scholarly journals Back-translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders

2017 ◽  
Author(s):  
Jessica Aylward ◽  
Claire Hales ◽  
Emma Robinson ◽  
Oliver J Robinson
Keyword(s):  
Reaction Time ◽  
Anxiety Disorders ◽  
Computational Model ◽  
Treatment Options ◽  
Reaction Times ◽  
Current Treatment ◽  
Anxiety Symptoms ◽  
Mood And Anxiety Disorders ◽  
Affective Bias ◽  
The Impact

AbstractBackgroundMood and anxiety disorders are ubiquitous but current treatment options are ineffective for large numbers of sufferers. Moreover, recent years have seen a number of promising pre-clinical interventions fail to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal-human translational pipelines. Here, we directly adapt–i.e. back-translate - a rodent measure of negative affective bias into humans, and explore its relationship with a)pathological mood and anxiety symptoms (study one) and b)transient induced anxiety (study two).MethodParticipants who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. N = 77(47 asymptomatic; Female = 21; 30 symptomatic; Female = 25) participants completed study one and N = 47 asymptomatic participants (25 female) completed study two. Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time; the drift diffusion model (DDM).ResultsSymptomatic individuals demonstrated increased negative affective bias relative to asymptomatic individuals (proportion high reward = 0.42(SD = 0.14), and 0.53(SD = 0.17), respectively) as well as reduced DDM drift rate (p = 0.004). No significant effects were observed for the within-subjects anxiety-induction in study 2.ConclusionHumans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm may, moreover, be primarily sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans, and link it to a computational model of reaction time.

scholarly journals Translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders

2019 ◽  
Vol 50 (2) ◽  
pp. 237-246 ◽  
Author(s):  
Jessica Aylward ◽  
Claire Hales ◽  
Emma Robinson ◽  
Oliver J. Robinson
Keyword(s):  
Anxiety Disorders ◽  
Treatment Options ◽  
Reaction Times ◽  
Current Treatment ◽  
Anxiety Symptoms ◽  
Mood And Anxiety Disorders ◽  
Affective Bias ◽  
Asymptomatic Individuals ◽  
Anxiety Induction ◽  
The Impact

AbstractBackgroundMood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal–human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety.MethodsAdult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time – the drift diffusion model (DDM) – from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards.ResultsBoth groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction.ConclusionsHumans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

scholarly journals The impact of stress on financial decision-making varies as a function of depression and anxiety symptoms

2014 ◽  
Author(s):  
Oliver J Robinson ◽  
Rebecca Bond ◽  
Jonathan P Roiser
Keyword(s):  
Decision Making ◽  
Anxiety Disorders ◽  
Trait Anxiety ◽  
Anxiety Symptoms ◽  
Financial Decision Making ◽  
Individual Vulnerability ◽  
Mood And Anxiety Disorders ◽  
Financial Decision ◽  
The Impact ◽  
Selection Of

Stress can precipitate the onset of mood and anxiety disorders. This may occur, at least in part, via a modulatory effect of stress on decision-making. Some individuals are, however, more resilient to the effects of stress than others. The mechanisms underlying such vulnerability differences are nevertheless unknown. In this study we attempted to begin quantifying individual differences in vulnerability by exploring the effect of experimentally induced stress on decision-making. Threat of unpredictable shock was used to induce stress in healthy volunteers (N=47) using a within-subjects, within-session design, and its impact on a financial decision-making task (the Iowa Gambling Task) was assessed alongside anxious and depressive symptomatology. As expected, participants learned to select advantageous decks and avoid disadvantageous decks. Importantly, we found that stress provoked a pattern of harm-avoidant behaviour (decreased selection of disadvantageous decks) in individuals with low levels of trait anxiety. By contrast, individuals with high trait anxiety demonstrated the opposite pattern: stress-induced risk-seeking (increased selection of disadvantageous decks). These contrasting influences of stress depending on mood and anxiety symptoms might provide insight into vulnerability to common mental illness. In particular, we speculate that those who adopt a more harm-avoidant strategy may be better able to regulate their exposure to further environmental stress, reducing their susceptibility to mood and anxiety disorders. The threat of shock paradigm we employed might therefore hold promise as a ‘stress-test’ for determining individual vulnerability to mood and anxiety disorders.

scholarly journals The impact of stress on financial decision-making varies as a function of depression and anxiety symptoms

2014 ◽  
Author(s):  
Oliver J Robinson ◽  
Rebecca Bond ◽  
Jonathan P Roiser
Keyword(s):  
Decision Making ◽  
Anxiety Disorders ◽  
Trait Anxiety ◽  
Anxiety Symptoms ◽  
Financial Decision Making ◽  
Individual Vulnerability ◽  
Mood And Anxiety Disorders ◽  
Financial Decision ◽  
The Impact ◽  
Selection Of

Stress can precipitate the onset of mood and anxiety disorders. This may occur, at least in part, via a modulatory effect of stress on decision-making. Some individuals are, however, more resilient to the effects of stress than others. The mechanisms underlying such vulnerability differences are nevertheless unknown. In this study we attempted to begin quantifying individual differences in vulnerability by exploring the effect of experimentally induced stress on decision-making. Threat of unpredictable shock was used to induce stress in healthy volunteers (N=47) using a within-subjects, within-session design, and its impact on a financial decision-making task (the Iowa Gambling Task) was assessed alongside anxious and depressive symptomatology. As expected, participants learned to select advantageous decks and avoid disadvantageous decks. Importantly, we found that stress provoked a pattern of harm-avoidant behaviour (decreased selection of disadvantageous decks) in individuals with low levels of trait anxiety. By contrast, individuals with high trait anxiety demonstrated the opposite pattern: stress-induced risk-seeking (increased selection of disadvantageous decks). These contrasting influences of stress depending on mood and anxiety symptoms might provide insight into vulnerability to common mental illness. In particular, we speculate that those who adopt a more harm-avoidant strategy may be better able to regulate their exposure to further environmental stress, reducing their susceptibility to mood and anxiety disorders. The threat of shock paradigm we employed might therefore hold promise as a ‘stress-test’ for determining individual vulnerability to mood and anxiety disorders.

scholarly journals Crosstalk between Existential Phenomenological Psychotherapy and Neurological Sciences in Mood and Anxiety Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Lehel Balogh ◽  
Masaru Tanaka ◽  
Nóra Török ◽  
László Vécsei ◽  
Shigeru Taguchi
Keyword(s):  
Anxiety Disorders ◽  
Biological Treatment ◽  
Sense Of Self ◽  
Phenomenological Approach ◽  
Neurological Damage ◽  
Mood And Anxiety Disorders ◽  
New Interpretation ◽  
And Behavior ◽  
The Impact ◽  
The Brain

Psychotherapy is a comprehensive biological treatment modifying complex underlying cognitive, emotional, behavioral, and regulatory responses in the brain, leading patients with mental illness to a new interpretation of the sense of self and others. Psychotherapy is an art of science integrated with psychology and/or philosophy. Neurological sciences study the neurological basis of cognition, memory, and behavior as well as the impact of neurological damage and disease on these functions, and their treatment. Both psychotherapy and neurological sciences deal with the brain; nevertheless, they continue to stay polarized. Existential phenomenological psychotherapy (EPP) has been in the forefront of meaning-centered counseling for almost a century. The phenomenological approach in psychotherapy originated in the works of Martin Heidegger, Ludwig Binswanger, Medard Boss, and Viktor Frankl, and it has been committed to accounting for the existential possibilities and limitations of one’s life. EPP provides philosophically rich interpretations and empowers counseling techniques to assist mentally suffering individuals by finding meaning and purpose to life. The approach has proven to be effective in treating mood and anxiety disorders. This narrative review article demonstrates the development of EPP, the therapeutic methodology, evidence-based accounts of its curative techniques, current understanding of mood and anxiety disorders in neurological sciences, and a possible converging path to translate and integrate meaning-centered psychotherapy and neuroscience, concluding that the EPP may potentially play a synergistic role with the currently prevailing medication-based approaches for the treatment of mood and anxiety disorders.

scholarly journals Cancer missense mutations in the BRC repeats of BRCA2 protein disrupt RAD51 binding and activity leading to chemotherapeutic sensitivity

2021 ◽  
Author(s):  
Judit Jimenez-Sainz ◽  
Joshua Mathew ◽  
Jennifer Garbarino ◽  
Joseph P Eder ◽  
Ryan B Jensen
Keyword(s):  
Genome Stability ◽  
Treatment Options ◽  
Suppressor Gene ◽  
Current Treatment ◽  
Missense Mutations ◽  
Dna Double Strand Breaks ◽  
Clinical Databases ◽  
Brca2 Protein ◽  
Hypomorphic Alleles ◽  
The Impact

BRCA2 is a tumor suppressor gene that maintains genome stability by mediating the high fidelity repair of DNA double-strand breaks (DSBs) through homology-directed repair (HDR). Pathogenic mutations in BRCA2 predispose to breast, ovarian, pancreatic, prostate, and other cancers. Mutations in BRCA2 leading to severe protein truncation predict pathogenicity, however, missense mutations with unknown functional consequences, designated Variants of Uncertain Significance (VUS), comprise 60% of BRCA2 sequence changes deposited in clinical databases. Classifying BRCA2 VUS correctly is critical for relaying clinically actionable information to patients concerning future cancer risk or current treatment options. In this study, we identified and biochemically characterized three BRCA2 VUS located in BRC repeats to determine the impact on canonical HDR functions. Two of the germline variants, S1221P and T1980I, map to conserved residues in BRC2 and BRC7, disrupt RAD51 binding, and are diminished in their ability to stabilize RAD51-ssDNA complexes. We provide supporting cellular evidence that S1221P and T1980I are significantly compromised in their response to chemotherapeutics and ionizing radiation. The third variant, T1346I, lies within the spacer region between BRC2 and BRC3 but remains fully functional. We conclude that T1346I has a neutral impact on BRCA2 function, while S1221P and T1980I are hypomorphic alleles that disrupt the ability of BRCA2 to fully engage and stabilize RAD51 nucleoprotein filaments.

Accurate reaction time methods demonstrate similar results from different sensory modalities

2021 ◽  
pp. 1-6
Author(s):  
Drew McRacken ◽  
Maddie Dyson ◽  
Kevin Hu
Keyword(s):  
Reaction Time ◽  
Sensory Modality ◽  
Reaction Times ◽  
Time Variability ◽  
Reaction Time Methods ◽  
Test Reaction ◽  
Reaction Time Variability ◽  
Sensory Modalities ◽  
Visual Reaction ◽  
The Impact

Over the past few decades, there has been a significant number of reports that suggested that reaction times for different sensory modalities were different – e.g., that visual reaction time was slower than tactile reaction time. A recent report by Holden and colleagues stated that (1) there has been a significant historic upward drift in reaction times reported in the literature, (2) that this drift or degradation in reaction times could be accounted for by inaccuracies in the methods used and (3) that these inaccurate methods led to inaccurate reporting of differences between visual and tactile based reaction time testing.  The Holden study utilized robotics (i.e., no human factors) to test visual and tactile reaction time methods but did not assess how individuals would perform on different sensory modalities.  This study utilized three different sensory modalities: visual, auditory, and tactile, to test reaction time. By changing the way in which the subjects were prompted and measuring subsequent reaction time, the impact of sensory modality could be analyzed. Reaction time testing for two sensory modalities, auditory and visual, were administered through an Arduino Uno microcontroller device, while tactile-based reaction time testing was administered with the Brain Gauge. A range of stimulus intensities was delivered for the reaction times delivered by each sensory modality. The average reaction time and reaction time variability was assessed and a trend could be identified for the reaction time measurements of each of the sensory modalities. Switching the sensory modality did not result in a difference in reaction time and it was concluded that this was due to the implementation of accurate circuitry used to deliver each test. Increasing stimulus intensity for each sensory modality resulted in faster reaction times. The results of this study confirm the findings of Holden and colleagues and contradict the results reported in countless studies that conclude that (1) reaction times are historically slower now than they were 50 years ago and (2) that there are differences in reaction times for different sensory modalities (vision, hearing, tactile). The implications of this are that utilization of accurate reaction time methods could have a significant impact on clinical outcomes and that many methods in current clinical use are basically perpetuating poor methods and wasting time and money of countless subjects or patients.

scholarly journals The risk for nonpsychotic postpartum mood and anxiety disorders during the COVID-19 pandemic

2020 ◽  
pp. 009121742098153
Author(s):  
Jelena Stojanov ◽  
Miodrag Stankovic ◽  
Olivera Zikic ◽  
Matija Stankovic ◽  
Aleksandar Stojanov
Keyword(s):  
Anxiety Disorders ◽  
Social Isolation ◽  
Household Income ◽  
Edinburgh Postnatal Depression Scale ◽  
Depression Scale ◽  
Postpartum Women ◽  
State Of Emergency ◽  
Mood And Anxiety Disorders ◽  
The Impact ◽  
Insight Into

Objective The coronavirus disease 2019 (COVID-19) appears to be the largest pandemic of our times. The aim was to recognize the risk factors for nonpsychotic postpartum mood and anxiety disorders (NPMADs) in women during the pandemic and state of emergency police lockdown in Serbia. Methods We assessed 108 postpartum women who completed the Edinburgh Postnatal Depression Scale (EPDS) and an additional survey constructed for this study. We also used the additional, previously mentioned survey, in 67 healthy age-matched women with children who were ≥2 years of age. The additional survey allowed us to gain insight into the impact of the pandemic as well as postpartum period on the risk of NPMADs. Results In 16 (14.8%) subjects we found a score ≥10 on EPDS. Higher rates on the EPDS were noticed in elderly, single, and unemployed, women who lost their jobs due to the pandemic, or women who were dissatisfied with their household income (p < 0.05). The risk of NPMADs was linked significantly to quarantine, and social isolation, the absence of social support, as well as having emotional problems. Postpartum women, compared to non-postpartum women, were more anxious and had feelings of helplessness during social isolation. Conclusion Understanding the factors that increase the risk of NPMADs during the pandemic could help prevent mental disorders during a possible future pandemic.

Self- and Parent-Rated Quality of Life of a Treatment Naïve Sample of Children With ADHD: The Impact of Age, Gender, Type of ADHD, and Comorbid Psychiatric Conditions According to Both a Categorical and a Dimensional Approach

2014 ◽  
Vol 21 (9) ◽  
pp. 721-730 ◽  
Author(s):  
Gyöngyvér Dallos ◽  
Mónika Miklósi ◽  
Ágnes Keresztény ◽  
Szabina Velő ◽  
Dóra Szentiványi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Anxiety Disorders ◽  
Female Gender ◽  
Dimensional Approach ◽  
Children With Adhd ◽  
Oppositional Defiant ◽  
Mood And Anxiety Disorders ◽  
Treatment Naïve ◽  
The Impact

Objective: Our aim was to evaluate the Quality of Life (QoL) of treatment naïve children with ADHD. Method: Data from 178 parent–child dyads were analyzed using multiple regression to assess the relationships between QoL, and characteristics of ADHD and comorbid psychopathology. Results: Lower self-reported QoL was associated with female gender, higher age, more symptoms of anxiety and trauma-related disorders in dimensional approach, and with the comorbid diagnoses of trauma-related disorders and oppositional defiant disorder (ODD)/conduct disorder (CD) in categorical approach. Lower parent-reported QoL was related to older age and increasing number of symptoms of mood and anxiety disorders on one hand, and any diagnosis of mood and anxiety disorders and ODD/CD on the other. Conclusion: Our results draw the attention to the importance of taking into account age, gender, and both self- and parent reports when measuring QoL of children with ADHD and both dimensional and categorical approaches should be used.

scholarly journals What does first-line therapy mean for paediatric multiple sclerosis in the current era?

2020 ◽  
pp. 135245852093764
Author(s):  
Yael Hacohen ◽  
Brenda Banwell ◽  
Olga Ciccarelli
Keyword(s):  
Multiple Sclerosis ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Cognitive Outcome ◽  
First Line ◽  
First Line Therapy ◽  
Highly Active ◽  
Paediatric Multiple Sclerosis ◽  
The Impact

Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.

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