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BMC Psychology Aug 2023Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple...
BACKGROUND
Psychopathological research is moving from a specific approach towards transdiagnosis through the analysis of processes that appear transversally to multiple pathologies. A phenomenon disrupted in several disorders is prepulse inhibition (PPI) of the startle response, in which startle to an intense sensory stimulus, or pulse, is reduced if a weak stimulus, or prepulse, is previously presented.
OBJECTIVE AND METHODS
The present systematic review analyzed the role of PPI deficit as a possible transdiagnostic process for four main groups of neuropsychiatric disorders: (1) trauma-, stress-, and anxiety-related disorders (2) mood-related disorders, (3) neurocognitive disorders, and (4) other disorders such as obsessive-compulsive, tic-related, and substance use disorders. We used Web of Science, PubMed and PsycInfo databases to search for experimental case-control articles that were analyzed both qualitatively and based on their potential risk of bias. A total of 64 studies were included in this systematic review. Protocol was submitted prospectively to PROSPERO 04/30/2022 (CRD42022322031).
RESULTS AND CONCLUSION
The results showed a general PPI deficit in the diagnostic groups mentioned, with associated deficits in the dopaminergic neurotransmission system, several areas implied such as the medial prefrontal cortex or the amygdala, and related variables such as cognitive deficits and anxiety symptoms. It can be concluded that the PPI deficit appears across most of the neuropsychiatric disorders examined, and it could be considered as a relevant measure in translational research for the early detection of such disorders.
Topics: Humans; Prepulse Inhibition; Reflex, Startle; Cognition Disorders; Mood Disorders; Anxiety Disorders; Acoustic Stimulation
PubMed: 37550772
DOI: 10.1186/s40359-023-01253-9 -
Psychopharmacology Nov 2023Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
Fear conditioning is an important aspect in the pathophysiology of anxiety disorders. The fear-potentiated startle test is based on classical fear conditioning and over the years, a broad range of drugs have been tested in this test. Synthesis of the available data may further our understanding of the neurotransmitter systems that are involved in the expression of conditioned fear.
METHODS
Following a comprehensive search in Medline and Embase, we included 68 research articles that reported on 103 drugs, covering 56 different drug classes. The systematic review was limited to studies using acute, systemic drug administration in naive animals.
RESULTS
Qualitative data synthesis showed that most clinically active anxiolytics, but not serotonin-reuptake inhibitors, reduced cued fear. Anxiogenic drugs increased fear potentiation in 35% of the experiments, reduced fear potentiation in 29% of the experiments, and were without effect in 29% of the experiments. Meta-analyses could be performed for five drug classes and showed that benzodiazepines, buspirone, 5-HT agonists, 5-HT antagonists, and mGluR2,3 agonists reduced cued conditioned fear. The non-cued baseline startle response, which may reflect contextual anxiety, was only significantly reduced by benzodiazepines and 5-HT antagonists. No associations were found between drug effects and methodological characteristics, except for strain.
CONCLUSIONS
The fear-potentiated startle test appears to have moderate to high predictive validity and may serve as a valuable tool for the development of novel anxiolytics. Given the limited available data, the generally low study quality and high heterogeneity additional studies are warranted to corroborate the findings of this review.
Topics: Animals; Anti-Anxiety Agents; Serotonin; Fear; Anxiety; Benzodiazepines; Reflex, Startle
PubMed: 36651922
DOI: 10.1007/s00213-022-06307-1 -
Pediatric Neurology Jul 2022Hereditary hyperekplexia (HPX) is a genetic neurodevelopmental disorder recently defined by the triad of (1) neonatal hypertonia, (2) excessive startle reflexes, and (3)... (Review)
Review
Hereditary hyperekplexia (HPX) is a genetic neurodevelopmental disorder recently defined by the triad of (1) neonatal hypertonia, (2) excessive startle reflexes, and (3) generalized stiffness following the startle. Defects in GLRA1 are the most common cause of HPX, inherited both in an autosomal dominant and autosomal recessive manner. GLRA1 mutations can also cause milder phenotypes in the startle syndromes spectrum, but the prevalence is uncertain and no clear genotype-phenotype correlation has emerged yet. Moreover, the prevalence of neurodevelopmental outcomes has not been clearly defined. Here we report a new family of patients with a typical HPX phenotype, linked to a novel GLRA1 mutation, inherited with a recessive pattern. We then perform a systematic review of the literature of GLRA1-related HPX, describing the main epidemiological features of 210 patients. We found that GLRA1-related phenotypes do not necessarily fulfill the current criteria for HPX, including also milder and later-onset phenotypes. Among clinical features of the disease, neurodevelopmental issues were reported in a third of the sample; interestingly, we found that these problems, particularly when severe, were more common in homozygous than in heterozygous patients. Additional clinical and preclinical studies are needed to define predictors of adverse neurodevelopmental outcomes and underlying mechanisms.
Topics: Humans; Muscle Rigidity; Phenotype; Receptors, Glycine; Reflex, Startle; Stiff-Person Syndrome
PubMed: 35636282
DOI: 10.1016/j.pediatrneurol.2022.05.002 -
Journal of Neurophysiology Apr 2022Control of limb movements may be impaired after stroke due to the loss of connectivity between the cerebral cortex and spinal cord. A notion to improve motor function in... (Meta-Analysis)
Meta-Analysis Review
Control of limb movements may be impaired after stroke due to the loss of connectivity between the cerebral cortex and spinal cord. A notion to improve motor function in stroke survivors is to use alternate motor fibers, such as the reticulospinal tract (RST), which originate from the brainstem and terminate at different levels of spinal cord. One way of targeting the RST is to use a "StartReact" protocol to foster premature release of a preplanned movement in response to a startling stimulus. Our aim was to find support for the preservation of such StartReact effect in stroke survivors. We conducted a systematic review with meta-analysis of literature published in English up to September 2020, to explore differences in motor responses to startling stimuli in StartReact effects. Protocol of the study was registered (PROSPERO Registration No. CRD42020191581). PubMed, Google Scholar, Web of Science, PsycINFO, and Science Direct were searched for relevant literature. The meta-analysis contained six studies involving a total of 151 stroke and healthy participants. Muscle onset latency data were extracted from the qualifying studies and compared using RevMan. StartReact effect was present in both stroke and healthy groups, represented by shortened muscle onset latency when startling stimulus was present. There was considerable heterogeneity of the outcome measures, which was attributed to the range of motor impairments among stroke survivors and methodologies used. Our findings support the notion of preservation of preprogramming ability and suitability of RST and StartReact effect for motor rehabilitation following stroke.
Topics: Acoustic Stimulation; Electromyography; Humans; Reflex, Startle; Stroke; Stroke Rehabilitation; Survivors
PubMed: 35235444
DOI: 10.1152/jn.00392.2021 -
Acta Psychologica Oct 2021The startle reflex has been suggested to operate as a psychophysiological marker of psychopathic personality, based on findings from studies using a range of different... (Review)
Review
The startle reflex has been suggested to operate as a psychophysiological marker of psychopathic personality, based on findings from studies using a range of different methodologies and participant samples. The present review aims at synthesizing existing evidence of the relationship between psychopathy and the startle reflex across task paradigms, psychopathic personality subtypes and subdimensions, participant samples (i.e., incarcerated/ clinical or non-offenders), and age groups using the triarchic model of psychopathy as a frame of reference. Systematic literature searches were conducted up until the 24th of March 2020 in PubMed, PsycINFO, and Web of Science. A total of 2311 potential studies were identified, out of which 40 met relevancy and quality criteria. Results indicate that reduced aversive startle potentiation is associated with psychopathic personality in general, but clusters of traits relating to the triarchic model constructs of boldness and meanness in particular. Available evidence suggest that startle paradigms could be meaningful for differentiating individuals with and without psychopathic personality. Findings support suggestions of psychopathic personality as a multifaceted, rather than a unitary construct. Reduced aversive startle potentiation has also been found in relation to psychopathic features in child-aged samples but work of this kind is limited and more research is needed. Future studies should focus on greater consistency in task paradigms and analytic strategies to enhance the capacity to compare and integrate findings across studies.
Topics: Adolescent; Affect; Aged; Antisocial Personality Disorder; Child; Humans; Reflex, Startle; Young Adult
PubMed: 34628215
DOI: 10.1016/j.actpsy.2021.103427 -
Human Brain Mapping Nov 2021Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the...
Startle reflex is modulated when a weaker sensory stimulus ("prepulse") precedes a startling stimulus ("pulse"). Prepulse Inhibition (PPI) is the attenuation of the startle reflex (prepulse precedes pulse by 30-500 ms), whereas Prepulse Facilitation (PPF) is the enhancement of the startle reflex (prepulse precedes pulse by 500-6000 ms). Here, we critically appraise human studies using functional neuroimaging to establish brain regions associated with PPI and PPF. Of 10 studies, nine studies revealed thalamic, striatal and frontal lobe activation during PPI in healthy groups, and activation deficits in the cortico-striato-pallido-thalamic circuitry in schizophrenia (three studies) and Tourette Syndrome (two studies). One study revealed a shared network for PPI and PPF in frontal regions and cerebellum, with PPF networks recruiting superior medial gyrus and cingulate cortex. The main gaps in the literature are (i) limited PPF research and whether PPI and PPF operate on separate/shared networks, (ii) no data on sex differences in neural underpinnings of PPI and PPF, and (iii) no data on neural underpinnings of PPI and PPF in other clinical disorders.
Topics: Functional Neuroimaging; Humans; Perception; Prepulse Inhibition; Reflex, Startle; Schizophrenia; Sensation; Tourette Syndrome
PubMed: 34414633
DOI: 10.1002/hbm.25631 -
Frontiers in Psychiatry 2020Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the...
Deficits in the gating of sensory stimuli, i.e., the ability to suppress the processing of irrelevant sensory input, are considered to play an important role in the pathogenesis of several neuropsychiatric disorders, in particular schizophrenia. Gating is disrupted both in schizophrenia patients and their unaffected relatives, suggesting that gating deficit may represent a biomarker associated with a genetic liability to the disorder. To assess the strength of the evidence for the etiopathogenetic links between genetic variation, gating efficiency, and schizophrenia, we carried out a systematic review of human genetic association studies of sensory gating (suppression of the P50 component of the auditory event-related brain potential) and sensorimotor gating (prepulse inhibition of the acoustic startle response). Sixty-three full-text articles met the eligibility criteria for inclusion in the review. In total, 117 genetic variants were reported to be associated with gating functions: 33 variants for sensory gating, 80 variants for sensorimotor gating, and four variants for both sensory and sensorimotor gating. However, only five of these associations (four for prepulse inhibition-CHRNA3 rs1317286, COMT rs4680, HTR2A rs6311, and TCF4 rs9960767, and one for P50 suppression-CHRNA7 rs67158670) were consistently replicated in independent samples. Although these variants and genes were all implicated in schizophrenia in research studies, only two polymorphisms ( rs6311 and rs9960767) were also reported to be associated with schizophrenia at a meta-analytic or genome-wide level of evidence. Thus, although gating is widely considered as an important endophenotype of schizophrenia, these findings demonstrate that evidence for a common genetic etiology of impaired gating functions and schizophrenia is yet unsatisfactory, warranting further studies in this field.
PubMed: 33324248
DOI: 10.3389/fpsyt.2020.550225 -
The World Journal of Biological... Jul 2021Startle response is an objective physiological measure integral to the human defense system and a promising target for endophenotype investigations of anxiety. Given the...
OBJECTIVES
Startle response is an objective physiological measure integral to the human defense system and a promising target for endophenotype investigations of anxiety. Given the alterations in startle reactivity observed among anxiety and related disorders, we searched for genetic variants associated with startle reactivity as they may be further involved in pathological anxiety risk.
METHODS
A systematic literature review was performed to identify genetic variants associated with startle reactivity in humans, specifically baseline and fear- or anxiety-potentiated startle.
RESULTS
The polymorphisms Val66Met (rs6265) from brain-derived neurotrophic factor (), Val158Met (rs4680) from catechol-O-methyltransferase (), and the serotonin transporter-linked polymorphic region (5-HTTLPR) from the serotonin transporter gene () were most commonly studied in human startle. In addition, several other genetic variants have also been identified as potential candidates that warrant further research, especially given their novelty in in the context of anxiety.
CONCLUSIONS
Similar to psychiatric genetic studies, the studies on startle reactivity primarily focus on candidate genes and are plagued by non-replication. Startle reactivity is a promising endophenotype that requires concerted efforts to collect uniformly assessed, large, well-powered samples and hypothesis-free genome-wide strategies. To further support startle as an endophenotype for anxiety, this review suggests advanced genetic strategies for startle research.
Topics: Anxiety; Anxiety Disorders; Catechol O-Methyltransferase; Endophenotypes; Genotype; Humans; Reflex, Startle; Serotonin Plasma Membrane Transport Proteins
PubMed: 33040669
DOI: 10.1080/15622975.2020.1834619 -
Early Intervention in Psychiatry Jun 2021Prepulse inhibition (PPI) is a measure of sensorimotor gating used to identify deficits in early-stage information processing and inhibitory function defects. Many...
BACKGROUND
Prepulse inhibition (PPI) is a measure of sensorimotor gating used to identify deficits in early-stage information processing and inhibitory function defects. Many studies support the presence of PPI deficits in schizophrenia patients. However, very few studies have explored PPI levels among first-degree relatives (FDR) of schizophrenia patients, and the results have been inconsistent. This review article explored PPI levels in FDR of schizophrenia patients.
METHODS
We performed a systematic literature review using the PubMed, Cochrane, Embase, EBSCO and Chinese databases from inception to January 2020. A series of related factors (eg, PPI paradigm, heritability and sample characteristics) and outcomes were summarized from the literature that met the inclusion criteria. The Newcastle-Ottawa Scale was used to assess the quality of the included studies.
RESULTS
A total of eight studies were eligible for systematic review after screening. A meta-analysis of the selected studies was not conducted due to the limitations of quantity and paradigm heterogeneity. A majority of the studies' subjects were siblings of schizophrenia patients and different paradigms were applied. Most of the included studies reported no difference in PPI values between FDR of schizophrenia patients and healthy controls.
CONCLUSION
Contrary to traditional certainty that unaffected FDR of schizophrenia patients have PPI defects, our review found no sufficient evidence supporting that the PPI level in FDR of schizophrenia patients was lower than in healthy controls. A prospective cohort study focusing on different outcomes such as developing schizophrenia is required to explore PPI levels in FDR of schizophrenia patients.
Topics: Acoustic Stimulation; Humans; Prepulse Inhibition; Prospective Studies; Reflex, Startle; Schizophrenia
PubMed: 32567764
DOI: 10.1111/eip.13003 -
BMC Psychiatry Sep 2019Prepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prepulse inhibition (PPI) is a measurement method for the sensory gating process, which helps the brain adapt to complex environments. PPI may be reduced in patients with bipolar disorder (BD). This study investigated PPI deficits in BD and pooled the effect size of PPI in patients with BD.
METHODS
We conducted a literature search on PPI in patients with BD from inception to July 27, 2019 in PubMed, Embase, Cochrane Library databases, and Chinese databases. No age, sex, and language restriction were set. The calculation formula was PPI = 100 - [100*((prepulse - pulse amplitude) / pulse amplitude)]. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies.
RESULTS
Ten eligible papers were identified, of which five studies including a total of 141 euthymic patients and 132 healthy controls (HC) were included in the meta-analysis. Compared with HC, euthymic patients with BD had significantly lower PPI at the 60 ms interstimulus interval (ISI) between pulse and prepulse (P = 0.476, I = 0.0%, SMD = - 0.32, 95% CI = - 0.54 - -0.10). Sensitivity analysis shows no significant change in the combined effect value after removing any single study. There was no publication bias using the Egger's test at 60 ms (P = 0.606). The meta-analysis of PPI at the 60 ms ISI could have significant clinical heterogeneity in mood episode state, as well as lack of data on BD I or II subtypes.
CONCLUSIONS
Euthymic patients with BD show PPI deficits at the 60 ms, suggesting a deficit in the early sensory gate underlying PPI. The PPI inhibition rate at a 60 ms interval is a stable index. More research is needed in the future to confirm this outcome, and to delve deeper into the mechanisms behind deficits.
Topics: Bipolar Disorder; Cyclothymic Disorder; Female; Humans; Male; Prepulse Inhibition; Reflex, Startle; Sensory Gating
PubMed: 31510965
DOI: 10.1186/s12888-019-2271-8