Association between formal thought disorders, neurocognition and functioning in the early stages of psychosis: a systematic review of the last half-century studies

Recent review articles provided an extensive collection of studies covering many aspects of format thought disorders (FTD) among their epidemiology and phenomenology, their neurobiological underpinnings, genetics as well as their transdiagnostic prevalence. However, less attention has been paid to the association of FTD with neurocognitive and functioning deficits in the early stages of evolving psychosis. Therefore, this systematic review aims to investigate the state of the art regarding the association between FTD, neurocognition and functioning in the early stages of evolving psychotic disorders in adolescents and young adults, by following the PRISMA flowchart. A total of 106 studies were screened. We included 8 studies due to their reports of associations between FTD measures and functioning outcomes measured with different scales and 7 studies due to their reports of associations between FTD measures and neurocognition. In summary, the main findings of the included studies for functioning outcomes showed that FTD severity predicted poor social functioning, unemployment, relapses, re-hospitalisations, whereas the main findings of the included studies for neurocognition showed correlations between attentional deficits, executive functions and FTD, and highlighted the predictive potential of executive dysfunctions for sustained FTD. Further studies in upcoming years taking advantage of the acceleration in computational psychiatry would allow researchers to re-investigate the clinical importance of FTD and their role in the transition from at-risk to full-blown psychosis conditions. Employing automated computer-assisted diagnostic tools in the early stages of psychosis might open new avenues to develop targeted neuropsychotherapeutics specific to FTD

Olfactory and gustatory dysfunctions in SARS-CoV-2 infection

Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection

Insula volumes in first-episode and chronic psychosis: A longitudinal MRI study

Background Alterations in insular grey matter (GM) volume has been consistently reported for affective and non-affective psychoses both in chronic and first-episode patients, ultimately suggesting that the insula might represent a good region to study in order to assess the longitudinal course of psychotic disorders. Therefore, in this longitudinal Magnetic Resonance Imaging (MRI) study, we aimed at further investigating the key role of insular volumes in psychosis. Material and Methods 68 First-Episode Psychosis (FEP) patients, 68 patients with Schizophrenia (SCZ), 47 Bipolar Disorder (BD) patients, and 94 Healthy Controls (HC) were enrolled and underwent a 1.5 T MRI evaluation. A subsample of 99 subjects (10 HC, 23 BD, 29 SCZ, 37 FEP) was rescanned after 2,53 ± 1,68 years. The insular cortex was manually traced and then divided into an anterior and posterior portion. Group and correlation analyses were then performed both at baseline and at follow-up. Results At baseline, greater anterior and lower posterior insular GM volumes were observed in chronic patients. At follow-up, we found that FEP patients had a significant GM volume increase from baseline to follow-up, especially in the posterior insula whereas chronic patients showed a relative stability. Finally, significant negative correlations between illness severity and pharmacological treatment and insular GM volumes were observed in the whole group of psychotic patients. Conclusions The longitudinal assessment of both chronic and first-episode patients allowed us to detect a complex pattern of GM abnormalities in selective sub-portions of insular volumes, ultimately suggesting that this structure could represent a key biological marker of psychotic disorders

The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

The membrane protein seizure 6–like (SEZ6L) is a neuronal substrate of the Alzheimer’s disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases

Sexual regional dimorphism of post-adolescent and middle age brain maturation. A multi-center 3T MRI study

Sex-related differences are tied into neurodevelopmental and lifespan processes, beginning early in the perinatal and developmental phases and continue into adulthood. The present study was designed to investigate sexual dimorphism of changes in gray matter (GM) volume in post-adolescence, with a focus on early and middle-adulthood using a structural magnetic resonance imaging (MRI) dataset of healthy controls from the European Network on Psychosis, Affective disorders and Cognitive Trajectory (ENPACT). Three hundred and seventy three subjects underwent a 3.0 T MRI session across four European Centers. Age by sex effects on GM volumes were investigated using voxel-based morphometry (VBM) and the Automated Anatomical Labeling atlas regions (ROI). Females and males showed overlapping and non-overlapping patterns of GM volume changes during aging. Overlapping age-related changes emerged in bilateral frontal and temporal cortices, insula and thalamus. Both VBM and ROI analyses revealed non-overlapping changes in multiple regions, including cerebellum and vermis, bilateral mid frontal, mid occipital cortices, left inferior temporal and precentral gyri. These findings highlight the importance of accounting for sex differences in cross-sectional analyses, not only in the study of normative changes, but particularly in the context of psychiatric and neurologic disorders, wherein sex effects may be confounded with disease-related changes

The heterogeneity of attenuated and brief limited psychotic symptoms: association of contents with age, sex, country, religion, comorbidities, and functioning

INTRODUCTION The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. METHOD A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. RESULT We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. CONCLUSION Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability

Basic Symptoms Are Associated With Age in Patients With a Clinical High-Risk State for Psychosis: Results From the PRONIA Study

In community studies, both attenuated psychotic symptoms (APS) and basic symptoms (BS) were more frequent but less clinically relevant in children and adolescents compared to adults. In doing so, they displayed differential age thresholds that were around age 16 for APS, around age 18 for perceptive BS, and within the early twenties for cognitive BS. Only the age effect has previously been studied and replicated in clinical samples for APS. Thus, we examined the reported age effect on and age thresholds of 14 criteria-relevant BS in a patient sample at clinical-high risk of psychosis (N = 261, age 15-40 yrs.), recruited within the European multicenter PRONIA-study. BS and the BS criteria, "Cognitive Disturbances" (COGDIS) and "Cognitive-perceptive BS" (COPER), were assessed with the "Schizophrenia Proneness Instrument, Adult version" (SPI-A). Using logistic regressions, prevalence rates of perceptive and cognitive BS, and of COGDIS and COPER, as well as the impact of social and role functioning on the association between age and BS were studied in three age groups (15-18 years, 19-23 years, 24-40 years). Most patients (91.2%) reported any BS, 55.9% any perceptive and 87.4% any cognitive BS. Furthermore, 56.3% met COGDIS and 80.5% COPER. Not exhibiting the reported differential age thresholds, both perceptive and cognitive BS, and, at trend level only, COPER were less prevalent in the oldest age group (24-40 years); COGDIS was most frequent in the youngest group (15-18 years). Functional deficits did not better explain the association with age, particularly in perceptive BS and cognitive BS meeting the frequency requirement of BS criteria. Our findings broadly confirmed an age threshold in BS and, thus, the earlier assumed link between presence of BS and brain maturation processes. Yet, age thresholds of perceptive and cognitive BS did not differ. This lack of differential age thresholds might be due to more pronounced the brain abnormalities in this clinical sample compared to earlier community samples. These might have also shown in more frequently occurring and persistent BS that, however, also resulted from a sampling toward these, i.e., toward COGDIS. Future studies should address the neurobiological basis of CHR criteria in relation to age

Basic Symptoms Are Associated With Age in Patients With a Clinical High-Risk State for Psychosis: Results From the PRONIA Study

In community studies, both attenuated psychotic symptoms (APS) and basic symptoms (BS) were more frequent but less clinically relevant in children and adolescents compared to adults. In doing so, they displayed differential age thresholds that were around age 16 for APS, around age 18 for perceptive BS, and within the early twenties for cognitive BS. Only the age effect has previously been studied and replicated in clinical samples for APS. Thus, we examined the reported age effect on and age thresholds of 14 criteria-relevant BS in a patient sample at clinical-high risk of psychosis (N = 261, age 15–40 yrs.), recruited within the European multicenter PRONIA-study. BS and the BS criteria, “Cognitive Disturbances” (COGDIS) and “Cognitive-perceptive BS” (COPER), were assessed with the “Schizophrenia Proneness Instrument, Adult version” (SPI-A). Using logistic regressions, prevalence rates of perceptive and cognitive BS, and of COGDIS and COPER, as well as the impact of social and role functioning on the association between age and BS were studied in three age groups (15–18 years, 19–23 years, 24–40 years). Most patients (91.2%) reported any BS, 55.9% any perceptive and 87.4% any cognitive BS. Furthermore, 56.3% met COGDIS and 80.5% COPER. Not exhibiting the reported differential age thresholds, both perceptive and cognitive BS, and, at trend level only, COPER were less prevalent in the oldest age group (24–40 years); COGDIS was most frequent in the youngest group (15–18 years). Functional deficits did not better explain the association with age, particularly in perceptive BS and cognitive BS meeting the frequency requirement of BS criteria. Our findings broadly confirmed an age threshold in BS and, thus, the earlier assumed link between presence of BS and brain maturation processes. Yet, age thresholds of perceptive and cognitive BS did not differ. This lack of differential age thresholds might be due to more pronounced the brain abnormalities in this clinical sample compared to earlier community samples. These might have also shown in more frequently occurring and persistent BS that, however, also resulted from a sampling toward these, i.e., toward COGDIS. Future studies should address the neurobiological basis of CHR criteria in relation to age

The heterogeneity of attenuated and brief limited psychotic symptoms::association of contents with age, sex, country, religion, comorbidities, and functioning

Introduction: The Attenuated Psychosis Symptoms (APS) syndrome mostly represents the ultra-high-risk state of psychosis but, as does the Brief Intermittent Psychotic Symptoms (BIPS) syndrome, shows a large variance in conversion rates. This may be due to the heterogeneity of APS/BIPS that may be related to the effects of culture, sex, age, and other psychiatric morbidities. Thus, we investigated the different thematic contents of APS and their association with sex, age, country, religion, comorbidity, and functioning to gain a better understanding of the psychosis-risk syndrome. Method: A sample of 232 clinical high-risk subjects according to the ultra-high risk and basic symptom criteria was recruited as part of a European study conducted in Germany, Italy, Switzerland, and Finland. Case vignettes, originally used for supervision of inclusion criteria, were investigated for APS/BIPS contents, which were compared for sex, age, country, religion, functioning, and comorbidities using chi-squared tests and regression analyses. Result: We extracted 109 different contents, mainly of APS (96.8%): 63 delusional, 29 hallucinatory, and 17 speech-disorganized contents. Only 20 contents (18.3%) were present in at least 5% of the sample, with paranoid and referential ideas being the most frequent. Thirty-one (28.5%) contents, in particular, bizarre ideas and perceptual abnormalities, demonstrated an association with age, country, comorbidity, or functioning, with regression models of country and obsessive-compulsive disorders explaining most of the variance: 55.8 and 38.3%, respectively. Contents did not differ between religious groups. Conclusion: Psychosis-risk patients report a wide range of different contents of APS/BIPS, underlining the psychopathological heterogeneity of this group but also revealing a potential core set of contents. Compared to earlier reports on North-American samples, our maximum prevalence rates of contents were considerably lower; this likely being related to a stricter rating of APS/BIPS and cultural influences, in particular, higher schizotypy reported in North-America. The various associations of some APS/BIPS contents with country, age, comorbidities, and functioning might moderate their clinical severity and, consequently, the related risk for psychosis and/or persistent functional disability