Deconstructing the familiality of the emotive component of psychotic experiences in the general population

OBJECTIVE: Genetic and environmental influences on variation in distress associated with subclinical psychotic experiences were examined. METHOD: A total of 289 twin pairs filled in the Community Assessment of Psychic Experiences, a self-report instrument assessing subclinical positive and negative psychotic experiences and associated distress (distresspos and distressneg). Using structural equation modelling, univariate and bivariate models were fitted. RESULTS: Univariate model fitting showed genetic and non-shared environmental influences on both distresspos and distressneg. Bivariate model fitting showed that 52% of the correlation between the two phenotypes (r=0.46) was because of shared genes and that non-shared environmental factors accounted for 48% of the correlation. CONCLUSION: Liability to psychosis not only refers to the development of psychosis per se, but also to the liability to develop dysfunctional emotional appraisals. The emotive component of psychosis liability involves genetic transmission of a general, non-symptom-specific distress factor that may be a target for molecular genetic research.     

Child psychopathology and lower cognitive ability: a general population twin study of the causes of association

Previous work has demonstrated associations between lower cognitive ability and childhood and adult non-psychotic psychopathology. As both cognitive ability (CA) and child psychopathology (CP) are influenced by genetic factors, one explanation for the association is that they are the pleiotropic manifestations of the same underlying genetic factors. The present paper examines three possible causes of the association: additive genetic factors, common environmental factors and individual-specific environmental factors. Three hundred and seventy-six twin pairs from the East Flanders Prospective Twin Survey were examined with the Child Behaviour Checklist and the Wechsler Intelligence Scale for Children-Revised. The cross-twin within-variable, within-twin cross-variable and cross-twin cross-variable correlations were calculated. Using structural equation modelling, bivariate models were fitted. The best fitting model was chosen, based on likelihood and parsimony. The observed phenotypic correlation between CP and CA was -0.19 (95% CI: -0.09, -0.27), with genetic factors accounting for about 84% of the observed correlation. Bivariate model fitting quantified the genetic correlation between CP and CA at -0.27 (95% CI: -0.12, -0.42) and the individual-specific environmental correlation at -0.17 (95% CI: -0.03, -0.31). In children, three different genetic factors may exist: one that solely affects the liability to CP, one that has only an effect on CA and one that influences both CP and CA. While individual-specific environmental factors can influence the liability to both traits, our results suggest that most of the environmental factors that increase the risk of CP do not influence CA and vice versa.     

Genetic and environmental bases of the interplay between magical ideation and personality

Sub-threshold psychotic symptoms are quite commonly present in general population. Among these, Magical Ideation (MI) has been proved to be a valid predictor of psychosis. However, the genetic and environmental influences on the interplay between MI and personality have not fully been explored. A total of 534 adult twins from the population-based Italian Twin Register were assessed for MI using the MI Scale (MIS) and for personality with the temperament and character inventory (TCI). A Multivariate Cholesky model was applied with Mx statistical program. The best-fitting model showed that additive genetic and unshared environmental factors explain approximately the same proportion of variance in MI, whereas a less strong genetic influence on personality traits emerged. Relevant correlations between MI and specific personality traits (novelty seeking, cooperativeness, self-directedness, self-transcendence) were found, suggesting shared influences for MI and these traits. Both genetic and environmental factors explained these correlations, with genetic factors playing a predominant role. Moderate-to-substantial genetic effects on MI and personality were found. Shared genetic and environmental effects underlie the phenotypic correlation between MI (psychosis-proneness) and personality traits, i.e. self-directedness (negative association) and self-transcendence (positive association), potentially representing predictive markers of psychosis liability related to schizotypy and personality.     

儿童品行问题与注意缺陷多动行为问题相互关系的双生子研究

目的 研究遗传因素、共享环境因素和非共享环境因素在儿童注意缺陷多动行为问题和品行问题相互关系中的作用.方法 采用困难和长处量表中的父母评定的注意缺陷多动(HYPER)和品行问题(CONO)分量表分作为定量表型,对西南双生子库中的140对双生子,采用表型的单因素和二因素结构方程模型,基于模型的似然值和拟合度寻找最优模型,分析遗传因素和环境因素的影响.结果 (1)同卵双生子注意缺陷多动行为问题与品行问题的相关性(r=0.55)明显高于异卵双生子(r=0.12);(2)注意缺陷多动行为问题与品行问题的表型相关性为0.44(P=0.00);(3)儿童注意缺陷多动行为问题与品行问题的相关性主要由遗传因素导致,遗传因素在品行问题与注意缺陷多动行为问题表型相关性中的贡献占70%,非共享环境因素占30%.结论 遗传因素对注意缺陷多动行为问题和品行问题的发生具有重要作用,遗传因素包括单纯影响注意缺陷多动行为问题的遗传因素、单纯影响品行障碍的遗传因素和对二者同时发生作用的遗传因素.大部分作用于注意缺陷多动行为问题的环境因素不会导致品行问题的发生.     

Cortical Gyrification,Psychotic-Like Experiences,and Cognitive Performance in Nonclinical Subjects

BackgroundPsychotic-like experiences (PLE) are present in nonclinical populations, yet their association with brain structural variation, especially markers of early neurodevelopment, is poorly understood. We tested the hypothesis that cortical surface gyrification, a putative marker of early brain development, is associated with PLE in healthy subjects. MethodsWe analyzed gyrification from 3 Tesla MRI scans (using CAT12 software) and PLE (positive, negative, and depressive symptom dimensions derived from the Community Assessment of Psychic Experiences, CAPE) in 103 healthy participants (49 females, mean age 29.13 ± 9.37 years). A subsample of 63 individuals completed tasks from the Wechsler Adult Intelligence Scale and Controlled Oral Word Association Test. Estimated IQ and a composite neuropsychological score were used to explore mediation pathways via cognition. ResultsPositive PLE distress was negatively associated with gyrification of the left precuneus. PLE depression dimension showed a negative association with gyrification in the right supramarginal and temporal region. There was no significant mediating effect of cognition on these associations. ConclusionOur results support a neurobiological psychosis spectrum, for the first time linking an early developmental imaging marker (rather than volume) to dimensional subclinical psychotic symptoms. While schizophrenia risk, neurodevelopment, and cognitive function might share genetic risk factors, additional mediation analyses did not confirm a mediating effect of cognition on the gyrification-psychopathology correlation.     

Investigating the Association Between Autistic-Like and Internalizing Traits in a Community-Based Twin Sample

ObjectivesRecent research has suggested that children with autistic spectrum disorders often experience comorbid symptoms of anxiety and depression. However, despite this overlap, no quantitative genetic studies have addressed the phenotypic overlap and the etiologic association between internalizing and autistic-like traits within the general population. This study aimed to investigate the phenotypic and etiologic relation between internalizing and autistic-like traits using a community-based twin sample.MethodWe investigated the co-occurrence of these traits in a population-based sample of 3,233 twin pairs aged 8 to 9 years, using both parent- and teacher-report questionnaires. Bivariate structural equation modeling techniques were used to determine the extent to which internalizing and autistic-like traits shared common genetic and environmental influences.ResultsOur results showed that there was a modest phenotypic correlation (r = 0.26-0.29) between autistic-like and internalizing traits. The traits were both substantially heritable but were largely independent with regard to their genetic influences (r_G = 0.12-0.19). Shared environmental influences were modest but were largely common to both traits. Similar results were found using both parent- and teacher-reported data.ConclusionsInternalizing and autistic-like traits showed moderate phenotypic overlap within the general population. This association was explained in small part by shared genetic factors, but the results suggested that most genetic influences were specific to either internalizing traits or autistic traits. Given these findings, we discuss the potential mechanisms that may underlie the relation between these traits. J. Am. Acad. Child Adolesc. Psychiatry, 2009;48(6):618-627.     

Neurocognitive performance and functional disability in the psychosis prodrome

OBJECTIVE: This study evaluates the pattern of neuropsychological deficits and their association with clinical symptomatology and social functioning in individuals identified as ultra-high-risk (UHR) for psychosis. METHODS: A sample of 45 UHR individuals was identified using the Structured Interview for Prodromal Syndromes (SIPS) from consecutive referrals to the Staglin Music Festival Center for the Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants were administered a neurocognitive test battery, as well as measures of global (Strauss-Carpenter Outcome Scale) and social functioning (UCLA Social Attainment Survey). RESULTS: Participants showed significant deficits in speed of processing, verbal learning and memory, and motor speed. Poorer verbal learning and memory performance was significantly associated with poorer social functioning, and there was a trend for poorer performance on reasoning and problem solving to be associated with poorer global functioning. Verbal memory independently predicted social functioning over and above severity of negative symptoms. Cognitive deficits were not associated with severity of clinical symptomatology. CONCLUSIONS: Despite the absence of fully psychotic symptoms, UHR individuals experience significant cognitive deficits, particularly on tasks requiring speeded information-processing and efficient recall from memory, and these deficits appear to be associated with functional disability in a manner parallel to that observed in patients with established psychotic illness.     

Common and specific genetic influences on aggressive and nonaggressive conduct disorder domains

OBJECTIVE: To explore the genetic and environmental influences on DSM-IV conduct disorder (CD) aggressive and nonaggressive subscales, taking into account age and sex differences. METHOD: A community sample of 1,100 twin pairs (ages 11-18) was interviewed using the Diagnostic Interview Schedule for Children. Bivariate analyses, using variable threshold models accounting for age and sex differences, were used to determine the extent to which the genetic and environmental influences on aggressive and nonaggressive CD domains are shared or unique. RESULTS: The phenotypic correlation between aggressive and nonaggressive CD domains was 0.32. The most parsimonious bivariate model included additive genetic effects and nonshared environmental effects only (AE model). CONCLUSIONS: The results of behavior genetic model fitting suggest that the DSM-IV CD domains are influenced by unique genetic and environmental factors, but also share some common genetic and environmental influences. A large percentage of the covariation (61%) is caused by genetic factors. These results are consistent with a previous report on the bivariate heritability of aggressive and nonaggressive antisocial behavior, but extend the findings to DSM-IV domains.     

Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder.

BACKGROUND: Neurocognitive deficits associated with attention-deficit/hyperactivity disorder (ADHD) might be useful intermediate endophenotypes for determining specific genetic pathways that contribute to ADHD. METHODS: This study administered 17 measures from prominent neuropsychological theories of ADHD (executive function, processing speed, arousal regulation and, motivation/delay aversion) in dizygotic (DZ) twin pairs discordant for ADHD and control twin pairs (ages 8-18 years) to compare performance between twins affected with ADHD (n = 266), their unaffected co-twins (n = 228), and control children from twin pairs without ADHD or learning difficulties (n = 332). RESULTS: The ADHD subjects show significant impairment on executive function, processing speed, and response variability measures compared with control subjects. Unaffected co-twins of ADHD subjects are significantly impaired on nearly all the same measures as their ADHD siblings, even when subclinical symptoms of ADHD are controlled. CONCLUSIONS: Executive function, processing speed, and response variability deficits might be useful endophenotypes for genetic studies of ADHD.     

Investigation of shared genetic effects for psychotic and obsessive symptoms in young adult twins

Genetic and environmental architecture of psychotic and obsessive symptoms are not completely elucidated. This study estimated for these symptoms (i) the genetic and environmental components, (ii) the within-individual association, and (iii) the extent to which this association originates from common genetic and environmental factors. Young adult twins (N = 701) from the population-based Italian Twin Register were assessed for psychotic and obsessive-compulsive symptoms by using the Symptom Check List (SCL-90). Multivariate Cholesky models were fitted by the Mx statistical program. No previous study used this design to examine the same dimensions. The best-fitting model included additive genetic and nonshared environmental components, each accounting for about half of total variance in the symptoms. Genetic influences on the different symptoms overlapped considerably (r_g = 0.81 to 0.99). Phenotypic correlations of psychotic symptoms and of psychotic with obsessive symptoms were high (r = 0.61 to 0.76), with 53% to 69% explained by shared genetic effects. This study shows substantial genetic influence on psychotic and obsessive symptoms, and indicates that their co-occurrence may be due to genetic factors to a greater extent than to environmental effects. These results encourage the search for genetic and environmental factors underlying the covariance between different psychotic traits as well as between psychotic and obsessive traits.     

Neuropsychological functioning in first-break, never-medicated adolescents with psychosis

The purpose of the current study was to examine neuropsychological functioning in a group of never-medicated first-break adolescents with psychosis. It is the first report of cognition in a sample of adolescents with psychosis in which all patients were drug-naive. Twenty-nine adolescent patients (mean age = 16.07; SD = 2.00; 15 male and 14 female patients) experiencing their first psychotic episode and 17 age-matched and sex-matched normal volunteers (mean age = 16.88; SD = 2.39; 9 male and 8 female subjects) were recruited and assessed with a neuropsychological battery. Measures of attention, memory, language, executive functioning, perceptual motor processing, and motor speed were obtained. Psychiatric symptomatology, estimated verbal IQ, and parental socioeconomic status were also determined. Patients with psychosis were significantly more impaired than normal volunteers; effect sizes were greatest in the areas of executive functioning, attention, and memory, and significantly smaller in areas of language, perceptual motor processing, and motor speed. The pattern was not altered when differences in verbal IQ and parental socioeconomic status were controlled. Sex and age interactions indicated that younger male patients were particularly impaired. The findings demonstrate neuropsychological deficits in adolescents with psychosis and suggest that cognitive deficits are core symptoms in psychotic disorders.     

Brain morphology and information processing at the completion of chemotherapy-only treatment for pediatric acute lymphoblastic leukemia

ABSTRACT

Background: Approximately 50% of survivors of childhood acute lymphoblastic leukemia (ALL) demonstrate cognitive impairments. However, the trajectory of change and contributing neuropathology is unclear, limiting our ability to tailor intervention content and timing. This study aimed to explore information processing abilities and brain morphology early post-treatment for pediatric ALL.

Procedure: Twenty-one children at the end of ALL treatment and 18 controls underwent neuropsychological assessment. A subset also completed structural magnetic resonance imaging.

Results: A principal component analysis generated two cognitive factors: information processing capacity and information processing speed. Compared to control group, the ALL group displayed deficits in capacity, but not speed. No group differences were identified in morphology. No relationship was identified between capacity or speed and morphology.

Conclusion: Early cognitive intervention should target information processing abilities using a system-wide approach. Future studies should employ alternative imaging techniques sensitive to white-matter microstructure when exploring pathology underlying information processing deficits.     

Déterminants génétiques des idées délirantes

The use of symptom dimensions of schizophrenia (positive, negative and disorganised) as quantitative phenotypes has been proposed as a mean to reduce the heterogeneity of schizophrenia and facilitate genetic research. The aim of the present study was to summarize the results of studies investigating the genetic background of the positive dimension. Several studies suggest a genetic contribution to the reality distortion dimension, but at a lesser degree than for the disorganised dimension. Few studies have investigated relationships between genetic factors and reality distortion dimension. However, some works suggest that genetic variation in DISC1 and COMT may be associated with delusions and hallucinations. As specific cognitive deficits have been suggested as explanations for the positive dimension, new strategies should focused on their correlations with genetic factors. For example, source-monitoring deficits (a presumed cognitive marker for increased proneness to psychotic symptoms) can be observed in subjects with 22q11 deletion syndrome, a region containing candidate genes such as Catechol-O-Methyltransferase (COMT) gene.     

A six-factor model of cognition in schizophrenia and related psychotic disorders: relationships with clinical symptoms and functional capacity

Confirmatory factor analysis was used to examine a proposed factor structure of a comprehensive neuropsychological battery used to study patients with schizophrenia and related psychotic disorders (n = 209). An a priori six-factor model and five nested models were evaluated successively, using maximum likelihood confirmatory factor analysis. In all multifactor models, the factors were significantly intercorrelated. A six-factor model with two pairs of correlated errors fit the neuropsychological data significantly better than competing models with fewer factors. The six factors included verbal crystallized, attention/working memory, verbal episodic memory, speed of information processing, visual episodic memory, and reasoning/problem solving. Severity of negative symptoms was significantly associated with worse performance on attention/working memory and verbal crystallized factors, but positive symptoms, depression, and a summary measure of psychopathology were not significantly related to neuropsychological performance. Impairment on a performance-based measure of functional capacity was significantly related to all neuropsychological factors. A simultaneous confirmatory factor analysis using the original sample and a group of healthy subjects (n = 131) demonstrated that the six-factor model of cognition was generalizable and applied equally well to both groups.     

The assessment of neuropsychological functioning in schizophrenia

Overwhelming evidence suggests that compromised neuropsychological function is frequently observed in schizophrenia. The neuropsychological profile is typically characterized by prominent specific deficits in memory and learning, working memory, executive functions, attention, and processing speed, which are evident on a background of a generalized cognitive deficit. This paper provides a review of studies of neuropsychological functioning in schizophrenia. The main cognitive ability areas affected in schizophrenia are described, and the degree of impairment in each ability area as found in studies of schizophrenia patients is summarized, based on meta-analytic findings. Recent studies that have compared neuropsychological functioning across psychotic disorders are presented, and finally, neuropsychological assessment batteries specifically developed for schizophrenia are introduced.     

Altered transfer of visual motion information to parietal association cortex in untreated first-episode psychosis: implications for pursuit eye tracking

Visual motion processing and its use for pursuit eye movement control represent a valuable model for studying the use of sensory input for action planning. In psychotic disorders, alterations of visual motion perception have been suggested to cause pursuit eye tracking deficits. We evaluated this system in functional neuroimaging studies of untreated first-episode schizophrenia (N=24), psychotic bipolar disorder patients (N=13) and healthy controls (N=20). During a passive visual motion processing task, both patient groups showed reduced activation in the posterior parietal projection fields of motion-sensitive extrastriate area V5, but not in V5 itself. This suggests reduced bottom-up transfer of visual motion information from extrastriate cortex to perceptual systems in parietal association cortex. During active pursuit, activation was enhanced in anterior intraparietal sulcus and insula in both patient groups, and in dorsolateral prefrontal cortex and dorsomedial thalamus in schizophrenia patients. This may result from increased demands on sensorimotor systems for pursuit control due to the limited availability of perceptual motion information about target speed and tracking error. Visual motion information transfer deficits to higher-level association cortex may contribute to well-established pursuit tracking abnormalities, and perhaps to a wider array of alterations in perception and action planning in psychotic disorders.     

Effects of information processing speed on learning,memory, and executive functioning in people living with HIV/AIDS

Introduction: It is unclear whether or to what degree literacy, aging, and other neurologic abnormalities relate to cognitive deficits among people living with HIV/AIDS in the combined antiretroviral therapy (CART) era. The primary aim of this study was to simultaneously examine the association of age, HIV-associated motor abnormalities, major depressive disorder, and reading level with information processing speed, learning, memory, and executive functions, and to determine whether processing speed mediated any of the relationships between cognitive and noncognitive variables. Method: Participants were 186 racially and ethnically diverse men and women living with HIV/AIDS who underwent comprehensive neurological, neuropsychological, and medical evaluations. Structural equation modeling was utilized to assess the extent to which information processing speed mediated the relationship between age, motor abnormalities, major depressive disorder, and reading level with other cognitive abilities. Results: Age, motor dysfunction, reading level, and current major depressive disorder were all significantly associated with information processing speed. Information processing speed fully mediated the effects of age on learning, memory, and executive functioning and partially mediated the effect of major depressive disorder on learning and memory. The effect of motor dysfunction on learning and memory was fully mediated by processing speed. Conclusions: These findings provide support for information processing speed as a primary deficit, which may account, at least in part, for many of the other cognitive abnormalities recognized in complex HIV/AIDS populations. The association of age and information processing speed may account for HIV/aging synergies in the generation of CART-era cognitive abnormalities.     

Disorganization and cognitive impairment in schizophrenia: independent symptom dimensions?

Cognitive deficits are increasingly considered as essential in schizophrenic disorders. Positive symptoms and cognitive deficits have been found to be independent, whereas negative symptoms show only weak correlations to cognitive impairment. However, the relationship to a third symptom dimension, disorganization, is yet unclear. In a sample of n = 151 schizophrenia inpatients (DSM-IV/SCID) we assessed cognitive impairment using a comprehensive neuropsychological test battery and symptoms of schizophrenia applying the Positive and Negative Syndrome Scale (PANSS). Factor analyses resulted in three neuropsychological (attention, memory, abstraction) and five symptom factor scores (negative, impulsiveness, positive, disorganization, depression). The disorganization factor did not correlate significantly with any of the neuropsychological factor scores. Even after controlling for different demographic and clinical variables partial correlation coefficients did not reach a significant level. Thus, we could not confirm the previously reported associations between disorganization and measures of cognitive impairment. Despite a considerable conceptual overlap between interview based symptom ratings and classic neuropsychological tests the empirical association is limited. Our results suggest that disorganization and cognitive impairment represent different symptom dimensions.     

Neuropsychological impairment and psychosis in mania

Deficits involving executive function, working memory, speed of information processing, and new learning occur in many people with mania. Factors that predict impairment remain poorly understood, but there are indications that psychotic features may correspond with increased risk of neurocognitive dysfunction during manic episodes. The current study examined neuropsychological function in 40 inpatients with bipolar I mania, 24 of whom presented with psychotic features. Compared to a control group, the inpatients showed worse executive function, speed of information processing, new learning, and dexterity. Nonetheless, presence of psychotic features failed to distinguish the inpatients with mania. Thus, psychotic features do not appear to increase neurobehavioral morbidity in people with mania, but presence of mania clearly corresponded with neurobehavioral dysfunction. Implications of these data for clinical practice and our understanding of bipolar disorder are discussed.     

Selective deficits in semantic verbal fluency in patients with a first affective episode with psychotic symptoms and a positive history of mania

Objectives:  Neurocognitive dysfunction is likely to represent a trait characteristic of bipolar disorder, but the extent to which it comprises 'core' deficits as opposed to those secondary to longstanding illness or intellectual decline is unclear. We investigated neuropsychological performance in an epidemiologically derived sample of patients with a first affective episode with psychotic symptoms and a positive history of mania, compared to community controls.
Methods:  Using a nested case-control, population-based study, measures of episodic and working memory, executive function, processing speed, and visual-spatial perception were compared between 35 patients with a first affective episode with psychotic symptoms and a positive history of mania, and 274 community controls, as well as a subgroup of 105 controls matched on current IQ ('good' versus 'poor') and IQ trajectory ('stable', 'declined', or 'improved') with the patients (three controls per case).
Results:  Compared to the extended control sample, probands showed a suggestive deficit in short-term verbal recall, and a significant deficit in semantic fluency. Only the latter was detectable in the comparison with the IQ-matched controls. All other neurocognitive domains showed intact performance or nonsignificant deficits of small effect sizes compared to both control groups. Semantic fluency showed no association with symptoms or duration of untreated illness.
Conclusions:  Patients with a first affective episode with psychotic symptoms and a positive history of mania show an isolated, selective deficit in semantic verbal fluency, against a background of generally preserved neurocognitive function. This pattern seems to contrast with the more widespread neuropsychological dysfunction seen in schizophrenia.