Neurobiological Basis of Reinforcement-Based Decision-Making in Adults With ADHD Treated With Lisdexamfetamine Dimesylate

Background: The objective of this study was to examine changes in the activation of the brain reward system following treatment with lisdexamfetamine (LDX) vs. placebo (PL) as a function of clinical improvement in attention deficit/hyperactivity disorder (ADHD) symptoms. Methods: Twenty adults with ADHD were included in a randomized cross-over study. Participants underwent two functional magnetic resonance imaging (fMRI) scans, after receiving 3 to 5 weeks of treatment with both LDX and PL. During scanning, participants performed the passive-avoidance learning task to assess reward-related learning using computational variables (e.g., estimated value and prediction error). Pre-treatment to post-treatment symptom change was assessed via the ADHD Rating Scale (ADHD-RS). The imaging contrasts were Object Choose or Object Refuse during the object choice component of the task, modulated by expected value (reward vs. nonreward cue), and Reward vs. Punishment during feedback, modulated by prediction error (expected vs. actual outcome). To address the primary objective, we performed group-level mass univariate analyses between pre-treatment to post-treatment percent change of the ADHD-RS total scores and the four contrast images under the choice and feedback conditions, with significance set at a whole-brain voxel-wise threshold of p < .05 with family-wise error (FWE) correction and an extent (cluster) threshold of 50 contiguous voxels. Results: Improvement in ADHD symptoms was accompanied by significant increases of brain activation during the Object Refuse, Reward and Punishment contrasts in a widespread network including left caudate and putamen, and right orbitofrontal cortex (i.e., reward-related signaling) and left middle frontal, superior frontal, and precentral gyri (i.e., executive control). Conclusions: These findings are the first to show that the increase in responsiveness of systems engaged in reward processing with LDX treatment is positively related to symptom improvement. Results support the hypothesis that LDX treatment may restore balance to dysfunction (e.g., hypoactivation) within the brain reward circuitry in adults with ADHD.

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Expectancies as predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease

Clinical Rheumatology ◽

10.1007/s10067-021-05760-1 ◽

2021 ◽

Author(s):

Henriët van Middendorp ◽

Anneleen Berende ◽

Fidel J. Vos ◽

Hadewych H. M. ter Hofstede ◽

Bart Jan Kullberg ◽

...

Keyword(s):

Lyme Disease ◽

Treatment Success ◽

Symptomatic Improvement ◽

Post Treatment ◽

Symptom Improvement ◽

Persistent Symptoms ◽

Treatment Expectancies ◽

End Of Treatment ◽

Pre Treatment

Abstract Introduction/Objective Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive. Methods A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health–related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone. At end-of-treatment (14 weeks after trial start) and follow-up (52 weeks), complete data of 231 and 170 (of initial 280) patients with persistent symptoms temporally related to a history of erythema migrans or otherwise confirmed symptomatic Lyme disease, or accompanied by B. burgdorferi IgG or IgM antibodies, were examined through hierarchical regression analyses. Results In addition to pre-treatment HRQoL, pre-treatment expectancies regarding symptom improvement were consistently associated with stronger physical and mental HRQoL improvements at both end-of-treatment and follow-up (95% CI range: .09;.54, p < .01 to .27;.92, p < .001). Post-treatment expectancies regarding having received antibiotics vs. placebo was associated with more HRQoL improvement at end-of-treatment, but not at follow-up (95% CI-range 1.00;4.75, p = .003 to −7.34; −2.22, p < .001). Conclusions The present study shows that, next to pre-treatment functioning, patients’ pre-treatment and post-treatment expectancies regarding improvement of persistent symptoms attributed to Lyme disease relate to a more beneficial symptom course. Expectancies of patients may be relevant to explain and potentially improve patient outcomes (e.g., by optimized communication about treatment success). Trial registration ClinicalTrials.gov, NCT01207739 (Registration date: 23–09-2010) Key Points• As there is currently no sufficient symptom resolution or symptomatic improvement for many patients with persistent symptoms attributed to Lyme disease, it is relevant to know which factors determine symptom progression and predict heterogeneity in treatment response.• Next to pre-treatment functioning, expectancies regarding symptom improvement and having received antimicrobial study medication are associated with a more beneficial symptom course after both shorter-term and longer-term antimicrobial treatment.• Expectancies are relevant to consider in treatment studies and may be useful in clinical settings to improve symptom course and treatment outcome (e.g., by optimized communication about treatment success).

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Daily dynamics of negative affect: indicators of rate of response to treatment and remission from depression?

10.31234/osf.io/hv65n ◽

2021 ◽

Author(s):

Marieke A. Helmich ◽

M. Wichers ◽

Frenk Peeters ◽

Evelien Snippe

Keyword(s):

Negative Affect ◽

Rating Scale ◽

Supportive Therapy ◽

Diagnostic Interview ◽

Response To Treatment ◽

Symptom Improvement ◽

Remission Status ◽

The Mean ◽

Pre Treatment ◽

Ecological Momentary

More instability (MSSD) and variability (SD) of negative affect (NA) have been related to current and future depressive symptoms. We investigated whether MSSD and SD of NA were predictive of the rate of symptom improvement during treatment and of reaching remission status. Forty-six individuals with major depressive disorder completed six days of ecological momentary assessments (10 beeps per day) before starting a combination of pharmacotherapy and supportive therapy. During and after treatment, the Hamilton Depression Rating Scale (HDRS) diagnostic interview was performed monthly for 18 months. Using multilevel modeling and logistic regression, a linear decrease in HDRS scores as well as reaching remission status (HDRS of ≤7 within or after five months) were predicted by the mean, SD and MSSD of NA in momentary assessments, and relevant baseline predictors. Mean NA, but not the SD or MSSD of NA, predicted rates of depressive symptom reduction over five months. The odds of remitting during treatment were not associated with any predictors. Our results suggest that pre-treatment assessments of NA instability and variability may not give an indication of the treatment response over time. Clinically, the mean of NA may be more promising as a baseline indicator of response potential.

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Baseline reward processing and ventrostriatal dopamine function are associated with pramipexole response in depression

Brain ◽

10.1093/brain/awaa002 ◽

2020 ◽

Vol 143 (2) ◽

pp. 701-710 ◽

Cited By ~ 6

Author(s):

Alexis E Whitton ◽

Jenna M Reinen ◽

Mark Slifstein ◽

Yuen-Siang Ang ◽

Patrick J McGrath ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Prediction Error ◽

Dopamine Agonists ◽

Dopamine Release ◽

Reward Processing ◽

Reward Learning ◽

Symptom Improvement ◽

Major Depressive ◽

Depressed Group

Abstract The efficacy of dopamine agonists in treating major depressive disorder has been hypothesized to stem from effects on ventrostriatal dopamine and reward function. However, an important question is whether dopamine agonists are most beneficial for patients with reward-based deficits. This study evaluated whether measures of reward processing and ventrostriatal dopamine function predicted response to the dopamine agonist, pramipexole (ClinicalTrials.gov Identifier: NCT02033369). Individuals with major depressive disorder (n = 26) and healthy controls (n = 26) (mean ± SD age = 26.5 ± 5.9; 50% female) first underwent assessments of reward learning behaviour and ventrostriatal prediction error signalling (measured using functional MRI). 11C-(+)-PHNO PET before and after oral amphetamine was used to assess ventrostriatal dopamine release. The depressed group then received open-label pramipexole treatment for 6 weeks (0.5 mg/day titrated to a maximum daily dose of 2.5 mg). Symptoms were assessed weekly, and reward learning was reassessed post-treatment. At baseline, relative to controls, the depressed group showed lower reward learning (P = 0.02), a trend towards blunted reward-related prediction error signals (P = 0.07), and a trend towards increased amphetamine-induced dopamine release (P = 0.07). Despite symptom improvements following pramipexole (Cohen’s d ranging from 0.51 to 2.16 across symptom subscales), reward learning did not change after treatment. At a group level, baseline reward learning (P = 0.001) and prediction error signalling (P = 0.004) were both associated with symptom improvement, albeit in a direction opposite to initial predictions: patients with stronger pretreatment reward learning and reward-related prediction error signalling improved most. Baseline D2/3 receptor availability (P = 0.02) and dopamine release (P = 0.05) also predicted improvements in clinical functioning, with lower D2/3 receptor availability and lower dopamine release predicting greater improvements. Although these findings await replication, they suggest that measures of reward-related mesolimbic dopamine function may hold promise for identifying depressed individuals likely to respond favourably to dopaminergic pharmacotherapy.

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The relation between dopamine D2 receptor blockade and the brain reward system: a longitudinal study of first-episode schizophrenia patients

Psychological Medicine ◽

10.1017/s0033291718004099 ◽

2019 ◽

Vol 50 (2) ◽

pp. 220-228 ◽

Cited By ~ 6

Author(s):

Sanne Wulff ◽

Mette Ødegaard Nielsen ◽

Egill Rostrup ◽

Claus Svarer ◽

Lars Thorbjørn Jensen ◽

...

Keyword(s):

Longitudinal Study ◽

Reward System ◽

Reward Processing ◽

Psychotic Symptoms ◽

First Episode ◽

Receptor Blockade ◽

Fmri Signal ◽

Brain Reward ◽

First Episode Schizophrenia ◽

The Brain

AbstractBackgroundPsychotic symptoms have been linked to salience abnormalities in the brain reward system, perhaps caused by a dysfunction of the dopamine neurotransmission in striatal regions. Blocking dopamine D2 receptors dampens psychotic symptoms and normalises reward disturbances, but a direct relationship between D2 receptor blockade, normalisation of reward processing and symptom improvement has not yet been demonstrated. The current study examined the association between blockade of D2 receptors in the caudate nucleus, alterations in reward processing and the psychopathology in a longitudinal study of antipsychotic-naïve first-episode schizophrenia patients.MethodsTwenty-two antipsychotic-naïve first-episode schizophrenia patients (10 males, mean age 23.3) and 23 healthy controls (12 males, mean age 23.5) were examined with single-photon emission computed tomography using 123I-labelled iodobenzamide. Reward disturbances were measured with functional magnetic resonance imaging (fMRI) using a modified version of the monetary-incentive-delay task. Patients were assessed before and after 6 weeks of treatment with amisulpride.ResultsIn line with previous results, patients had a lower fMRI response at baseline (0.2 ± 0.5 v. 0.7 ± 0.6; p = 0.008), but not at follow-up (0.5 ± 0.6 v. 0.6 ± 0.7), and a change in the fMRI signal correlated with improvement in Positive and Negative Syndrome Scale positive symptoms (ρ = −0.435, p = 0.049). In patients responding to treatment, a correlation between improvement in the fMRI signal and receptor occupancy was found (ρ = 0.588; p = 0.035).ConclusionThe results indicate that salience abnormalities play a role in the reward system in schizophrenia. In patients responding to a treatment-induced blockade of dopamine D2 receptors, the psychotic symptoms may be ameliorated by normalising salience abnormalities in the reward system.

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Internet-delivered eye movement desensitization and reprocessing (iEMDR): an open trial

F1000Research ◽

10.12688/f1000research.2-79.v1 ◽

2013 ◽

Vol 2 ◽

pp. 79

Author(s):

Jay Spence ◽

Nickolai Titov ◽

Luke Johnston ◽

Blake F Dear ◽

Bethany Wootton ◽

...

Keyword(s):

Eye Movement ◽

Treatment Protocol ◽

Behavioural Therapy ◽

Post Treatment ◽

Effect Sizes ◽

Future Research ◽

Symptom Improvement ◽

Post Traumatic Stress ◽

Pre Treatment

Recent research indicates internet-delivered cognitive behavioural therapy (iCBT) can reduce symptoms of post traumatic stress disorder (PTSD). This study examined the efficacy of an internet-delivered treatment protocol that combined iCBT and internet-delivered eye movement desensitization and reprocessing (iEMDR), in an uncontrolled trial. Eleven of the 15 participants completed post-treatment questionnaires. Large effect sizes were found from pre-treatment to 3-month follow-up (d = 1.03 – 1.61) on clinician-assessed and self-reported measures of PTSD, anxiety and distress, with moderate effect sizes (d = 0.59 – 0.70) found on measures of depression and disability. At post-treatment, 55% of the participants no longer met criteria for PTSD and this was sustained at follow-up. Symptom worsening occurred in 3 of 15 (20%) of the sample from pre- to post-treatment; however, these participants reported overall symptom improvement by follow-up. Future research directions for iEMDR are discussed.

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Internet-delivered eye movement desensitization and reprocessing (iEMDR): an open trial

F1000Research ◽

10.12688/f1000research.2-79.v2 ◽

2013 ◽

Vol 2 ◽

pp. 79 ◽

Cited By ~ 4

Author(s):

Jay Spence ◽

Nickolai Titov ◽

Luke Johnston ◽

Blake F Dear ◽

Bethany Wootton ◽

...

Keyword(s):

Eye Movement ◽

Treatment Protocol ◽

Behavioural Therapy ◽

Post Treatment ◽

Effect Sizes ◽

Future Research ◽

Symptom Improvement ◽

Post Traumatic Stress ◽

Pre Treatment

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Effects of Minimal Acupuncture in Children with Infantile Colic – a Prospective, Quasi-Randomised Single Blind Controlled Trial

Acupuncture in Medicine ◽

10.1136/aim.26.3.171 ◽

2008 ◽

Vol 26 (3) ◽

pp. 171-182 ◽

Cited By ~ 50

Author(s):

Marianne Reinthal ◽

Sven Andersson ◽

Marianne Gustafsson ◽

Kaety Plos ◽

Iréne Lund ◽

...

Keyword(s):

Side Effects ◽

Rating Scale ◽

Controlled Trial ◽

Numeric Rating Scale ◽

Post Treatment ◽

Control Group ◽

Seek Health Care ◽

Parental Assessment ◽

The Difference ◽

Pre Treatment

Background Colic causes crying in 10–30% of infants and is one of the primary reasons parents seek health care. Treatments are generally not totally effective and some cause side effects. In this study we aimed to test the effect of light needling (minimal acupuncture) on crying. Methods Forty children (median six weeks of age) with excessive crying unresponsive to conventional therapies, were recruited from 21 Child Welfare Clinics within an area of western Sweden, and quasi-randomised to control or light needling treatment. Parents were unaware of which group their child was assigned to. Children were given light needling acupuncture on one point (LI4) on both hands for approximately 20 seconds on four occasions, or received the same care except needling. Parental assessment questionnaires were used pre- and post-treatment to assess crying intensity, frequency, duration of crying and pain related behaviour throughout the day in six hour periods. Results Light needling resulted in a significant reduction in the rated crying intensity (assessed by a numeric rating scale, 0 to 10). For example, during the morning time period 0600–1200 hours, the median (range) rated crying intensity changed from 6 (1 to 9) pre-treatment to 2 (0 to 5) post-treatment (P=0.002), in the light needling group. The corresponding ratings for the children in the control group was 6 (0 to 10) and 5 (0 to 10) respectively. The difference between the groups was significant (P=0.016). There were also significant differences between the groups for the afternoon (1200–1800 hours), and evening (1800–midnight) time periods. Pain related behaviour like facial expression, was also significantly less pronounced in the light needling group as compared to the control group post-treatment, (P=0.027). The parents rated the light needling as more effective in improving symptoms than the control group (P<0.001). Conclusion Four treatments with light needling on one point in the hand may alleviate crying and pain related behaviour without any noted side effects.

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An initial exploration of hair cortisol responses to antidepressants in unmedicated patients with depression

Journal of International Medical Research ◽

10.1177/0300060519889431 ◽

2019 ◽

Vol 48 (3) ◽

pp. 030006051988943 ◽

Cited By ~ 1

Author(s):

Xiuli Song ◽

Wei Cui ◽

Zugui Peng ◽

Liansheng Zhao ◽

Xuezhu Yu ◽

...

Keyword(s):

Hpa Axis ◽

Rating Scale ◽

Cortisol Concentration ◽

Post Treatment ◽

Hair Cortisol ◽

Long Term Effects ◽

Scale Scores ◽

Healthy Control ◽

Cortisol Responses ◽

Pre Treatment

Objective Major depressive disorder is associated with abnormal functioning of the hypothalamic–pituitary–adrenal (HPA) axis. Studies using hair cortisol to measure the effect of antidepressants on the HPA axis are lacking. The aim of this study was to explore the long-term effects of antidepressants on hair cortisol concentration (HCC). Methods Participants were 42 patients and 36 healthy individuals. The patients took antidepressants for 4 weeks. Patient HCC was measured pre-treatment and post-treatment. The HCC of healthy controls was also measured. Results Patient post-treatment HCC (mean ± standard deviation: 34.40 ± 32.57 pmol/mg) was significantly higher than patient pre-treatment HCC (17.42 ± 12.40 pmol/mg) and healthy control HCC (10.22 ± 7.99 pmol/mg). No significant correlation was found between Hamilton Depression Rating Scale scores and HCC at pre-treatment or post-treatment. Conclusions Hair cortisol concentration analysis could be used to monitor the dynamics of the effects of antidepressants on the HPA axis.

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Effects of Kinesio Taping in Supraspinatus Tendinitis

Journal of Clinical and Nursing Research ◽

10.26689/jcnr.v5i6.2428 ◽

2021 ◽

Vol 5 (6) ◽

pp. 67-71

Author(s):

Jawad Anwar ◽

Farjad Afzal ◽

Muhammad Mustafa Qamar ◽

Ayesha Basharat

Keyword(s):

Shoulder Pain ◽

Rating Scale ◽

Post Treatment ◽

Mean Difference ◽

Dash Score ◽

Kinesio Taping ◽

Musculoskeletal Problems ◽

Effective Program ◽

Pre Treatment ◽

Supraspinatus Tendinitis

Background: Shoulder pain is one of the most commonly reported musculoskeletal problems after low back pain. One common reason for the shoulder pain is supraspinatus tendinitis that is often associated with impingement syndrome. Objective: To find the effects of kinesio taping in reducing pain and disability in subjects with supraspinatus tendinitis. Methodology: In this study, patients were randomly allocated the treatment using a set of predefined inclusion and exclusion criteria. Subjects were managed with kinesio taping. Pre- and post-evaluation of the patients was done using Numerical Pain Rating Scale (NPRS) and Disability of Arm Shoulder & Hand Questionnaire (DASH) score and the data gathered was entered and analyzed using SPSS version 23. Results: Mean difference of 2.65 was reported between the pretreatment and post treatment values of NPRS in KT taping group which was significant (P < 0.05). Mean difference of 27.25 was reported between the pre-treatment and post-treatment values of DASH score in KT taping group which was significant (P < 0.05). Conclusion: Kinesio taping is an effective Program in management of supraspinatus tendinitis.

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Core ADHD Symptom Improvement With Atomoxetine Versus Methylphenidate

Journal of Attention Disorders ◽

10.1177/1087054710379737 ◽

2010 ◽

Vol 15 (8) ◽

pp. 674-683 ◽

Cited By ~ 43

Author(s):

Philip L. Hazell ◽

Michael R. Kohn ◽

Ruth Dickson ◽

Richard J. Walton ◽

Renee E. Granger ◽

...

Keyword(s):

Children And Adolescents ◽

Adhd Symptom ◽

Rating Scale ◽

Meta Analysis ◽

Absolute Difference ◽

Comparable Efficacy ◽

Symptom Improvement ◽

Adhd Symptoms ◽

Symptom Response ◽

Noninferiority Margin

Objective: Previous studies comparing atomoxetine and methylphenidate to treat ADHD symptoms have been equivocal. This noninferiority meta-analysis compared core ADHD symptom response between atomoxetine and methylphenidate in children and adolescents. Method: Selection criteria included randomized, controlled design; duration 6 weeks; and assessment of ADHD Rating Scale–IV–Parent Version: Investigator Administered and Scored (ADHDRS) scores. Six-week response rates, defined as ≥40% reduction in ADHDRS total score, were compared using a noninferiority margin of −15%. Results: Seven studies met inclusion criteria ( N = 1,368). After 6 weeks, 53.6% (95% confidence interval [CI] 48.6%-58.4%) of atomoxetine-treated patients ( n = 811) had responded compared with 54.4% (47.6%-61.1%) for methylphenidate ( n = 557), with atomoxetine demonstrating noninferiority to methylphenidate (absolute difference −0.9%, 95% CI −9.2%-7.5%). Conclusion: After 6 weeks of treatment atomoxetine and methylphenidate had comparable efficacy in reducing core ADHD symptoms in children and adolescents.

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