0000000000963597
AUTHOR
Tilo Kircher
S-Ketamine-Induced NMDA Receptor Blockade during Natural Speech Production and Its Implications for Formal Thought Disorder in Schizophrenia: A Pharmaco-fMRI Study
Structural and functional changes in the lateral temporal language areas have been related to formal thought disorder (FTD) in schizophrenia. Continuous, natural speech production activates the right lateral temporal lobe in schizophrenia, as opposed to the left in healthy subjects. Positive and negative FTD can be elicited in healthy subjects by glutamatergic NMDA blockade with ketamine. It is unclear whether the glutamate system is related to the reversed hemispheric lateralization during speaking in patients. In a double-blind, crossover, placebo-controlled study, 15 healthy, male, right-handed volunteers overtly described 7 pictures for 3 min each while BOLD signal changes were acquired…
Low concentration of ziprasidone in human milk: a case report
Although second-generation antipsychotics are established as the first-line treatment for schizophrenia, female patients are often excluded from this efficient treatment for safety reasons in pregnancy or whilst breastfeeding. For this reason, research on this subject mostly relies on case reports, although there is a great need to establish modern guidelines for treatment. Milk-to-plasma (M:P) ratios have been reported for clozapine (2.79–4.32; Winans, 2001), olanzapine (0.10–0.84; Gardiner et al. 2003), risperidone/9-OH risperidone (0.10–0.42/0.24–0.50; Gentile, 2004) and aripiprazole (0.18–0.20; Schlotterbeck et al. 2007). According to one case report, the infant ingests 0.09–0.43% of th…
Modality-specific dysfunctional neural processing of social-abstract and non-social-concrete information in schizophrenia
Highlights • Social/non-social information processing in three modalities was investigated in SZ. • SZ showed reduced activation for social information only in gesture modality. • Reduced activation in SZ was observed for non-social information only in speech. • Neural Neural processing in bimodal condition is not different between patients and controls.
Evidence for gesture-speech mismatch detection impairments in schizophrenia.
Patients with schizophrenia suffer from impairments in the perception and production of gestures. The extent to which patients can access the semantic association between speech and co-verbal gestures in concrete or abstract/metaphorical meaning contexts is unknown. We investigated 1) how patients differ from controls in gesture matching performance, 2) how performance differs in the context of abstract versus concrete meaning, and 3) whether formal thought disorder (FTD) symptom severity predicts task impairment. Forty-five patients with schizophrenia spectrum disorders (two subgroups, mild and severe) took part in this study. Participants were presented with video clips, each showing an a…
Feeling addressed! The neural processing of social communicative cues in patients with major depression
Abstract The feeling of being addressed is the first step in a complex processing stream enabling successful social communication. Social impairments are a relevant characteristic of patients with major depressive disorder (MDD). Here, we investigated a mechanism which—if impaired—might contribute to withdrawal or isolation in MDD, namely, the neural processing of social cues such as body orientation and gesture. During funtional magnetic resonance imaging (fMRI) data acquisition, 33 patients with MDD and 43 healthy control subjects watched video clips of a speaking actor: one version with a gesture accompanying the speech and one without gesture. Videos were filmed simultaneously from two …
MicroRNA hsa-miR-4717-5p regulates RGS2 and may be a risk factor for anxiety-related traits
Regulator of G-protein Signaling 2 (RGS2) is a key regulator of G-protein-coupled signaling pathways involved in fear and anxiety. Data from rodent models and genetic analysis of anxiety-related traits and disorders in humans suggest down-regulation of RGS2 expression to be a risk factor for anxiety. Here we investigated, whether genetic variation in microRNAs mediating posttranscriptional down-regulation of RGS2 may be a risk factor for anxiety as well. 75 microRNAs predicted to regulate RGS2 were identified by four bioinformatic algorithms and validated experimentally by luciferase reporter gene assays. Specificity was confirmed for six microRNAs (hsa-miR-1271-5p, hsa-miR-22-3p, hsa-miR-3…
Neural Basis of Speech-Gesture Mismatch Detection in Schizophrenia Spectrum Disorders
AbstractPatients with schizophrenia spectrum disorders (SSD) exhibit an aberrant perception and comprehension of abstract speech-gesture combinations associated with dysfunctional activation of the left inferior frontal gyrus (IFG). Recently, a significant deficit of speech-gesture mismatch detection was identified in SSD, but the underlying neural mechanisms have not yet been examined. A novel mismatch-detection fMRI paradigm was implemented manipulating speech-gesture abstractness (abstract/concrete) and relatedness (related/unrelated). During fMRI data acquisition, 42 SSD patients (schizophrenia, schizoaffective disorder, or other non-organic psychotic disorder [ICD-10: F20, F25, F28; DS…
Aripiprazole in human milk
Second-generation antipsychotics are now the established first-line treatment for schizophrenia. However, there are limited data on the use of these compounds in pregnant and breastfeeding women with mental disorders. For ethical reasons, research on these subjects mostly relies on collection of single datasets of cases in order to establish treatment guidelines.
Hand Gestures Alert Auditory Cortices
When acquiring a foreign language, the first challenge is to break into the speech stream to identify basic linguistic units. The present study tested the hypothesis that hand gestures facilitate this process by alerting auditory cortices to attend to and identify meaningful phonemic information. During fMRI data acquisition, participants watched videos of an actor speaking in Russian under three conditions. Sentences were produced with just speech alone or were accompanied by two types of hand gestures: 1) metaphoric gesture and 2) free gesture. The main finding was that there was increased auditory cortex activation when both types of gestures accompanied speech compared to speech alone, …
The EEG and fMRI signatures of neural integration: An investigation of meaningful gestures and corresponding speech
Abstract One of the key features of human interpersonal communication is our ability to integrate information communicated by speech and accompanying gestures. However, it is still not fully understood how this essential combinatory process is represented in the human brain. Functional magnetic resonance imaging (fMRI) studies have unanimously attested the relevance of activation in the posterior superior temporal sulcus/middle temporal gyrus (pSTS/MTG), while electroencephalography (EEG) studies have shown oscillatory activity in specific frequency bands to be associated with multisensory integration. In the current study, we used fMRI and EEG to separately investigate the anatomical and o…
Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.
Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After t…
Do Patients With Depression Prefer Literal or Metaphorical Expressions for Internal States? Evidence From Sentence Completion and Elicited Production
In everyday communication metaphoric expressions are frequently used to refer to abstract concepts, such as feelings or mental states. Patients with depression are said to prefer literal over figurative language, i.e. they may show a concreteness bias. Given that both emotional functioning and the processing of figurative language may be altered in this clinical population, our study aims at investigating whether and how these dysfunctions are reflected in the understanding and production of metaphorical expressions for internal states. We used two behavioral approaches: a sentence completion task and elicited speech production. In the first experiment, patients with ICD 10 depression (n = …
Factor analyses of multidimensional symptoms in a large group of patients with major depressive disorder, bipolar disorder, schizoaffective disorder and schizophrenia
Abstract Background There is an ongoing discussion about which neurobiological correlates or symptoms separate the major psychoses (i.e. Major Depressive Disorder MDD, Bipolar Disorder BD, and Schizophrenia SZ). Psychopathological factor analyses within one of these disorders have resulted in models including one to five factors. Factor analyses across the major psychoses using a comprehensive set of psychopathological scales in the same patients are lacking. It is further unclear, whether hierarchical or unitarian models better summarize phenomena. Method Patients (n = 1182) who met DSM-IV criteria for MDD, BD, SZ or schizoaffective disorder were assessed with the SANS, SAPS, HAMA, HAM-D, …
Modality-specific dysfunctional neural processing of social and non-social information in schizophrenia
Abstract Background Schizophrenia (SZ) is characterized by marked social dysfunctions encompassing potential deficits in the processing of social and non-social information, especially in everyday settings where multiple modalities are present. To date, the neurobiological basis of these deficits remains elusive. Methods In a functional magnetic resonance imaging (fMRI) study, 17 patients with schizophrenia or schizoaffective disorder, and 18 matched controls watched videos of an actor speaking, gesturing (unimodal), and both speaking and gesturing (bimodal) about social or non-social events in a naturalistic way. Participants had to judge whether each video contains person-related (social)…
Is formal thought disorder in schizophrenia related to structural and functional aberrations in the language network? A systematic review of neuroimaging findings
Formal thought disorder (FTD) is a core feature of schizophrenia, a marker of illness severity and a predictor of outcome. The underlying neural mechanisms are still a matter of debate. This study aimed at 1) reviewing the literature on the neural correlates of FTD in schizophrenia, and 2) testing the hypothesis that FTD correlates with structural and functional aberrations in the language network. Medline, PsychInfo, and Embase were searched for neuroimaging studies, which applied a clinical measure to assess FTD in adults with schizophrenia and were published in English or German in peer-reviewed journals until December 2016. Of 412 articles identified, 61 studies were included in the rev…
What we learn about bipolar disorder from large-scale neuroimaging
Abstract MRI‐derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta‐Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis‐driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Workin…
Neural processing of nouns and verbs in spontaneous speech of patients with schizophrenia.
Previous fMRI-studies investigating the production of nouns and verbs in healthy participants reported predominantly activation in the left inferior frontal gyrus (IFG) for both classes of words with increased neural responses for verbs. To date, comparable imaging data for spontaneous speech in patients with schizophrenia is missing. These results are novel and may contribute to understand the neural basis of noun and verb production in a "natural" environment. Fifteen patients with schizophrenia and fifteen healthy control participants described pictures for one minute each while BOLD signal changes were measured with fMRI. In an event-related design, activations related to noun and verb …
GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder.
Contains fulltext : 177350.pdf (Publisher’s version ) (Closed access) The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes. We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1. A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 x 10-8; rs191260602, P=3.9 x 10-8). We followed up on this finding in a larger dimensional AC…