment Randomized Trial (SMART).

Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The study purpose is to assess efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response. During phase 1, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in Phase 2 to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically-verified smoking reduction and 7-day abstinence prevalence at post-treatment, 6-month and 12-month follow-up. Phase 1 responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6- and 12-months) if they received low-magnitude incentives. Notably, initial exposure to CM vs. SoC did not increase rate of phase 1 response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early treatment non-responders. Weekly CM sessions in the first four weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation. This represents the first trial to examine the use of contingency management for smoking cessation among people with HIV within the context of a Sequential Multiple Assignment, Randomized Trial (SMART) design.

Differential Protein Expression in Extracellular Vesicles Defines Treatment Responders and Non-Responders in Multiple Sclerosis.

Multiple sclerosis (MS) remains the leading cause of neurological disability among young adults worldwide, underscoring the urgent need to define the best therapeutic strategy. Recent advances in proteomics have deepened our understanding of treatment mechanisms and revealed promising biomarkers for predicting therapeutic outcomes. This study focuses on the identification of a protein profile of circulating extracellular vesicles (EVs) derived from neurons, oligodendrocytes, and B and T cells able to differentiate treatment responders and non-responders in 80 patients with MS. In the patients who responded to treatment, T cell-derived EVs were enriched in LV151, a protein involved in the promotion of anti-inflammatory cytokines, whereas Bcell-derived EVs showed elevated PSMD6 and PTPRC, related to immunoproteasome function. Oligodendrocyte- and neuron-derived EVs showed upregulated CO6A1 and COEA1, involved in extracellular matrix reorganisation, as well as LAMA5, NonO, SPNT, and NCAM, which are critical for brain repair. In contrast, non-responders showed higher levels of PSMD7 and PRS10 from B cell-derived EVs, associated with DNA damage, and increased levels of PERM and PERL from T cell-derived EVs, linked to nuclear factor kappa B activation and drug-resistant proteins such as HS90A and RASK. These findings highlight a distinct panel of proteins in EVs that could serve as an early indicator of treatment efficacy in MS.

Distinct saliva DNA methylation profiles in relation to treatment outcome in youth with posttraumatic stress disorder

In youth with posttraumatic stress disorder (PTSD) non-response rates after treatment are often high. Epigenetic mechanisms such as DNA methylation (DNAm) have previously been linked to PTSD pathogenesis, additionally DNAm may affect response to (psychological) therapies. Besides investigating the direct link between DNAm and treatment response, it might be helpful to investigate the link between DNAm and previously associated biological mechanisms with treatment outcome. Thereby gaining a deeper molecular understanding of how psychotherapy (reflecting a change in the environment) relates to epigenetic changes and the adaptability of individuals. To date, limited research is done in clinical samples and no studies have been conducted in youth. Therefore we conducted a study in a Dutch cohort of youth with and without PTSD (n = 87, age 8–18 years). We examined the cross-sectional and longitudinal changes of saliva-based genome-wide DNA methylation (DNAm) levels, and salivary cortisol secretion. The last might reflect possible abbreviations on the hypothalamic–pituitary– adrenal (HPA) axis. The HPA-axis is previously linked to DNAm and the development and recovery of PTSD. Youth were treated with 8 sessions of either Eye Movement Reprocessing Therapy (EMDR) or Trauma Focused Cognitive behavioral Therapy (TF-CBT). Our epigenome wide approach showed distinct methylation between treatment responders and non-responders on C18orf63 gene post-treatment. This genomic region is related to the PAX5 gene, involved in neurodevelopment and inflammation response. Additionally, our targeted approach indicated that there were longitudinal DNAm changes in successfully treated youth at the CRHR2 gene. Methylation at this gene was further correlated with cortisol secretion pre- and post-treatment. Awaiting replication, findings of this first study in youth point to molecular pathways involved in stress response and neuroplasticity to be associated with treatment response.

A Comprehensive Review of Schizophrenia and Antipsychotic Metabolism as a Predictor of Treatment Response.

Some patients with schizophrenia fail to respond to standard antipsychotics and are considered treatment-resistant. In these cases, clozapine is the only antipsychotic with proven efficacy, but its use is complicated by severe adverse effects, complex monitoring requirements, and non-response. Variation within the CYP450 enzymes CYP1A2, CYP2D6, CYP3A4, and CYP2C19 has been linked to the differential metabolism of antipsychotics. Testing for CYP450 single nucleotide polymorphisms may be a useful predictor of treatment resistance and could inform pharmacogenetic recommendations to identify potential treatment non-responders. Nonetheless, it remains uncertain whether differential antipsychotic metabolism is directly related to treatment efficacy. This comprehensive narrative review endeavours to delve into the molecular and genetic basis of schizophrenia, and discuss the current treatments available. In particular, we aim to examine the aetiology of treatment resistance in schizophrenia through available literatureand discuss current challenges within the field.

Secondary Analysis of Human Bulk RNA-Seq Dataset Suggests Potential Mechanisms for Letrozole Resistance in Estrogen-Positive (ER+) Breast Cancer.

Estrogen receptor-positive (ER+) breast cancer is common among postmenopausal women and is frequently treated with Letrozole, which inhibits aromatase from synthesizing estrogen from androgens. Decreased estrogen slows the growth of tumors and can be an effective treatment. The increase in Letrozole resistance poses a unique problem for patients. To better understand the underlying molecular mechanism(s) of Letrozole resistance, we reanalyzed transcriptomic data by comparing individuals who responded to Letrozole therapy (responders) to those who were resistant to treatment (non-responders). We identified SOX11 and S100A9 as two significant differentially expressed genes (DEGs) between these patient cohorts, with "PLK1 signaling events" being the most significant signaling pathway. We also identified PRDX4 and E2F8 gene products as being the top mechanistic transcriptional markers for ER+ treatment resistance. Many of the significant DEGs that we identified play a known role in ER+ breast cancer or other types of cancer, which partially validate our results. Several of the gene products we identified are novel in the context of ER+ breast cancer. Many of the genes that we identified warrant further research to elucidate the more specific molecular mechanisms of Letrozole resistance in this patient population and could potentially be used as prognostic markers with further wet lab validation. We anticipate that these findings could contribute to improved detection and therapeutic outcomes in aromatase-resistant ER+ breast cancer patients.

What can be learned from real-world data about chronic spontaneous urticaria?

Background: Chronic spontaneous urticaria (CSU) is a common disease with complex pathogenesis. Patients' clinical characteristics and responses to treatment vary. Objective: We aimed to investigate the role of data obtained from routinely recommended tests in predicting the response to omalizumab, the only biologic agent approved for treatment, and in defining the clinical characteristics of the patients. Methods: A retrospective study of patients who started omalizumab treatment for CSU between 2015 and 2022 at the Department of Dermatology, Pamukkale University, was conducted. Response criteria were based on the urticaria control test, and patients with a urticaria control test score <12 at 6 months were considered treatment non-responders. Eosinophil and basophil counts, neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and total immunoglobulin E (IgE) levels of the patients were evaluated before treatment and at the sixth month of treatment. Results: A total of 23.1% of the patients were unresponsive to omalizumab. The response rate to the omalizumab treatment of the patients with a total IgE level ≤ 30 IU/L (n = 4 [5.7%]) was significantly lower than patients with total IgE level > 30 IU/L (n = 66 [94.3%]) (p = 0.015). The mean ± standard deviation SIRI levels were significantly higher in non-responders versus responders (1.53 ± 1.03 versus 1.15 ± 7.76; p = 0.026). Eosinophil counts positively correlated with basophil counts (r = 587; p < 0.001) and IgE levels (r = 0.290; p = 0.005) but a negative correlation was found with levels of NLR (r = -0.475; p < 0.001), SIRI (r = -0.259; p = 0.013), and SII (r = -0.285; p = 0.006). NLR levels were lower in CSU patients with atopy, than in those without atopy (1.9 ± 0.9 vs 2.9 ± 2.1, p = 0.022). Conclusion: We suggest that eosinopenia and high NLR levels are linked to autoimmune CSU. Predicting a poor response to omalizumab seems possible with total IgE levels < 30 IU/L and high SIRI levels.

Development and Validation of a Simple and Multifaceted Instrument, Chronic Constipation-Therapeutic Efficacy and Satisfaction Test, for the Clinical Evaluation of Patients with Chronic Constipation

Introduction: This study evaluated the psychometric properties of the newly developed chronic constipation-therapeutic efficacy and satisfaction test (CC-TEST) among patients with chronic constipation. Methods: Japanese patients with moderate or severe chronic constipation underwent a 4-week remedy. The baseline, 2-week, and 4-week assessments included the CC-TEST, Constipation Scoring System (CSS), Medical Outcome Study Short Form-8 Health Survey (SF-8), and Hospital Anxiety and Depression Scale (HADS). The CC-TEST comprises three domains: (1) symptoms; chronic constipation symptom severity (seven items), defecation status (five items), (2) impact for daily life; dissatisfaction with daily life level (DS; four items), and (3) therapeutic response; therapeutic efficacy measured by patients and medication compliance (four items). Results: Of 201 eligible patients at baseline, 110 completed the 4-week treatment and the survey responses. Cronbach’s α values for the stool, defecation, and abdominal symptom subscales, as well as the total symptom score and DS subscale, showed good internal consistency reliability (0.72–0.80). Pearson’s r for comparisons between corresponding items (CC-TEST symptoms with CSS, and CC-TEST DS with SF-8 physical and mental component summary scores) was significant. After 4 weeks, scores for symptoms, defecation status, and DS items/subscales notably decreased, with a significant effect size (p < 0.005, Cohen’s d; 0.30–1.16). Statistically significant differences emerged between treatment responders and nonresponders using the three responder definitions, in changes in scores for most CC-TEST symptoms, defecation status, and DS items/subscales (p < 0.05). Conclusion: CC-TEST demonstrates commendable reliability, convergent and known-group validity, and responsiveness to treatment effects. As a simple, comprehensive, and versatile patient-reported outcome measure, CC-TEST may be well suited for clinical trials and primary care of Japanese patients with chronic constipation.

Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Sequential Acute Courses of Transcranial Magnetic Stimulation in Major Depressive Disorder: A Retrospective Analysis in a Veteran Cohort

BackgroundRepetitive transcranial magnetic stimulation (TMS) is now widely accepted as an effective non-pharmacologic treatment for treatment-resistant depression. However, whether repeated acute TMS courses can recapture the antidepressant effects of the initial acute course is still an open question, especially in the Veteran population. We present here a retrospective analysis of a specialty clinic within the Veteran Affairs Hospital System to help address this question. AimsFollowing an acute treatment course of TMS, we sought to determine the treatment response of a subsequent TMS course. We hypothesized that those who responded to an initial acute TMS course would respond in a similar manner to a subsequent treatment course. Methods116 cases referred for evaluation for TMS between September 2017 to April 2021 were reviewed. 63 Veterans completed at least one acute course of TMS and 12 completed at least two courses and met inclusion criteria for this review. 6 met criteria for treatment response in the first course, while the other 6 were initial treatment nonresponders. Symptoms were evaluated via self-reported scales at baseline and weekly throughout treatment. Clinical response to subsequent treatment (>50% symptom reduction as measured by the PHQ-9) was compared to initial treatment response. ResultsOf the initial treatment responders (n = 6), all six responded to a second acute course, with an 85.3% symptom reduction. Of the initial treatment nonresponders (n = 6), three responded to a second acute course. No adverse events were reported in those who completed a second course, and the Veterans tolerated the treatment well. ConclusionsOur findings support the growing understanding that a second acute TMS treatment course for treatment-resistant depression is safe, well-tolerated, and effective in initial responders and some non-responders. Despite multiple confounders in a naturalistic setting, robust initial treatment response was sustained in a second acute course. Low power limits generalizability, and larger powered, prospective studies are needed.

Expected symptom change trajectories for the early identification of probable treatment nonresponse in VA PTSD specialty care clinics: A proof-of-concept.

The purpose of measurement-based care (MBC) is to detect treatment nonresponse sufficiently early in treatment to adjust treatment plans and prevent failure or dropout. Thus, the potential of MBC is to provide the infrastructure for a flexible, patient-centered approach to evidence-based care. However, MBC is underutilized across the Department of Veterans Affairs (VA) posttraumatic stress disorder (PTSD) specialty clinics, likely because no actionable, empirically determined guidelines for using repeated measurement effectively are currently available to clinicians. With data collected as part of routine care in VA PTSD specialty clinics across the United States in the year prior to COVID-19 (n = 2,182), we conducted a proof-of-concept for a method of generating session-by-session benchmarks of probable patient nonresponse to treatment, which can be visualized alongside individual patient data using the most common measure of PTSD symptoms used in VA specialty clinics, the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (PCL-5). Using survival analysis, we first identified the probability of cases reaching clinically significant change at each session, as well as any significant moderators of treatment response. We then generated a multilevel model with initial symptom burden predicting the trajectory of PCL-5 scores across sessions. Finally, we determined the slowest changing 50% and 60% of all cases to generate benchmarks at each session for each level of the predictor(s) and then assessed the accuracy of these benchmarks at each session for classifying treatment responders and nonresponders. The final models were able to accurately identify nonresponders as early as the sixth session of treatment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perceived Negative Effects of Tic Management Strategies in Adults With Tic Disorders.

Behavior therapy is a well-established and empirically supported treatment for tic disorders (TDs). However, concerns have been expressed about the negative effects of behavioral interventions, such as tic worsening, tic substitution, and excessive effort. This study explored perceived negative effects of tic management strategies in adults with TDs and predictors of these experiences. Participants (N = 72) completed semi-structured interviews 11 years after receiving behavior therapy or supportive therapy in a randomized clinical trial. We examined responses to interview questions about managing tics and predictors of reported negative effects. Most participants did not experience tic worsening (84%) or tic substitution (75%) from tic management strategies. The majority felt they could manage tics while participating in their environment (87%) and did not report life interference from tic management (77%). About half (45%) felt less present when managing tics. Treatment non-responders in the original trial were more likely to report negative effects of tic management strategies. No differences in reported negative consequences were found between those who received behavior therapy versus supportive therapy, suggesting that behavior therapy specifically does not lead to such adverse effects. These findings could reduce misconceptions about behavior therapy for TDs and enhance its acceptability and utilization.

Painful physical symptoms and antidepressant treatment outcome in depression: a systematic review and meta-analysis.

Painful physical symptoms (PPS) are highly prevalent in patients with major depressive disorder (MDD). Presence of PPS in depressed patients are potentially associated with poorer antidepressant treatment outcome. We aimed to evaluate the association of baseline pain levels and antidepressant treatment outcomes. We searched PubMed, Embase and Cochrane Library databases from inception through February 2023 based on a pre-registered protocol (PROSPERO: CRD42022381349). We included original studies that reported pretreatment pain measures in antidepressant treatment responder/remitter and non-responder/non-remitter among patients with MDD. Data extraction and quality assessment were performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses by two reviewers independently. The primary outcome was the difference of the pretreatment pain levels between antidepressant treatment responder/remitter and non-responder/non-remitter. Random-effects meta-analysis was used to calculate effect sizes (Hedge's g) and subgroup and meta-regression analyses were used to explore sources of heterogeneity. A total of 20 studies were included. Six studies reported significantly higher baseline pain severity levels in MDD treatment non-responders (Hedge's g = 0.32; 95% CI, 0.13-0.51; P = 0.0008). Six studies reported the presence of PPS (measured using a pain severity scale) was significantly associated with poor treatment response (OR = 1.46; 95% CI, 1.04-2.04; P = 0.028). Five studies reported significant higher baseline pain interference levels in non-responders (Hedge's g = 0.46; 95% CI, 0.32-0.61; P < 0.0001). Four studies found significantly higher baseline pain severity levels in non-remitters (Hedge's g = 0.27; 95% CI, 0.14-0.40; P < 0.0001). Eight studies reported the presence of PPS significantly associated with treatment non-remission (OR = 1.70; 95% CI, 1.24-2.32; P = 0.0009). This study suggests that PPS are negatively associated with the antidepressant treatment outcome in patients with MDD. It is possible that better management in pain conditions when treating depression can benefit the therapeutic effects of antidepressant medication in depressed patients.

Association between resting-state connectivity patterns in the defensive system network and treatment response in spider phobia—a replication approach

Although highly effective on average, exposure-based treatments do not work equally well for all patients with anxiety disorders. The identification of pre-treatment response-predicting patient characteristics may enable patient stratification. Preliminary research highlights the relevance of inhibitory fronto-limbic networks as such. We aimed to identify pre-treatment neural signatures differing between exposure treatment responders and non-responders in spider phobia and to validate results through rigorous replication. Data of a bi-centric intervention study comprised clinical phenotyping and pre-treatment resting-state functional connectivity (rsFC) data of n = 79 patients with spider phobia (discovery sample) and n = 69 patients (replication sample). RsFC data analyses were accomplished using the Matlab-based CONN-toolbox with harmonized analyses protocols at both sites. Treatment response was defined by a reduction of >30% symptom severity from pre- to post-treatment (Spider Phobia Questionnaire Score, primary outcome). Secondary outcome was defined by a reduction of >50% in a Behavioral Avoidance Test (BAT). Mean within-session fear reduction functioned as a process measure for exposure. Compared to non-responders and pre-treatment, results in the discovery sample seemed to indicate that responders exhibited stronger negative connectivity between frontal and limbic structures and were characterized by heightened connectivity between the amygdala and ventral visual pathway regions. Patients exhibiting high within-session fear reduction showed stronger excitatory connectivity within the prefrontal cortex than patients with low within-session fear reduction. Whereas these results could be replicated by another team using the same data (cross-team replication), cross-site replication of the discovery sample findings in the independent replication sample was unsuccessful. Results seem to support negative fronto-limbic connectivity as promising ingredient to enhance response rates in specific phobia but lack sufficient replication. Further research is needed to obtain a valid basis for clinical decision-making and the development of individually tailored treatment options. Notably, future studies should regularly include replication approaches in their protocols.

Changes in Inflammatory Cytokines in Responders and Non-Responders to TNFα Inhibitor and IL-17A Inhibitor: A Study Examining Psoriatic Arthritis Patients.

This study aimed to examine the changes in biomarker levels in responders and non-responders to tumor necrosis factor alpha inhibitor (TNFi) and interleukin-17A inhibitor (IL-17Ai) in psoriatic arthritis (PsA) patients over a 4-month period after treatment initiation. A total of 68 PsA patients initiating either TNFi, IL-17Ai, or methotrexate treatment were included. Blood plasma and clinical outcome measures were collected adjacent to treatment initiation and after four months. A commercially available multiplex immunoassay was included to evaluate 54 biomarkers. Mean changes were used to evaluate change over time. A statistically significant decrease in pro-inflammatory cytokines IL-6 (log-transformed mean change -0.97, 95%CI -4.30; 2.37, [p = 0.032]) and an increase in anti-inflammatory IL-10 (0.38, 95%CI 1.74; 2.50 [p = 0.010]) were seen in TNFi responders. Meanwhile, a statistically significant increase in the target cytokine IL-17A was seen in both IL-17Ai responders (2.49, 95%CI -1.84; 6.85 [p = 0.031]) and non-responders (2.48, 95%CI -1.46; 6.41 [p = 0.001]). This study demonstrated differing changes in cytokine levels when comparing treatment responders and non-responders, highlighting the need to improve the understanding of the different immune response mechanisms explaining different responses to medical treatment in PsA patients.