scholarly journals Modulation of the renin-angiotensin system inhibits memory advantage for negative emotional material via decreasing hippocampus activation and its coupling with the amygdala

2021 ◽  
Author(s):  
Ting Xu ◽  
Xinqi Zhou ◽  
Guojuan Jiao ◽  
Yixu Zeng ◽  
Weihua Zhao ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Emotional Experience ◽  
Positive Association ◽  
Emotional Memory ◽  
Functional Coupling ◽  
Post Traumatic Stress ◽  
Double Blind ◽  
Emotion Memory ◽  
Ptsd Symptomatology ◽  
Negative Stimuli

Exaggerated arousal and dysregulated emotion-memory interactions are key pathological dysregulations that accompany the development of post-traumatic stress disorder (PTSD). Current treatments for PTSD are of moderate efficacy and preventing the dysregulations already during exposure to threatening events may attenuate the development of PTSD-symptomatology. The present proof-of-concept study examined the potential of a single dose of the angiotensin II type 1 receptor (AT1R) antagonist losartan (LT) to attenuate the mnemonic advantage of threatening stimuli and the underlying neural mechanism. In a preregistered double-blind, between-subject, placebo-controlled pharmaco-fMRI study we combined an emotional subsequent memory paradigm with LT (n=29) or placebo treatment (n=30) and a surprise memory test after 24h washout. LT generally improved memory performance and abolished emotional memory enhancement for negative yet not positive material while emotional experience during encoding remained intact. LT further suppressed the hippocampus activity during encoding of subsequently remembered negative stimuli and abolished the positive association between higher activity in this region and subsequent better memory for negative material observed under placebo. On the network level LT reduced coupling between the hippocampus and the basolateral amygdala during successful encoding of negative stimuli. Overall, our findings suggest that LT has the potential to selectively attenuate memory formation for negative yet not positive information by decreasing hippocampus activity and its functional coupling strength with the left amygdala. These findings suggest a promising potential of LT to prevent preferential encoding and remembering of negative events, a mechanism that could prevent the emotion-memory dysregulations underlying the development of PTSD-symptomatology.

scholarly journals Effect of tryptophan depletion on conditioned threat memory expression: role of intolerance of uncertainty

2020 ◽  
Author(s):  
Jonathan W Kanen ◽  
Frederique E Arntz ◽  
Robyn Yellowlees ◽  
David M Christmas ◽  
Annabel Price ◽  
...  
Keyword(s):  
Emotional Responses ◽  
Intolerance Of Uncertainty ◽  
Emotional Memory ◽  
Tryptophan Depletion ◽  
Post Traumatic Stress ◽  
Obsessive Compulsive ◽  
Double Blind ◽  
Compulsive Disorder ◽  
Emotional Responding

AbstractBackgroundResponding emotionally to danger is critical for survival. Normal functioning also requires flexible alteration of emotional responses when a threat becomes safe. Aberrant threat and safety learning occurs in many psychiatric disorders including post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and schizophrenia, where emotional responses can persist pathologically. Whilst there is evidence that threat and safety learning can be modulated by the serotonin systems, there have been few studies in humans. We addressed a critical clinically relevant question: How does pharmacological lowering of serotonin affect the retention of conditioned threat memory?MethodsForty-seven healthy participants underwent threat conditioning on Day 1 followed by an extinction session. Emotional responding was assessed by the skin conductance response (SCR). On Day 2, we employed acute dietary tryptophan depletion to lower serotonin temporarily, in a double-blind placebo-controlled randomized between-groups design. We then tested for the return of conditioned threat memory spontaneous recovery). We also measured self-reported intolerance of uncertainty, known to modulate threat memory expression.ResultsThe expression of emotional memory was attenuated in participants who had undergone tryptophan depletion. Individuals who were more intolerant of uncertainty showed even greater attenuation of emotion following depletion.ConclusionsThese results support the view that serotonin is involved in predicting aversive outcomes and refine our understanding of the role of serotonin in the persistence of emotional responsivity, with implications for individual differences in vulnerability to psychopathology.

scholarly journals Can Anhedonia Be Considered a Suicide Risk Factor? A Review of the Literature

Medicina ◽  
2019 ◽  
Vol 55 (8) ◽  
pp. 458 ◽  
Author(s):  
Bonanni ◽  
Gualtieri ◽  
Lester ◽  
Falcone ◽  
Nardella ◽  
...  
Keyword(s):  
Suicidal Behavior ◽  
Affective Disorders ◽  
Suicide Attempts ◽  
Positive Association ◽  
Negative Association ◽  
Schizophrenia Spectrum Disorders ◽  
Post Traumatic Stress ◽  
Significant Positive Association ◽  
Search Terms ◽  
Schizophrenia Spectrum

Background and Objectives: At present, data collected from the literature about suicide and anhedonia are controversial. Some studies have shown that low levels of anhedonia are associated with serious suicide attempts and death by suicide, while other studies have shown that high levels of anhedonia are associated with suicide. Materials and Methods: For this review, we searched PubMed, Medline, and ScienceDirect for clinical studies published from 1 January 1990 to 31 December 2018 with the following search terms used in the title or in the abstract: “anhedonia AND suicid*.” We obtained a total of 155 articles; 133 items were excluded using specific exclusion criteria, the remaining 22 articles included were divided into six groups based on the psychiatric diagnosis: mood disorders, schizophrenia spectrum disorders, post-traumatic stress disorder (PTSD), other diagnoses, attempted suicides, and others (healthy subjects). Results: The results of this review reveal inconsistencies. Some studies reported that high anhedonia scores were associated with suicidal behavior (regardless of the diagnosis), while other studies found that low anhedonia scores were associated with suicidal behavior, and a few studies reported no association. The most consistent association between anhedonia and suicidal behavior was found for affective disorders (7 of 7 studies reported a significant positive association) and for PTSD (3 of 3 studies reported a positive association). In the two studies of patients with schizophrenia, one found no association, and one found a negative association. For patients who attempted suicide (undiagnosed), one study found a positive association, one a positive association only for depressed attempters, and one a negative association. Conclusions: We found the most consistent positive association for patients with affective disorders and PTSD, indicating that the assessment of anhedonia may be useful in the evaluation of suicidal risk.

scholarly journals Effects of transcranial static magnetic stimulation over the primary motor cortex on local and network spontaneous electroencephalogram oscillations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sumiya Shibata ◽  
Tatsunori Watanabe ◽  
Yoshihiro Yukawa ◽  
Masatoshi Minakuchi ◽  
Ryota Shimomura ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Power Spectrum ◽  
Magnetic Stimulation ◽  
Primary Motor Cortex ◽  
Cortical Excitability ◽  
Controlled Study ◽  
Functional Coupling ◽  
Phase Lag ◽  
Theta Band ◽  
Double Blind

AbstractTranscranial static magnetic stimulation (tSMS) is a novel non-invasive brain stimulation technique that reduces cortical excitability at the stimulation site. We investigated the effects of tSMS over the left primary motor cortex (M1) for 20 min on the local electroencephalogram (EEG) power spectrum and interregional EEG coupling. Twelve right-handed healthy subjects participated in this crossover, double-blind, sham-controlled study. Resting-state EEG data were recorded for 3 min before the intervention and 17 min after the beginning of the intervention. The power spectrum at the left central electrode (C3) and the weighted phase lag index (wPLI) between C3 and the other electrodes was calculated for theta (4–8 Hz), alpha (8–12 Hz), and beta (12–30 Hz) frequencies. The tSMS significantly increased theta power at C3 and the functional coupling in the theta band between C3 and the parietal midline electrodes. The tSMS over the left M1 for 20 min exhibited modulatory effects on local cortical activity and interregional functional coupling in the theta band. The neural oscillations in the theta band may have an important role in the neurophysiological effects induced by tSMS over the frontal cortex.

scholarly journals Environmental enrichment prevents the late effect of acute stress-induced fear extinction deficit: the role of hippocampal AMPA-GluA1 phosphorylation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Leonardo Santana Novaes ◽  
Letícia Morais Bueno-de-Camargo ◽  
Carolina Demarchi Munhoz
Keyword(s):  
Environmental Enrichment ◽  
Basolateral Amygdala ◽  
Acute Stress ◽  
Fear Memory ◽  
Fear Extinction ◽  
Post Traumatic Stress ◽  
Related Disorder ◽  
Memory Extinction ◽  
Post Traumatic

AbstractThe persistence of anxiety and the deficit of fear memory extinction are both phenomena related to the symptoms of a trauma-related disorder, such as post-traumatic stress disorder (PTSD). Recently we have shown that single acute restraint stress (2 h) in rats induces a late anxiety-related behavior (observed ten days after stress), whereas, in the present work, we found that the same stress impaired fear extinction in animals conditioned ten days after stress. Fourteen days of environmental enrichment (EE) prevented the deleterious effect of stress on fear memory extinction. Additionally, we observed that EE prevented the stress-induced increase in AMPA receptor GluA1 subunit phosphorylation in the hippocampus, but not in the basolateral amygdala complex and the frontal cortex, indicating a potential mechanism by which it exerts its protective effect against the stress-induced behavioral outcome.

A randomized, double-blind, placebo-controlled trial on the efficacy and tolerability of sertraline in Iranian veterans with post-traumatic stress disorder

2011 ◽  
Vol 41 (10) ◽  
pp. 2159-2166 ◽  
Author(s):  
Y. Panahi ◽  
B. Rezazadeh Moghaddam ◽  
A. Sahebkar ◽  
M. Abbasi Nazari ◽  
F. Beiraghdar ◽  
...  
Keyword(s):  
Placebo Group ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Controlled Trial ◽  
Post Traumatic Stress ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Post Traumatic ◽  
The Mean

BackgroundUnlike civilian post-traumatic stress disorder (PTSD), the efficacy of sertraline for the treatment of combat-related PTSD has not yet been proven. The present study aimed to evaluate the clinical efficacy of sertraline against combat-related PTSD in a randomized, double-blind, placebo-controlled trial.MethodSeventy Iranian veterans of the Iran–Iraq war who met the DSM-IV criteria for diagnosis of PTSD were randomized to receive either flexibly dosed sertraline (50–200 mg/day) (n=35, completers=32) or placebo (n=35, completers=30) for 10 weeks. Efficacy was evaluated by the Impact of Event Scale – Revised (IES-R) and the Clinical Global Impression scale – Severity (CGI-S) and Improvement (CGI-I) ratings. Responder criteria were defined as a ⩾30% reduction in the IES-R total score plus a CGI-I rating of ‘much’ or ‘very much’ improved.ResultsOn both intention-to-treat (ITT) and per protocol (completer) methods of analysis, the mean reductions in the IES-R total and subscale (re-experiencing/intrusion, avoidance/numbing and hyperarousal) scores (p<0.001) and also in the CGI-S score (p<0.01) were significantly greater in the sertraline group than in the placebo group. For the CGI-I, the mean endpoint score was significantly lower in the sertraline group than in the placebo group (p⩽0.001). The number of responders in the sertraline group was significantly higher than in the placebo group (44% v. 3%, p⩽0.001). Sertraline was well tolerated, with a 6% discontinuation rate as a result of adverse reactions.ConclusionsThe results of this study suggest that sertraline can be an effective, safe and tolerable treatment for combat-related PTSD in Iranian veterans.

scholarly journals Altered sleep behavior in a genetic mouse model of impaired fear extinction

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva Maria Fritz ◽  
Matthias Kreuzer ◽  
Alp Altunkaya ◽  
Nicolas Singewald ◽  
Thomas Fenzl
Keyword(s):  
Sleep Disturbances ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Emotional Memory ◽  
Fear Extinction ◽  
Face Validity ◽  
Poor Sleep ◽  
Post Traumatic Stress ◽  
Secondary Symptom ◽  
Sleep Behavior

AbstractSleep disturbances are a common complaint of anxiety patients and constitute a hallmark feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that poor sleep is not only a secondary symptom of anxiety- and trauma-related disorders but represents a risk factor in their development, for example by interfering with emotional memory processing. Fear extinction is a critical mechanism for the attenuation of fearful and traumatic memories and multiple studies suggest that healthy sleep is crucial for the formation of extinction memories. However, fear extinction is often impaired in anxiety- and trauma-related disorders—an endophenotype that is perfectly modelled in the 129S1/SvImJ inbred mouse strain. To investigate whether these mice exhibit altered sleep at baseline that could predispose them towards maladaptive fear processing, we compared their circadian sleep/wake patterns to those of typically extinction-competent C57BL/6 mice. We found significant differences regarding diurnal distribution of sleep and wakefulness, but also sleep architecture, spectral features and sleep spindle events. With regard to sleep disturbances reported by anxiety- and PTSD patients, our findings strengthen the 129S1/SvImJ mouse models’ face validity and highlight it as a platform to investigate novel, sleep-focused diagnostic and therapeutic strategies. Whether the identified alterations causally contribute to its pathological anxiety/PTSD-like phenotype will, however, have to be addressed in future studies.

Cannabidiol Has a Unique Effect on Global Brain Activity: A Pharmacological, Functional MRI Study in Awake Mice 

2021 ◽  
Author(s):  
Aymen Sadaka ◽  
Ana Ozuna ◽  
Richard Ortiz ◽  
Praveen Kulkarni ◽  
Clare Johnson ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Brain Activity ◽  
Stress Disorders ◽  
Functional Coupling ◽  
Specific Information ◽  
Imaging Data ◽  
Post Traumatic Stress ◽  
Brain Areas ◽  
Dose Dependent ◽  
The Brain

Abstract Background: The phytocannabinoid cannabidiol (CBD) is a potential treatment for post-traumatic stress disorders. How does CBD interact with the brain to alter behavior? We hypothesized that CBD would produce a dose-dependent reduction in brain activity and functional coupling in neural circuitry associated with fear and defense. Methods: During the scanning session awake mice were given vehicle or CBD (3, 10, or 30 mg/kg I.P.) and imaged for 10 min post treatment. Mice were also treated with the 10 mg/kg dose of CBD and imaged one hr later for resting state BOLD functional connectivity (rsFC). Imaging data were registered to a 3D MRI mouse atlas providing site-specific information on 138 different brain areas. Blood samples were collected for CBD measurements.Results: CBD produced a dose-dependent polarization of activation along the rostral-caudal axis of the brain. The olfactory bulb and prefrontal cortex showed an increase in positive BOLD whereas the brainstem and cerebellum showed a decrease in BOLD signal. This negative BOLD affected many areas connected to the ascending reticular activating system (ARAS). The ARAS was decoupled to much of the brain but was hyperconnected to the olfactory system and prefrontal cortex. The pattern of ARAS connectivity closely overlapped with brain areas showing high levels N-acyl-phosphatidylethanolamines-specific phospholipase D (NAPE-PLD) messenger RNA.Conclusion: The CBD-induced decrease in ARAS activity is consistent with an emerging literature suggesting that CBD reduces autonomic arousal under conditions of emotional and physical stress. The putative target and mechanism of action is NAPE-PLD the enzyme responsible for the biosynthesis of lipid signaling molecules like anandamide.

Eye-Movement Desensitisation: A Simple Treatment for Post-Traumatic Stress Disorder?

1993 ◽  
Vol 27 (2) ◽  
pp. 288-293 ◽  
Author(s):  
Andrew C. Page ◽  
Rocco D. Crino
Keyword(s):  
Effective Treatment ◽  
Eye Movement ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Stress Disorder ◽  
Controlled Trial ◽  
Post Traumatic Stress ◽  
Double Blind ◽  
Cost Effective Treatment ◽  
Post Traumatic

Eye-movement desensitisation has been identified in a number of case studies to be an effective treatment for post-traumatic stress disorder (PTSD). A further case study reporting success is presented. The treatment appears rapid and may represent a potentially cost-effective treatment for PTSD. However, no treatment study to date has conformed to the ideal methodology of a double-blind placebo controlled trial and therefore its efficacy remains to be demonstrated. A minimal but stringent set of criteria for identification of treatment efficacy are outlined. The implications of eye-movement desensitisation being identified as an effective treatment for PTSD are discussed.

scholarly journals Different preprocessing strategies lead to different conclusions: A [11C]DASB-PET reproducibility study

2019 ◽  
Vol 40 (9) ◽  
pp. 1902-1911
Author(s):  
Martin Nørgaard ◽  
Melanie Ganz ◽  
Claus Svarer ◽  
Vibe G Frokjaer ◽  
Douglas N Greve ◽  
...  
Keyword(s):  
Motion Correction ◽  
Positive Association ◽  
Sequential Data ◽  
Double Blind ◽  
Data Set ◽  
Reproducibility Study ◽  
Positron Emission ◽  
The Impact ◽  
Data Analytic

Positron emission tomography (PET) neuroimaging provides unique possibilities to study biological processes in vivo under basal and interventional conditions. For quantification of PET data, researchers commonly apply different arrays of sequential data analytic methods (“preprocessing pipeline”), but it is often unknown how the choice of preprocessing affects the final outcome. Here, we use an available data set from a double-blind, randomized, placebo-controlled [11C]DASB-PET study as a case to evaluate how the choice of preprocessing affects the outcome of the study. We tested the impact of 384 commonly used preprocessing strategies on a previously reported positive association between the change from baseline in neocortical serotonin transporter binding determined with [11C]DASB-PET, and change in depressive symptoms, following a pharmacological sex hormone manipulation intervention in 30 women. The two preprocessing steps that were most critical for the outcome were motion correction and kinetic modeling of the dynamic PET data. We found that 36% of the applied preprocessing strategies replicated the originally reported finding ( p < 0.05). For preprocessing strategies with motion correction, the replication percentage was 72%, whereas it was 0% for strategies without motion correction. In conclusion, the choice of preprocessing strategy can have a major impact on a study outcome.

Transcranial direct current stimulation (TDCS) of the prefrontal cortex in therapy-resistant depression: A double-blind, placebo-controlled study

2011 ◽  
Vol 26 (S2) ◽  
pp. 1151-1151
Author(s):  
U. Palm ◽  
C. Schiller ◽  
Z. Fintescu ◽  
M. Obermeier ◽  
D. Keeser ◽  
...  
Keyword(s):  
Antidepressant Treatment ◽  
Positive Association ◽  
Control Treatment ◽  
Controlled Study ◽  
Study Phase ◽  
Double Blind ◽  
Treatment Conditions ◽  
Severity Of Depression ◽  
The 1960S ◽  
Therapy Resistant Depression

BackgroundTDCS for modulating neurophysiology is known since the 1960s. tDCS trials in patients with depression showed promising results.Methods22 patients with therapy resistant major depression (DSM-IV criteria) were included in a four week cross-over trial, 10 received 1 mA tDCS, 12 received 2 mA tDCS, 2 dropped out. Patients received add-on tDCS under a stable antidepressant treatment over 3 weeks and were randomized to active or sham tDCS treatment. The sham condition was evaluated in 10 healthy volunteers and was indistinguishable.Both, active (1 mA resp. 2 mA) and placebo tDCS were applied for 20 min per day and for two weeks and then switched to the other condition. The anode was positioned over F3 and the cathode over the contralateral supraorbital region. For placebo tDCS a novel sham device (neuroConn, llmenau, Germany) was used which is indistinguishable for the applying person. Severity of depression was assessed by HAMD, BDI, CGI and CORE scales and raters were blind to treatment conditions.ResultsMean HAMD decreased by 25% in the whole population after four weeks of tDCS. Active tDCS performed significantly better (p = 0.0492) than the control treatment. However this positive association was restricted to the first study phase as there was also a significant (p = 0.0271) influence of the study phase in the cross-over design and an almost significant (p = 0.0864) interaction between treatment and study phase.ConclusionThough active tDCS was not superior to sham treatment, we observed hangover effects in weeks 3 and 4 depending on the first condition.

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