Variance In Treatment Response Research Articles

Predicting response to cognitive processing therapy: Does trauma history matter?

Cognitive processing therapy (CPT) has reliably demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD) for most patients, however, not all patients derive the same benefit from CPT. The aim of the present study is to identify trauma-related variables that predict differential response to CPT in a sample of treatment-seeking veterans in order to improve individual responses to CPT. The present study evaluated demographic, therapy, and trauma-related variables as possible predictors of variable response to CPT in a sample of 259 treatment-seeking veterans who received treatment in an outpatient clinic. Nearly 43% of veterans completed group or individual CPT and of completers, 76.1% reported clinically significant improvement in PTSD symptoms. Although most variability in treatment response was attributable to person-level characteristics, no demographic, treatment, or trauma-related variables were associated with change in PTSD symptoms or explained variance in treatment response (all ps > 0.05). These results suggest that CPT can be effectively implemented in its various forms to a broad range of patients (i.e., male or female, of any age or race, trauma type, or time since traumatic event) when the treatment is completed and applied by a trained provider. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

533-P: Predicting Treatment Response in Painful Diabetic Neuropathy Using Magnetic Resonance Brain Imaging

Background: Painful diabetic polyneuropathy (DPN) is difficult to manage as treatment response is often varied. The aim of this study was to explore the central mechanisms to explain the variance in treatment response. Methods: Forty-five consecutive patients who received intravenous lidocaine treatment for painful DPN were screened. All subjects completed a treatment efficacy questionnaire. Twenty-nine patients (responders n=14 and non-responders n=15) along with 26 healthy controls subsequently underwent multimodal brain magnetic resonance (MR) imaging to acquire anatomical and resting state functional data (3T, Achieva, Phillips Healthcare). Results: There was no significant difference in age (p=0.53), pain duration (p=0.89), diabetes duration (p=0.19) and clinical parameters of neuropathy (TCNS, p=0.16 and NTSS-6, p=0.61) between responders and non-responders to lidocaine treatment. Neither was there a difference in the use of concurrent neuropathic pain treatments. Non-responders to lidocaine had significantly lower mean S1 cortical volumes and mean number of vertices compared to responders and healthy controls (ANOVA p=0.02 and 0.02 respectively). There was no significant difference in S1 cortical volumes or vertices between responders and healthy controls. There was significantly greater resting state functional connectivity in lidocaine responders between the insula cortex [F(4)(13)=10.33; p-FDR=0.01] and the orbital frontal cortex [T(20)=3.88; p-FDR=0.02], amygdala [T(20)=3.65; p-FDR=0.02] and anterior cingulate gyrus [T(20)=4.04; p-FDR=0.01]. Conclusion: To the best of our knowledge, this is the first assessment of CNS mechanisms of treatment response in painful DPN. Key nociceptive processing areas showed decreased grey matter density (S1 cortex) and reduced functional connectivity (insula) relating to treatment response. MR neuroimaging may serve as a Central Pain Signature which could be used to predict treatment response. Disclosure K. Teh: None. I.D. Wilkinson: None. G.P. Sloan: None. S. Tesfaye: Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation, Wörwag Pharma. Speaker’s Bureau; Self; Abbott, AstraZeneca, Grunenthal Group, Napp Pharmaceuticals, Novo Nordisk Inc., Pfizer Inc. D. Selvarajah: None. Funding European Foundation for the Study of Diabetes; University of Sheffield

VCAM-1 Density and Tumor Perfusion Predict T-cell Infiltration and Treatment Response in Preclinical Models

Cancer immunotherapies have demonstrated durable responses in a range of different cancers. However, only a subset of patients responds to these therapies. We set out to test if non-invasive imaging of tumor perfusion and vascular inflammation may be able to explain differences in T-cell infiltration in pre-clinical tumor models, relevant for treatment outcomes. Tumor perfusion and vascular cell adhesion molecule (VCAM-1) density were quantified using magnetic resonance imaging (MRI) and correlated with infiltration of adoptively transferred and endogenous T-cells. MRI biomarkers were evaluated for their ability to detect tumor rejection 3 days after T-cell transfer. Baseline levels of these markers were used to assess their ability to predict PD-L1 treatment response. We found correlations between MRI-derived VCAM-1 density and infiltration of endogenous or adoptively transferred T-cells in some preclinical tumor models. Blocking T-cell binding to endothelial cell adhesion molecules (VCAM-1/ICAM) prevented T-cell mediated tumor rejection. Tumor rejection could be detected 3 days after adoptive T-cell transfer prior to tumor volume changes by monitoring the extracellular extravascular volume fraction. Imaging tumor perfusion and VCAM-1 density before treatment initiation was able to predict the response of MC38 tumors to PD-L1 blockade. These results indicate that MRI based assessment of tumor perfusion and VCAM-1 density can inform about the permissibility of the tumor vasculature for T-cell infiltration which may explain some of the observed variance in treatment response for cancer immunotherapies.

Predictors for Excellent Versus Partial Response to Prolonged Exposure Therapy: Who Needs Additional Sessions?

In practice, the duration of psychotherapy is determined by the patient's response to treatment. Identifying predictors for treatment responses is of great clinical utility to guide clinicians in their treatment planning. Demographic characteristics, trauma history, comorbidity, and early reduction of posttraumatic stress disorder (PTSD) symptoms were examined as predictors of excellent versus partial response to prolonged exposure therapy (PE) for PTSD. Participants were 96 female assault survivors with chronic PTSD who received at least eight PE sessions with or without cognitive restructuring. Participants were classified as excellent responders (n = 27) or partial responders (n = 69) based on whether they achieved at least 70% improvement in self-reported PTSD severity on the PTSD Symptom Scale-Self-Report at the end of Session 8. Excellent responders terminated therapy after Session 9, and partial responders were offered up to three additional sessions. Logistic regression was conducted to investigate predictors of response to PE. Results showed that prior interpersonal violence and comorbid alcohol use disorder were associated with partial response. Comorbid depressive disorder and early PTSD symptom reduction were associated with excellent response. Being treated by a cognitive behavioral therapy expert predicted higher excellent response for patients with a history of prior interpersonal violence. The model accounted for 56.6% of the variance in treatment response and correctly predicted responder status for 83.3% of the sample. These findings contribute to the field's understanding of factors that predict or moderate response to PE and have implications for treatment planning.

Remote Brain Iron Accumulation: A Useful Biomarker for Stroke Recovery?

Remote Brain Iron Accumulation: A Useful Biomarker for Stroke Recovery?

Structural similarity networks predict clinical outcome in early-phase psychosis.

Despite recent advances, there is still a major need for prediction of treatment success in schizophrenia, a condition long considered a disorder of dysconnectivity in the brain. Graph theory provides a means to characterize the connectivity in both healthy and abnormal brains. We calculated structural similarity networks in each participant and hypothesized that the "hubness", i.e., the number of edges connecting a node to the rest of the network, would be associated with clinical outcome. This prospective controlled study took place at an academic research center and included 82 early-phase psychosis patients (23 females; mean age [SD] = 21.6 [5.5] years) and 58 healthy controls. Medications were administered in a double-blind randomized manner, and patients were scanned at baseline prior to treatment with second-generation antipsychotics. Symptoms were assessed with the Brief Psychiatric Rating Scale at baseline and over the course of 12 weeks. Nodal degree of structural similarity networks was computed for each subject and entered as a predictor of individual treatment response into a partial least squares (PLS) regression. The model fit was significant in a permutation test with 1000 permutations (P = 0.006), and the first two PLS regression components explained 29% (95% CI: 27; 30) of the variance in treatment response after cross-validation. Nodes loading strongly on the first PLS component were primarily located in the orbito- and prefrontal cortex, whereas nodes loading strongly on the second PLS component were primarily located in the superior temporal, precentral, and middle cingulate cortex. These data suggest a link between brain network morphology and clinical outcome in early-phase psychosis.

L-Dopa responsiveness is associated with distinctive connectivity patterns in advanced Parkinson's disease.

Neuronal loss and dopamine depletion alter motor signal processing between cortical motor areas, basal ganglia, and the thalamus, resulting in the motor manifestations of Parkinson's disease. Dopamine replacement therapy can reverse these manifestations with varying degrees of improvement. To evaluate functional connectivity in patients with advanced Parkinson's disease and changes in functional connectivity in relation to the degree of response to l-dopa, 19 patients with advanced Parkinson's disease underwent resting-state functional magnetic resonance imaging in the on-medication state. Scans were obtained on a 3-Tesla scanner in 3 × 3 × 2.5 mm3 voxels. Seed-based bivariate regression analyses were carried out with atlas-defined basal ganglia regions as seeds, to explore relationships between functional connectivity and improvement in the motor section of the UPDRS-III following an l-dopa challenge. False discovery rate-corrected P was set at < 0.05 for a 2-tailed t test. A greater improvement in UPDRS-III scores following l-dopa administration was characterized by higher resting-state functional connectivity between the prefrontal cortex and the striatum (P = 0.001) and lower resting-state functional connectivity between the pallidum (P = 0.001), subthalamic nucleus (P = 0.003), and the paracentral lobule (supplementary motor area, mesial primary motor, and primary sensory areas). Our findings show characteristic basal ganglia resting-state functional connectivity patterns associated with different degrees of l-dopa responsiveness in patients with advanced Parkinson's disease. l-Dopa exerts a graduated influence on remapping connectivity in distinct motor control networks, potentially explaining some of the variance in treatment response. © 2017 International Parkinson and Movement Disorder Society.

Antipsychotic induced metabolic changes & treatment response: A prospective study

BackgroundMetabolic side effects of antipsychotics contribute to morbidity and non-compliance in treatment of psychosis. Multiple studies suggest that metabolic side effects correlate with response to antipsychotic treatment. However, few studies have systematically looked at this. We conducted an exploratory, naturalistic, prospective, trans-diagnostic study to examine this association. Methods100 patients with psychosis, initiated on antipsychotic treatment alone, were assessed on Brief Psychiatric Rating Scale (BPRS), visual analog scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and fasting serum lipid and glucose profiles at baseline, 2–4 weeks (n=71) and 8–12 weeks (n=39). ResultsSubjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2–4 weeks) increase in appetite and triglyceride levels (R2=0.257; p=0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2–4 weeks) increase in triglyceride levels (R2=0.169; p=0.009). ConclusionsEarly appetite and triglyceride changes predicted antipsychotic treatment response. Involvement of dopaminergic, serotonergic and histaminergic neural pathways could explain the association between appetite and treatment response. Insulin signaling pathways have been implicated in lipid changes with antipsychotics. Study findings suggest metabolic side effects may be early predictors of antipsychotic response. These findings warrant further examination to elucidate the interaction between metabolic pathways and psychotic illnesses, and possibly mechanism of action of antipsychotics beyond dopamine blockade.

Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication

We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness.

SAT0012 Estimating heritability of response to treatment with anti-TNF biologic agents using linear mixed models

BackgroundThe effectiveness of treatment with anti-TNF inhibitors in rheumatoid arthritis (RA) is variable with a significant minority of patients experiencing poor response. Ideally clinicians would like to identify which patients...

1336 – Early metabolic side effects as predictors of antipsychotic treatment response: a 2-month prospective study

Metabolic side-effects of antipsychotics increase morbidity and non-compliance rates. Interestingly, preliminary evidence suggests that metabolic side-effects correlate with response to antipsychotic treatment. Few studies have examined the nature of this association in a prospective study design. We conducted an exploratory, naturalistic, prospective, trans- diagnostic study to examine this association. To study the relation between metabolic side-effects and clinical improvement with antipsychotics, in psychotic illnesses [non-affective psychoses and mania-1st episode]. 100 (84 drug-free for at least one month) patients with psychosis initiated on antipsychotic treatment alone (65% on risperidone) were assessed on Brief Psychiatric Rating Scale (BPRS), visual analogue scale for appetite, anthropometric measurements (weight, waist circumference, body mass index), and serum lipid and glucose profiles at baseline, 2-4 weeks (n = 71) and 8-12weeks (n = 39). Subjects who dropped out at first/second follow-ups did not differ from those who followed-up, in age, sex, illness duration and BPRS scores. On forward stepwise multiple linear regression analysis, early (2-4weeks) increase in appetite and triglyceride levels (R 2 = 0.257; p = 0.003) together predicted 26% variance in treatment response (BPRS score reduction) at first follow-up. At second follow-up 16% of variance in treatment response was predicted by early (2-4 weeks) increase in triglyceride levels (R 2 = 0.169; p = 0.009) alone. Early appetite and triglyceride changes predicted antipsychotic treatment response. Future research should (a) examine neural mechanisms that operate in both appetite regulation and antipsychotic action to further the understanding of psychosis and its treatment, and (b) identify early markers of treatment response

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient.

The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study

It remains unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in RA. We investigated the relationship between the presence and levels of different RF and ACPA isotypes and the response to TNF blockade in an exploratory study. A total of 101 active RA patients were prospectively treated with infliximab (3 mg/kg). Changes in disease activity were monitored by the 28-joint DAS (DAS-28). Serum levels of different isotypes [immunoglobulins M, G and A (IgM, IgG and IgA)] of RF and anti-citrullinated peptide antibodies were measured by ELISA. The mean DAS-28 decreased from 5.9 (1.1) at baseline to 4.0 (1.3) at Week 16 of infliximab treatment (P < 0.001). High baseline levels of different isotypes of RF (all P < 0.008), ACPA IgM (P = 0.008) and ACPA IgG (P = 0.07) were associated with an absolute decrease in DAS-28 after TNF blockade. This relationship persisted after adjusting for DAS-28 at baseline. However, the different isotypes of baseline RF and ACPA levels accounted for only a small proportion of variance in treatment response (RF: R² between 7 and 12% and ACPA: R² between 4 and 7%). The simultaneous presence of all three isotypes of RF or ACPA had no additive value. Presence as well as the titres of RF and IgM ACPA at baseline are significantly correlated with better response to infliximab treatment. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Trial Registration. ISRCTN Register, http://www.controlled-trials.com/isrctn/, ISRCTN36847425.

A gene score of nine LDL and HDL regulating genes is associated with fluvastatin-induced cholesterol changes in women

While conventional pharmacogenetic studies have considered single gene effects, we tested if a genetic score of nine LDL- and HDL-associated single nucleotide polymorphisms, previously shown to predict cardiovascular disease, is related to fluvastatin-induced lipid change. In patients with asymptomatic plaque in the right carotid artery, thus candidates for statin therapy, we related score LDL [APOB(rs693), APOE(rs4420638), HMGCR(rs12654264), LDLR(rs1529729), and PCSK9(rs11591147)] and score HDL [ABCA1(rs3890182), CETP(rs1800775), LIPC(rs1800588), and LPL(rs328)] as well as the combined score LDL+HDL to fluvastatin-induced LDL reduction (+/- metoprolol) (n = 395) and HDL increase (n = 187) following 1 year of fluvastatin treatment. In women, an increasing number of unfavorable alleles (i.e., alleles conferring higher LDL and lower HDL) of score LDL+HDL (P = 0.037) and of score LDL (P = 0.023) was associated with less pronounced fluvastatin-induced LDL reduction. Furthermore, in women, both score LDL+HDL (P = 0.001) and score HDL (P = 0.022) were directly correlated with more pronounced fluvastatin-induced HDL increase, explaining 5.9-11.6% of the variance in treatment response in women. There were no such associations in men. This suggests that a gene score based on variation in nine different LDL- and HDL-associated genes is of importance for the magnitude of fluvastatin HDL increase in women with asymptomatic plaque in the carotid artery.

Association of rheumatoid factor and anti-cyclic citrullinated peptide positivity, but not carriage of shared epitope or PTPN22 susceptibility variants, with anti-tumour necrosis factor response in rheumatoid arthritis

Objective:To determine whether rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibodies, or carriage of shared epitope (SE) and PTPN22 genetic susceptibility variants predict response to therapy in patients with rheumatoid...

Predicting Treatment Response During the Acute Phase of Hospitalization

This study sought to determine if an initial assessment for an acute inpatient population was able to predict treatment response as measured by progress through clinical pathways. In addition, we sought to analyze the impact of comorbidity on treatment response. A total of 170 adults (18-75 years) admitted for an acute inpatient hospitalization, received a full assessment including the Brief Symptom Inventory. Based on assessment results, patients were placed on one of five clinical pathways. Treatment response was measured by the number of days spent on each level of the clinical pathway. Results revealed an unexpected, significant negative correlation between symptom severity on admission and movement through the clinical pathway; that is, patients with more severe symptomatic presentations at assessment made more rapid progress through the clinical pathways. However, comorbidity showed the strongest relationship with treatment response. Taken together, these variables explained 52% of the variance in treatment response. Responsiveness to antipsychotic medications, as well as high levels of subjective distress and the consequent motivation to achieve relief, may help explain the unexpected relationship between symptom severity and treatment response. Findings also demonstrated the utility of an initial assessment in predicting treatment response.