Cognition In Schizophrenia Patients Research Articles

The identification of novel schizophrenia-related metabolites using untargeted lipidomics.

Human lipidome still remains largely unexplored among Chinese schizophrenia patients. We aimed to identify novel lipid molecules associated with schizophrenia and cognition among schizophrenia patients. The current study included 96 male schizophrenia patients and 96 gender-matched healthy controls. Untargeted lipidomics profiling was conducted among all participants. Logistic regression models were used to assess metabolite associations with schizophrenia. We further assessed the incremental predictive value of identified metabolites beyond conventional risk factors on schizophrenia status. In addition, identified metabolites were tested for association with cognitive function among schizophrenia patients using linear regression models. A total of 34 metabolites were associated with schizophrenia. Addition of these identified metabolites to age, body mass index, smoking, and education significantly increased the risk reclassification of schizophrenia. Among the schizophrenia-related metabolites, 10 were further associated with cognition in schizophrenia patients, including four metabolites associated with immediate memory, two metabolites associated with delayed memory, three metabolites associated with visuospatial, four metabolites associated with language, one metabolite associated with attention, and two metabolites associated with the total score. Our findings provide novel insights into the biological mechanisms of schizophrenia, suggesting that lipid metabolites may serve as potential diagnostic or therapeutic targets of schizophrenia.

Schizophrenia and Nicotine - A Bittersweet Psychiatric Story

Abstract Background: Schizophrenia is a chronic mental disorder affecting mood, perception, and most importantly cognition. This severely interferes with the functioning of such patients. On the other hand, nicotine use (both smoke and smokeless tobacco) is very much prevalent in schizophrenic patients, much more than normal population. This study aims to find the relation between nicotine use and cognition in schizophrenic patients. Methodology: Fifty-six new patients diagnosed with schizophrenia of both sexes between ages 18 and 60 years, giving valid and informed consent, were selected for the study. Fagerstrom test for nicotine dependence was done and the patients were divided into two groups: scores 4 or less (low-to-moderate dependence) and scores 5 or more (severe dependence). The Cognitive Assessment Interview was performed. Then, an independent sample t-test was used to compare the scores on various cognitive domains between the two groups. Results: The cognitive scores were better in the group with severe tobacco dependence, both globally and across individual domains. These associations were statistically significant (P = 0.001). The mean difference was highest in the social cognition group. Among all the domains, the t-value was highest for the speed of processing domain, indicating that this particular cognitive domain has the best discriminative value when compared between two groups of nicotine users. Conclusions: Hence, to conclude, whether nicotine has indeed a beneficial effect on cognition in schizophrenia has to be investigated longitudinally so that a possible treatment option to address cognitive impairment in schizophrenia is obtained. Extensive longitudinal studies needs to be conducted to better understand the long-term effect of tobacco use and cognition in schizophrenia patients.

Inference of social cognition in schizophrenia patients with neurocognitive domains and neurocognitive tests using automated machine learning

AimIt has been suggested that single neurocognitive domain or neurocognitive test can be used to determine the overall cognitive function in schizophrenia using machine learning algorithms. It is unknown whether social cognition in schizophrenia patients can be estimated with machine learning based on neurocognitive domains or neurocognitive tests. MethodsTo predict social cognition in schizophrenia, we applied an automated machine learning (AutoML) framework resulting from the analysis of predictive factors such as six neurocognitive domain scores and nine neurocognitive test scores of 380 schizophrenia patients in the Taiwanese population. Four clinical parameters (i.e., age, gender, subgroup, and education) were also used as predictive factors. We utilized an AutoML framework called Tree-based Pipeline Optimization Tool (TPOT) to generate predictive pipelines automatically. ResultsThe analysis revealed that all neurocognitive domains and tests except the reasoning and problem solving domain/test showed significant associations with social cognition. In addition, a TPOT-generated pipeline can best predict social cognition in schizophrenia using seven predictive factors, including five neurocognitive domains (i.e., speed of processing, sustained attention, working memory, verbal learning and memory, and visual learning and memory) and two clinical parameters (i.e., age and gender). This predictive pipeline consists of machine learning algorithms such as function transformers, an approximate feature map, independent component analysis, and linear regression. ConclusionThe study indicates that an AutoML framework such as TPOT may provide a promising way to produce truly effective machine learning pipelines for predicting social cognition in schizophrenia using neurocognitive domains and/or neurocognitive tests.

Aberrant cortico-thalamo-cerebellar network interactions and their association with impaired cognitive functioning in patients with schizophrenia

Evidence indicating abnormal functional connectivity (FC) among the cortex, thalamus, and cerebellum in schizophrenia patients has increased. However, the role of the thalamus and cerebellum when integrated into intrinsic networks and how those integrated networks interact in schizophrenia patients are largely unknown. We generated an integrative network map by merging thalamic and cerebellar network maps, which were parcellated using a winner-take-all approach, onto a cortical network map. Using cognitive networks, the default mode network (DMN), the dorsal attention network (DAN), the salience network (SAL), and the central executive network (CEN) as regions of interest, the FC of 48 schizophrenia patients was compared with that of 57 healthy controls (HCs). The association between abnormal FC and cognitive impairment was also investigated in patients. FC was lower between the SAL-CEN, SAL-DMN, and DMN-CEN and within-CEN in schizophrenia patients than in HCs. Hypoconnectivity between the DMN-CEN was correlated with impaired cognition in schizophrenia patients. Our findings broadly suggest the plausible role of the thalamus and cerebellum in integrative intrinsic networks in patients, which may contribute to the disrupted triple network and cognitive dysmetria in schizophrenia.

Cross-Cultural Adaptation and Validation of the Serbian Version of the Brief Assessment of Cognition in Schizophrenia Scale.

The Brief Assessment of Cognition in Schizophrenia (BACS) scale was developed for the assessment of cognitive function in patients with schizophrenia. The objective of this study was to cross-culturally adapt and validate the BACS in to the Serbian language. The study was conducted at the Laza Lazarevic Clinic for Mental Disorders and the Clinic for Psychiatry of the University Clinical Center of Serbia from March 2021 to January 2022. The study enrolled 61 inpatients diagnosed with schizophrenia and 61 healthy controls matched for age and sex. Compared with the healthy control group, the schizophrenia patient group had worse cognitive function in all dimensions measured using BACS (p < 0.001 for all measures). The mean standardized composite BACS score was z = -2.46, and symbol coding (z = -2.54) was the most deficient function. Principal component analysis suggests a two-factor structure, where the first factor consisted of loading the measures of verbal and working memory, attention, speed of information processing, and executive function, while the second factor regarded the loading of motor speed. Cronbach's alpha coefficient demonstrated an excellent level of internal consistency (0.798). These outcomes suggest that the Serbian BACS neurocognitive battery's psychometric properties are satisfactory, with good overall discriminant validity and high internal consistency. The Serbian BACS appears to be a quick and reliable neuropsychological instrument for evaluating global cognition in schizophrenia patients in Serbia.

The Relationship Between Cannabis, Cognition, and Schizophrenia: It's Complicated.

The consequences of cannabis use, especially in the context of schizophrenia, have gained increased importance with the legalization of cannabis in North America and across the globe. Cannabis use has multifaceted impacts on cognition in schizophrenia patients and healthy subjects. Healthy subjects, particularly those who initiated cannabis use at earlier ages and used high-potency cannabis for longer durations, exhibited poorer cognition mainly in working memory and attention. Cannabis use in schizophrenia has been associated with symptom exacerbation, longer and more frequent psychotic episodes, and poorer treatment outcomes. However, cannabis-using patients have better overall cognitive performance compared to patients who were not cannabis users. Interestingly, these effects were only apparent in lifetime cannabis users, but not in current (or within last 6months) users. Moreover, higher frequency and earlier age of cannabis use initiation (i.e., before 17years of age) were associated with better cognitive performance, although they had an earlier illness onset. Three possible hypotheses seem to come forward to explain this paradox. First, some components of cannabis may have antipsychotic or cognitive-enhancing properties. Secondly, chronic cannabis use may alter endocannabinoid signaling in the brain which could be a protective factor for developing psychosis or cognitive impairments. A third explanation could be their representation of a phenotypically distinct patient group with more intact cognitive functioning and less neurodevelopmental pathology. Multiple factors need to be considered to understand the complex relationship between cannabis, cognitive function, and schizophrenia. In short, age at initiation, duration and rate of cannabis use, abstinence duration, co-use of substances and alcohol, prescribed medications, relative cannabinoid composition and potency of cannabis, presence of genetic and environmental vulnerability factors are prominent contributorsto the variability in outcomes. Animal studies support the disruptive effects of Δ9-tetrahydrocannabinol (THC) administration during adolescence on attention and memory performance. They provide insights about interaction of cannabinoid receptors with other neurotransmitter systems, such as GABA and glutamate, and other regulatory molecules, such as PSD95 and synaptophysin. Cannabidiol (CBD), on the other hand, can improve cognitive deficits seen in neurodevelopmental and chemically-induced animal models of schizophrenia. Future studies focusing on bridging the translational gaps between human and animal studies, through the use of translationally relevant methods of exposure (e.g., vaping), consistent behavioral assessments, and congruent circuit interrogations (e.g., imaging) will help to further clarify this complex picture.

No association between cortical dopamine D2 receptor availability and cognition in antipsychotic-naive first-episode psychosis

Cognitive impairment is an important predictor of disability in schizophrenia. Dopamine neurotransmission in cortical brain regions has been suggested to be of importance for higher-order cognitive processes. The aim of this study was to examine the relationship between extrastriatal dopamine D2-R availability and cognitive function, using positron emission tomography and the high-affinity D2-R radioligand [11C]FLB 457, in an antipsychotic-naive sample of 18 first-episode psychosis patients and 16 control subjects. We observed no significant associations between D2-R binding in the dorsolateral prefrontal cortex or hippocampus (β = 0.013–0.074, partial r = −0.037–0.273, p = 0.131–0.841). Instead, using Bayesian statistics, we found moderate support for the null hypothesis of no relationship (BFH0:H1 = 3.3–8.2). Theoretically, our findings may suggest a lack of detrimental effects of D2-R antagonist drugs on cognition in schizophrenia patients, in line with clinical observations.

Glycine transporter inhibitor promising for cognition in schizophrenia patients

Patients with schizophrenia who were randomized to the novel glycine transporter inhibitor BI 425809 saw significant improvement in cognition compared with placebo in a 12‐week Phase 2 study. The most promising results were reported for daily doses of 10 and 25 mg. Study results were published in the March 2021 issue of Lancet Psychiatry.

Retinal ganglion cell dysfunction is correlated with disturbed visual cognition in schizophrenia patients with visual hallucinations

Patients with schizophrenia have altered visual cognition and retinal functions. No studies have explored if retinal anomalies are related to visual cognition and the presence of visual hallucinations (VH).We explored functional responses of the retinal ganglion cells in schizophrenia patients with or without VH and conducted a neuropsychological evaluation to explore the links between cognition and retinal function.The VH+ group showed poorer visual cognition and we found correlations between the amplitudes of the P50 and the N95 waves and visual cognition.Our results provide arguments for a link between retinal dysfunction, impaired visual processing and VH in schizophrenia.

Polygenic Risk Scores Shed Light on the Relationship between Schizophrenia and Cognitive Functioning: Review and Meta-Analysis.

Schizophrenia is a multifactorial disease associated with widespread cognitive impairment. Although cognitive deficits are one of the factors most strongly associated with functional impairment in schizophrenia (SZ), current treatment strategies hardly tackle these impairments. To develop more efficient treatment strategies in patients, a better understanding of their pathogenesis is needed. Recent progress in genetics, driven by large genome-wide association studies (GWAS) and the use of polygenic risk scores (PRS), has provided new insights about the genetic architecture of complex human traits, including cognition and SZ. Here, we review the recent findings examining the genetic links between SZ and cognitive functions in population-based samples as well as in participants with SZ. The performed meta-analysis showed a negative correlation between the polygenetic risk score of schizophrenia and global cognition (p < 0.001) when the samples rely on general and healthy participants, while no significant correlation was detected when the three studies devoted to schizophrenia patients were meta-analysed (p > 0.05). Our review and meta-analysis therefore argues against universal pleiotropy for schizophrenia alleles and cognition, since cognition in SZ patients would be underpinned by the same genetic factors than in the general population, and substantially independent of common variant liability to the disorder.

Polygenic burden associated to oligodendrocyte precursor cells and radial glia influences the hippocampal volume changes induced by aerobic exercise in schizophrenia patients

Hippocampal volume decrease is a structural hallmark of schizophrenia (SCZ), and convergent evidence from postmortem and imaging studies suggests that it may be explained by changes in the cytoarchitecture of the cornu ammonis 4 (CA4) and dentate gyrus (DG) subfields. Increasing evidence indicates that aerobic exercise increases hippocampal volume in CA subfields and improves cognition in SCZ patients. Previous studies showed that the effects of exercise on the hippocampus might be connected to the polygenic burden of SCZ risk variants. However, little is known about cell type-specific genetic contributions to these structural changes. In this secondary analysis, we evaluated the modulatory role of cell type-specific SCZ polygenic risk scores (PRS) on volume changes in the CA1, CA2/3, and CA4/DG subfields over time. We studied 20 multi-episode SCZ patients and 23 healthy controls who performed aerobic exercise, and 21 multi-episode SCZ patients allocated to a control intervention (table soccer) for 3 months. Magnetic resonance imaging-based assessments were performed with FreeSurfer at baseline and after 3 months. The analyses showed that the polygenic burden associated with oligodendrocyte precursor cells (OPC) and radial glia (RG) significantly influenced the volume changes between baseline and 3 months in the CA4/DG subfield in SCZ patients performing aerobic exercise. A higher OPC- or RG-associated genetic risk burden was associated with a less pronounced volume increase or even a decrease in CA4/DG during the exercise intervention. We hypothesize that SCZ cell type-specific polygenic risk modulates the aerobic exercise-induced neuroplastic processes in the hippocampus.

Connectivity strength of the EEG functional network in schizophrenia and bipolar disorder

The application of graph theory measures in the study of functional brain networks allows for the description of their general properties and their alterations in mental illness. Among these measures, connectivity strength (CS) estimates the degree of functional connectivity of the whole network. Previous studies in schizophrenia patients have reported higher baseline CS values and modulation deficits in EEG spectral properties during cognitive activity. The specificity of these alterations and their relationships with pharmacological treatments remain unknown. Therefore, in the present study, we assessed functional CS on EEG-based brain networks in 79 schizophrenia and 29 bipolar patients in addition to 63 healthy controls. The subjects performed a P300 task during the EEG recordings from which the pre-stimulus and the task-related modulation CS values were computed in the global and theta bands. These values were compared between the groups and between the patients who had and had not received different treatments. The global band pre-stimulus CS was significantly higher in the schizophrenia group compared with the bipolar and control groups. Theta band CS modulation was decreased in schizophrenia and bipolar patients. Treatment with antipsychotics, lithium, benzodiazepines, and anticonvulsants did not significantly alter these CS values. The first-episode and chronic schizophrenia patients did not show significant differences in CS values. Higher global band pre-stimulus CS values were associated with worse general cognition in schizophrenia patients. These data support increased connectivity in the whole-brain network that is specific to schizophrenia and suggest a general hyper-synchronized basal state that might hamper cognition in this syndrome.

Nonpharmacological treatment of dyscognition in schizophrenia: effects of aerobic exercise .

Cognitive symptoms are a core feature of schizophrenia and are related to an unfavorable disease outcome. So far, there are no satisfactory pharmacological approaches to address cognitive symptoms. For some time now, aerobic exercise has been demonstrated in various trials to be a promising candidate for this indication. The aim of this brief qualitative review was to present the most recent meta-analyses regarding the capacity of exercise to improve cognition in schizophrenia patients. Additionally, we give a short overview of the effects in other conditions, like healthy subjects and patients with major depression. We conducted a focused literature search using the PubMed database, concentrating on meta-analyses which are based on a systematic search. The most recent meta-analysis investigating the efficacy of aerobic exercise on cognitive impairments in schizophrenia patients provides evidence that exercise has positive effects on cognitive functioning in this population. However, the effect seems not to be specific; there were positive findings regarding healthy subjects and patients with depressive disorders as well, even if they were less consistent. As most available trials have a small to modest sample size and have no consensus with regard to the intervention regime, nor to the assessment of cognition, the findings are difficult to generalize. In the future, standardized clinical trials focusing on the long-term effects of exercise are needed to evaluate whether the improvements in cognition are sustainable.

Parkinsonism is associated to fronto-caudate disconnectivity and cognition in schizophrenia

The present work studies the possible relation of parkinsonism and fronto-caudate dysconnectivity, as well as its relation to cognition in schizophrenia patients. We assessed parkinsonism using Simpson-Angus scale and prefronto-caudate connectivity using diffusion magnetic resonance in 22 schizophrenia patients (11 first-episodes) and 14 healthy controls. Fractional anisotropy was calculated for the white matter tracts directly linking rostral middle prefrontal (RMPF) and superior medial prefrontal (SMPF) regions with caudate nucleus. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia Scale (BACS). Total parkinsonism scores were negatively related to fractional anisotropy in the right SMPF-caudate tract in patients, which was also found in the first-episode patients alone, but not in controls. Parkinsonism was also inversely associated in patients to performance in social cognition, verbal memory, working memory and performance speed tests. In conclusion, our data support the involvement of fronto-striatal dysconnectivity in parkinsonism in schizophrenia.

Social motivation in patients with schizophrenia spectrum disorders: how it is recognized in the rehabilitation process

The practice of psychosocial intervention for schizophrenia patients is dominated by cognitive–behavioural techniques. There is good justification for this on the basis of the empirical evidence, which speaks in favour of the efficacy of these approaches. Deficits in neurocognition and poor social skills in patients are considered the main targets of psychiatric rehabilitation programmes. However, there are research findings that suggest that distorted social motivation in the form of social anhedonia affects social cognition in schizophrenia patients. The authors describe a compound model of social cognition that includes its motivational component. The model rests on methodological assumptions of the Vygotskian Cultural-Historical Theory of Development, including that of the unity of intellectual and affective processes. The authors review the history of research into cognitive deficits in schizophrenia based on this assumption, and also the most recent empirical evidence confirming that social anhedonia contributes significantly to the impaired social cognition in schizophrenia. The authors conclude that rehabilitation programmes for schizophrenia patients must include psychosocial interventions focused on the remediation of social cognition impairment by means of techniques targeting the remediation of social motivation deficits.

P.1.i.008 - Social cognition in schizophrenia patients and their siblings: the role of insula

Despite evidence of pervasive social-cognitive deficits in schizophrenia, little is known of moral cognition in this population. While recent research indicates that impairment of explicit moral reasoning is explained by these individuals' other cognitive deficits, their capacities for basic moral judgment are unknown.45 people with schizophrenia and 27 healthy controls completed the Moral-Conventional Distinction Task: a classic task that assesses judgment of violations of moral or social convention on permissibility, severity, and authority-contingence. Justifications of judgments were also probed. Basic cognition was indexed by measures of IQ, verbal memory, and information processing speed. Self-report inventories were used to assess different facets of ‘empathy’ (e.g., perspective-taking, or theory of mind, and empathic concern), and aggressive tendencies.Groups did not differ significantly in judgments of permissibility or authority-contingency, or justifications of judgments. Patients did, however, rate violations of social (but not moral) convention more harshly. They also took longer to judge impermissibility of moral (but nor social) transgressions. Slower moral judgment in patients was associated with lower levels of self-reported empathic concern, while harsher condemnation of social transgression was associated with poorer (self-reported) perspective-taking.Findings provide no evidence that moral judgment is fundamentally compromised in schizophrenia. Evidence of slower moral judgment in schizophrenia does suggest, however, that patients were less influenced by automatic aversive responses to amoral conduct. The association found between poorer (self-reported) perspective-taking and greater condemnation of social transgressions also suggests that an insensitivity to others' extenuating motives may exacerbate social misunderstandings in schizophrenia.

Gender differences measured by the MATRICS consensus cognitive battery in chronic schizophrenia patients

Using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), previous study showed significant gender differences for cognitive deficits in immediate and delayed memory in schizophrenia patients. However, RBANS does not include reasoning and problem solving, and social cognition. These cognitive functions can significantly affect the outcomes and daily life in patients. This study examined the gender differences of cognition using the measurement and treatment research to improve cognition in schizophrenia (MATRICS) consensus cognitive battery (MCCB), especially focusing on reasoning and problem solving, and social cognition in schizophrenia patients. The results showed that healthy controls exemplified better cognition than patients in both genders in all examined MCCB scores. Male healthy controls had better reasoning and problem solving and working memory than females, but these gender differences were not presented in schizophrenia patients. Also, male schizophrenia patients showed worse cognition than females on social cognition, processing speed, verbal learning and visual learning. Our results support that male schizophrenia patients had more cognitive impairment than females on reasoning and problem solving, social cognition, processing speed, working memory, verbal learning and visual learning.

Relationship between effortful motivation and neurocognition in schizophrenia

Effortful motivation and reward valuation learning deficits are associated with negative symptoms and impaired cognition in schizophrenia (SZ) patients. Whereas clinical assessments of motivation and reward value typically rely upon clinician ratings or self-report scales, behavioral measures often confound these constructs. Simple reverse-translated behavioral tasks that independently quantify motivation and reward valuation—which could then be linked to cognition—may facilitate the development of pro-cognitive therapeutics by bridging the “preclinical-to-clinical” gap. This study determined whether novel behavioral measures of effortful motivation and reward valuation are associated with impaired cognition in SZ patients (n=36). Patients completed the Progressive Ratio Breakpoint task (PRBT; physical effort motivation) and the Probabilistic Learning Task (PLT; reward learning/valuation) in conjunction with the MATRICS Consensus Cognitive Battery (MCCB). SZ patients exhibited statistically significant deficits in global cognition and all individual MCCB subdomains. Significant correlations were observed between PRBT and MCCB global cognition (r=0.52), speed of processing (r=0.56) and attention vigilance (r=0.48) subdomains, but not with PLT or clinical symptoms. Results indicate that effort and reward learning deficits are dissociable targets that can improve our understanding of cognitive impairments associated among patients with SZ. More importantly, the results support the long-standing notion that the measurement of cognitive impairments in SZ is highly linked to a willingness to expend effort. The availability of a PRBT designed for use in both rodents and humans could improve our understanding of the nature of cognitive impairments in neuropsychiatric disorders and accelerate the development of novel pro-cognitive therapeutics.

Social Cognition in Schizophrenia Patients and Their First-Degree Relatives.

Social cognition is a person's ability to configure the designs of relationships between themselves and others and to use these designs to guide social behaviors in a flexible manner. The models that are the most studied and describe social cognition are the theory of mind (ToM) and emotion recognition. This study was aimed to detect ToM and emotion recognition disorders in schizophrenia patients and their first-degree relatives. Thirty schizophrenia patients in remission, the first-degree relatives of schizophrenia patients (n=30), and 30 healthy volunteers who were paired with the patients in terms of age and duration of education were included in the study. The Positive and Negative Symptom Scale (PANSS), Dokuz-Eylül Theory of Mind Scale (DEToMS), Reading the Mind in the Eyes test, Facial Emotion Identification Test (FEIT), and Facial Emotion Discrimination Test (FEDT) were performed by the patients participating in this study. ToM and emotion recognition were found to be defective in the schizophrenia patients and their relatives. The performances of ToM and emotion recognition were ranked as the schizophrenia group, family group, and control group, from the worst to the best. The schizophrenia group showed poor performance in all sub-components except irony. In the family group, the empathy subcomponent showed similar performance with the control group, whereas the subcomponents of the second-order false belief, metaphor, and faux pas tests showed similar performance with the patient group. There were differences among the three groups in the first-order false belief subscale as well as the total DEToMS. The patient and family groups showed the poorest performances, whereas the control group showed the best performance. The detection of ToM and emotion recognition disorders in the remission period, regardless of the attack period and asymptomatic first-degree relatives, may support the view that the period of schizophrenia is an independent continuous variable.

Heritability of Neuropsychological Measures in Schizophrenia and Nonpsychiatric Populations: A Systematic Review and Meta-analysis.

Schizophrenia is characterized by neuropsychological deficits across many cognitive domains. Cognitive phenotypes with high heritability and genetic overlap with schizophrenia liability can help elucidate the mechanisms leading from genes to psychopathology. We performed a meta-analysis of 170 published twin and family heritability studies of >800 000 nonpsychiatric and schizophrenia subjects to accurately estimate heritability across many neuropsychological tests and cognitive domains. The proportion of total variance of each phenotype due to additive genetic effects (A), shared environment (C), and unshared environment and error (E), was calculated by averaging A, C, and E estimates across studies and weighting by sample size. Heritability ranged across phenotypes, likely due to differences in genetic and environmental effects, with the highest heritability for General Cognitive Ability (32%-67%), Verbal Ability (43%-72%), Visuospatial Ability (20%-80%), and Attention/Processing Speed (28%-74%), while the lowest heritability was observed for Executive Function (20%-40%). These results confirm that many cognitive phenotypes are under strong genetic influences. Heritability estimates were comparable in nonpsychiatric and schizophrenia samples, suggesting that environmental factors and illness-related moderators (eg, medication) do not substantially decrease heritability in schizophrenia samples, and that genetic studies in schizophrenia samples are informative for elucidating the genetic basis of cognitive deficits. Substantial genetic overlap between cognitive phenotypes and schizophrenia liability (average rg = -.58) in twin studies supports partially shared genetic etiology. It will be important to conduct comparative studies in well-powered samples to determine whether the same or different genes and genetic variants influence cognition in schizophrenia patients and the general population.