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1.
Conscious Cogn ; 119: 103667, 2024 03.
Article En | MEDLINE | ID: mdl-38428277

The sense of agency (SoA) is central to human experience. The comparator model, contrasting sensory prediction and action feedback, is influential but limited in explaining SoA. We investigated mechanisms beyond the comparator model, focusing on the processing of unpredictable stimuli, perimotor components of SoA, and their relation to schizotypy. ERPs were recorded from 18 healthy participants engaged in button-pressing tasks while perceiving tones with varying causal relationships with their actions. We investigated the processing of non-causally related tones, contrasted this to causally related tones, and examined perimotor correlates of subjective expectancy and experience of agency. We confirmed N100 attenuation for self-generated stimuli but found similar effects for expectancy-dependent processing of random tones. SoA also correlated with perimotor ERP components, modulated by schizotypy. Thus, neural processes preceding actions contribute to the formation of SoA and are associated with schizotypy. Unpredictable events also undergo sensory attenuation, implying additional mechanisms contributing to SoA.


Evoked Potentials , Motivation , Humans , Evoked Potentials/physiology
2.
Schizophr Res ; 264: 49-57, 2024 Feb.
Article En | MEDLINE | ID: mdl-38096659

Resting-state electroencephalography (EEG) microstates are brief periods (60-120 ms) of quasi-stable scalp field potentials, indicating simultaneous activity of large-scale networks. Microstates are assumed to reflect basic neuronal information processing. A common finding in psychosis spectrum disorders is that microstates classes C and D are altered. Whereas evidence in adults with schizophrenia is substantial, little is known about effects in underage patients, particularly in those at clinical high risk for psychosis (CHR) and first-episode psychosis (FEP). The present study used 74-channel EEG to investigate microstate effects in a large sample of patients with CHR (n = 100) and FEP (n = 33), clinical controls (CC, n = 18), as well as age-matched healthy controls (HC, n = 68). Subjects span an age range from 9 to 35 years, thus, covering underage patients as well as the most vulnerable period for the emergence of psychosis and its prodrome. Four EEG microstates classes were analyzed (A-D). In class D, CHR and FEP patients showed a decrease compared to HC, and CHR patients also to CC. An increase in class C was found in CHR and FEP compared to HC but not to CC. Results were independent of age and no differences were found between the psychosis spectrum groups. The findings suggest an age-independent decrease of microstate class D to be specific to the psychosis spectrum, whereas the increase in class C seems to reflect unspecific psychopathology. Overall, present data strengthens the role of microstate D as potential biomarker for psychosis, as early as in adolescence and already in CHR status.


Psychotic Disorders , Schizophrenia , Humans , Young Adult , Adolescent , Child , Adult , Psychotic Disorders/diagnosis , Electroencephalography , Brain/physiology
3.
Front Public Health ; 11: 1309654, 2023.
Article En | MEDLINE | ID: mdl-38259798

Background: Pregabalin is a gamma-aminobutyric acid (GABA) analog that was approved in the EU in 2004 for the treatment of neuropathic pain, generalized anxiety disorder and epilepsy. Since its introduction, pregabalin abuse and misuse has increased significantly. In Switzerland, clinical reports suggest that pregabalin misuse is common among patients in forensic hospitals and prisons. However, data on pregabalin use is scarce, especially in these settings. Therefore, we conducted a study to explore patterns of pregabalin use among prison and forensic patients. Methods: We used a questionnaire to survey physicians working in prison and forensic medicine in German-speaking countries. A total of 131 responses were received. Results: According to the physicians' subjective assessment, 82.5% of them had observed a recent increase in pregabalin use by their patients and 89.1% of them reported that their patients requested pregabalin without a clear medical indication. Patients misusing pregabalin in combination with other illicit substances were observed by 93.3% of the physicians surveyed. According to 73.5% of the physicians surveyed, they had already encountered patients on pregabalin doses of more than 600 mg/day (the maximum recommended daily dose); the highest dose reported was 4,200 mg/day. According to 85.0% of physicians surveyed, they have observed patients experiencing withdrawal symptoms from pregabalin, with the most commonly reported symptoms being displeasure and high aggression. Regarding the nationality of pregabalin-misusing patients, 58.3% of the interviewed physicians reported to be rather in contact with foreign patients, mainly from Northwest Africa (Maghreb). Only 45.0% of the surveyed physicians prescribe pregabalin. Among patients who developed behavioral problems while taking pregabalin, none of the physicians (0.0%) showed a tendency to continue pregabalin at the same dose; all respondents chose to reduce/substitute/discontinue. Conclusion: Our study has provided confirmatory evidence that the use of pregabalin presents a significant issue in forensic and prison medicine across German-speaking countries. Prescribing pregabalin in this field can compound use disorder problems and exacerbate challenges in daily life for those in forensic institutions or prisons. It is necessary that all physicians who prescribe pregabalin are clearly informed about the management (including the risks) of this drug.


Physicians , Prisons , Humans , Pregabalin/therapeutic use , gamma-Aminobutyric Acid , Hospitals
4.
Early Interv Psychiatry ; 16(3): 289-301, 2022 03.
Article En | MEDLINE | ID: mdl-33960114

AIM: Early detection of, and intervention for, psychosis during its prodromal phase has the potential to alter the course of the disease and has therefore become a major objective of modern clinical psychiatry. An increasing number of early detection and intervention services have been established in Europe and worldwide. This study aims to describe and evaluate an early detection and intervention service for children, adolescents and adults (FETZ Bern) aged from eight to 40 years with a population catchment area of 1.035 million in Bern, Switzerland. METHODS: Routine demographic, diagnostic and service usage data were collected upon admission to the service. Using a retrospective, descriptive and naturalistic study design, data was analysed for different age groups (children, adolescents and adults) and where available, outcome data after 12 and 24 months was evaluated. RESULTS: The FETZ Bern has received 827 referrals with full diagnostic data available for 353 patients. The majority of the assessed patients were young males. While 40% met criteria for a clinical high-risk state of psychosis, 20% were diagnosed with fully manifest psychosis at time of admission, and another 40% had one or more non-psychotic axis-I diagnoses. CONCLUSIONS: The FETZ Bern is the first early detection centre worldwide assessing children aged younger than 12 years, as well as adolescents and young adults in one service. Given that developmental peculiarities are important in understanding and ultimately treating psychosis, the FETZ Bern, with its emphasis on developmental peculiarities, should be considered as a model for other similar services.


Psychotic Disorders , Adolescent , Adult , Child , Child, Preschool , Early Diagnosis , Hospitalization , Humans , Infant , Male , Psychotic Disorders/diagnosis , Psychotic Disorders/epidemiology , Psychotic Disorders/therapy , Referral and Consultation , Retrospective Studies , Young Adult
5.
Neuroscience ; 479: 140-156, 2021 12 15.
Article En | MEDLINE | ID: mdl-34687795

Patients with schizophrenia present with various symptoms related to different domains. Abnormalities of auditory and visual perception are parts of a more general problem. Nevertheless, the relationship between the lifetime history of auditory verbal hallucination (AVH), one of the most prevalent symptoms in schizophrenia, and visuospatial deficits remains unclear. This study aimed to investigate differences in hemispheric involvement and visuospatial processing between healthy controls (HCs) and schizophrenia patients with and without AVHs. HCs (N = 20), schizophrenia patients with AVH (AVH group, N = 16), and schizophrenia patients without hallucinations (NH group, N = 10) participated in a 4-choice reaction task with lateralized stimuli. An event-related potential (ERP)-microstate approach was used to analyze ERP differences between the conditions and groups. The schizophrenia patients without hallucinations had slower responses than the HCs. An early visual N1 contralateral to stimulation side was prominent in all groups of participants but with decreased amplitude in the patients with schizophrenia, especially in the AVH group over the right hemisphere. The amplitude of P3b, a cognitive evaluation component, was also decreased in schizophrenia. Compared to AVH and HC groups, the patients in the NH group had altered microstate patterns: P3b was replaced by a novelty component, P3a. Although the difference between both patient groups was only based on the presence of AVHs, our findings indicated that patients had specific visuospatial deficits associated with a lifetime history of hallucinations: patients with AVHs showed early visual component alterations in the right hemisphere, and those without AVHs had more prominent visuospatial impairment.


Schizophrenia , Evoked Potentials , Hallucinations , Humans , Magnetic Resonance Imaging , Schizophrenia/complications , Visual Perception
6.
Psychol Med ; 51(15): 2666-2674, 2021 11.
Article En | MEDLINE | ID: mdl-32404212

BACKGROUND: Clinical high-risk (CHR) for psychosis is indicated by ultra-high risk (UHR) and basic symptom (BS) criteria; however, conversion rates are highest when both UHR and BS criteria are fulfilled (UHR&BS). While BSs are considered the most immediate expression of neurobiological aberrations underlying the development of psychosis, research on neurobiological correlates of BS is scarce. METHODS: We investigated gray matter volumes (GMV) of 20 regions of interest (ROI) previously associated with UHR criteria in 90 patients from the Bern early detection service: clinical controls (CC), first-episode psychosis (FEP), UHR, BS and UHR&BS. We expected lowest GMV in FEP and UHR&BS, and highest volume in CC with UHR and BS in-between. RESULTS: Significantly, lower GMV was detected in FEP and UHR&BS patients relative to CC with no other significant between-group differences. When ROIs were analyzed separately, seven showed a significant group effect (FDR corrected), with five (inferior parietal, medial orbitofrontal, lateral occipital, middle temporal, precuneus) showing significantly lower GM volume in the FEP and/or UHR&BS groups than in the CC group (Bonferroni corrected). In the CHR group, only COGDIS scores correlated negatively with cortical volumes. CONCLUSIONS: This is the first study to demonstrate that patients who fulfill both UHR and BS criteria - a population that has been associated with higher conversion rates - exhibit more severe GMV reductions relative to those who satisfy BS or UHR criteria alone. This result was mediated by the BS in the UHR&BS group, as only the severity of BS was linked to GMV reductions.


Gray Matter/pathology , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/pathology , Adolescent , Adult , Child , Female , Humans , Male , Parietal Lobe/diagnostic imaging , Parietal Lobe/pathology , Psychiatric Status Rating Scales , Risk Factors , Switzerland , Young Adult
7.
Front Psychiatry ; 11: 535652, 2020.
Article En | MEDLINE | ID: mdl-33024435

BACKGROUND: Depersonalization (DP) and derealization (DR) are symptoms of a disruption of perceptual integration leading to an altered quality of subjective experiences such as feelings of unreality and detachment from the self (DP) or the surroundings (DR). Both DP and DR often occur in concert with other symptoms, for example in subjects at clinical high-risk (CHR) for psychosis, but also appear isolated in the form of DP/DR disorder. Despite evidence that DP/DR causes immense distress, little is known about their neurobiological underpinnings. Therefore, we investigated the neural correlates of DP/DR using pseudo-continuous arterial spin labeling MRI. METHODS: We evaluated the frequency of DP/DR symptoms in a clinical sample (N = 217) of help-seeking individuals from the Early Detection and Intervention Centre for Mental Crisis (CHR, n = 97; clinical controls (CC), n = 91; and first-episode psychosis (FEP), n = 29). Further, in a subsample of those CHR subjects who underwent MRI, we investigated the resting-state regional cerebral blood flow (rCBF). Here, individuals with (n = 21) and without (n = 23) DP/DR were contrasted. Finally, rCBF was measured in a small independent second sample of patients with DP/DR disorder (n = 6) and healthy controls (HC, n = 6). RESULTS: In the complete clinical sample, significantly higher frequency of DP/DR was found in CHR compared to CC (50.5 vs. 16.5%; χ2 (2) = 24.218, p ≤ 0.001, Cramer's V = 0.359) as well as in FEP compared to CC (37.9 vs. 16.5%; χ2 (2) = 5.960, p = 0.015, Cramer's V = 0.223). In MRI, significantly lower rCBF was detected in the left orbitofrontal cortex in CHR with vs. without DP/DR (x/y/z = -16/42/-22, p < 0.05, FWE corrected). In patients with DP/DR disorder, significantly higher rCBF was detected in the left caudate nucleus (x/y/z = -18/-32/18, p < 0.05) compared to HC. CONCLUSIONS: This study shows that DP/DR symptoms are frequently found in CHR subjects. Investigating two separate DP/DR populations with an identical neuroimaging technique, our study also indicates that there may be divergent pathophysiological mechanisms-decreased neuronal activity in the orbitofrontal cortex, but increased activity within the caudate nucleus-leading to a final common pathway with similar psychopathological symptoms. This suggests that both top-down (orbitofrontal cortex) and bottom-up (caudate nucleus) mechanisms could contribute to the emergence of DP/DR.

8.
Schizophr Res ; 212: 196-203, 2019 10.
Article En | MEDLINE | ID: mdl-31405623

BACKGROUND: Abnormal involuntary movements (AIM) may occur throughout the course of psychosis. While AIM are thought to indicate striatal abnormalities, the functional and structural correlates of increased AIM remain elusive. Here, we examined the prevalence of AIM in patients with clinical high risk for psychosis (CHR), first episode psychosis (FEP) and clinical controls (CC). Furthermore, we tested the association of AIM with regional cerebral blood flow (rCBF), grey matter volume (GMV), and premorbid IQ. METHODS: We conducted a video-based analysis of AIM in patients with CHR (n = 45), FEP (n = 10) and CC (n = 39), recruited in the Early Detection and Intervention Center, Bern. Premorbid intelligence was evaluated using the Peabody Picture Vocabulary test. Additionally, arterial spin labeling MRIs and structural MRIs were acquired in a subgroup of the sample to investigate the association of AIM with rCBF and GMV. RESULTS: Higher total AIM scores were detected in CHR (p = 0.02) and FEP (p = 0.04) as compared to CC. When separated for different muscle groups, lips and perioral movements were significantly increased in CHR patients as compared to CC (p = 0.009). AIM scores correlated positively with rCBF in the premotor cortex, Brodmann area 6 (p < 0.05, FWE corrected). Negative correlations were found between AIM and GMV of the corresponding caudal middle frontal gyrus (p = 0.04, FWE corrected) and premorbid intelligence (p = 0.02). CONCLUSIONS: AIM were more frequent in the psychosis spectrum than in clinical controls. Neuroimaging findings indicate an involvement of cortical motor areas in abnormal motor behavior, instead of pure basal ganglia pathology.


Dyskinesias/physiopathology , Psychotic Disorders/physiopathology , Adolescent , Adult , Brain/physiopathology , Brain Mapping , Case-Control Studies , Cerebrovascular Circulation/physiology , Cognition Disorders/diagnosis , Cognition Disorders/physiopathology , Cognition Disorders/psychology , Dyskinesias/diagnosis , Dyskinesias/psychology , Female , Gray Matter/physiopathology , Humans , Magnetic Resonance Imaging , Male , Nerve Net/physiopathology , Neuropsychological Tests , Psychotic Disorders/diagnosis , Psychotic Disorders/psychology , Regional Blood Flow/physiology , Risk Factors , Spin Labels , Young Adult
9.
Schizophr Res ; 210: 188-196, 2019 08.
Article En | MEDLINE | ID: mdl-30683524

Schizotypy and clinical high risk (CHR) criteria can identify individuals who are at increased risk for developing psychosis in community and patient samples. However, both approaches have rarely been combined, and very little is known about their associations. Therefore, we examined the factorial structure of CHR and related symptoms and schizotypy features as well as their interrelationship for the first time in a comprehensive approach. In a sample of 277 patients (22 ±â€¯6 years) from two early detection services, structural equation modeling including confirmatory factor analysis was performed to test a theory-driven model using four Wisconsin Schizotypy Scales, 14 predictive basic symptoms (BS) of the Schizophrenia Proneness Instrument, and positive, negative, and disorganized symptoms from the Structured Interview for Psychosis-Risk Syndromes. The data fitted well to the six hypothesized latent factors consisting of negative schizotypy, positive schizotypy including perceptual BS, negative symptoms, positive symptoms, disorganized symptoms and cognitive disturbances. As postulated, schizotypy features were significantly associated with positive, negative and disorganized symptoms through cognitive disturbances. Additionally, positive and negative schizotypy also had a direct association with the respective symptom-domain. While the identified factorial structure corresponds well to dimensional models of schizotypy and psychoses, our model extends earlier models by indicating that schizotypy features are associated with positive, negative and disorganized symptoms directly or indirectly via subjective cognitive disturbances. This calls for more attention to subjective cognitive deficits in combination with heightened schizotypy in the early detection and intervention of psychoses - or even of an Attenuated Psychosis Syndrome.


Cognitive Dysfunction/physiopathology , Psychotic Disorders/physiopathology , Schizotypal Personality Disorder/physiopathology , Adolescent , Adult , Cognitive Dysfunction/etiology , Diagnostic Self Evaluation , Early Diagnosis , Female , Humans , Male , Psychotic Disorders/complications , Risk , Schizotypal Personality Disorder/complications , Young Adult
11.
Schizophr Res ; 201: 231-236, 2018 11.
Article En | MEDLINE | ID: mdl-29983268

BACKGROUND: Patients at clinical high risk (CHR) for psychosis exhibit increased striatal cerebral blood flow (CBF) during the resting state and impaired cognitive function. However, the relation between CBF and cognitive impairment is unknown. We therefore studied the association between striatal CBF and executive functioning and evaluated the functional connectivity (FC) between dorsal striatum and the frontal cortex in CHR. METHODS: In total, 47 participants [29 with CHR, 18 matched clinical controls (CC)] were assessed for ultra-high-risk criteria and basic symptoms and were tested for executive functioning using the trail making test-B (TMT-B). Resting state mean CBF and FC were calculated from arterial spin labeling 3T MRI data. RESULTS: Striatal CBF was highest in CHR patients with TMT-B deficits and was significantly higher than that in CC with and without TMT-B impairment. Further, a significantly lower CBF FC between the dorsal striatum and the anterior cingulate cortex was revealed in CHR. CONCLUSIONS: Our study suggests that higher striatal CBF might represent focal pathology in CHR and is associated with disrupted cingulo-striatal FC and executive dysfunctions.


Corpus Striatum/physiopathology , Executive Function/physiology , Frontal Lobe/physiopathology , Psychotic Disorders/physiopathology , Regional Blood Flow , Brain Mapping , Cerebrovascular Circulation , Cognition/physiology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/etiology , Cognitive Dysfunction/physiopathology , Corpus Striatum/diagnostic imaging , Cross-Sectional Studies , Female , Frontal Lobe/diagnostic imaging , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Neural Pathways/physiopathology , Prodromal Symptoms , Psychotic Disorders/diagnostic imaging , Psychotic Disorders/drug therapy , Psychotic Disorders/psychology , Rest , Risk , Young Adult
12.
Ther Umsch ; 75(1): 19-29, 2018 Jun.
Article De | MEDLINE | ID: mdl-29909766

Phenomenology, clinical diagnostics and treatment of hallucinations Abstract. Hallucinations are perceptions without any stimulus. They occur typically in schizophrenia, but they can be found in other psychiatric or medical disorders as well. Recently, hallucinations have been increasingly reported to occur with a high prevalence in the general population and they are conceptualised as continuum from a physiological to pathological especially psychotic phenomenon. Schizophrenic hallucinations exhibit a special proximity to language and for this they can be considered as diagnostic. Clinically, physicians should explore detailed the semiology of hallucinations in the diagnostic workup. Neurobiology of acoustic hallucinations involve brain regions which are important for hearing, speaking and understanding. This observation is independent of the underlying aetiology of the hallucinations. Standard treatment of psychotic hallucinations consists of antipsychotic substances. In case of resistance electrical brain stimulation methods are increasingly applied. Especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are used.


Hallucinations/diagnosis , Hallucinations/therapy , Schizophrenia/diagnosis , Schizophrenia/therapy , Schizophrenic Psychology , Antipsychotic Agents/adverse effects , Antipsychotic Agents/therapeutic use , Brain/drug effects , Brain/physiopathology , Combined Modality Therapy , Hallucinations/physiopathology , Hallucinations/psychology , Humans , Psychotherapy , Schizophrenia/physiopathology , Transcranial Direct Current Stimulation , Transcranial Magnetic Stimulation
13.
Clin EEG Neurosci ; 49(6): 367-378, 2018 Nov.
Article En | MEDLINE | ID: mdl-29569473

Auditory verbal hallucinations depend on a broad neurobiological network ranging from the auditory system to language as well as memory-related processes. As part of this, the auditory N100 event-related potential (ERP) component is attenuated in patients with schizophrenia, with stronger attenuation occurring during auditory verbal hallucinations. Changes in the N100 component assumingly reflect disturbed responsiveness of the auditory system toward external stimuli in schizophrenia. With this premise, we investigated the therapeutic utility of neurofeedback training to modulate the auditory-evoked N100 component in patients with schizophrenia and associated auditory verbal hallucinations. Ten patients completed electroencephalography neurofeedback training for modulation of N100 (treatment condition) or another unrelated component, P200 (control condition). On a behavioral level, only the control group showed a tendency for symptom improvement in the Positive and Negative Syndrome Scale total score in a pre-/postcomparison ( t(4) = 2.71, P = .054); however, no significant differences were found in specific hallucination related symptoms ( t(7) = -0.53, P = .62). There was no significant overall effect of neurofeedback training on ERP components in our paradigm; however, we were able to identify different learning patterns, and found a correlation between learning and improvement in auditory verbal hallucination symptoms across training sessions ( r = 0.664, n = 9, P = .05). This effect results, with cautious interpretation due to the small sample size, primarily from the treatment group ( r = 0.97, n = 4, P = .03). In particular, a within-session learning parameter showed utility for predicting symptom improvement with neurofeedback training. In conclusion, patients with schizophrenia and associated auditory verbal hallucinations who exhibit a learning pattern more characterized by within-session aptitude may benefit from electroencephalography neurofeedback. Furthermore, independent of the training group, a significant spatial pre-post difference was found in the event-related component P200 ( P = .04).


Evoked Potentials, Auditory/physiology , Hallucinations/physiopathology , Neurofeedback , Schizophrenia/physiopathology , Acoustic Stimulation/methods , Adult , Brain Mapping , Electroencephalography/methods , Evoked Potentials/physiology , Female , Humans , Male , Middle Aged , Neurofeedback/methods , Schizophrenia/diagnosis
14.
Schizophr Bull ; 44(1): 182-192, 2018 01 13.
Article En | MEDLINE | ID: mdl-28575528

Increased striatal dopaminergic activity and decreased prefrontal functioning have been reported in individuals at clinical high risk (CHR) for psychosis. Abnormal metabolic rate might affect resting-state cerebral blood flow (rCBF) in the respective regions. Here, we examined if striatal and prefrontal rCBF differ between patients with CHR, first-episode psychosis (FEP), chronic schizophrenia-spectrum disorder (SZ) and controls. Two cohorts with a total of 122 participants were included and analyzed separately: 32 patients with SZ and 31 healthy controls (HC) from the University Hospital of Psychiatry, and 59 patients from the Bern Early Recognition and Intervention Center (29 with CHR, 12 with FEP, and 18 clinical controls [CC]). Ultra-high risk criteria were assessed with the Structured Interview for Psychosis-Risk Syndromes, basic symptom criteria with the Schizophrenia Proneness Instrument. rCBF was measured with pseudo-continuous arterial spin labeling 3T-Magnetic Resonance Imaging. Striatal rCBF was significantly increased and prefrontal rCBF significantly decreased in the SZ group compared to HC group and in the CHR and FEP groups compared to CC group. Striatal rCBF correlated significantly with positive symptom scores in SZ and CHR. An inverse correlation between striatal and frontal rCBF was found in controls (HC, CC), but not in patient groups (SZ, FEP, CHR). This is the first study to demonstrate increased neuronal activity within the striatum, but reduced prefrontal activity in patients with CHR, FEP, and SZ compared to the respective controls. Our results indicate that alterations in striatal and prefrontal rCBF are reflecting metabolic abnormalities preceding the onset of frank psychosis.


Cerebrovascular Circulation/physiology , Corpus Striatum , Prefrontal Cortex , Psychotic Disorders/physiopathology , Schizophrenia/physiopathology , Adolescent , Adult , Corpus Striatum/blood supply , Corpus Striatum/diagnostic imaging , Corpus Striatum/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Prefrontal Cortex/blood supply , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Psychotic Disorders/diagnostic imaging , Risk , Schizophrenia/diagnostic imaging , Young Adult
15.
Clin EEG Neurosci ; 49(2): 79-92, 2018 Mar.
Article En | MEDLINE | ID: mdl-28516807

Previous studies showed a global reduction of the event-related potential component N100 in patients with schizophrenia, a phenomenon that is even more pronounced during auditory verbal hallucinations. This reduction assumingly results from dysfunctional activation of the primary auditory cortex by inner speech, which reduces its responsiveness to external stimuli. With this study, we tested the feasibility of enhancing the responsiveness of the primary auditory cortex to external stimuli with an upregulation of the event-related potential component N100 in healthy control subjects. A total of 15 healthy subjects performed 8 double-sessions of EEG-neurofeedback training over 2 weeks. The results of the used linear mixed effect model showed a significant active learning effect within sessions ( t = 5.99, P < .001) against an unspecific habituation effect that lowered the N100 amplitude over time. Across sessions, a significant increase in the passive condition ( t = 2.42, P = .03), named as carry-over effect, was observed. Given that the carry-over effect is one of the ultimate aims of neurofeedback, it seems reasonable to apply this neurofeedback training protocol to influence the N100 amplitude in patients with schizophrenia. This intervention could provide an alternative treatment option for auditory verbal hallucinations in these patients.


Attention/physiology , Auditory Perception/physiology , Evoked Potentials, Auditory/physiology , Neurofeedback/physiology , Acoustic Stimulation/methods , Adolescent , Adult , Auditory Cortex/physiopathology , Brain Mapping/methods , Electroencephalography/methods , Female , Hallucinations/physiopathology , Healthy Volunteers/psychology , Humans , Male , Young Adult
16.
Front Psychiatry ; 8: 242, 2017.
Article En | MEDLINE | ID: mdl-29249990

Suicidality is highly prevalent in patients at clinical high risk (CHR) for psychosis. Childhood adversities and trauma are generally predictive of suicidality. However, the differential effects of adversity/trauma-domains and CHR-criteria, i.e., ultra-high risk and basic symptom criteria, on suicidality remain unclear. Furthermore, the underlying mechanisms and, thus, worthwhile targets for suicide-prevention are still poorly understood. Therefore, structural equation modeling was used to test theory-driven models in 73 CHR-patients. Mediators were psychological variables, i.e., beliefs about one's own competencies as well as the controllability of events and coping styles. In addition, symptomatic variables (depressiveness, basic symptoms, attenuated psychotic symptoms) were hypothesized to mediate the effect of psychological mediators on suicidality as the final outcome variable. Results showed two independent pathways. In the first pathway, emotional and sexual but not physical adversity/trauma was associated with suicidality, which was mediated by dysfunctional competence/control beliefs, a lack of positive coping-strategies and depressiveness. In the second pathway, cognitive basic symptoms but not attenuated psychotic symptoms mediated the relationship between trauma/adversity and suicidality. CHR-patients are, thus, particularly prone to suicidality if adversity/trauma is followed by the development of depressiveness. Regarding the second pathway, this is the first study showing that adversity/trauma led to suicidality through an increased risk for psychosis as indicated by cognitive basic symptoms. As insight is generally associated with suicidality, this may explain why self-experienced basic symptoms increase the risk for it. Consequently, these mediators should be monitored regularly and targeted by integrated interventions as early as possible to enhance resilience against suicidality.

17.
Eur Child Adolesc Psychiatry ; 26(11): 1401-1405, 2017 Nov.
Article En | MEDLINE | ID: mdl-28456857

Higher frequencies of perceptual and lesser clinical significance of non-perceptual attenuated psychotic symptoms (APS) have been reported by 8- to 15-year-old of the general population compared to 16- to 40-year-old. We examined if such an age-effect can also be detected in a clinical never-psychotic sample (N = 133) referred to a specialized service for clinical suspicion of developing psychosis. APS and brief intermittent psychotic symptoms (BIPS) were assessed using items P1-P3 and P5 (non-perceptual), and P4 (perceptual) of the Structured Interview for Psychosis-Risk Syndromes, current axis-I disorders with the Mini-International Neuropsychiatric Interview, and psychosocial functioning with the Social and Occupational Functioning Assessment Scale. In the sample, 64% reported APS (61%) or BIPS (7%); any perceptual APS/BIPS was reported by 43% and any non-perceptual APS/BIPS by 44%. In correspondence to the results in the general population sample, perceptual but not non-perceptual APS/BIPS were significantly more frequent in younger age groups below the age of 16 (8-12 years: odds ratio (OR) = 4.7 (1.1-19.5); 13-15 years: OR = 2.7 (0.9-7.7); 20-24-year-old as reference group). An age-effect of APS/BIPS on the presence of any current axis-I disorder (59%) or functional difficulties (67%) was not detected. However, when onset requirements of APS criteria (onset/worsening in past year) were met, the likelihood of a psychiatric diagnosis increased significantly with advancing age. Overall, the replicated age-effect on perceptual APS/BIPS in this clinical sample highlights the need to examine ways to distinguish clinically relevant perceptual APS/BIPS from perceptual aberrations likely remitting over the course of adolescence.


Psychotic Disorders/diagnosis , Adolescent , Adult , Age Factors , Child , Early Diagnosis , Female , Humans , Male , Prevalence , Risk , Young Adult
18.
Prog Neurobiol ; 148: 1-20, 2017 Jan.
Article En | MEDLINE | ID: mdl-27890810

Auditory verbal hallucinations (AVH) occur in psychotic disorders, but also as a symptom of other conditions and even in healthy people. Several current theories on the origin of AVH converge, with neuroimaging studies suggesting that the language, auditory and memory/limbic networks are of particular relevance. However, reconciliation of these theories with experimental evidence is missing. We review 50 studies investigating functional (EEG and fMRI) and anatomic (diffusion tensor imaging) connectivity in these networks, and explore the evidence supporting abnormal connectivity in these networks associated with AVH. We distinguish between functional connectivity during an actual hallucination experience (symptom capture) and functional connectivity during either the resting state or a task comparing individuals who hallucinate with those who do not (symptom association studies). Symptom capture studies clearly reveal a pattern of increased coupling among the auditory, language and striatal regions. Anatomical and symptom association functional studies suggest that the interhemispheric connectivity between posterior auditory regions may depend on the phase of illness, with increases in non-psychotic individuals and first episode patients and decreases in chronic patients. Leading hypotheses involving concepts as unstable memories, source monitoring, top-down attention, and hybrid models of hallucinations are supported in part by the published connectivity data, although several caveats and inconsistencies remain. Specifically, possible changes in fronto-temporal connectivity are still under debate. Precise hypotheses concerning the directionality of connections deduced from current theoretical approaches should be tested using experimental approaches that allow for discrimination of competing hypotheses.


Auditory Perception/physiology , Hallucinations/physiopathology , Language , Memory/physiology , Nerve Net/physiopathology , Hallucinations/pathology , Humans , Nerve Net/pathology
19.
J Abnorm Psychol ; 125(7): 923-932, 2016 10.
Article En | MEDLINE | ID: mdl-27583768

[Correction Notice: An Erratum for this article was reported in Vol 125(7) of Journal of Abnormal Psychology (see record 2016-47529-004). In the article, there was an error in the Author Note. The affiliation of Daniela Hubl was incorrectly listed as "University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern." It should have been listed as "University Hospital of Psychiatry and Psychotherapy, University of Bern." All versions of this article have been corrected.] Schizotypy is considered an indicator of psychosis-proneness and therefore, a precursor to schizophrenia-spectrum psychosis. In the early detection of psychosis, the widely used ultra high-risk criteria refer to the positive features of schizotypy and schizotypal personality disorders (SPD). In clinical high risk (CHR) samples, self-reported or clinically assessed SPD, notably the lack of close friends, has been suggested to facilitate the prediction of psychosis. In community samples, self-reported schizotypy has mainly been assessed psychometrically using the 4 Wisconsin Schizotypy Scales (WSS; Chapman, Chapman, Kwapil, Eckbald, & Zinser, 1994), and the positive schizotypy dimension was consistently predictive of psychosis (Debbané et al., 2015). However, psychometrically assessed schizotypy has not yet been studied as a potential predictor of psychosis in CHR samples. To bridge this gap, we studied the psychosis-predictive value of 3 of the WSSs and their association with CHR state in a clinical sample. One hundred 28 patients (23 ± 7 years; 81% considered CHR) from 2 early detection services were followed for 12 to 101 months. Within 48 months, 36 (28.1%) converted to psychosis. Only physical anhedonia was associated with CHR state, and high scores for physical anhedonia were predictive of conversion in conjunction with the CHR state. Physical anhedonia rather than positive schizotypy scales might separate future converters from nonconverters in clinical samples already presenting a phenomenologically more extreme range on the psychosis continuum. Given their reported psychosis-predictive value in nonclinical samples, psychometric schizotypy measures in general might be useful for the initial screening of psychosis-proneness in the community, whereas physical anhedonia might be particularly useful in CHR samples. (PsycINFO Database Record


Psychiatric Status Rating Scales , Psychotic Disorders/diagnosis , Schizotypal Personality Disorder/diagnosis , Adolescent , Adult , Anhedonia , Child , Female , Humans , Male , Psychotic Disorders/complications , Risk Factors , Schizotypal Personality Disorder/complications , Self Report , Young Adult
20.
Brain Topogr ; 29(5): 716-27, 2016 09.
Article En | MEDLINE | ID: mdl-27209172

A 'sense of self' is essentially the ability to distinguish between self-generated and external stimuli. It consists of at least two very basic senses: a sense of agency and a sense of ownership. Disturbances seem to provide a basic deficit in many psychiatric diseases. The aim of our study was to manipulate those qualities separately in 28 patients with schizophrenia (14 auditory hallucinators and 14 non-hallucinators) and 28 healthy controls (HC) and to investigate the effects on the topographies and the power of the event-related potential (ERP). We performed a 76-channel EEG while the participants performed the task as in our previous paper. We computed ERPs and difference maps for the conditions and compared the amount of agency and ownership between the HC and the patients. Furthermore, we compared the global field power and the topographies of these effects. Our data showed effects of agency and ownership in the healthy controls and the hallucinator group and to a lesser degree in the non-hallucinator group. We found a reduction of the N100 during the presence of agency, and a bilateral temporal negativity related to the presence of ownership. For the agency effects, we found significant differences between HC and the patients. Contrary to the expectations, our findings were more pronounced in non-hallucinators, suggesting a more profoundly disturbed sense of agency compared to hallucinators. A contemporary increase of global field power in both patient groups indicates a compensatory recruitment of other mechanisms not normally associated with the processing of agency and ownership.


Evoked Potentials, Auditory/physiology , Hallucinations/physiopathology , Schizophrenia/physiopathology , Adult , Case-Control Studies , Electroencephalography , Evoked Potentials/physiology , Female , Humans , Male , Middle Aged , Self Concept , Young Adult
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