Biomarkers as proxies for cognitive reserve: The role of high density lipoprotein cholesterol in first episode of psychosis.

INTRODUCTION: The proxies used to compose cognitive reserve (CR) for patients of a first episode of psychosis (FEP) have varied in the literature. The development of FEP is linked to peripheral pathways of the central nervous system, yet despite this knowledge, no research has considered the introduction of biomarkers as proxies for CR. Meanwhile, schizophrenia has been linked to the metabolic system, indicating that alterations in the levels of biological parameters, in particular high-density lipoproteins (HDL), cause worse global functioning and cognitive impairment. For these reasons, the present study aimed to create a quantifiable and objective CR index that adjusts for the multifactorial nature of FEP. MATERIALS AND METHODS: We included 668 FEP patients and 217 healthy controls. Participants were assessed for sociodemographic information, years of education, employment status, premorbid IQ and biological parameters: waist circumference, hypertension, and levels of HDL, triglycerides, and glucose. RESULTS: The findings suggest that the years of education proxy showed correlational and higher relationship with HDL levels for both FEP patients (r=0.23, b=0.185) and controls (r=0.31, b=0.342). We found that the CR index composed of years of education and HDL levels showed a higher explanatory power for the phenomenon than the classic CR index composed of years of education, employment status and premorbid IQ. CONCLUSIONS: This article proposes an objective and quantifiable method to measure CR that is more the multifactorial nature of FEP.

Intelligence quotient changes over 10 years: Diversity of cognitive profiles in first episode of psychosis and healthy controls.

OBJECTIVE: This study aimed to analyse whether intelligence quotient (IQ) improves, declines, or remains stable over 10 years among FEP patients and healthy subjects. METHODS: A group of FEP patients enrolled in a Program of First Episode Psychosis in Spain called PAFIP, and a sample of Healthy Controls (HC) completed the same neuropsychological battery at baseline and approximately 10 years later, which included the WAIS vocabulary subtest to estimate premorbid IQ and 10-year IQ. Cluster analysis was performed separately in the patient group and the HC group to determine their profiles of intellectual change. RESULTS: One hundred and thirty-seven FEP patients were grouped into five clusters: "Improved low IQ" (9.49 % of patients), "Improved average IQ" (14.6 %), "Preserved low IQ" (17.52 %), "Preserved average IQ" (43.06 %), and "Preserved high IQ" (15.33 %). Ninety HC were grouped into three clusters: "Preserved low IQ" (32.22 % of the HC), "Preserved average IQ" (44.44 %), and "Preserved high IQ" (23.33 %). The first two clusters of FEP patients, characterized by a low IQ, earlier age at illness onset, and lower educational attainment, showed a substantial cognitive improvement. The remaining clusters demonstrated cognitive stability. CONCLUSIONS: The FEP patients showed intellectual improvement or stability, but no decline post-onset of psychosis. However, their profiles of intellectual change are more heterogeneous than that of HC over 10 years. Particularly, there is a subgroup of FEP patients with a significant potential for long-term cognitive enhancement.

Exploring the impact of COVID-19 on newborn neurodevelopment: a pilot study.

The COVID-19 pandemic can seize the opportunity to explore the hypothesis of prenatal exposure to viral infections increases the risk for neurodevelopmental disorders. Advancing our knowledge in this regard would improve primary prevention of mental disorders in children. For this pilot study, six-week-old infants born to mothers exposed (n = 21) or unexposed (n = 21) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were assessed in Santander-Cantabria (Spain) using the Neonatal Behavioral Assessment Scale (NBAS). Groups comparisons were performed to explore the effects that infection and timing of exposure (in terms of the three trimesters of pregnancy). The infants' competencies and performances on the NBAS were generally similar in the exposed and unexposed to SARS-CoV-2 groups. The most significant difference found was a less optimally response to cuddliness (item on the state regulation domain) particularly in infants born to mothers exposed in the third trimester of pregnancy, and in pull-to-sit (item on the motor system domain). Although our interpretations must be careful, these preliminary results highlight the possible association between prenatal SARS-CoV-2 exposure and poorer development in motor skills and infant interactive behavior. Further longitudinal studies are needed to explore these relationships and disentangle the biological mechanisms implicated.

Education and long-term outcomes in first episode psychosis: 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Lower levels of education have been associated with the development of psychosis. Investigating educational achievement in the first episode of psychosis (FEP) patients may shed light on the origins of the alterations and on the variability of outcomes in psychotic disorders. METHODS: Education achievement was explored in a large sample (n = 659) of FEP patients enrolled in programa de atención a fases iniciales de psicosis (PAFIP), a research and assistance program conducted in Spain. Patients were stratified according to the Spanish educational system according to their attendance in primary (low), secondary (medium) or university studies (high). The three groups were compared on available premorbid, clinical and neuropsychological variables. A subgroup of patients (n = 209), comprising the 10-year follow-up PAFIP cohort, were again compared. RESULTS: Overall, 49% and 37% of FEP patients had low and medium levels of education, respectively. In total, 13% of the patients with a higher level of education were more frequently women (64%) and older at illness onset (36 years old), reported better premorbid adjustment, presented less severe positive symptoms and better functioning; and showed higher premorbid intelligence quotient and better performance on all the explored cognitive domains. Ten years later the FEP patients in the medium- and high-education groups had good global functioning and a neurocognitive performance within the normal limits. CONCLUSIONS: Higher education is associated with better initial conditions and more favourable outcomes after an FEP. Sharing this information with the world's educational systems is essential to targeting resources and designing innovative programs or strategies to compensate for student difficulties.

A family study on first episode of psychosis patients: Exploring neuropsychological performance as an endophenotype.

INTRODUCTION: Family studies provide a suitable approach to analyzing candidate endophenotypes of schizophrenia, including cognitive features. OBJECTIVE: To characterize different neurocognitive functions in a group of patients with first episode of psychosis (FEP), their first-degree relatives (parents and siblings), and healthy controls (HC), in order to identify potential endophenotypes for schizophrenia spectrum disorders (SSD). METHODS: Participants were assessed in the context of a national project in Spain called PAFIP-FAMILIAS. They completed the same neuropsychological battery, which included tests of verbal memory, visual memory, processing speed, working memory, executive functions, motor dexterity, attention, and theory of mind. Group comparisons were performed using one-way ANOVA, followed by tests of multiple comparisons when appropriate. RESULTS: One hundred thirty-three FEP patients were included, as well as 244 of their first-degree relatives (146 parents and 98 siblings) and 202 HC. In general, relatives showed an intermediate performance between the HC and the FEP patients in all neurocognitive domains. However, the domains of executive functions and attention stood out, as relatives (especially parents) showed similar performance to FEP patients. This was replicated when selecting patients subsequently diagnosed with schizophrenia and their relatives. CONCLUSION: These findings suggest that executive and attention dysfunctions might have a family aggregation and could be relevant cognitive endophenotypes for psychotic disorders. The study shows the potential of exploring intra-family neuropsychological performance supporting neurobiological and genetic research in SSD.

Database of word-level statistics for Mandarin Chinese (DoWLS-MAN).

In this article we present the Database of Word-Level Statistics for Mandarin Chinese (DoWLS-MAN). The database addresses the lack of agreement in phonological syllable segmentation specific to Mandarin by offering phonological features for each lexical item according to 16 schematic representations of the syllable (8 with tone and 8 without tone). Those lexical statistics that differ per phonological word and nonword due to changes in syllable segmentation are of the variant category and include subtitle lexical frequency, phonological neighborhood density measures, homophone density, and network science measures. The invariant characteristics consist of each items' lexical tone, phonological transcription, and syllable structure among others. The goal of DoWLS-MAN is to provide researchers both the ability to choose stimuli that are derived from a segmentation schema that supports an existing model of Mandarin speech processing, and the ability to choose stimuli that allow for the testing of hypotheses on phonological segmentation according to multiple schemas. In an exploratory analysis we illustrate how multiple schematic representations of the phonological mental lexicon can aid in hypothesis generation, specifically in terms of phonological processing when reading Chinese orthography. Users of the database can search among over 92,000 words, over 1600 out-of-vocabulary Chinese characters, and 4300 phonological nonwords according to either Chinese orthography, pinyin, or ASCII phonetic script. Users can also generate a list of phonological words and nonwords according to user-defined ranges and categories of lexical characteristics. DoWLS-MAN is available to the public for search or download at https://dowls.site .

Effective Connectivity Study Guiding the Neuromodulation Intervention in Figurative Language Comprehension Using Optical Neuroimaging.

The current study is aimed at establishing links between brain network examination and neural plasticity studies measured by optical neuroimaging. Sixteen healthy subjects were recruited from the University of Macau to test the Granger Prediction Estimation (GPE) method to investigate brain network connectivity during figurative language comprehension. The method is aimed at mapping significant causal relationships across language brain networks, captured by functional near-infrared spectroscopy measurements (fNIRS): (i) definition of regions of interest (ROIs) based on significant channels extracted from spatial activation maps; (ii) inspection of significant causal relationships in temporal resolution, exploring the experimental task agreement; and (iii) early identification of stronger causal relationships that guide neuromodulation intervention, targeting impaired connectivity pathways. Our results propose top-down mechanisms responsible for perceptive-attention engagement in the left anterior frontal cortex and bottom-up mechanism in the right hemispheres during the semantic integration of figurative language. Moreover, the interhemispheric directional flow suggests a right hemisphere engagement in decoding unfamiliar literal sentences and fine-grained integration guided by the left hemisphere to reduce ambiguity in meaningless words. Finally, bottom-up mechanisms seem activated by logographic-semantic processing in literal meanings and memory storage centres in meaningless comprehension. To sum up, our main findings reveal that the Granger Prediction Estimation (GPE) integrated strategy proposes an effective link between assessment and intervention, capable of enhancing the efficiency of the treatment in language disorders and reducing the neuromodulation side effects.

Author Correction: Phonological network fluency identifies phonological restructuring through mental search.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Phonological network fluency identifies phonological restructuring through mental search.

We investigated network principles underlying mental search through a novel phonological verbal fluency task. Post exclusion, 95 native-language Mandarin speakers produced as many items that differed by a single lexical tone as possible within one minute. Their verbal productions were assessed according to several novel graded fluency measures, and network science measures that accounted for the structure, cohesion and interconnectedness of lexical items. A multivariate regression analysis of our participants' language backgrounds included their mono- or multi-lingual status, English proficiency, and fluency in other Chinese languages/dialects. Higher English proficiency predicted lower error rates and greater interconnectedness, while higher fluency in other Chinese languages/dialects revealed lower successive similarity and lower network coherence. This inverse relationship between English and other Chinese languages/dialects provides evidence of the restructuring of the phonological mental lexicon.

Patterns of recovery course in early intervention for FIRST episode non-affective psychosis patients: The role of timing.

BACKGROUND: Prevention of symptom relapse and promotion of functional recovery are the two main goals of early intervention following a first episode of non-affective psychosis (FEP). The identification of patterns of recovery is important in developing and implementing recovery focused interventions at set time interval. METHOD: Patterns of recovery course, in terms of symptomatic and functional remission, were explored at 1 and 3-year follow-up in a sample of 373 consecutive FEP patients. Relapses during this period were considered. RESULTS: Four patterns of recovery course were defined: good stable (26%), good unstable (21%), poor unstable (10%), poor stable (43%). Those who met criteria for good stable recovery were more likely have less severe baseline negative symptoms (OR = 2.092; 95% CI = 0.99-4.419) and to not be diagnosed with schizophrenia (OR = 2.242; 95% CI = 1.015-4.954). Short DUP (OR = 2.152; 95% CI = 0.879-5.27) and low premorbid IQ (OR = 2.281; 95% CI = 0.954-5.457) increased the likelihood of good unstable recovery. Less severe baseline negative symptoms (OR = 3.851; 95% CI = 1.422-10.435) and single status (OR = 4.307; 95% CI = 1.014-18.293) increased the likelihood of a poor unstable recovery. Poor unstable pattern was significantly associated with a high relapse rate (73%). CONCLUSIONS: Our results shed light on identifying different recovery patterns in FEP. Despite evidence for early intervention effectiveness, we should explore ways to prevent relapse and improve long-term recovery, particularly in reference to the role of timing in the design of interventions.

Premorbid IQ subgroups in first episode non affective psychosis patients: Long-term sex differences in function and neurocognition.

BACKGROUND: Low IQ has been associated with schizophrenia, even to the point of being posited as a possible causal factor for psychosis. However, individuals with normal and high IQ also develop psychotic illnesses. The aim of this study was to characterize premorbid IQ subgroups at first episode of psychosis (FEP). METHODS: The study sample comes from a large epidemiological, 3-year longitudinal, intervention program on psychosis containing individuals living in a catchment area in Spain. Estimated premorbid IQ (epIQ) scores were used to build low (<90), normal (90-110) and high (>110) epIQ subgroups in samples of FEP patients (N=292) and healthy controls (N=199). The epIQ subgroups were compared in sociodemographic, neuropsychological, clinical and premorbid characteristics. Long-term functional and cognitive outcome, with a focus on sex differences, were also explored. RESULTS: Low-epIQ was more frequently found in FEP patients (28.8%) than in healthy controls (14.6%). Low-epIQ patients were more likely to have worse premorbid adjustment, belong to low socioeconomic status families, have less years of education, and to be single, unemployed, and younger. They presented more severe impairments in processing speed, executive and global cognitive function. Female patients with low-epIQ showed better baseline function and more stable outcome than males. CONCLUSIONS: Our results indicate that low premorbid IQ is a morbid manifestation, easily detected in a subgroup of FEP patients that predicts poorer outcome particularly in males. This perspective provides important information for the tailoring of subgroup-specific early intervention programs for psychosis.

Cannabis use in male and female first episode of non-affective psychosis patients: Long-term clinical, neuropsychological and functional differences.

BACKGROUND: Numerous studies show the existence of a high prevalence of cannabis use among patients with psychosis. However, the differences between men and women who debut with a first episode of psychosis (FEP) regarding cannabis use have not been largely explored. The aim of this study was to identify the specific sex factors and differences in clinical evolution associated with cannabis use. METHOD: Sociodemographic characteristics at baseline were considered in our sample of FEP patients to find differences depending on sex and the use of cannabis. Clinical, functional and neurocognitive variables at baseline, 1-year, and 3-years follow-up were also explored. RESULTS: A total of 549 patients, of whom 43% (N = 236) were cannabis users, 79% (N = 186) male and 21% (N = 50) female, were included in the study. There was a clear relationship between being male and being a user of cannabis (OR = 5.6). Cannabis users were younger at illness onset. Longitudinal analysis showed that women significantly improved in all three dimensions of psychotic symptoms, both in the subgroup of cannabis users and in the non-users subgroup. Conversely, subgroups of men did not show improvement in the negative dimension. In cognitive function, only men presented a significant time by group interaction in processing speed, showing a greater improvement in the subgroup of cannabis users. CONCLUSION: Despite knowing that there is a relationship between cannabis use and psychosis, due to the high prevalence of cannabis use among male FEP patients, the results showed that there were very few differences in clinical and neurocognitive outcomes between men and women who used cannabis at the start of treatment compared to those who did not.

Incidence and risk factors of acute akathisia in 493 individuals with first episode non-affective psychosis: a 6-week randomised study of antipsychotic treatment.

INTRODUCTION: Acute akathisia is a neuropsychiatric syndrome with a negative effect on illness outcome. Its incidence in patients treated with antipsychotics has shown to be highly variable across studies. OBJECTIVES: Our goals were to investigate prevalence, risk factors for the development of acute akathisia, and differences in incidence between antipsychotics in a sample of 493 first episode non-affective psychosis patients. METHODS: This is a pooled analysis of three prospective, randomized, flexible-dose, and open-label clinical trials. Patients were randomized assigned to different arms of treatment (haloperidol, quetiapine, olanzapine, ziprasidone, risperidone, or aripiprazole). Akathisia was determined using the Barnes Akathisia Scale at 6 weeks after antipsychotic initialization. Univariate analyses were performed to identify demographic, biochemical, substance use, clinical, and treatment-related predictors of acute akathisia. Considering these results, a predictive model based of a subsample of 132 patients was constructed with akathisia as the dependent variable. RESULTS: The overall incidence of akathisia was 19.5%. No differences in demographic, biochemical, substance use, and clinical variables were found. Significant incidence differences between antipsychotics were observed (Χ 2 = 68.21, p = 0.000): haloperidol (57%), risperidone (20%), aripiprazole (18.2%), ziprasidone (17.2%), olanzapine (3.6%), and quetiapine (3.5%). The predictive model showed that the type of antipsychotic (OR = 21.3, p = 0.000), need for hospitalization (OR = 2.6, p = 0.05), and BPRS total score at baseline (OR = 1.05, p = 0.03) may help to predict akathisia emergence. CONCLUSIONS: Among second generation antipsychotics, only olanzapine and quetiapine should be considered as akathisia-sparing drugs. The type of antipsychotic, having been hospitalized, and a more severe symptomatology at intake seem to predict the development of acute akathisia.

Evidence for Trait Related Theory of Mind Impairment in First Episode Psychosis Patients and Its Relationship with Processing Speed: A 3 Year Follow-up Study.

This study aimed to confirm whether first-episode psychosis patients present a stable trait impairment in theory of mind (ToM) and to examine the potential relationship between ToM and clinical symptomatology and neurocognition. Patients with a first episode of psychosis (N = 160) and healthy controls (N = 159) were assessed with an extensive neuropsychological test battery, which included a mental state decoding task known as "The Reading the Mind in the Eyes" (Eyes test), at baseline and reassessed after 1 and 3 years. The clinical group performed below healthy controls on the Eyes test while not showing test-retest differences between baseline and follow-up administrations. Analyses revealed age, education and premorbid IQ as potential moderators. Poorer performance on the Eyes test was not linked to clinical symptomatology but was associated with greater neurocognitive deficit, particularly related to processing speed. The persistence of ToM deficits in patients suggests that there are trait related metalizing impairments in first episode psychosis. This study shows the influence of processing speed and moderator variables on efficient ToM.