Altered auditory processing in patients with panic disorder: A pilot study

Pfleiderer, Bettina; Zinkirciran, Sariye; Michael, Nikolaus; Hohoff, Christa; Kersting, Anette; Arolt, Volker; Deckert, Jürgen; Domschke, Katharina

doi:10.3109/15622975.2010.490273

Cited by 17 publications

(8 citation statements)

References 69 publications

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“…Thus, increases in tph2 in the cDRV may influence encoding of specific sensorimotor events. This hypothesis is consistent with findings that panic disorder patients have altered processing of sensory information …”

Section: Discussionsupporting

confidence: 92%

ELEVATED tph2 mRNA EXPRESSION IN A RAT MODEL OF CHRONIC ANXIETY

et al. 2012

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Background Allelic variations in TPH2, the gene encoding tryptophan hydroxylase 2, the rate-limiting enzyme for brain serotonin (5-HT) biosynthesis, may be genetic predictors of panic disorder and panic responses to panicogenic challenges in healthy volunteers. To test the hypothesis that tph2 mRNA is altered in chronic anxiety states, we measured tph2 expression in an established rat model of panic disorder. Methods We implanted 16 adult, male rats with bilateral guide cannulae and then primed them with daily injections of the corticotropin-releasing factor (CRF) receptor agonist, urocortin 1 (UCN1, 6 fmoles/100 nl per side, n = 8) or vehicle (n = 8) into the basolateral amygdaloid complex (BL) for 5 consecutive days. Anxiety-like behavior was assessed, 24 hr prior to and 48 hr following priming, in the social interaction (SI) test. A third group (n = 7) served as undisturbed home cage controls. All rats were killed 3 days after the last intra-BL injection to analyze tph2 and slc6a4 (gene encoding the serotonin transporter, SERT) mRNA expression in the dorsal raphe nucleus (DR), the main source of serotonergic projections to anxiety-related brain regions, using in situ hybridization histochemistry. Results UCN1 priming increased anxiety-related behavior in the SI test compared to vehicle-injected controls and elevated tph2, but not slc6a4, mRNA expression in DR subregions, including the ventrolateral DR/ventrolateral periaqueductal gray (DRVL/VLPAG), a subregion previously implicated in control of panic-related physiologic responses. Tph2 mRNA expression in the DRVL/VLPAG was correlated with increased anxiety-related behavior. Conclusion Our data support the hypothesis that chronic anxiety states are associated with dysregulated tph2 expression.

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Section: Discussionsupporting

confidence: 92%

ELEVATED tph2 mRNA EXPRESSION IN A RAT MODEL OF CHRONIC ANXIETY

et al. 2012

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“…One of the EEG microstates (identical with class A in the present study) was reported to be correlated with negative blood-oxygen-level dependence (BOLD) activations primarily in bilateral superior and middle temporal gyri [18], areas that are implicated in phonological processing in RSNs [19]-[20]. Thus, more percent total time in microstates of class A in the present study may suggest an abnormality in the temporal lobe, which would not be specific for PD but which has been reported in previous structural studies [46]–[47] or in functional studies of the auditory system [48]–[49] in patients with PD.…”

Section: Discussionsupporting

confidence: 51%

EEG Microstate Analysis in Drug-Naive Patients with Panic Disorder

et al. 2011

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Patients with panic disorder (PD) have a bias to respond to normal stimuli in a fearful way. This may be due to the preactivation of fear-associated networks prior to stimulus perception. Based on EEG, we investigated the difference between patients with PD and normal controls in resting state activity using features of transiently stable brain states (microstates). EEGs from 18 drug-naive patients and 18 healthy controls were analyzed. Microstate analysis showed that one class of microstates (with a right-anterior to left-posterior orientation of the mapped field) displayed longer durations and covered more of the total time in the patients than controls. Another microstate class (with a symmetric, anterior-posterior orientation) was observed less frequently in the patients compared to controls. The observation that selected microstate classes differ between patients with PD and controls suggests that specific brain functions are altered already during resting condition. The altered resting state may be the starting point of the observed dysfunctional processing of phobic stimuli.

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“…Importantly, our assay distinguishes between the effects of a compound on behavioral modulation (e.g., habituation, sensitivity) and alterations in kinematic performance. Given that deficits in modulation of the mammalian acoustic startle response represent an endophenotype common to many neuropsychiatric disorders (73)(74)(75), future screening with the assay described here can be applied to distinguish between many kinematic and behavioral processes as the primary target of already available drugs, and also can be applied toward the systematic identification of more "behavior-specific" compounds.…”

Section: Conservation Of Neural Substrates Of Learning Between Zebrafmentioning

confidence: 99%

Chemical modulation of memory formation in larval zebrafish

Wolman

Jain

Liss

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

179

272

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Whole organism-based small-molecule screens have proven powerful in identifying novel therapeutic chemicals, yet this approach has not been exploited to identify new cognitive enhancers. Here we present an automated high-throughput system for measuring nonassociative learning behaviors in larval zebrafish. Using this system, we report that spaced training blocks of repetitive visual stimuli elicit protein synthesis-dependent long-term habituation in larval zebrafish, lasting up to 24 h. Moreover, repetitive acoustic stimulation induces robust short-term habituation that can be modulated by stimulation frequency and instantaneously dishabituated through cross-modal stimulation. To characterize the neurochemical pathways underlying short-term habituation, we screened 1,760 bioactive compounds with known targets. Although we found extensive functional conservation of short-term learning between larval zebrafish and mammalian models, we also discovered several compounds with previously unknown roles in learning. These compounds included a myristic acid analog known to interact with Src family kinases and an inhibitor of cyclin dependent kinase 2, demonstrating that high-throughput chemical screens combined with high-resolution behavioral assays provide a powerful approach for the discovery of novel cognitive modulators.acoustic startle response | sensorimotor gating A ll organisms, from protozoa to humans, use nonassociative habituation learning as a means to update behavioral responses to sensory input based on recent stimulation history (1). Considered a simple form of learning, habituation reflects a suppressed behavioral response to repeated inconsequential stimulation and serves as a mechanism by which the nervous system filters irrelevant stimuli. Defective habituation not only is indicative of a learning deficit, but also is prevalent in neuropsychiatric conditions, such as schizophrenia, attention deficit hyperactivity disorder, posttraumatic stress disorder, and drug addiction (2-5). Numerous assays have shown that the parameters and rules for habituation learning are similar across phyla (6-9), suggesting conservation of the underlying molecular mechanisms. For example, training session design and stimulation frequency is predictive of the time scale of memory retention. Massed exposure to repeated stimulation at short interstimulus intervals (ISIs) elicits an acquisition of learned information with short-term recall memory, indicated by a change in behavior that does not persist for long after the repeated stimulation is terminated. In contrast, a distributed training protocol with multiple training sessions consisting of stimulation at longer ISIs and rest periods between training blocks induces the acquisition and storage of learned behavior that is capable of being recalled for a more extended period. Thus, intrasession, short-term habituation represents working memory, whereas intersession, long-term habituation includes the storage and retrieval of memory.Existing strategies to measure vertebrate lea...

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Altered auditory processing in patients with panic disorder: A pilot study

Abstract: Our results support the hypothesis of an aberrant processing of sensory information in PD patients. This phenomenon may underlie an enhanced responsiveness to anxiety-relevant or irrelevant stimuli possibly increasing PD vulnerability.

Cited by 17 publications

References 69 publications

ELEVATED tph2 mRNA EXPRESSION IN A RAT MODEL OF CHRONIC ANXIETY

ELEVATED tph2 mRNA EXPRESSION IN A RAT MODEL OF CHRONIC ANXIETY

EEG Microstate Analysis in Drug-Naive Patients with Panic Disorder

Chemical modulation of memory formation in larval zebrafish

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