Genetic influences on prepulse inhibition of startle reflex in humans

Anokhin, Andrey P.; Heath, Andrew C.; Myers, Erin M.; Ralano, Angela S.; Wood, Suzanne

doi:10.1016/j.neulet.2003.09.014

Cited by 106 publications

(25 citation statements)

References 19 publications

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“…Our heritability estimates for HM are consistent with those for another non-voluntary movement such as eye blink startle reflex suppression, which has a heritability of 50% (Anokhin et al, 2003). However, our estimates for HM are somewhat less than those reported for resting tremor (i.e., 93–99%) (Lorenz et al, 2004), which is caused by contraction of opposing muscle groups (Walker, 1990), or eye blink startle magnitude (i.e., 70%) (Anokhin et al, 2003).…”

Section: Discussionsupporting

confidence: 79%

“…However, our estimates for HM are somewhat less than those reported for resting tremor (i.e., 93–99%) (Lorenz et al, 2004), which is caused by contraction of opposing muscle groups (Walker, 1990), or eye blink startle magnitude (i.e., 70%) (Anokhin et al, 2003). Eye blink startle reflex suppression and resting tremor are frequently associated with Parkinson’s disease (Anokhin et al, 2003; Lorenz et al, 2004). Furthermore, eye blink startle reflex suppression is implicated in the biological bases of schizophrenia and has been proposed as a possible endophenotype for genetic studies (Anokhin et al, 2003).…”

Section: Discussioncontrasting

confidence: 76%

“…Eye blink startle reflex suppression and resting tremor are frequently associated with Parkinson’s disease (Anokhin et al, 2003; Lorenz et al, 2004). Furthermore, eye blink startle reflex suppression is implicated in the biological bases of schizophrenia and has been proposed as a possible endophenotype for genetic studies (Anokhin et al, 2003). Both types of non-voluntary movement are associated with impaired cerebellum connectivity (Manto et al, 2012; Walker, 1990).…”

Section: Discussionmentioning

confidence: 99%

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Heritability of head motion during resting state functional MRI in 462 healthy twins

et al. 2014

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Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% female; 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD=3.16), range 16–29). Heritability estimates for three HM components—mean translation (MT), maximum translation (MAXT) and mean rotation (MR)—ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two-thirds (genetic correlations range 0.76–1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h2=42%). Using a sub-sample (N=35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent “traits” over repeated scans (r=0.53–0.59); reliability was even higher for the composite metric (r=0.66). In addition, phenotypic and cross-trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: truenormalh2¯=0.23 (sd=0.041), BA45: truenormalh2¯=0.26 (sd=0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated.

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Section: Discussionsupporting

confidence: 79%

Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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Heritability of head motion during resting state functional MRI in 462 healthy twins

et al. 2014

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“…The minimum number of valid startles was set to five per category. The software automatically detected the highest amplitude peak in a time frame of 20-120 ms after the onset of the blink reflex-eliciting burst [42]. Magnitudes were calculated for the three categories.…”

Section: Methodsmentioning

confidence: 99%

Is There a Negative Interpretation Bias in Depressed Patients? An Affective Startle Modulation Study

Käse

Dresler²,

Andreatta³

et al. 2013

Neuropsychobiology

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Background/Aims: Scientists proposed that patients with depression favour negative interpretations when appraising ambiguity. As self-report measures seem prone to response bias, implicit measures of emotional valence should be additionally used. Methods: A total of 16 patients with depression and 19 controls underwent an acoustic imagery task comprising neutral and negative words, as well as ambiguous words that could be understood either way. Affective startle modulation and direct interrogation were used to assess implicit and explicit emotional valence, respectively. We expected a negative bias for ambiguous words in the patient group, resulting in augmented startle magnitudes and preference for negative interpretations of the ambiguous words in the interrogation. Results: Surprisingly, both groups preferred neutral interpretations and showed augmented startle magnitudes to ambiguous words. Furthermore, both groups displayed an emotional startle potentiation for negative words. Conclusion: In summary, our results do not confirm a negative interpretation bias or a blunted emotional response in patients with major depression. The mismatch between self-report and affective startle reaction to ambiguous targets might reflect defensive mobilization or attention effects.

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“…Nicotine restores PPI in animals after phencyclidine (PCP, a psychotomimetic drug in humans [63]) -induced impairment in DBA/2 mice [62]. Genetic factors contributing to over 50% variability [64], heritability in mice [65] and common neuroanatomical basis between nicotine and PPI [66] has been shown. Pre-attentive measures, such as smooth pursuit and anti-saccadic eye movements, respectively the moving slowly eyes to follow a strong visual stimulus and the inhibition of the reflexive saccade toward the target to move to the opposite direction, are also impaired in schizophrenics [67].…”

Section: Schizophrenia and 7 Nachrsmentioning

confidence: 99%

Nicotinic Receptors and the Treatment of Attentional and Cognitive Deficits in Neuropsychiatric Disorders: Focus on the α7 Nicotinic Acetylcholine Receptor as a Promising Drug Target for Schizophrenia

Chiamulera¹,

Fumagalli

2007

CNSAMC

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A large body of evidence shows that 7 nicotinic acetylcholine receptor (nAChR) is an important mechanism underlying attentional and cognitive deficits in schizophrenia. Several compounds acting as activators of 7 nAChRs have been identified and investigated for a potential therapeutic application. However, considering the complexity of neuropsychiatric disorders and the difficulty to meet an ideal product profile for drug discovery in the field, there is the need to define empirical product profiles from available data for the major 7 activators. Two classes of compounds are described, partial/full 7 agonists and 7 positive allosteric modulators (PAMs). Their critical pharmacological features are analysed by focussing on type of activity/selectivity at 7 nAChR, action in vivo in laboratory animal models, desired clinical activity, pharmacokinetics (PK)/dosing and safety/tolerability issues. Although the characterization of type of efficacy in vitro succeeded in the extrapolation to animal models and to patients, more efforts are needed to improve selectivity, PK/dosing and safety/tolerability features for 7 agonists. Such as limitations have not been seen for 7 PAMs, so that this class may offer a potential back-up strategy for 7 activators development. The empirical profiles proposed here might give pragmatical indications for the development and the optimization of 7 activators. Few issues need to be further optimized, i), in the clinic, mostly PK profiling, and, ii), at a preclinical level, downstream 7 receptors mechanisms involved in cognitive deficits. A successfully translation of 7 activators research for the treatment of schizophrenic patients will rely on a continuous clinical/preclinical cross-talk approach.

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Genetic influences on prepulse inhibition of startle reflex in humans

Cited by 106 publications

References 19 publications

Heritability of head motion during resting state functional MRI in 462 healthy twins

Heritability of head motion during resting state functional MRI in 462 healthy twins

Is There a Negative Interpretation Bias in Depressed Patients? An Affective Startle Modulation Study

Nicotinic Receptors and the Treatment of Attentional and Cognitive Deficits in Neuropsychiatric Disorders: Focus on the α7 Nicotinic Acetylcholine Receptor as a Promising Drug Target for Schizophrenia

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Genetic influences on prepulse inhibition of startle reflex in humans

Cited by 106 publications

References 19 publications

Heritability of head motion during resting state functional MRI in 462 healthy twins

Heritability of head motion during resting state functional MRI in 462 healthy twins

Is There a Negative Interpretation Bias in Depressed Patients? An Affective Startle Modulation Study

Nicotinic Receptors and the Treatment of Attentional and Cognitive Deficits in Neuropsychiatric Disorders: Focus on the &#945;7 Nicotinic Acetylcholine Receptor as a Promising Drug Target for Schizophrenia

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Nicotinic Receptors and the Treatment of Attentional and Cognitive Deficits in Neuropsychiatric Disorders: Focus on the α7 Nicotinic Acetylcholine Receptor as a Promising Drug Target for Schizophrenia