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Acta Paediatrica (Oslo, Norway : 1992) Nov 2023We discuss the aetiology of recurrent abdominal pain of non-organic origin, according to the Rome Criteria for Functional Gastrointestinal Disorders and a psychogenic... (Review)
Review
We discuss the aetiology of recurrent abdominal pain of non-organic origin, according to the Rome Criteria for Functional Gastrointestinal Disorders and a psychogenic hypothesis. Stress activates the brain-gut axis, which is important for local gut symptoms, such as abdominal pain, but it also causes pain in other areas, including the head, back and chest. Our research has indicated that the startle reflex plays a dominant role in this stress-induced pain pattern, which is manifested in the whole body. Localised abdominal pain can be part of a general negative stress reaction that causes multiple pains in other areas of the body.
PubMed: 37565357
DOI: 10.1111/apa.16946 -
RotaRod and acoustic startle reflex performance of two potential mouse models for Meniere's disease.The European Journal of Neuroscience Aug 2023Meniere's disease (MD) is a disorder of the inner ear characterized by chronic episodes of vertigo, tinnitus, increased aural pressure, and sensorineural hearing loss....
Meniere's disease (MD) is a disorder of the inner ear characterized by chronic episodes of vertigo, tinnitus, increased aural pressure, and sensorineural hearing loss. Causes of MD are unknown, but endolymphatic hydrops is a hallmark. In addition, 5%-15% of MD cases have been identified as familial. Whole-genome sequencing studies of individuals with familial MD identified DTNA and FAM136A as candidate genes for autosomal dominant inheritance of MD. Although the exact roles of these genes in MD are unknown, FAM136A encodes a mitochondrial protein, and DTNA encodes a cytoskeletal protein involved in synapse formation and maintenance, important for maintaining the blood-brain barrier. It is also associated with a particular aquaporin. We tested vestibular and auditory function in dtna and fam136a knockout (KO) mice, using RotaRod and startle reflex-based clicker tests, respectively. Three-factor analysis of variance (ANOVA) results indicated that sex, age, and genotype were significantly correlated with reduced mean latencies to fall ("latencies") for male dtna KO mice, while only age was a significant factor for fam136a KO mice. Fam136a KO mice lost their hearing months before WTs (9-11 months vs. 15-20 months). In male dtna KO mice, divergence in mean latencies compared with other genotypes was first evident at 4 months of age, with older males having an even greater decrease. Our results indicate that fam136a gene mutations generate hearing problems, while dtna gene mutations produce balance deficits. Both mouse models should help to elucidate hearing loss and balance-related symptoms associated with MD.
Topics: Animals; Mice; Male; Meniere Disease; Reflex, Startle; Hearing Loss, Sensorineural; Vestibule, Labyrinth; Mutation
PubMed: 37461313
DOI: 10.1111/ejn.16083 -
Scientific Reports Aug 2023Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity... (Randomized Controlled Trial)
Randomized Controlled Trial
Ketamine is a rapid-acting antidepressant that also influences neural reactivity to affective stimuli. However, the effect of ketamine on behavioral affective reactivity is yet to be elucidated. The affect-modulated startle reflex paradigm (AMSR) allows examining the valence-specific aspects of behavioral affective reactivity. We hypothesized that ketamine alters the modulation of the startle reflex during processing of unpleasant and pleasant stimuli and weakens the resting-state functional connectivity (rsFC) within the modulatory pathway, namely between the centromedial nucleus of the amygdala and nucleus reticularis pontis caudalis. In a randomized, double-blind, placebo-controlled, cross-over study, thirty-two healthy male participants underwent ultra-high field resting-state functional magnetic resonance imaging at 7 T before and 24 h after placebo and S-ketamine infusions. Participants completed the AMSR task at baseline and one day after each infusion. In contrast to our hypothesis, ketamine infusion did not impact startle potentiation during processing of unpleasant stimuli but resulted in diminished startle attenuation during processing of pleasant stimuli. This diminishment significantly correlated with end-of-infusion plasma levels of ketamine and norketamine. Furthermore, ketamine induced a decrease in rsFC within the modulatory startle reflex pathway. The results of this first study on the effect of ketamine on the AMSR suggest that ketamine might attenuate the motivational significance of pleasant stimuli in healthy participants one day after infusion.
Topics: Male; Humans; Reflex, Startle; Cross-Over Studies; Ketamine; Brain; Emotions
PubMed: 37587171
DOI: 10.1038/s41598-023-40099-4 -
Phytotherapy Research : PTR Dec 2023Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal),...
Schizophrenia is a chronic brain disorder characterized by positive symptoms (delusions or hallucinations), negative symptoms (impaired motivation or social withdrawal), and cognitive impairment. In the present study, we explored whether D-pinitol could ameliorate schizophrenia-like behaviors induced by MK-801, an N-methyl-D-aspartate receptor antagonist. Acoustic startle response test was conducted to evaluate the effects of D-pinitol on sensorimotor gating function. Social interaction and novel object recognition tests were employed to measure the impact of D-pinitol on social behavior and cognitive function, respectively. Additionally, we examined whether D-pinitol affects motor coordination. Western blotting was conducted to investigate the mechanism of action of D-pinitol. Single administration of D-pinitol at 30, 100, or 300 mg/kg improved the sensorimotor gating deficit induced by MK801 in the acoustic startle response test. D-Pinitol also reversed social behavior deficits and cognitive impairments induced by MK-801 without causing any motor coordination deficits. Furthermore, D-pinitol reversed increased expression levels of pNF-kB induced by MK-801 treatment and consequently increased expression levels of TNF-α and IL-6 in the prefrontal cortex. These results suggest that D-pinitol could be a potential candidate for treating sensorimotor gating deficits and cognitive impairment observed in schizophrenia by down-regulating transcription factor NF-κB and pro-inflammatory cytokines in the prefrontal cortex.
Topics: Mice; Animals; Dizocilpine Maleate; Reflex, Startle; Schizophrenia; Cognitive Dysfunction
PubMed: 37654104
DOI: 10.1002/ptr.8002 -
Psychophysiology Sep 2023A heightened sensitivity to unpredictable threat has been identified as a potential transdiagnostic mechanism of psychopathology. The majority of supporting research has...
A heightened sensitivity to unpredictable threat has been identified as a potential transdiagnostic mechanism of psychopathology. The majority of supporting research has been conducted in adults, and it is unclear whether psychophysiological indicators of sensitivity to unpredictable threat are comparable in youth during developmental periods associated with increased risk for psychopathology. In addition, no studies have examined whether sensitivity to unpredictable threat is correlated between parents and their offspring. The present study examined defensive motivation (startle reflex) and attentional engagement (probe N100, P300) in anticipation of predictable and unpredictable threat in a sample of 15-year-old adolescents (N = 395) and a biological parent (N = 379). Adolescents, compared to their parents, demonstrated greater startle potentiation and probe N100 enhancement in anticipation of unpredictable threat. In addition, overall startle potentiation in anticipation of threat was correlated between the adolescents and their parents. Adolescence is a key developmental period characterized by heightened defensive motivation and attentional engagement in anticipation of both predictable and unpredictable threat. Sensitivity to threat might index is one mechanism of vulnerability that is at least partially shared between parents and their offspring.
Topics: Adult; Humans; Adolescent; Reflex, Startle; Anticipation, Psychological; Evoked Potentials; Motivation; Parents; Anxiety
PubMed: 37076982
DOI: 10.1111/psyp.14311 -
Scientific Reports Aug 2023Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We...
Two studies examined the amplitude of the startle response as a function of the Dark Tetrad of personality (narcissism, Machiavellianism, psychopathy, and sadism). We measured electromyographic activity of the orbicularis oculi muscle evoked by a startle stimulus while participants viewed images on a computer screen. Both studies revealed a negative correlation between general startle reactivity (averaged across positive, negative, and neutral images) and sadistic tendencies. In Study 2, all four dark traits were negative correlates of general startle reactivity. Study 2 also examined the personality correlates of aversive startle potentiation (ASP; indexed by greater reactivity while viewing negatively-valenced images than positive or neutral images). ASP correlated negatively with a variety of personality measures of psychopathy and sadism, their facets, and related personality tendencies (callousness, risk-taking, and restricted affect). These findings suggest that ordinary people with high levels of callousness and antagonism display physiological evidence of non-reactivity (i.e., blunted acoustic startle in general), whereas psychopathy and sadism are preferentially associated with reduced ASP.
Topics: Humans; Reflex, Startle; Sadism; Antisocial Personality Disorder; Personality Disorders; Personality
PubMed: 37648765
DOI: 10.1038/s41598-023-41043-2 -
International Journal of... Dec 2023Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The...
Facial EMG startle response and self-report reactions after exposure to severely underweight and severely obese body images in individuals with disordered eating: An examination of motivational responses.
Examining appetitive and aversive responses toward body image stimuli of those with disordered eating may illuminate motivational systems unique to eating pathology. The current study extended previous literature by examining self-report and startle responses to a range of body sizes. In this cross-sectional design, female, adult participants (n = 45) were sorted into disordered eating (DE; n = 22) and healthy control (HC; n = 23) groups based on Eating Disorder Examination Questionnaire global scores that were one standard deviation above or below normative values. Participants viewed eight computer-generated female body pictures from each group: severely underweight (BMI < 16.0), average (BMI 18.5-24.99), and severely obese (BMI > 40.0). Startle responses and self-reported valence and anxiety scores were collected to assess implicit and explicit reactions. 2 × 3 ANCOVA/ANOVAs were used to examine startle responses and self-report differences between groups, in response to image types. Results indicated startle responses did not differ between groups. There was a significant main effect for body picture type (p < .001), after controlling for psychotropic medication. Startle responses were higher for severely underweight body images compared to severely obese body images, although non-significant at post-hoc. The DE group reported higher levels of anxiety and sadness when viewing body images compared to the HC group. Average bodies were rated as less anxiety provoking and more positive than severely underweight and obese bodies. Group differences in anxiety and valence scores could be due to more maladaptive cognitions related to fear of weight gain among people with disordered eating.
Topics: Adult; Humans; Female; Body Image; Self Report; Reflex, Startle; Cross-Sectional Studies; Thinness; Feeding and Eating Disorders; Obesity
PubMed: 37802389
DOI: 10.1016/j.ijpsycho.2023.112249 -
JAMA Psychiatry Jun 2024Current interventions for posttraumatic stress disorder (PTSD) are efficacious, yet effectiveness may be limited by adverse effects and high withdrawal rates.... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Current interventions for posttraumatic stress disorder (PTSD) are efficacious, yet effectiveness may be limited by adverse effects and high withdrawal rates. Acupuncture is an emerging intervention with positive preliminary data for PTSD.
OBJECTIVE
To compare verum acupuncture with sham acupuncture (minimal needling) on clinical and physiological outcomes.
DESIGN, SETTING, AND PARTICIPANTS
This was a 2-arm, parallel-group, prospective blinded randomized clinical trial hypothesizing superiority of verum to sham acupuncture. The study was conducted at a single outpatient-based site, the Tibor Rubin VA Medical Center in Long Beach, California, with recruitment from April 2018 to May 2022, followed by a 15-week treatment period. Following exclusion for characteristics that are known PTSD treatment confounds, might affect biological assessment, indicate past nonadherence or treatment resistance, or indicate risk of harm, 93 treatment-seeking combat veterans with PTSD aged 18 to 55 years were allocated to group by adaptive randomization and 71 participants completed the intervention protocols.
INTERVENTIONS
Verum and sham were provided as 1-hour sessions, twice weekly, and participants were given 15 weeks to complete up to 24 sessions.
MAIN OUTCOMES AND MEASURES
The primary outcome was pretreatment to posttreatment change in PTSD symptom severity on the Clinician-Administered PTSD Scale-5 (CAPS-5). The secondary outcome was pretreatment to posttreatment change in fear-conditioned extinction, assessed by fear-potentiated startle response. Outcomes were assessed at pretreatment, midtreatment, and posttreatment. General linear models comparing within- and between-group were analyzed in both intention-to-treat (ITT) and treatment-completed models.
RESULTS
A total of 85 male and 8 female veterans (mean [SD] age, 39.2 [8.5] years) were randomized. There was a large treatment effect of verum (Cohen d, 1.17), a moderate effect of sham (d, 0.67), and a moderate between-group effect favoring verum (mean [SD] Δ, 7.1 [11.8]; t90 = 2.87, d, 0.63; P = .005) in the intention-to-treat analysis. The effect pattern was similar in the treatment-completed analysis: verum d, 1.53; sham d, 0.86; between-group mean (SD) Δ, 7.4 (11.7); t69 = 2.64; d, 0.63; P = .01). There was a significant pretreatment to posttreatment reduction of fear-potentiated startle during extinction (ie, better fear extinction) in the verum but not the sham group and a significant correlation (r = 0.31) between symptom reduction and fear extinction. Withdrawal rates were low.
CONCLUSIONS AND RELEVANCE
The acupuncture intervention used in this study was clinically efficacious and favorably affected the psychobiology of PTSD in combat veterans. These data build on extant literature and suggest that clinical implementation of acupuncture for PTSD, along with further research about comparative efficacy, durability, and mechanisms of effects, is warranted.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02869646.
Topics: Humans; Adult; Male; Stress Disorders, Post-Traumatic; Female; Middle Aged; Combat Disorders; Veterans; Young Adult; Treatment Outcome; Acupuncture Therapy; Reflex, Startle; Prospective Studies; Acupuncture, Ear
PubMed: 38381417
DOI: 10.1001/jamapsychiatry.2023.5651 -
Behavioural Brain Research Aug 2023Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the...
Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes according to the age of infection and sex in mice: neonatally infected animals presented an increase in PPI and delayed startle latency. However, adult-infected male mice presented lower startle amplitude, while a PPI impairment was observed 14 days after infection in both sexes. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the startle reflex testing in ZIKV-exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.
Topics: Female; Male; Animals; Mice; Reflex, Startle; Prepulse Inhibition; Zika Virus; Zika Virus Infection; Acoustic Stimulation
PubMed: 37263423
DOI: 10.1016/j.bbr.2023.114519 -
Developmental Neuroscience Oct 2023The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies...
The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress. The use of variable frequency ultrasound in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of prenatal stress induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.
PubMed: 37857257
DOI: 10.1159/000534687