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

Regolazione emotiva e metacognizione nei bambini e negli adolescenti

As literature indicates, people experience emotions following the evaluation of a real or perceived event (Frijda, 1986; Zajonc, 1998; Davidson, Scherer & Goldsmith, 2003; Barrett, 2006; Brackett, et al., 2006; Izard, 2007; Panksepp, 2007). These can cause difficulties in emotional regulatory mechanisms that cause distress in relationship to oneself, to other people and to the world, occasionally resulting in full-blown psychopathology (Stults- Kolehmainen & Sinha, 2014; Extremera & Rey, 2015). Diverse theoretical currents report outcomes of altered metacognitive fuction both in learning (Flavell, 1979; Cottini, 2004), evaluating and monitoring thought (Wells & Matthews, 1995/2014), as well as in the expression of reasoning in terms of mental status on oneself and others behavior (Fonagy, 2000). The goal of this study is to examine whether disfunction of emotive regulation in children causes “metacognitive errors” that leads to development of severe psychopathological diseases.La letteratura riporta che, a seguito della valutazione di un evento reale o immaginato, le persone sperimentano delle emozioni (Frijda, 1986; Zajonc, 1998; Davidson, Scherer & Goldsmith, 2003; Barrett, 2006; Brackett, et al., 2006; Izard, 2007; Panksepp, 2007). Queste, se intense possono causare difficoltà di regolazione emotiva (Stults-Kolehmainen & Sinha, 2014; Extremera & Rey, 2015). Ne consegue disagio nel rapporto con se stessi e con il mondo e talvolta sofferenza psicopatologica (Cohen, Janicki- Deverts, & Miller, 2007). Diverse teorie a confronto registrano esiti di un alterato funzionamento metacognitivo sia nell’apprendimento (Flavell, 1979; Cottini, 2004) sia nella valutazione e monitoraggio del pensiero (Wells & Matthews, 1995/2014), nonchè nell’espressione della capacità di ragionare sul proprio e altrui comportamento in termini di stati mentali (Fonagy, 2000).Questo lavoro mira a esaminare fonti secondo cui la disfunzione della regolazione emotiva nei bambini comporta “errori metacognitivi” che conducono allo sviluppo di disturbi psicopatologiciimportanti. L’obiettivo di questo lavoro è quello di esaminare fonti a sostegno della tesi, già ampiamente documentata per gli adulti, secondo cui la disfunzione della regolazione emotiva nei bambini comporta “errori metacognitivi” che conducono allo sviluppo di disturbi psicopatologici importanti

The influence of 5-HTTLPR, BDNF Rs6265 and COMT Rs4680 polymorphisms on impulsivity in bipolar disorder: the role of gender

Impulsivity has been proposed as an endophenotype for bipolar disorder (BD); moreover, impulsivity levels have been shown to carry prognostic significance and to be quality-of-life predictors. To date, reports about the genetic determinants of impulsivity in mood disorders are limited, with no studies on BD individuals. Individuals with BD and healthy controls (HC) were recruited in the context of an observational, multisite study (GECOBIP). Subjects were genotyped for three candidate single-nucleotide polymorphisms (SNPs) (5-HTTLPR, COMT rs4680, BDNF rs6265); impulsivity was measured through the Italian version of the Barratt Impulsiveness Scale (BIS-11). A mixed-effects regression model was built, with BIS scores as dependent variables, genotypes of the three polymorphisms as fixed effects, and centers of enrollment as random effect. Compared to HC, scores for all BIS factors were higher among subjects with euthymic BD (adjusted β for Total BIS score: 5.35, p < 0.001). No significant interaction effect was evident between disease status (HC vs. BD) and SNP status for any polymorphism. Considering the whole sample, BDNF Met/Met homozygosis was associated with lower BIS scores across all three factors (adjusted β for Total BIS score: -10.2, p < 0.001). A significant 5-HTTLPR x gender interaction was found for the SS genotype, associated with higher BIS scores in females only (adjusted β for Total BIS score: 12.0, p = 0.001). Finally, COMT polymorphism status was not significantly associated with BIS scores. In conclusion, BD diagnosis did not influence the effect on impulsivity scores for any of the three SNPs considered. Only one SNP-the BDNF rs6265 Met/Met homozygosis-was independently associated with lower impulsivity scores. The 5-HTTLPR SS genotype was associated with higher impulsivity scores in females only. Further studies adopting genome-wide screening in larger samples are needed to define the genetic basis of impulsivity in BD

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

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 clinical relevance of formal thought disorder in the early stages of psychosis: results from the PRONIA study

Background: Formal thought disorder (FTD) has been associated with more severe illness courses and functional deficits in patients with psychotic disorders. However, it remains unclear whether the presence of FTD characterises a specific subgroup of patients showing more prominent illness severity, neurocognitive and functional impairments. This study aimed to identify stable and generalizable FTD-subgroups of patients with recent-onset psychosis (ROP) by applying a comprehensive data-driven clustering approach and to test the validity of these subgroups by assessing associations between this FTD-related stratification, social and occupational functioning, and neurocognition. Methods: 279 patients with ROP were recruited as part of the multi-site European PRONIA study (Personalised Prognostic Tools for Early Psychosis Management; www.pronia.eu). Five FTD-related symptoms (conceptual disorganization, poverty of content of speech, difficulty in abstract thinking, increased latency of response and poverty of speech) were assessed with Positive and Negative Symptom Scale (PANSS) and the Scale for the Assessment of Negative Symptoms (SANS). Results: The results with two patient subgroups showing different levels of FTD were the most stable and generalizable clustering solution (predicted clustering strength value = 0.86). FTD-High subgroup had lower scores in social (p fdr < 0.001) and role (p fdr < 0.001) functioning, as well as worse neurocognitive performance in semantic (p fdr < 0.001) and phonological verbal fluency (p fdr < 0.001), short-term verbal memory (p fdr = 0.002) and abstract thinking (p fdr = 0.010), in comparison to FTD-Low group. Conclusions: Clustering techniques allowed us to identify patients with more pronounced FTD showing more severe deficits in functioning and neurocognition, thus suggesting that FTD may be a relevant marker of illness severity in the early psychosis pathway