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

The Neurophysiology of Auditory Hallucinations – A Historical and Contemporary Review

Electroencephalography and magnetoencephalography are two techniques that distinguish themselves from other neuroimaging methodologies through their ability to directly measure brain-related activity and their high temporal resolution. A large body of research has applied these techniques to study auditory hallucinations. Across a variety of approaches, the left superior temporal cortex is consistently reported to be involved in this symptom. Moreover, there is increasing evidence that a failure in corollary discharge, i.e., a neural signal originating in frontal speech areas that indicates to sensory areas that forthcoming thought is self-generated, may underlie the experience of auditory hallucinations

Dopamine D-2 up-regulation in psychosis patients after antipsychotic drug treatment

Purpose of reviewRecently, it has been questioned whether the re-emergence of psychotic symptoms following antipsychotic discontinuation or dose reduction is attributable to underlying psychotic vulnerability or to rebound effects of chronic use of antipsychotic medication. It was repeatedly shown that relapse rates are high after discontinuation of maintenance treatment. A potential contributing factor could be the increase in density of postsynaptic dopamine D2 receptors in the striatum and the higher affinity of D2 receptors for dopamine after chronic blockade.Recent findingsTo date, little clinical evidence is available for the mechanisms involved in postsynaptic striatal D2 receptor up-regulation after use of antipsychotic medication, and most knowledge comes from animal studies.SummaryFurther research is needed to investigate whether antipsychotic medication causes neuroadaptations leading to a dopamine supersensitive state in humans, how long such hypersensitive states may last and what differences exist between high and low D2 affinity antipsychotic drugs. Further, information is needed on discontinuation schedules that provide optimal protection for relapse during hypersensitive periods

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

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

Role of the gut microbiome in three major psychiatric disorders

Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia-spectrum disorders (SSD) are heterogeneous psychiatric disorders, which place significant burden on patient's well-being and global health. Disruptions in the gut-microbiome may play a role in these psychiatric disorders. This review presents current data on composition of the human gastrointestinal microbiota, and its interaction mechanisms in the gut-brain axis in MDD, BD and SSD. Diversity metrics and microbial relative abundance differed across studies. More studies reported inconsistent findings (n = 7) or no differences (n = 8) than studies who reported lower α-diversity in these psychiatric disorders (n = 5). The most consistent findings across studies were higher relative abundances of the genera Streptococcus, Lactobacillus, and Eggerthella and lower relative abundance of the butyrate producing Faecalibacterium in patients with psychiatric disorders. All three increased genera were associated with higher symptom severity. Confounders, such as medication use and life style have not been accounted for. So far, the results of probiotics trials have been inconsistent. Most traditional and widely used probiotics (consisting of Bifidobacterium spp. and Lactobacillus spp.) are safe, however, they do not correct potential microbiota disbalances in these disorders. Findings on prebiotics and faecal microbiota transplantation (FMT) are too limited to draw definitive conclusions. Disease-specific pro/prebiotic treatment or even FMT could be auspicious interventions for prevention and therapy for psychiatric disorders and should be investigated in future trials

The influence of semantic top-down processing in auditory verbal hallucinations

AbstractBackgroundAuditory verbal hallucinations (AVH) are one of the most prominent symptoms of schizophrenia but have also been reported in the general population. Several cognitive models have tried to elucidate the mechanism behind auditory verbal hallucinations, among which a top-down model. According to this model, perception is biased towards top-down information (e.g., expectations), reducing the influence of bottom-up information coming from the sense organs. This bias predisposes to false perceptions, i.e., hallucinations.MethodsThe current study investigated this hypothesis in non-psychotic individuals with frequent AVH, psychotic patients with AVH and healthy control subjects by applying a semantic top-down task. In this task, top-down processes are manipulated through the semantic context of a sentence. In addition, the association between hallucination proneness and semantic top-down errors was investigated.ResultsNon-psychotic individuals with AVH made significantly more top-down errors compared to healthy controls, while overall accuracy was similar. The number of top-down errors, corrected for overall accuracy, in the patient group was in between those of the other two groups and did not differ significantly from either the non-psychotic individuals with AVH or the healthy controls. The severity of hallucination proneness correlated with the number of top-down errors.DiscussionThese findings confirm that non-psychotic individuals with AVH are stronger influenced by top-down processing (i.e., perceptual expectations) than healthy controls. In contrast, our data suggest that in psychotic patients semantic expectations do not play a role in the etiology of AVH. This finding may point towards different cognitive mechanisms for pathological and nonpathological hallucinations

Stronger than your voices:A cognitive behavioral therapy for youth suffering from auditory verbal hallucinations

Objective: Auditory verbal hallucinations (AVHs) are a common feature in youth and mostly transient. Nevertheless, while present, AVH can cause considerable distress. Children and adolescents seeking help for distressing AVH represent a heterogeneous group in terms of underlying factors, yet they consistently suffer from their AVH. Until now, a youth-specific psychotherapeutic intervention for AVH was lacking. Experts in the field of treating AVH in both adults and youngsters collaborated with service users to develop the cognitive behavioral therapy (CBT) "Stronger Than Your Voices" (STYV). We investigated feasibility and clinical outcomes of the STYV therapy. Methods: Patients were derived from children and adolescents seeking help for AVH at the UMC Utrecht outpatient clinic with an indication for STYV therapy. Therapists preferably originated from referring health care facilities and were required to have sufficient general knowledge and experience with CBT. They received a short individual training to apply STYV. After, patients and their therapists could participate this naturalistic pilot study, assessing feasibility, tolerability, and clinical change when applying the STYV therapy. Results: Six participants (10-16 years old), all suffering from comorbid psychopathology, provided pre and post measures, all completing STYV therapy without experiencing an aggravation of symptoms. AVH total impact decreased 40% with Cohen's d within-group effect size (1.28) also suggesting clinically meaningful change. Therapists were positive about STYV therapy and manual. Conclusion: The STYV therapy is feasible for youth with distressing AVH. First results indicate that STYV may be clinically effective. A trial to further test effectiveness in a larger sample is needed

Unhealthy diet in schizophrenia spectrum disorders

PURPOSE OF REVIEW: The high mortality and prevalence of metabolic syndrome in patients with schizophrenia spectrum disorders (SSD) is maintained by poor diet. This narrative review summarizes recent literature to provide a reflection of current eating habits, dietary preferences, and nutritional status of SSD patients. Elucidating these factors provides new insights for potential lifestyle treatment strategies for SSD. RECENT FINDINGS: Only 10.7% of the SSD patients had a healthy dietary pattern, against 23% of the general population. The dietic component of the Keeping the Body in Mind Xtend lifestyle program increased diet quality with 10% for young people with first-episode psychosis, compared to baseline, which was predominantly driven by increased vegetable variety and amounts. SUMMARY: Recent findings render poor dietary habits as potential targets for treatment of SSD patients. Further studies into anti-inflammatory diets and associations with gut-brain biomarkers are warranted. When proven, structured and supervised diet interventions may help SSD patients escape from this entrapment, as only supplementing nutrients or providing dietary advice lacks the impact to significantly reduce the risk of chronic physical illnesses