Christine Norra

Mismatch negativity generation in the human 5HT2A agonist and NMDA antagonist model of psychosis

RationaleMany studies have reported deficits of mismatch negativity (MMN) in schizophrenic patients. Pharmacological challenges with hallucinogens in healthy humans are used as models for psychotic states. Previous studies reported a significant reduction of MMN after ketamine (N-methyl-d-aspartate acid [NMDA] antagonist model) but not after psilocybin (5HT2A agonist model).ObjectivesThe aim of the present study was to directly compare the two models of psychosis using an intraindividual crossover design.Materials and methodsFifteen healthy subjects participated in a randomized, double-blind, crossover study with a low and a high dose of the 5HT2A agonist dimethyltryptamine (DMT) and the NMDA antagonist S-ketamine. During electroencephalographic recording, the subjects were performing the AX-version of a continuous performance test (AX-CPT). A source analysis of MMN was performed on the basis of a four-source model of MMN generation.ResultsNine subjects completed both experimental days with the two doses of both drugs. Overall, we found blunted MMN and performance deficits in the AX-CPT after both drugs. However, the reduction in MMN activity was overall more pronounced after S-ketamine intake, and only S-ketamine had a significant impact on the frontal source of MMN.ConclusionsThe NDMA antagonist model and the 5HT2A agonist model of psychosis display distinct neurocognitive profiles. These findings are in line with the view of the two classes of hallucinogens modeling different aspects of psychosis.

Impact of sleep‐related breathing disorders on health‐related quality of life in patients with chronic heart failure

Quality of life in patients with chronic heart failure (HF) is often severely compromised. Sleep‐related breathing disorders (SRBD) like Cheyne–Stokes Respiration (CSR) or obstructive sleep apnea (OSAS) are often observed in patients with severe HF resulting in fragmentation of sleep, excessive daytime sleepiness and an increased mortality. While an apnea/hypopnea‐index (AHI) >30/h represents an independent predictor of poor prognosis, clinical relevance of even minor SRBD with an AHI <30/h remains unclear with respect to quality of life, exercise capacity or depression rate.

Enhanced intensity dependence as a marker of low serotonergic neurotransmission in borderline personality disorder.

Dysfunction of central serotonergic activity has been assumed in patients with borderline personality disorder (BPD) characterized by a prominent impulsive behavioral style. Following the high serotonergic innervation of the primary auditory cortex, there is increasing evidence of the intensity dependence of auditory evoked potentials (AEP), especially the N1/P2 component, indicating serotonergic neurotransmission in animals and humans. 15 females who met the IPDE-criteria for BPD and a group of comparative healthy females (controls) completed extensive personality questionnaires which gave special regard to impulsiveness. We obtained event-related AEP through the application of various loudness stimuli. We examined the relevant N1/P2 amplitude of the tangential dipole of the auditory evoked response using dipole source analysis. The augmentation of the N1/P2 amplitude of tangential dipole source activity with rising stimulus intensity was significantly pronounced in BPD as opposed to controls, accompanied by a reduction in N1 and P2 latencies. The strong loudness dependency of AEP correlated with aspects of impulsiveness. These data imply reduced inhibiting control over cortical sensory processing in BPD. Our findings contribute a further argument to the hypothesis of low serotonergic neurotransmission in BDP and may point to a trait character of impulsiveness in this personality disorder.

Cognitive and affective empathy in depression linked to executive control

Depression has been linked to executive dysfunction and emotion recognition impairments, associated with abnormalities in fronto-temporal and subcortical brain regions. Little is known about changes of different empathy subcomponents during depression, with potential impairments being related to the interpersonal difficulties of depressed patients. Twenty patients treated for an episode of unipolar depression and 20 matched healthy controls were assessed. Measures of dispositional and behavioural empathy components were administered along with tests of cognitive flexibility, response inhibition and working memory. Relative to controls, depressed patients showed higher self-reported dispositional empathy scores, mainly driven by increased personal distress scores. Patients and controls did not differ significantly in terms of behavioural cognitive empathy, empathic concern and personal affective involvement or in their executive function performance. In the patients, cognitive flexibility and response inhibition accuracy were associated with behavioural empathy. While an increased disposition towards feeling personal distress in response to other peoples suffering seems to be in generally related to depressive symptoms, behavioural empathy might depend on the functional integrity of executive control during an episode of clinical depression. Impairments in this regard could contribute to the interpersonal difficulties depressed patients are frequently faced with which might have important implications for treatment.

Early sensory encoding of affective prosody: Neuromagnetic tomography of emotional category changes

In verbal communication, prosodic codes may be phylogenetically older than lexical ones. Little is known, however, about early, automatic encoding of emotional prosody. This study investigated the neuromagnetic analogue of mismatch negativity (MMN) as an index of early stimulus processing of emotional prosody using whole-head magnetoencephalography (MEG). We applied two different paradigms to study MMN; in addition to the traditional oddball paradigm, the so-called optimum design was adapted to emotion detection. In a sequence of randomly changing disyllabic pseudo-words produced by one male speaker in neutral intonation, a traditional oddball design with emotional deviants (10% happy and angry each) and an optimum design with emotional (17% happy and sad each) and nonemotional gender deviants (17% female) elicited the mismatch responses. The emotional category changes demonstrated early responses (<200 ms) at both auditory cortices with larger amplitudes at the right hemisphere. Responses to the nonemotional change from male to female voices emerged later ( approximately 300 ms). Source analysis pointed at bilateral auditory cortex sources without robust contribution from other such as frontal sources. Conceivably, both auditory cortices encode categorical representations of emotional prosodic. Processing of cognitive feature extraction and automatic emotion appraisal may overlap at this level enabling rapid attentional shifts to important social cues.

Depression in patients with Huntington disease correlates with alterations of the brain stem raphe depicted by transcranial sonography

BACKGROUND Transcranial sonography (TCS) has become a new diagnostic tool in the evaluation of extrapyramidal disorders. Studies of TCS report alterations of the mesencephalic raphe in patients with depression. The aim of this study was to evaluate TCS findings in patients with Huntington disease in correlation with their neurologic and psychiatric status. METHODS We recruited patients with genetically confirmed Huntington disease. The neurological and psychiatric status of participants was assessed by independent physicians. Echogenicities were investigated according to examination protocol for extrapyramidal disorders using a Siemens Sonoline Elegra system. The sonography examiner was blinded for clinical data. RESULTS We included 39 patients in our study; 21 patients (53.8%) showed symptoms of depression at the time of evaluation and, of those, 15 (71.4%) had hypoechogenic raphe structures. Thirty patients (76.9%) had a history of depressive episodes, 19 (63.3%) of them with hypoechogenic raphe structures. All 9 patients without a history of depressive episodes showed normal echogenicity of raphe structures (sensitivity 63.3%, specificity 100%). Twelve (70.6%) of the 17 patients with Huntington disease who showed psychiatric disturbances prior to the occurrence of motor symptoms exhibited pathological raphe echogenicity (sensitivity 70.6%, specificity 68.2%). LIMITATIONS Most of the patients were taking antichoreatic medication, which particularly influences neurologic status. Thus, a meaningful interpretation of the correlation between TCS findings and neurologic features was limited. CONCLUSION As a novel finding, a relation between mesencephalic raphe echogenicity and depressive state could be identified in patients with Huntington disease. An alteration of the serotonergic brain stem raphe might be involved in the pathogenesis of depression in these patients.

Development and validation of the Rasch-based depression screening (DESC) using Rasch analysis and structural equation modelling

Questionnaires for the assessment of depression benefit from modern test construction like item-response-modelling. We developed two parallel 10 item depression questionnaires, the Rasch-based Depression Screening version 1 (DESC-I) and 2 (DESC-II), by combining Rasch analysis and structural equation modelling on patient samples suffering primarily from a mental disorder or from somatic diseases. Both scales base upon a Rasch homogeneous item bank and proved unidimensionality and good model fit. Cut-off scores with good sensitivity and specificity were developed using ROC analyses. Results suggest that DESC may be appropriately used to screen for depression and may be beneficial for repeated measurements.

1H-MR spectroscopy in ultra-high risk and first episode stages of schizophrenia

Using proton magnetic resonance spectroscopy biochemical characteristics in early stages of schizophrenia were examined. N-acetylaspartate, choline and creatine were measured in hippocampus, anterior cingulate gyrus (ACC) and medial prefrontal cortex (mPFC) of 24 first episode and 30 ultra-high risk patients. Careful LCModel analyses revealed no differences between the patient groups and 31 healthy controls, casting doubt upon the idea of metabolic changes in early stages of psychosis.

Theories of delusional disorders. An update and review.

Delusional syndromes can occur in a number of psychiatric, neurological or other disorders. They can also be caused by neurotoxic agents (e.g., heavy metals) as well as substance addiction. There are several hypotheses on the underlying cognitive or emotional processes associated with organic factors of delusional disorders, depending on the patient groups examined and the methods used. The aim of this paper is to provide a comprehensive review and critical assessment of the various, rather heterogeneous theories in this field.

High-Frequency Somatosensory Thalamocortical Oscillations and Psychopathology in Schizophrenia

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO – assumed to be of inhibitory nature – could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms.