Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders

PURPOSE OF REVIEW: Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders. RECENT FINDINGS: Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ. SUMMARY: Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate

Reproducibility of visual-field asymmetries:Nine replication studies investigating lateralization of visual information processing

Numerous behavioral studies suggest that the processing of various types of visual stimuli and features may be more efficient in either the left or the right visual field. However, not all of these visual-field asymmetries (VFAs) have been observed consistently. Moreover, it is typically unclear whether a failure to observe a particular VFA can be ascribed to certain characteristics of the participants and stimuli, to a lack of statistical power, or to the actual absence of an effect. To increase our understanding of lateralization of visual information processing, we have taken a rigorous methodological and statistical approach to examine the reproducibility of various previously reported VFAs. We did so by performing (near-)exact replications of nine representative previous studies, aiming for sufficient power to detect the effects of interest, and taking into consideration all relevant dependent variables (reaction times and error rates). Following Bayesian analyses –on our data alone as well as on the combined evidence from the original and replication studies– we find precise and reliable evidence that support VFAs in the processing of faces, emotional expressions, global and local information, words, and in the distribution of spatial attention. In contrast, we find less convincing evidence for VFAs in processing of high and low spatial frequencies. Finally, we find no evidence for VFAs in categorical perception of color and shape oddballs, and in the judgments of categorical and coordinate spatial relations. We discuss our results in the light of their implications for theories of visual lateralization

The role of religiosity types in the phenomenology of hallucinations:A large cross-sectional community-based study in a predominantly Muslim society

Religiosity is a multidimensional construct known to influence the occurrence of hallucinations. However, it remains unknown how different religiosity types affect clinically relevant phenomenological features of hallucinations. Therefore, we wished to explore associations between intrinsic and extrinsic (non-organizational and organizational) religiosity and hallucinations severity, distress or impact on daily function in a non-clinical Muslim population. We recruited a representative sample of full-time students at Qatar's only national university via systematic random sampling and administered the Questionnaire of Psychotic Experiences online. The study design was cross-sectional. Using structural equation modeling, we estimated effects of the religiosity types on hallucinations severity, distress or impact on daily function in the past week while accounting for sociodemographic variables, anxiety, depressive symptoms, and, delusions. Extrinsic non-organizational religiosity (ENORG) was associated with experiencing reduced distress or impact on daily function from hallucinations both directly and indirectly through intrinsic religiosity. In contrast, extrinsic non-organizational religiosity (EORG) was associated with increased hallucinations distress or impact albeit only through higher intrinsic religiosity. We found no association between any religiosity types and hallucinations severity. Younger and married participants from lower socio-economic class had comparatively more severe hallucinations and more distress from them. Qatari nationality was positively associated EORG and negatively associated with hallucinations distress or impact. Evidence of differential associations between the religiosity types, socioeconomic and cultural groups, and distress or impact from past week's hallucinations supports the importance of alignment between religious, mental health, and well-being education

Deafferentation as a cause of hallucinations

PURPOSE OF REVIEW: The association between hallucinations and sensory loss, especially vision- and hearing-impairment, has been firmly established over the past years. The deafferentation theory, a decrease of the threshold for activation in the brain and the consequential imbalance between excitatory and inhibitory brain networks, is hypothesized to underly this relationship. Here we review the studies investigating this theory with a focus on the most recent literature to better understand the contribution of sensory loss to hallucinations. RECENT FINDINGS: A large cross-sectional study has recently confirmed the relationship between auditory impairment and deafferentation. However, the underlying mechanisms of deafferentation are still under debate, with hyperexcitability and deviations in bottom-up and top-down processes being the most likely explanations. Social isolation following sensory impairment increases the risk for hallucinations. Better knowledge and awareness about the contribution of deafferentation and loneliness would benefit diagnosis and treatment of hallucinations. SUMMARY: Studies imply activity in higher order areas, corresponding to the functional mapping of sensory system, and a general state of higher excitability as neurobiological explanation. Auditory deafferentation, tinnitus and other auditory hallucinations, likely lie on a continuum. Social isolation mediates psychotic symptoms in sensory-impaired individuals. Currently, there is no standard treatment for deafferentation hallucinations

Semantic and Acoustic Markers in Schizophrenia-Spectrum Disorders:A Combinatory Machine Learning Approach

BACKGROUND AND HYPOTHESIS: Speech is a promising marker to aid diagnosis of schizophrenia-spectrum disorders, as it reflects symptoms like thought disorder and negative symptoms. Previous approaches made use of different domains of speech for diagnostic classification, including features like coherence (semantic) and form (acoustic). However, an examination of the added value of each domain when combined is lacking as of yet. Here, we investigate the acoustic and semantic domains separately and combined. STUDY DESIGN: Using semi-structured interviews, speech of 94 subjects with schizophrenia-spectrum disorders (SSD) and 73 healthy controls (HC) was recorded. Acoustic features were extracted using a standardized feature-set, and transcribed interviews were used to calculate semantic word similarity using word2vec. Random forest classifiers were trained for each domain. A third classifier was used to combine features from both domains; 10-fold cross-validation was used for each model. RESULTS: The acoustic random forest classifier achieved 81% accuracy classifying SSD and HC, while the semantic domain classifier reached an accuracy of 80%. Joining features from the two domains, the combined classifier reached 85% accuracy, significantly improving on separate domain classifiers. For the combined classifier, top features were fragmented speech from the acoustic domain and variance of similarity from the semantic domain. CONCLUSIONS: Both semantic and acoustic analyses of speech achieved ~80% accuracy in classifying SSD from HC. We replicate earlier findings per domain, additionally showing that combining these features significantly improves classification performance. Feature importance and accuracy in combined classification indicate that the domains measure different, complementing aspects of speech.</p

Anomalies in language as a biomarker for schizophrenia

PURPOSE OF REVIEW: After more than a century of neuroscience research, reproducible, clinically relevant biomarkers for schizophrenia have not yet been established. This article reviews current advances in evaluating the use of language as a diagnostic or prognostic tool in schizophrenia. RECENT FINDINGS: The development of computational linguistic tools to quantify language disturbances is rapidly gaining ground in the field of schizophrenia research. Current applications are the use of semantic space models and acoustic analyses focused on phonetic markers. These features are used in machine learning models to distinguish patients with schizophrenia from healthy controls or to predict conversion to psychosis in high-risk groups, reaching accuracy scores (generally ranging from 80 to 90%) that exceed clinical raters. Other potential applications for a language biomarker in schizophrenia are monitoring of side effects, differential diagnostics and relapse prevention. SUMMARY: Language disturbances are a key feature of schizophrenia. Although in its early stages, the emerging field of research focused on computational linguistics suggests an important role for language analyses in the diagnosis and prognosis of schizophrenia. Spoken language as a biomarker for schizophrenia has important advantages because it can be objectively and reproducibly quantified. Furthermore, language analyses are low-cost, time efficient and noninvasive in nature

Spontaneous brain activity underlying auditory hallucinations in the hearing-impaired

Auditory hallucinations, the perception of a sound without a corresponding source, are common in people with hearing impairment. Two forms can be distinguished: simple (i.e., tinnitus) and complex hallucinations (speech and music). Little is known about the precise mechanisms underlying these types of hallucinations. Here we tested the assumption that spontaneous activity in the auditory pathways, following deafferentation, underlies these hallucinations and is related to their phenomenology. By extracting (fractional) Amplitude of Low Frequency Fluctuation [(f)ALFF] scores from resting state fMRI of 18 hearing impaired patients with complex hallucinations (voices or music), 18 hearing impaired patients with simple hallucinations (tinnitus or murmuring), and 20 controls with normal hearing, we investigated differences in spontaneous brain activity between these groups. Spontaneous activity in the anterior and posterior cingulate cortex of hearing-impaired groups was significantly higher than in the controls. The group with complex hallucinations showed elevated activity in the bilateral temporal cortex including Wernicke's area, while spontaneous activity of the group with simple hallucinations was mainly located in the cerebellum. These results suggest a decrease in error monitoring in both hearing-impaired groups. Spontaneous activity of language-related areas only in complex hallucinations suggests that the manifestation of the spontaneous activity represents the phenomenology of the hallucination. The link between cerebellar activity and simple hallucinations, such as tinnitus, is new and may have consequences for treatment. (C) 2020 The Author(s). Published by Elsevier Ltd

The experience of felt presence in a general population sample.

Felt presence is a widely occurring experience, but remains under-recognised in clinical and research practice. To contribute to a wider recognition of the phenomenon, we aimed to assess the presentation of felt presence in a large population sample ( = 10 447) and explore its relation to key risk factors for psychosis. In our sample 1.6% reported experiencing felt presence in the past month. Felt presence was associated with visual and tactile hallucinations and delusion-like thinking; it was also associated with past occurrence of adverse events, loneliness and poor sleep. The occurrence of felt presence may function as a marker for general hallucination proneness

Towards a unified understanding of lateralized vision:A large-scale study investigating principles governing patterns of lateralization using a heterogeneous sample

While functional lateralization of the human brain has been a widely studied topic in the past decades, few studies to date have gone further than investigating lateralization of single, isolated processes. With the present study, we aimed to arrive at a more unified view by investigating lateralization patterns in face and word processing, and associated lower-level visual processing. We tested a large and heterogeneous participant group, and used a number of tasks that had been shown to produce replicable indices of lateralized processing of visual information of different types and complexity. Following Bayesian statistics, group-level analyses showed the expected right hemisphere (RH) lateralization for face, global form, low spatial frequency processing, and spatial attention, and left hemisphere (LH) lateralization for visual word and local feature processing. Compared to right-handed individuals, lateralization patterns of left-handed and especially those who are RH-dominant for language deviated from this 'typical' pattern. Our results support the notion that face and word processes come to be lateralized to homologue areas of the two hemispheres, under influence of the RHand LH-specializations in global form, local feature, and low and high spatial frequency processing. As such, we present a more unified understanding of lateralized vision, providing evidence for the input asymmetry and causal complementarity principles of lateralized visual information processing. The absence of correlations between spatial attention and lateralization of the other processes supports the notion of their independent lateralization, conform the statistical complementarity principle. (C) 2020 The Author(s). Published by Elsevier Ltd

The role of religiosity types in the phenomenology of hallucinations: A large cross-sectional community-based study in a predominantly Muslim society

Religiosity is a multidimensional construct known to influence the occurrence of hallucinations. However, it remains unknown how different religiosity types affect clinically relevant phenomenological features of hallucinations. Therefore, we wished to explore associations between intrinsic and extrinsic (non-organizational and organizational) religiosity and hallucinations severity, distress or impact on daily function in a non-clinical Muslim population. We recruited a representative sample of full-time students at Qatar's only national university via systematic random sampling and administered the Questionnaire of Psychotic Experiences online. The study design was cross-sectional. Using structural equation modeling, we estimated effects of the religiosity types on hallucinations severity, distress or impact on daily function in the past week while accounting for sociodemographic variables, anxiety, depressive symptoms, and, delusions. Extrinsic non-organizational religiosity (ENORG) was associated with experiencing reduced distress or impact on daily function from hallucinations both directly and indirectly through intrinsic religiosity. In contrast, extrinsic non-organizational religiosity (EORG) was associated with increased hallucinations distress or impact albeit only through higher intrinsic religiosity. We found no association between any religiosity types and hallucinations severity. Younger and married participants from lower socio-economic class had comparatively more severe hallucinations and more distress from them. Qatari nationality was positively associated EORG and negatively associated with hallucinations distress or impact. Evidence of differential associations between the religiosity types, socioeconomic and cultural groups, and distress or impact from past week's hallucinations supports the importance of alignment between religious, mental health, and well-being education