Exploring parenthood in first episode of psychosis: the potential role of the offspring in the outcome of women.

PURPOSE: The study aimed to explore the role of parenthood at first episode of psychosis (FEP) on recovery, with a focus on potential sex differences. METHODS: Sociodemographic, clinical, and neurocognitive information was considered on 610 FEP patients form the PAFIP cohort (Spain). Baseline and three-year follow-up comparisons were carried out. Chi-square tests and ANCOVA analysis were performed controlling for the effect of age and years of education. RESULTS: Men comprised 57.54% of the sample, with only 5.41% having offspring when compared to 36.29% of women. Parenthood was related to shorter duration of untreated illness (DUI) in women with children (12.08 months mothers vs. 27.61 months no mothers), showing mothers better premorbid adjustment as well. Childless men presented the worst premorbid adjustment and the highest cannabis and tobacco consumption rates. Mothers presented better global cognitive function, particularly in attention, motor dexterity and executive function at three-year follow-up. CONCLUSIONS: Diminished parental rates among FEP men could be suggested as a consequence of a younger age of illness onset. Sex roles in caregiving may explain the potential role of parenthood on premorbid phase, with a better and heathier profile, and a more favorable long-term outcome in women. These characteristics may be relevant when adjusting treatment specific needs in men and women with and without offspring.

Studying the relationship between intelligence quotient and schizophrenia polygenic scores in a family design with first-episode psychosis population.

BACKGROUND: The intelligence quotient (IQ) of patients with first-episode psychosis (FEP) and their unaffected relatives may be related to the genetic burden of schizophrenia (SCZ). The polygenic score approach can be useful for testing this question. AIM: To assess the contribution of the polygenic risk scores for SCZ (PGS-SCZ) and polygenic scores for IQ (PGS-IQ) to the individual IQ and its difference from the mean IQ of the family (named family-IQ) through a family-based design in an FEP sample. METHODS: The PAFIP-FAMILIES sample (Spain) consists of 122 FEP patients, 131 parents, 94 siblings, and 176 controls. They all completed the WAIS Vocabulary subtest for IQ estimation and provided a DNA sample. We calculated PGS-SCZ and PGS-IQ using the continuous shrinkage method. To account for relatedness in our sample, we performed linear mixed models. We controlled for covariates potentially related to IQ, including age, years of education, sex, and ancestry principal components. RESULTS: FEP patients significantly deviated from their family-IQ. FEP patients had higher PGS-SCZ than other groups, whereas the relatives had intermediate scores between patients and controls. PGS-IQ did not differ between groups. PGS-SCZ significantly predicted the deviation from family-IQ, whereas PGS-IQ significantly predicted individual IQ. CONCLUSIONS: PGS-SCZ discriminated between different levels of genetic risk for the disorder and was specifically related to patients' lower IQ in relation to family-IQ. The genetic background of the disorder may affect neurocognition through complex pathological processes interacting with environmental factors that prevent the individual from reaching their familial cognitive potential.

Processing speed in first episode of psychosis and first-degree relatives: A candidate endophenotype of spectrum schizophrenia disorders.

OBJECTIVE: The processing speed (PS) is highly impacted in individuals experiencing their first episode of psychosis (FEP). Conducting family studies can help to determine whether PS can serve as an endophenotype of schizophrenia spectrum disorders (SSDs), offering valuable insights into the prevention and diagnosis of SSDs. METHOD: A comprehensive cognitive battery, encompassing tests for PS, verbal memory, visual memory, working memory, executive functions, motor dexterity, and attention, was administered to a sample consisting of 133 FEP patients, 146 parents, 98 siblings, and 202 healthy controls (HCs). Univariate analyses (analysis of covariance [ANCOVA]) were conducted to compare the different cognitive domains between groups, utilizing sex, age, and years of education as covariates and Bonferroni corrections. Effect sizes (ESs) were calculated for estimating the magnitude of differences between groups. RESULTS: Group comparisons revealed significant differences in all cognitive domains. PS was the most impaired function in patients. Parents and siblings had intermediate PS performance between FEP patients and HC. Large ES were observed in PS between FEP versus siblings, FEP versus controls, parents versus controls, and parents versus siblings. CONCLUSIONS: Despite not meeting all the necessary criteria, the PS observed in FEP patients and their first-degree relatives suggests its potential as a promising endophenotype of SSDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Familiality of the Intelligence Quotient in First Episode Psychosis: Is the Degree of Family Resemblance Associated With Different Profiles?

BACKGROUND AND HYPOTHESIS: There is uncertainty about the relationship between the family intelligence quotient (IQ) deviation and the risk for schizophrenia spectrum disorders (SSD). This study tested the hypothesis that IQ is familial in first episode psychosis (FEP) patients and that their degree of familial resemblance is associated with different profiles. STUDY DESIGN: The participants of the PAFIP-FAMILIAS project (129 FEP patients, 143 parents, and 97 siblings) completed the same neuropsychological battery. IQ-familiality was estimated through the Intraclass Correlation Coefficient (ICC). For each family, the intra-family resemblance score (IRS) was calculated as an index of familial similarity. The FEP patients were subgrouped and compared according to their IRS and IQ. STUDY RESULTS: IQ-familiality was low-moderate (ICC = 0.259). A total of 44.9% of the FEP patients had a low IRS, indicating discordancy with their family-IQ. Of these patients, those with low IQ had more schizophrenia diagnosis and a trend towards poorer premorbid adjustment in childhood and early adolescence. Whereas FEP patients with low IQ closely resembling their family-IQ were characterized by having the lowest performance in executive functions. CONCLUSIONS: The deviation from the familial cognitive performance may be related to a particular pathological process in SSD. Individuals with low IQ who do not reach their cognitive familial potential show difficulties in adjustment since childhood, probably influenced by environmental factors. Instead, FEP patients with high phenotypic family resemblance might have a more significant genetic burden for the disorder.

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.

A Proxy Approach to Family Involvement and Neurocognitive Function in First Episode of Non-Affective Psychosis: Sex-Related Differences.

Schizophrenia spectrum disorders (SSD) often show cognitive deficits (CD) impacting daily life. Family support has been shown to be protective against CD, yet the relationship between these in psychotic patients remains complex and not fully understood. This study investigated the association between a subdomain of family support, namely, family involvement (estimated through a proxy measure), cognitive functioning, and sex in first-episode psychosis (FEP) patients. The sample included 308 patients enrolled in the Program for Early Phases of Psychosis (PAFIP), divided into 4 groups based on their estimated family involvement (eFI) level and sex, and compared on various variables. Women presented lower rates of eFI than men (37.1% and 48.8%). Higher eFI was associated with better cognitive functioning, particularly in verbal memory. This association was stronger in women. The findings suggest that eFI may be an important factor in FEP patients' cognitive functioning. This highlights the importance of including families in treatment plans for psychotic patients to prevent CD. Further research is needed to better understand the complex interplay between family support, sex, and cognitive functioning in psychotic patients and develop effective interventions that target these factors.

Cognitive reserve as a moderator of outcomes in five clusters of first episode psychosis patients: a 10-year follow-up study of the PAFIP cohort.

BACKGROUND: Cognitive reserve (CR) has been associated with the development and prognosis of psychosis. Different proxies have been used to estimate CR among individuals. A composite score of these proxies could elucidate the role of CR at illness onset on the variability of clinical and neurocognitive outcomes. METHODS: Premorbid intelligence quotient (IQ), years of education and premorbid adjustment were explored as proxies of CR in a large sample (N = 424) of first-episode psychosis (FEP) non-affective patients. Clusters of patients were identified and compared based on premorbid, clinical and neurocognitive variables at baseline. Additionally, the clusters were compared at 3-year (N = 362) and 10-year (N = 150) follow-ups. RESULTS: The FEP patients were grouped into five CR clusters: C1 (low premorbid IQ, low education and poor premorbid) 14%; C2 (low premorbid IQ, low education and good premorbid adjustment) 29%; C3 (normal premorbid IQ, low education and poor premorbid adjustment) 17%; C4 (normal premorbid IQ, medium education and good premorbid adjustment) 25%; and C5 (normal premorbid IQ, higher education and good premorbid adjustment) 15%. In general, positive and negative symptoms were more severe in the FEP patients with the lowest CR at baseline and follow-up assessments, while those with high CR presented and maintained higher levels of cognitive functioning. CONCLUSIONS: CR could be considered a key factor at illness onset and a moderator of outcomes in FEP patients. A high CR could function as a protective factor against cognitive impairment and severe symptomatology. Clinical interventions focused on increasing CR and documenting long-term benefits are interesting and desirable.

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.

Sex differences in cognitive reserve among first episode of psychosis patients.

INTRODUCTION: Cognitive reserve (CR) has recently been considered a key factor in the onset of a first episode of psychosis (FEP). However, the differences in CR in FEP patients according to sex have not yet been investigated. MATERIAL AND METHODS: CR was estimated among 443 FEP patients (246 men and 197 women) and 156 healthy controls (96 men and 60 women) by using the proxies premorbid IQ, years of education and employment status. A neuropsychological battery was administrated to measure neurocognitive specific domains. Analyses of variance were used to make comparisons between groups. RESULTS: FEP women had greater CR than FEP men. This circumstance was not observed in healthy controls. Among the group of patients with low CR, FEP women outperformed FEP men in the cognitive domains verbal memory and processing speed. Meanwhile, among the FEP patients with high CR, men showed better performance in attention than women. CONCLUSIONS: Differences in CR observed between FEP men and women could be related to a number of specific factors, such as, age at illness onset, education level, and variability in performance in verbal memory, processing speed, and attention domains. These results provide background information about CR in FEP patients that will be useful in the design of sex specific cognitive remediation interventions.

Theory of Mind as an endophenotype for schizophrenia spectrum disorder: Study in first episode of psychosis patients and first-degree relatives.

BACKGROUND: Deficits in Theory of Mind (ToM) had been suggested as a possible endophenotype for unaffected relatives of first episode of psychosis (FEP) patients. There are a limited number of studies which have evaluated ToM deficits among the siblings and parents of FEP patients. AIM: This study aimed to explore ToM deficits and its correlates among FEP patients, their siblings, parents, and controls. METHODOLOGY: FEP patients (N=102), their parents (N=135), siblings (N=97), and controls (N=167) were evaluated on ToM performance with the Reading the Mind in the Eyes Test (Eyes Test). Interview for sociodemographic variables of age, sex, years of education, and IQ estimation and neurocognitive tests were administered to all groups. RESULTS: FEP patients had a significantly lower performance on the Eyes Test compared to their siblings and controls. However, no significant differences were found between siblings and parents or siblings and controls. CONCLUSION: Attending our results, we found no evidence for ToM deficits as an endophenotype of SSDs. Furthermore, ToM accuracy may be mediated by interaction with other cognitive domains and play a protective role against psychosis in unaffected siblings.

Overlap between genetic variants associated with schizophrenia spectrum disorders and intelligence quotient: a systematic review.

BACKGROUND: To study whether there is genetic overlap underlying the risk for schizophrenia spectrum disorders (SSDs) and low intelligence quotient (IQ), we reviewed and summarized the evidence on genetic variants associated with both traits. METHODS: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and preregistered it in PROSPERO. We searched the Medline databases via PubMed, PsycInfo, Web of Science and Scopus. We included studies in adults with a diagnosis of SSD that explored genetic variants (single nucleotide polymorphisms [SNPs], copy number variants [CNVs], genomic insertions or genomic deletions), estimated IQ and studied the relationship between genetic variability and both traits (SSD and IQ). We synthesized the results and assessed risk of bias using the Quality of Genetic Association Studies (Q-Genie) tool. RESULTS: Fifty-five studies met the inclusion criteria (45 case-control, 9 cross-sectional, 1 cohort), of which 55% reported significant associations for genetic variants involved in IQ and SSD. The SNPs more frequently explored through candidate gene studies were in COMT, DTNBP1, BDNF and TCF4. Through genome-wide association studies, 2 SNPs in CHD7 and GATAD2A were associated with IQ in patients with SSD. The studies on CNVs suggested significant associations between structural variants and low IQ in patients with SSD. LIMITATIONS: Overall, primary studies used heterogeneous IQ measurement tools and had small samples. Grey literature was not screened. CONCLUSION: Genetic overlap between SSD and IQ supports the neurodevelopmental hypothesis of schizophrenia. Most of the risk polymorphisms identified were in genes relevant to brain development, neural proliferation and differentiation, and synaptic plasticity.

Corrigendum: Exploring the relationship between deficits in social cognition and neurodegenerative dementia: A systematic review.

[This corrects the article DOI: 10.3389/fnagi.2022.778093.].

Exploring the Relationship Between Deficits in Social Cognition and Neurodegenerative Dementia: A Systematic Review.

Background: Neurodegenerative diseases might affect social cognition in various ways depending on their components (theory of mind, emotional processing, attribution bias, and social perception) and the subtype of dementia they cause. This review aims to explore this difference in cognitive function among individuals with different aetiologies of dementia. Methods: The following databases were explored: MEDLINE via PubMed, Cochrane Library, Lilacs, Web of Science, and PsycINFO. We selected studies examining social cognition in individuals with neurodegenerative diseases in which dementia was the primary symptom that was studied. The neurodegenerative diseases included Alzheimer's disease, Lewy body disease and frontotemporal lobar degeneration. The search yielded 2,803 articles. Results: One hundred twenty-two articles were included in the present review. The summarised results indicate that people with neurodegenerative diseases indeed have deficits in social cognitive performance. Both in populations with Alzheimer's disease and in populations with frontotemporal dementia, we found that emotional processing was strongly affected. However, although theory of mind impairment could also be observed in the initial stages of frontotemporal dementia, in Alzheimer's disease it was only appreciated when performing highly complex task or in advanced stages of the disease. Conclusions: Each type of dementia has a differential profile of social cognition deterioration. This review could provide a useful reference for clinicians to improve detection and diagnosis, which would undoubtedly guarantee better interventions. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020152562, PROSPERO, identifier: CRD42020152562.

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.

Entire duration of active psychosis and neurocognitive performance in first-episode non-affective psychosis.

AIM: To explore if the entire duration of active psychosis (DAP) is related to neurocognitive performance at baseline and at 3-year follow-up in patients with first episode psychosis (FEP). METHODS: DAP was estimated for 481 FEP patients. A neuropsychological battery was administered to measure neurocognitive specific domains, and a global indicator of neurocognitive impairment (global deficits score, GDS) was calculated. According to the DAP quartiles, four subgroups were formed, and these were compared. In addition, a logistic regression analysis was carried out to predict neurocognitive impairment at 3-year follow-up. RESULTS: FEP patients with the longest DAP (more than 18.36 months) presented a more severe global neurocognitive impairment evidenced in their GDS, both at baseline (F = 5.53; p˂ .01) and at 3-year follow-up (F = 4.16; p˂ .01). Moreover, a subgroup of participants with DAP between 7.40 and 18.36 months showed a specific attentional decline over the 3-year follow-up (F = 3.089; p˂ .05).The logistic regression model showed that sex (Wald = 7.29, p < .010), premorbid adjustment (Wald = 7.24, p < .010), attention (Wald = 12.10, p < .001), verbal memory (Wald = 16.29, p < .001) and visual memory (Wald = 9.41, p < .010) were significant predictors of neurocognitive impairment 3 years after the FEP. The variables composing the DAP were not significant predictors in this model. CONCLUSIONS: DAP seems to be related to global neurocognitive impairment in FEP patients. These findings contribute in several ways to our understanding of the effects of active psychosis on the brain, and provide the basis for future research.