Association between reduced extraversion and right posterior fusiform gyrus gray matter reduction in chronic schizophrenia

OBJECTIVE: The authors examined the association between volume of the fusiform gyrus, a region involved in face processing, and the personality trait of extraversion in patients with schizophrenia. METHOD: Male patients (N=24) and age-matched male comparison subjects (N=26) completed NEO Five-Factor Inventory personality measures of extraversion and underwent high-spatial-resolution magnetic resonance imaging of anterior and posterior fusiform gyrus gray matter. RESULTS: Low extraversion scores were significantly correlated with gray matter volume reductions in the right posterior fusiform gyrus for patients but not comparison subjects. CONCLUSIONS: Reduced right posterior fusiform gyrus volume may contribute to disease-related social disturbances, characterized by both low extraversion and reduced sensitivity to human faces.     

Personality dimensions in schizophrenia: associations with symptoms and coping

While individual differences in personality exist among persons with schizophrenia and predate the onset of illness, less is known about their relationship to outcome. This study examined whether levels of three personality dimensions-neuroticism, extraversion, and agreeableness-are associated with symptomatology and coping in persons with schizophrenia. Symptom, personality, and coping measures were obtained for 59 participants with schizophrenia. Personality and coping measures were obtained for 17 persons in a community comparison group. Relative to the community comparison groups, participants with schizophrenia had higher levels of neuroticism, lower levels of extraversion and agreeableness, and tended to employ more avoidant styles of coping. Participants with schizophrenia who had higher levels of neuroticism had greater positive and emotional discomfort symptoms and greater preferences for avoidant coping strategies. Participants with schizophrenia who had higher levels of agreeableness had lower levels of positive and excitement symptoms. No links were found between extraversion and outcome measures. Implications for understanding how personality may affect outcome are discussed.     

Personality dimensions and neuropsychological performance in first-degree relatives of patients with schizophrenia and by affective psychosis

Several studies have found a significant increase in the prevalence of some personality disorders in the first-degree relatives of patients with schizophrenia; other studies have found subtle neuropsychological deficits in these relatives. However, little is known about the specificity of the personality traits reported or about the relationship between these traits and the neuropsychological deficits. One hundred first-degree relatives of patients with schizophrenia (AS) and 88 first-degree relatives of affective psychotic (APA) patients completed the Eysenck Personality Questionnaire which measures extraversion, neuroticism, psychoticism. They were also administered the National Adult Reading Test (NART), the Trail Making Test (TMT) and a Verbal Fluency Test (VFT). In the AS group, the male relatives scored significantly higher on the psychoticism scale than the male relatives in the APA group. There were no significant differences in personality between female relatives of the 2 patients groups. In the AS group, the NART scores were superior when the psychoticism scores were lower and the TMT performance was better when the extraversion scores were higher. These results seem to indicate some specificity as well as sex differences of the psychoticism dimension. Moreover, the relationship between the personality dimensions and the neuropsychological performance could indicate that psychoticism increases vulnerability to schizophrenia whereas extraversion decreases it.     

Neuropsychological performance in schizotypal personality disorder: importance of working memory

BACKGROUND: Cognitive deficits consistently have been reported in schizophrenia patients and in patients with schizotypal personality disorder. For this study, the authors wanted to identify which of the domains of cognitive impairment represent "core" deficits of schizophrenia, comparing subjects with schizotypal personality disorder to two comparison groups: healthy volunteers and patients with personality disorders unrelated to schizophrenia. METHOD: Three groups completed a neuropsychological battery: patients with DSM-III-R schizotypal personality disorder (N=82); patients with DSM-III-R personality disorders unrelated to schizophrenia (i.e., a personality disorder other than schizotypal, schizoid, or paranoid [N=44]); and healthy volunteers (N=63). The battery included the California Verbal Learning Test, Trailmaking Test parts A and B, the Dot test of working memory, the Stroop Color and Word Test, the Paced Auditory Serial Addition Test, the WMS visual reproduction test, and the WAIS-R vocabulary and block design. RESULTS: Normative standards for performance that controlled for age, gender, and education were created from the scores of the healthy volunteers. Overall, schizotypal personality disorder patients performed significantly worse than the healthy volunteers and those with personality disorders unrelated to schizophrenia. Specifically, patients with schizotypal personality disorder demonstrated impaired performance on the Paced Auditory Serial Addition Test, WMS visual reproduction test, Dot test, and California Verbal Learning Test. In addition, in a regression analysis, performance on the Paced Auditory Serial Addition Test demonstrated the largest effect size. Indeed, it accounted for unique variance above and beyond all other cognitive measures, since controlling for Paced Auditory Serial Addition Test performance abolished group differences across all other measures. CONCLUSIONS: Patients with schizotypal personality disorder demonstrated moderate cognitive impairment compared with healthy volunteers (significant for seven out of 11 measures). These differences reached statistical significance for tasks of working memory, episodic memory, and delayed recall. Working memory performance accounted for the group differences. This study supports the view that working memory represents a core deficit of schizophrenia spectrum disorders.     

Personality dimensions in schizophrenia: associations with symptoms and coping concurrently and 12 months later

BACKGROUND: Research has indicated that stable individual differences in personality exist among persons with schizophrenia, and that they likely predate the onset of illness. Less is known about whether individual differences in personality are related to levels of psychopathology and function. SAMPLING AND METHODS: This study tested the hypotheses that levels of neuroticism, extraversion and agreeableness are associated with symptomatology and coping in schizophrenia both concurrently and as measured 12 months later for 46 participants with schizophrenia or schizoaffective disorder. Baseline assessments were conducted, which included measurements of the personality dimensions of neuroticism, extraversion and agreeableness measured using the NEO, coping preferences using the Ways of Coping Questionnaire and symptoms using the Positive and Negative Syndrome Scale. The symptom and coping measures were repeated 12 months after the date of the baseline assessment. RESULTS: Univariate correlations comparing baseline assessments suggested that higher neuroticism and lower extraversion were concurrently linked to more emotional discomfort and avoidant coping. Agreeableness was linked only to positive symptoms. Correlations controlling for baseline levels revealed greater levels of neuroticism at baseline, predicted a preference for resigning when under stress and higher emotional discomfort 12 months later. Lesser levels of agreeableness continued to predict greater positive symptoms 12 months later. No long-term associations were found between coping and symptoms at 12 months with levels of extraversion. CONCLUSIONS: The results suggest individual differences in personality are associated with psychopathology in schizophrenia and may affect function over time. More research is needed with broader samples and with more frequent follow-up assessments.     

Elevated noise power in gamma band related to negative symptoms and memory deficit in schizophrenia

Patients with schizophrenia have low extraversion and high neuroticism. These personality traits affect the everyday life of patients with schizophrenia, making it important to investigate neurobiological basis of personality traits. In healthy people, extraversion is associated with hemodynamic responses in the amygdala and electrophysiological brain activity such as event-related potential and event-related desynchronization during emotional face processing. Patients with schizophrenia show abnormal neural activity during emotional face processing, such as an N170 amplitude reduction. However, few studies to date have reported an association between personality traits and neural activity during emotional face processing in schizophrenia. In the present study, we examined N170 during emotional face processing, and association with personality traits in patients with schizophrenia. Fifteen male patients with chronic schizophrenia and 15 healthy male subjects participated in this study. Patients with schizophrenia had reduced N170 amplitudes (p=0.007). While healthy subjects had increased N170 amplitudes in response to emotional faces compared with neutral faces (p=0.003), patients with schizophrenia showed no difference in N170 amplitudes between emotional and neutral faces (p=0.60). Reduced N170 amplitude in response to neutral faces was correlated with low extraversion scores in patients with schizophrenia (r(s)=-0.69, p=0.005). The abnormal N170 and its association with extraversion in schizophrenia were found at the right rather than the left posterior temporal electrode. An abnormal N170 in schizophrenia may reflect impairments in the structural encoding of emotional faces, and indiscrimination between emotional and neutral faces at this stage of information processing. The association between abnormal N170 amplitudes and extraversion suggests that abnormal neural activity in the early stages of emotional face processing may underlie low extraversion characteristic of schizophrenia.     

Cognitive dimensions in first-episode schizophrenia spectrum disorders

BACKGROUND: The severity and pattern of cognitive deficits in epidemiological cohorts of patients with first-episode schizophrenia spectrum disorders still remains unclear. We aimed to characterize the basic cognitive functioning of a representative sample of patients with a first-episode schizophrenia spectrum disorders. METHOD: One hundred thirty-one patients experiencing first-episode psychosis and 28 healthy volunteers were administered a comprehensive neuropsychological evaluation. To reduce the number of cognitive test measures into meaningful cognitive dimensions, before analyzing differences between patient and healthy volunteer samples, exploratory factor analysis was carried out on data collected in patients group. The method of extraction was Principal Components Analysis with oblique rotation. RESULTS: An eight-factor model including verbal learning/memory, verbal comprehensive abilities, speed of processing/executive functioning, motor dexterity, motor speed, sustained attention, and impulsivity emerged. A significant below average performance in all cognitive dimensions, except impulsivity, was found. Patient's performance in speed of processing/executive functioning, motor dexterity and sustained attention dimensions exceeded one standard deviation below healthy comparison subjects. CONCLUSIONS: At early stages of the illness, patients display a marked impairment in several functionally relevant cognitive domains.     

Neuropsychological dysfunction in antipsychotic-naive first-episode unipolar psychotic depression

OBJECTIVE: The profile of neuropsychological impairment associated with unipolar psychotic depression remains unclear. The authors used a neuropsychological test battery to characterize the neuropsychiatric profile of patients with unipolar psychotic depression, relative to that of patients with nonpsychotic unipolar depression, patients with schizophrenia, and healthy comparison subjects. METHOD: Study subjects included antipsychotic-naive patients with a first episode of psychotic unipolar depression (N=20), antipsychotic-naive and unmedicated patients with nonpsychotic unipolar depression (N=14), antipsychotic-naive patients with first-episode schizophrenia (N=86), and healthy volunteers (N=81). Groups were matched on age, sex, race, education, parental socioeconomic status, and estimated premorbid intelligence. Psychotic patients were followed clinically for 2 years to confirm diagnosis. All participants completed a standard neuropsychological battery, including tests of general intelligence, executive function, attention, verbal memory, motor skills, and visual-spatial perception. RESULTS: Patients with psychotic depression had a pattern of neuropsychological dysfunction that was similar to but less severe than that of patients with schizophrenia. In contrast, patients with nonpsychotic unipolar depression had a neuropsychological profile that was similar to that of healthy individuals but that included mild dysfunction on tests of attention. Neuropsychological test performance was generally independent of acute clinical symptoms, but some pairwise group differences were attenuated by covariation for symptom severity. CONCLUSIONS: The similar neuropsychological profiles for schizophrenia and psychotic depression suggest that these psychotic disorders may have common pathophysiological features. The dramatic differences in performance between the patients with psychotic depression and those with nonpsychotic depression point to a marked distinction in neurocognitive function associated with the expression of psychosis in depressed patients.     

Personality traits in schizophrenia and related personality disorders

We investigated whether schizophrenia spectrum disorders share common personality characteristics or traits. Participants with a diagnosis of schizophrenia or schizoaffective disorder (SZ) or with a schizophrenia spectrum personality disorder (schizophrenia spectrum PD: schizoid, paranoid, and schizotypal personality disorder) were compared with non-psychiatric control subjects on the five-factor model of personality and the psychosis-proneness scales. On the five-factor personality scales, SZ subjects showed higher levels of neuroticism, and lower levels of openness, agreeableness, extraversion, and conscientiousness than control subjects. Higher scores on openness and lower scores on neuroticism distinguished schizophrenia spectrum PD from SZ. On the psychosis-proneness scales, both PD and SZ participants scored high relative to non-psychiatric control participants on magical ideation and perceptual aberration, while PD participants scored intermediate between non-psychiatric control participants and SZ on social anhedonia. Discriminant analysis indicated that schizophrenia spectrum patients could be distinguished from PDs by more severe social withdrawal and maladjustment, while subjects with PDs could be best distinguished from control subjects on the basis of odd or novel ideation and decreased conscientiousness.     

EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder

OBJECTIVE: The authors tested whether neural synchronization deficits were present in subjects with schizophrenia and schizotypal personality disorder. METHOD: Amplitude-modulated tones were used to evaluate auditory steady-state evoked potential entrainment in a combined group of 21 subjects with schizophrenia or schizoaffective disorder, 11 subjects with schizotypal personality disorder, and 22 nonpsychiatric comparison subjects. RESULTS: The schizophrenia or schizoaffective disorder group exhibited decreased power compared to the schizotypal personality disorder and nonpsychiatric comparison groups. There were no differences between groups in N100 amplitude. CONCLUSIONS: Subjects with schizophrenia but not subjects with schizotypal personality disorder have deficits in steady-state responses to periodic stimuli, despite an intact response to sensory-evoked potentials (N100). These deficits reflect aberrant neural synchronization or resolution and may contribute to disturbed perceptual and cognitive integration in schizophrenia.     

A comparative profile analysis of neuropsychological function in men and women with schizotypal personality disorder

The purpose of this study was to compare the cognitive profiles of men and women with clinically defined schizotypal personality disorder (SPD). We examined the neuropsychological profile of SPD in 26 right-handed females and 31 right-handed males who met DSM-IV criteria for SPD, and matched comparison subjects. Cognitive performance was assessed on measures of abstraction, verbal and spatial intelligence, learning and memory, language, attention, and motor skills. Neuropsychological profiles were constructed by standardizing test scores based on the means and standard deviations of comparison groups matched for sex, age, handedness, ethnicity and parental SES. Overall, SPD subjects showed mild, general decrements in performance in most cognitive domains. However, unlike male SPD subjects, female SPDs did not show relative deficits in verbal learning and abstraction. The results suggest a less severe pattern of cognitive deficits in women with SPD compared to men, consistent with hypotheses of gender differences in cognitive function in schizophrenia.     

Neuropsychological function in subjects with psychotic and affective disorders. Relationship to diagnostic category and duration of illness.

OBJECTIVE: To explore the links between neuropsychological performance, diagnostic category and duration of illness in subjects with psychotic and affective disorders. METHODS: Memory and executive abilities were tested in consecutively admitted patients with schizophrenia (N = 20), other non-schizophrenic psychotic disorders (N = 29), bipolar disorder (N = 33) and major depression (N = 19). RESULTS: Subjects with schizophrenia had poorer global memory performances than subjects with major depression, and poorer delayed verbal memory abilities than those from the other three diagnostic groups. Executive abilities explored by the Stroop test and the Wisconsin Card Sorting Test did not differ between diagnostic groups. Neuropsychological performances were not influenced by previous duration of illness. CONCLUSION: Memory deficits are the most discriminatory cognitive features between subjects with schizophrenia and those with other psychotic or mood disorders. The fact that cognitive deficits are static whatever the diagnostic group indirectly suggests that they may have a neurodevelopmental origin in subjects with schizophrenia, but perhaps also in subjects with other psychotic and mood disorders.     

The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data

The relationship between major depressive disorder (MDD) and bipolar disorder (BD) remains controversial. Previous research has reported differences and similarities in risk factors for MDD and BD, such as predisposing personality traits. For example, high neuroticism is related to both disorders, whereas openness to experience is specific for BD. This study examined the genetic association between personality and MDD and BD by applying polygenic scores for neuroticism, extraversion, openness to experience, agreeableness and conscientiousness to both disorders. Polygenic scores reflect the weighted sum of multiple single-nucleotide polymorphism alleles associated with the trait for an individual and were based on a meta-analysis of genome-wide association studies for personality traits including 13 835 subjects. Polygenic scores were tested for MDD in the combined Genetic Association Information Network (GAIN-MDD) and MDD2000+ samples (N=8921) and for BD in the combined Systematic Treatment Enhancement Program for Bipolar Disorder and Wellcome Trust Case–Control Consortium samples (N=6329) using logistic regression analyses. At the phenotypic level, personality dimensions were associated with MDD and BD. Polygenic neuroticism scores were significantly positively associated with MDD, whereas polygenic extraversion scores were significantly positively associated with BD. The explained variance of MDD and BD, ∼0.1%, was highly comparable to the variance explained by the polygenic personality scores in the corresponding personality traits themselves (between 0.1 and 0.4%). This indicates that the proportions of variance explained in mood disorders are at the upper limit of what could have been expected. This study suggests shared genetic risk factors for neuroticism and MDD on the one hand and for extraversion and BD on the other.     

An evaluation of longitudinal neurocognitive performance among middle-aged and older schizophrenia patients: use of mixed-model analyses

The purpose of this study was to evaluate the trajectory of neuropsychological performance among middle-aged and older patients with schizophrenia using hierarchical linear modeling (HLM). Using the Mattis Dementia Rating Scale (DRS), we assessed cognitive performance of 143 schizophrenia outpatients (Mean age=53.1 years, SD=8.8) and 66 healthy comparison subjects (Mean age=61.8 years, SD=8.8). All participants had DRS data from two or more testing sessions with average intervals between sessions being 15 months (range=6-55). Using HLM, we found cognitive performance to be stable over time in both schizophrenia patients and healthy comparison subjects. Age, gender, ethnicity, and education did not affect trajectories. We also analyzed the data using more traditional statistical approaches to longitudinal data and found similar results. In sum, we found cognitive impairment to be stable over time among outpatients with schizophrenia, regardless of the statistical methodology used to analyze longitudinal data.     

Does Self-perceived Mood Predict More Variance in Cognitive Performance Than Clinician-Rated Symptoms in Schizophrenia?

Symptoms are known to account for a small variance in some cognitive functions in schizophrenia, but the influence of self-perceived mood remains largely unknown. The authors examined the influence of subjective mood states, psychopathology, and depressive symptoms in cognitive performance in a single investigation in schizophrenia. A group of 40 stable medicated patients with schizophrenia (20 men, 20 women) and 30 healthy comparison subjects (15 men, 15 women) were assessed on neurocognitive measures of verbal abilities, attention, executive functioning, language, memory, motor functioning, and information processing. All subjects provided self-ratings of mood prior to cognitive testing. Patients were also rated on psychopathology and depressive symptoms. Patients performed worse than comparison subjects on most cognitive domains. Within the patient group, subjective feelings of depression-dejection, fatigue-inertia, confusion, and tension-anxiety predicted (controlling for symptoms) poor performance on measures of attention, executive function, and verbal memory. In the same group of patients, clinician-rated symptoms of psychopathology and depression predicted significantly poor performance only on tests of motor function. In comparison subjects, vigor related to better, and fatigue and inertia to worse, spatial motor performance. Self-perceived negative mood state may be a better predictor of cognitive deficits than clinician-rated symptoms in chronic schizophrenia patients.     

Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder.

OBJECTIVE: Impaired neuropsychological performance involving abstraction-flexibility, memory, motor function, and attention has frequently been reported in schizophrenia as well as in attention deficit hyperactivity disorder (ADHD). This study represents an attempt to compare groups of adolescents with schizophrenia and ADHD on a comprehensive neuropsychological test battery. Such a comparison affords the opportunity to ascertain differences in the degree, profile, and specificity of impairments. METHOD: The performance of 19 adolescents with schizophrenia, 20 adolescents with ADHD, and 30 normal adolescents on a broad battery of cognitive tests was compared. RESULTS: The schizophrenic group showed the most pronounced deficits on tests of abstraction, visual memory, and motor function in comparison with the subjects with ADHD, while the ADHD subjects had the most pronounced deficits on measures of attention, verbal memory, and learning. CONCLUSIONS: The subjects with schizophrenia appeared to have a more general pattern of brain dysfunction, whereas the impairment of the ADHD subjects seemed to be relatively specific to tests associated with frontal lobe function.     

Personality traits of agreeableness and extraversion are associated with ADH4 variation.

BACKGROUND: Personality traits are associated with substance dependence (SD); genetic factors may influence both. Strong associations between ADH4 variation and SD have been reported. We aimed to investigate the relationship between ADH4 variation and personality traits in the present study. METHODS: We assessed dimensions of the five-factor model of personality in 243 subjects with SD (175 European Americans [EAs] and 68 African Americans [AAs]) and 296 healthy control subjects (256 EAs and 40 AAs). We also genotyped 7 ADH4 markers (spanning the locus) and 38 unlinked ancestry-informative markers in these subjects. The relationships between the diplotypes, alleles, and genotypes at ADH4 and personality traits were examined using multivariate analysis of covariance (MANCOVA), controlling for potential confounders. RESULTS: Generally, SD patients, older individuals, and male subjects scored higher on neuroticism and lower on other personality factors. Personality factors were associated with the diplotypes. The allele A or genotype A/A of single nucleotide polymorphism (SNP)6 (rs1800759 at the gene promoter) was significantly associated with agreeableness scores. There were associations between extraversion and SNP1 (hcv2033010 at the 3' end) and SNP2 (rs1042364 in exon 9) in subjects with higher conscientiousness scores. CONCLUSIONS: The personality traits of agreeableness and extraversion are related to ADH4 polymorphism. Among the ADH4 markers that appear to predispose to certain personality traits, the functional variant rs1800759 (SNP6) in the promoter region is most important. We conclude that personality traits and SD have a partially overlapping genetic basis.     

Longitudinal study of symptoms and cognitive function in chronic schizophrenia

There is conflicting evidence of a relationship between changes in symptoms and cognitive functioning in schizophrenia. This study investigated longitudinal changes in psychopathology and cognitive functioning in chronic schizophrenia utilising three different dimensional models of symptomatology. Sixty-two patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder were examined on two occasions over a period of 6 months for symptom improvement, measured by Positive and Negative Syndrome Scale (PANSS) [Kay et al., Schizophr. Bull. 13 (1987) 261]. Participants also completed a comprehensive battery of neuropsychological tasks designed to assess attention, verbal and non-verbal memory, psychomotor processing and executive/frontal functioning on both occasions. Twenty-five control subjects were assessed for comparison purposes. Severity of negative symptoms predicted poor neuropsychological performance on IQ, verbal fluency and memory measures at occasion one. However, using regression analyses, significant improvements in symptom ratings over time using two-, three- or five-dimensional models did not predict improvements in any aspect of cognitive functioning measured, except motor speed. The results do not suggest a causal relationship between the course of symptoms and neuropsychological functioning in chronic schizophrenia.     

Impact of modafinil on prefrontal executive function in schizophrenia

OBJECTIVE: The purpose of this study was to investigate the acute effects of modafinil on prefrontal activation and cognitive control of motor activity in people with schizophrenia and prominent negative symptoms. METHOD: In a crossover design, 12 subjects with schizophrenia were studied twice, receiving either modafinil or placebo prior to functional magnetic resonance imaging (fMRI). Inside the scanner, they performed a task probing cognitive control that required deliberate variation of motor activity in time. RESULTS: Modafinil administration was associated with significantly greater activation of the dorsolateral prefrontal cortex during fMRI. Its physiological and behavioral effects were correlated. This was most evident in individuals with worse baseline executive function. Focal response to modafinil in the left dorsolateral prefrontal cortex and baseline letter fluency scores predicted most of the variance in the drug's effect on cognitive control. CONCLUSIONS: Modafinil did not improve cognitive control in all schizophrenia patients. Increased activation in the dorsolateral prefrontal cortex and in neuropsychological performance were observed in patients with suboptimal baseline function.     

Genome-wide association scan for five major dimensions of personality

Personality traits are summarized by five broad dimensions with pervasive influences on major life outcomes, strong links to psychiatric disorders and clear heritable components. To identify genetic variants associated with each of the five dimensions of personality we performed a genome-wide association (GWA) scan of 3972 individuals from a genetically isolated population within Sardinia, Italy. On the basis of the analyses of 362 129 single-nucleotide polymorphisms we found several strong signals within or near genes previously implicated in psychiatric disorders. They include the association of neuroticism with SNAP25 (rs362584, P=5 x 10(-5)), extraversion with BDNF and two cadherin genes (CDH13 and CDH23; Ps<5 x 10(-5)), openness with CNTNAP2 (rs10251794, P=3 x 10(-5)), agreeableness with CLOCK (rs6832769, P=9 x 10(-6)) and conscientiousness with DYRK1A (rs2835731, P=3 x 10(-5)). Effect sizes were small (less than 1% of variance), and most failed to replicate in the follow-up independent samples (N up to 3903), though the association between agreeableness and CLOCK was supported in two of three replication samples (overall P=2 x 10(-5)). We infer that a large number of loci may influence personality traits and disorders, requiring larger sample sizes for the GWA approach to confidently identify associated genetic variants.