Cognition as predictor of current and follow‐up depressive symptoms in the general population

Objective: This study assessed the relationship between stress reactivity (trait 1) and psychosis (trait 2) across genetically related persons (cross‐twin, cross‐trait design) to examine whether stress reactivity is an uncontaminated and unconfounded familial marker of psychosis risk. Method: Reactivity to stress and subclinical psychotic experiences were assessed in 289 female, general population twin‐pairs. Cross‐trait, within‐twin associations investigating the association between stress reactivity and subclinical psychotic experiences in each person, were calculated. In addition, cross‐trait, cross‐twin associations were calculated to assess whether stress reactivity in one twin was moderated by subclinical psychotic experiences in the co‐twin. Results: Cross‐trait, within‐twin analyses showed significant associations between stress reactivity and subclinical psychotic experiences in each person. In addition, the cross‐trait cross‐twin analyses showed that stress reactivity in twin 1 was significantly moderated by subclinical experiences in the co‐twin. Conclusion: The results suggest that the psychosis phenotype cosegregates with increased emotional reactivity to stress in daily life.     

Sex differences in clustering and switching in verbal fluency tasks.

Sex differences in executive speech tasks, favoring women, have been noted in behavioral studies and functional imaging studies. In the present study, the clustering and switching components of semantic and phonemic verbal fluency tests were examined in 40 healthy men and 40 healthy women. Possible sex differences in the influence of cognitive factors such as speed of information processing, word knowledge, and/or verbal long-term memory on these verbal fluency factors were also assessed. The results showed that women switched more often between categories in the phonemic fluency test, whereas men showed a trend toward a larger cluster size leading to a smaller total number of words generated. Additionally, higher performance on the Digit Symbol test was associated with better performance on the semantic and phonemic verbal fluency test in men, whereas in women, better memory performance was associated with better performance on these verbal fluency tests. Our data indicate that men and women are using different processing strategies for phonemic verbal fluency tests to optimize verbal fluency task performance. In the current study, women adopted a more successful strategy of balancing clustering and switching in the phonemic fluency task.     

Evidence for a relationship between mentalising deficits and paranoia over the psychosis continuum

OBJECTIVE: Failing of mentalising has been suggested to underlie certain symptoms of psychosis. An as yet unresolved issue is whether mentalising deficits reflect a characteristic which can also be detected in people at risk for psychosis or people with evidence of subclinical expression of psychosis. This study wanted to assess an aspect of mentalising in four groups with different levels of psychosis vulnerability, and to examine associations between mentalising and symptoms of psychosis. METHOD: The study included i) 40 patients with psychosis, ii) 49 non-psychotic first-degree relatives (familial risk), iii) 41 subjects from the general population with a high level of positive psychotic experiences (psychometric risk) and iv) 54 healthy controls. All subjects performed the 'Hinting Task'. RESULTS: There was a significant association between psychosis risk and impairment on the Hinting Task (beta linear trend=0.37, p<0.001). Using the control group as the reference, the association with impairment on the Hinting Task was highest for the patient group (beta=0.46, p<0.001), whereas the familial risk group (beta=0.16, p=0.06) displayed an intermediate probability of failure. The psychometric risk group did not significantly differ from the control group (beta=0.04, p=0.653). In the patient group, impairment on the Hinting Task was associated with current hallucinations and paranoid symptoms. In the familial risk group, there was an association between the Hinting Task and paranoid symptoms. DISCUSSION: These results suggest that vulnerability to psychosis is expressed as an impairment in mentalising, which may have a mediating role in the formation of certain positive symptoms of psychosis.     

Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations

Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[¹⁸F]fluoro-L-DOPA [[¹⁸F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.     

Validity and reliability of the CAPE: a self-report instrument for the measurement of psychotic experiences in the general population

OBJECTIVE: General population longitudinal cohort studies have demonstrated the prognostic validity of self-reported psychotic experiences, but data on reliability and cross-validation with interview-based measures of these experiences are sparse. This study tested the reliability and validity of the Community Assessment of Psychic Experiences (CAPE42). METHOD: At baseline, the CAPE42 was used to measure the subclinical psychosis phenotype in a general population sample (n = 765). At follow-up (mean interval: 7.7 months), the Structured Interview for Schizotypy, Revised (SIS-R), the Brief Psychiatric Rating Scale (BPRS), and the CAPE42 were administered (n = 510). RESULTS: Baseline self-reported dimensions of psychosis were specifically and independently associated with their equivalent interview-based dimension at follow-up (standardized effect sizes of 0.4-0.5) and with their equivalent self-reported measure (standardized effect sizes of 0.6-0.8). CONCLUSION: The results indicate that self-reported dimensions of psychotic experiences in general population samples appear to be stable, reliable and valid.     

Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence

Wigman JTW, van Winkel R, Ormel J, Verhulst FC, van Os J, Vollebergh WAM. Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence. Objective: Both genetic and environmental factors are thought to play a role in the development of psychotic outcomes; however, their respective contributions over time, including possible developmental interactions, remain largely unknown. Method: The contribution of parental general and psychotic psychopathology as proxies of genetic risk to the development of subthreshold psychosis and its hypothesized interaction with childhood trauma were studied in a general population sample of 2230 adolescents, followed from age 10–16 years. Outcome measures were: i) level of psychotic experiences at age 16 years and ii) persistence of such experiences over the total follow‐up period. Results: General parental psychopathology was associated with CAPE score (OR = 1.08; P < 0.043 for highest quintile) and suggestively predicted psychosis persistence (OR, 1.16; P < 0.072). Psychotic parental psychopathology was suggestively associated with CAPE score (OR, 2.25; P < 0.063 for highest quintile), predicted membership of the Persistent group (OR, 3.72; P < 0.039) and suggestively predicted membership of the Decreasing group (OR 2.04; P < 0.051). Childhood trauma was associated with CAPE score and with all developmental trajectories of subclinical psychosis. No evidence was found for an interaction between trauma and parental psychopathology. Conclusion: The development and persistence of subthreshold psychotic symptoms may be conditional on non‐interacting proxy genetic and environmental influences.     

Functional anatomy of cognitive development: fMRI of verbal fluency in children and adults

OBJECTIVE: To identify age-dependent activation patterns of verbal fluency with functional MRI (fMRI). BACKGROUND: Few fMRI language studies have been performed in children, and none provide comparison data to adult studies. Normative data are important for interpretation of similar studies in patients with epilepsy. METHODS: A total of 10 normal children (5 boys, 5 girls; mean age, 10.7 years; range, 8.1 to 13.1 years) and 10 normal adults (5 men, 5 women; mean age, 28.7 years; range, 19.3 to 48 years) were studied on a 1.5-T Signa MRI scanner using BOLD echo planar imaging of the frontal lobes with a verbal fluency paradigm, covert word generation to letters. Studies were analyzed with a cross-correlation algorithm (r = 0.7). A region-of-interest analysis was used to determine the extent, magnitude, and laterality of brain activation. RESULTS: Children and adults activated similar regions, predominantly in left inferior frontal cortex (Broca's area) and left middle frontal gyrus (dorsolateral prefrontal cortex). Children had, on average, 60% greater extent of activation than adults, with a trend for greater magnitude of activation. Children also had significantly more right hemisphere and inferior frontal gyrus activation than adults. CONCLUSIONS: In a test of verbal fluency, children tended to activate cortex more widely than adults, but activation patterns for fluency appear to be established by middle childhood. Thus, functional MRI using verbal fluency paradigms may be applied to pediatric patient populations for determining language dominance in anterior brain regions. The greater activation found in children, including the right inferior frontal gyrus, may reflect developmental plasticity for the ongoing organization of neural networks, which underlie language capacity.     

Semantic verbal fluency deficit as a familial trait marker in schizophrenia

This study examined neurocognitive deficits as familial vulnerability factors to schizophrenia. Twenty-three Chinese schizophrenic patients, 21 of their non-psychotic siblings and 26 healthy volunteers, matched for age, sex and education, were assessed by using a battery of neurocognitive tests including: Wisconsin Card Sorting Test (WCST), semantic verbal fluency, logical memory, digit span, information, comprehension and similarity. The results showed that siblings had significantly less word output in the verbal fluency test as compared to controls. No significant difference was found between siblings and controls for other tests except that a trend difference was noted for the performance on the similarity test and number of categories completed on the WCST. The verbal fluency abnormality can be considered as a familial trait marker for schizophrenia. Relationships between the residual symptoms after an acute psychotic episode and the magnitude of familial risk were examined. More severe residual symptoms of probands at clinical remission could be predicted by their older age of onset and by better verbal fluency performance in their non-psychotic siblings. This tentatively suggests that patients with a milder genetic form of schizophrenic illness may have a more severe environmental contribution to cerebral insult according to the multifactorial/threshold model. The environmental cerebral insult may cause structural abnormalities leading to incomplete remission of clinical symptoms.     

Subjective experience of cognitive failures as possible risk factor for negative symptoms of psychosis in the general population

Objective: The aim of this study was to examine whether proneness to subjective cognitive failure (cognitive based mistakes) increases the risk for the development of symptoms of psychosis and to what degree any association was familial. Methods: At baseline, the Cognitive Failure Questionnaire (CFQ) and the Community Assessment of Psychic Experiences (CAPE) questionnaire were administered in a general population sample of genetically related individuals (n = 755). Individuals scoring high (>75th percentile) or average on the CAPE (between 40th and 60th percentile) (n = 488) were reinterviewed with the CAPE and Structured Interview for Schizotypy—Revised (SIS-R) at follow-up (mean interval = 7.7 months, SD = 4.8 months). Results: Cross-trait, within-relative analysis showed a significant association between the CFQ and the negative dimension, assessed with both the CAPE and SIS-R, whereas no association was found between the CFQ and the positive dimension. Cross-trait, between-relative analyses showed no association between the CFQ in one relative and any of the dimensions of the subclinical psychosis phenotype in the other relative. Conclusion: Proneness to subjective cognitive failure possibly contributes to the development or persistence of negative symptoms and can be seen as potential risk factor for negative symptoms of psychosis. This overlap is due to individual effects rather than familial liability.     

Primary progressive aphasia: relationship between gender and severity of language impairment.

BACKGROUND/AIMS: Factors influencing the course and severity of symptoms in primary progressive aphasia (PPA), a language-based dementia, have not been fully elucidated. The current study examined the influence of gender on performance on tests of naming and verbal fluency in patients with PPA. Comparisons were also made within a group of probable Alzheimer disease (AD) patients to determine whether gender differences were present in the most common form of neurodegenerative dementia. METHODS: Performance was compared by gender within each diagnostic group on 3 language measures: the Boston Naming Test, category fluency (animals), and lexical fluency (FAS). Scores were compared at baseline (Visit 1) and in a subset of participants 6 to 15 months later (Visit 2). RESULTS: Compared to men, women with PPA demonstrated significantly greater impairment on word fluency tests at both visits and also had a more aggressive rate of decline between visits. AD patients showed no differences by gender on any measure. CONCLUSIONS: The results suggest gender-based vulnerability in PPA where women express more severe language impairments than men given a similar duration of illness.     

A Population Based Analysis of Subclinical Psychosis and Help-Seeking Behavior

Clinically defined psychosis is recognizable and distinguishable from nonclinical or subclinical psychosis by virtue of its clinical relevance (ie, its associated distress and its need for care and/or treatment). According to the continuum hypothesis, subclinical psychosis is merely quantitatively different from more extreme phenotypic expressions and as such should also be indicative of distress and help-seeking behavior but to a lesser extent. Using data from the Adult Psychiatric Morbidity Survey, the current study focused on self-reported psychosis and help-seeking experiences in a general population sample free from clinically defined psychosis (N = 7266). After statistically controlling for the effects of a series of potential help-seeking correlates the findings showed that subclinical psychosis symptom experience was significantly associated with various forms of help-seeking behavior. Individuals who reported subclinical experiences of thought control, paranoia, and strange experiences were on average 2 times more likely to attend their general practitioner for emotional problems compared with those individuals who reported no psychosis. Individuals who reported subclinical experiences of paranoia were 3 times more likely to be in receipt of counseling/therapy compared with those with no experience of paranoia. Multiple subclinical psychotic experiences also predicted elevated help-seeking behavior. These findings may have a positive impact on the detection of individuals who are at increased risk of psychological distress and aid in the design and implementation of more effective treatments at both clinical and subclinical levels.     

U.S. psychologists' suicide rates have declined since the 1960s

In the 1960s and early 1970s, proportionately more professional women committed suicide than did women in the general population, while professional men committed suicide at rates similar to men in the general population. To provide more recent information, this study explored suicide rates among U.S.-resident American Psychological Association members during the years 1981 to 1990. The suicide rate for women in the Association was found to be 7.6 per 100,000 population per year, a rate that is lower than in the 1960s and similar to women in the general population. The rate for men was found to be 7.8 per 100,000 population per year, a rate that is lower than in the 1960s and lower than among men in the general population. Effects of increasing numbers of women in the professions in general, or in psychology in particular, may explain the decline in suicide rates.     

Strauss (1969) revisited: a psychosis continuum in the general population?

Although dichotomously defined for clinical purposes, psychosis may exist as a continuous phenotype in nature. A random sample of 7076 men and women aged 18-64years were interviewed by trained lay interviewers with the Composite International Diagnostic Interview (CIDI). Those with evidence of psychosis according to the CIDI were additionally interviewed by psychiatrists. For the 17 CIDI core psychosis items, we compared a psychiatrist's rating of hallucinations and/or delusions (Clinical Psychosis; sample prevalence 4.2%) with three other possible positive CIDI ratings of the same items: (i) symptom present, but not clinically relevant (NCR Symptom; sample prevalence 12.9%); (ii) symptom present, but the result of drugs or somatic disorder (Secondary Symptom; sample prevalence 0.6%); (iii) symptom appears present, but there is a plausible explanation (Plausible Symptom; sample prevalence 4.0%). Of the 1237 individuals with any type of positive psychosis rating (sample prevalence 17.5%), only 26 (2.1%) had a DSM-III-R diagnosis of non-affective psychosis. All the different types of psychosis ratings were strongly associated with the presence of psychiatrist-rated Clinical Psychosis (NCR Symptom: OR=3.4; 95% CI: 2.9-3.9; Secondary Symptom: OR=4.5; 95% CI: 2.7-7.7; Plausible Symptom: OR=5.8; 95% CI: 4.7-7.1). Associations with lower age, single marital status, urban dwelling, lower level of education, lower quality of life, depressive symptoms and blunting of affect did not differ qualitatively as a function of type of rating of the psychotic symptom, were similar in individuals with and without any CIDI lifetime diagnosis, and closely resembled those previously reported for schizophrenia. Presence of any rating of hallucinations was strongly associated with any rating of delusions (OR=6.7; 95% CI: 5.6-8.1), regardless of presence of any CIDI lifetime diagnosis. The observation by Strauss (1969. Hallucinations and delusions as points on continua function. Arch. Gen. Psychiatry 21, 581-586) that dichotomously diagnosed psychotic symptoms in clinical samples are, in fact, part of a continuum of experiences, may also apply to the general population. The boundaries of the psychosis phenotype may extend beyond the clinical concept of schizophrenia.     

Gender differences in violent behaviors: relationship to clinical symptoms and psychosocial factors

OBJECTIVE: Men are more violent than women in the general population, but this has not been found to be the case among psychiatric inpatients. The reason for this exception is poorly understood. The present study investigated gender differences in violent behaviors among patients with major psychiatric disorders. It examined various clinical symptoms and psychosocial factors to determine their differential impact on violence in men and women. METHOD: Physical assaults and verbal assaults committed by psychiatric inpatients were recorded prospectively. Patients whose violent incident occurred during their first 2 months of hospitalization were eligible for the study. Patient history of community violence was also obtained. Psychiatric symptoms and ward behaviors were assessed upon entry into the study and after 4 weeks. RESULTS: A similar percentage of women and men had an incident of physical assault in the hospital. Among the patients entered into the study, the women had a much higher level of verbal assaults throughout the evaluation period and a higher level of early physical assaults (i.e., within the first 10 days of the 4-week study period). Positive psychotic symptoms were more likely to result in assaults in women than in men. Physical assaults in the community, on the other hand, were more common in men and were associated with substance abuse, property crime, and a history of school truancy. CONCLUSIONS: There are gender differences in the patterns of violent behavior among patients with major psychiatric disorders. Furthermore, psychiatric symptoms and psychosocial risk factors have a different impact on this behavior in men and women. This has important implications for the prediction and differential treatment of violent behavior.     

Intracranial capacity and brain volumes are associated with cognition in healthy elderly men

BACKGROUND: Brain size and intracranial capacity are correlated with cognitive performance in young healthy adults, but data are lacking on these relationships in older healthy adults. OBJECTIVE: To test the hypotheses that intracranial capacity, volumes of specific brain regions, and a measure of the shared variance between brain regions are positively associated with cognitive function in a sample of healthy, unmedicated elderly men (n = 97; mean age 67.8, SD 1.3). METHODS: Individuals underwent MRI, with measurements of intracranial area and volumetric measurements of hippocampi, temporal lobes, and frontal lobes. Cognitive testing included measures of premorbid intelligence, fluid intelligence, verbal memory, visuospatial memory, verbal fluency, and attention and processing speed. RESULTS: Cognitive tests showed significant positive intercorrelations throughout, and regional brain volumes were also universally, significantly, and positively intercorrelated. Intracranial area and several regional brain volumes correlated with tests of premorbid and fluid intelligence and tests of visuospatial memory. Tests of verbal memory and verbal fluency did not correlate significantly with brain volumes. Structural equation modeling demonstrated that the relationships between specific cognitive tests and regional brain volumes could best be summarized by a significant positive relationship between a general brain size factor and a general cognitive factor, and not by associations between individual tests and particular brain regions. CONCLUSIONS: In healthy elderly men, there are significant relationships between multiple cognitive tests and both intracranial capacity and regional brain volumes. These relationships may be largely due to longstanding associations between general cognitive ability and overall brain size.     

Lateralization of verbal ability in pre-psychotic children

Deficits in lateralization have been reported in handedness, language and anatomical asymmetry in schizophrenia, but the relationship between these anomalies has been unclear. Extending earlier work demonstrating that degrees of lateralization are related to verbal ability in the general population, we here investigate the relationship in children who later developed psychosis. Using data from a box-marking test and an index of receptive verbal ability in the UK National Child Development study, we constructed three-dimensional plots of verbal ability in relation to left- and right-hand skill at the age of 11 years, and compared the performance of 34 children who by age 28 had developed schizophrenia and 21 who had developed affective psychosis with 12,782 in the total population. In the total population, verbal skill is decreased in those who are close to the L=R line. Children premorbid for schizophrenia are less lateralized and their verbal skill is lower than predicted by their hand skill, with a similar trend in children premorbid for affective psychosis. Thus pre-psychotic children deviate from the general population in the trajectory of lateralization of words. The findings are consistent with the concept that in psychosis at some critical stage in development there is a failure of lateralization of the components of language.     

Sexual orientation and neurocognitive ability: A meta-analysis in men and women

The cross-sex-shift hypothesis predicts that homosexual men and women will be similar in certain neurobehavioral traits to their opposite-sex counterparts. Accordingly, it predicts that homosexual men should perform in the direction of heterosexual women, and homosexual women in the direction of heterosexual men, on neurocognitive tests that show normative sex differences. We conducted a meta-analysis on the relationship between sexual orientation and cognitive performance, and tested the effects of potential moderating variables separately by sex. A total of 106 samples and 254,231 participants were included. The meta-analysis revealed that homosexual men performed like heterosexual women in both male-favouring (e.g., spatial cognition) and female-favouring (e.g., verbal fluency) cognitive tests, while homosexual women performed like heterosexual men only in male-favouring tests. The magnitude of the sexual orientation difference varied across cognitive domains (larger for spatial abilities). It was also larger in studies comparing exclusive heterosexuals with exclusive homosexuals compared to studies comparing exclusive heterosexuals with non-exclusive homosexuals for both sexes. The results may narrow down potential sites for sexual orientation-related neural differences.     

Young people at risk for psychosis: case finding and sample characteristics of the Oulu Brain and Mind Study

Aim: Set within the general population‐based Northern Finland Birth Cohort 1986, the Oulu Brain and Mind Study aims to explore the causes and pathogenesis of psychotic illness by following young people at risk for psychosis due to having a first‐degree relative with psychotic illness or due to having experienced psychotic‐like symptoms themselves. We report the study methods and explore the relationship between these definitions of high risk for psychosis and operational criteria for a prodromal psychosis syndrome based on interview. Methods: Prospectively collected data from earlier follow‐ups of this cohort were combined with health register data to categorize subjects as those with familial risk (n = 272), symptomatic risk (n = 117), psychosis (n = 78), attention deficit hyperactivity disorder (ADHD) (n = 103) and a sample of controls (n = 193) drawn randomly from the remaining cohort. The Structured Interview for Prodromal Syndromes (SIPS) was applied to all, 295 participants together with questionnaires measuring psychosis vulnerability and schizotypal traits. Results: There were 29 (10%) current prodromal cases. Criteria for the current prodromal syndrome were fulfilled by 12% of the familial risk group and 19% of the symptomatic risk group, compared with 5% of the ADHD group and 4% of controls. Conclusion: We successfully detected young people with a prodromal psychosis syndrome although relatively few subjects deemed to be at high risk met the full operational criteria according to the SIPS interview. Combining methods from familial, clinical and psychometric high‐risk approaches provides a tractable method for studying risk of psychosis in the general population.     

Familial aggregation of psychotic symptoms in Huntington's disease

OBJECTIVE: The mutation responsible for Huntington's disease is an elongated and unstable trinucleotide (CAG) repeat on the short arm of chromosome 4. Psychotic symptoms are more common in patients with Huntington's disease than in the general population. This study explored the relationship of psychosis in Huntington's disease patients with the number of CAG repeats and family history of psychosis. METHOD: Forty-four patients with Huntington's disease, 22 with and 22 without psychotic symptoms, were recruited from two university-affiliated medical genetics clinics in Seattle and Vancouver, B.C. Psychiatric assessments of the subjects were made through chart review, and diagnoses were validated by structured interviews in a subset of patients. The demographic and clinical characteristics of the psychotic and nonpsychotic patients were compared. RESULTS: The two groups did not differ in demographic and clinical characteristics, except that subjects with psychosis were significantly more likely than nonpsychotic subjects to have a first-degree relative with psychosis. In eight of nine families in which Huntington's disease probands with psychosis had a first-degree relative with psychosis, the relative's psychosis co-occurred with Huntington's disease. In the Huntington's disease probands with psychosis, the onset of psychosis correlated with the onset of the neurological symptoms of Huntington's disease, and the age at onset of psychosis was lower in probands with a higher number of CAG repeats. CONCLUSIONS: Patients with Huntington's disease and psychotic symptoms may have a familial predisposition to develop psychosis. This finding suggests that other genetic factors may influence susceptibility to a particular phenotype precipitated by CAG expansion in the Huntington's disease gene.     

The association between endogenous free testosterone and cognitive performance: a population-based study in 35 to 90 year-old men and women

The relationship between testosterone (T) and cognition has yielded conflicting evidence, showing both positive and negative influences of T on cognitive performance. The association between free testosterone (FT) and cognition was revisited in a large population-based sample of 1276 women and 1107 men (35-90 years of age), assessed individually on visuospatial, verbal fluency, semantic, and episodic memory tasks. For men, higher FT levels were associated with better visuospatial abilities, semantic memory, and episodic memory, with greater positive influence with increasing age. Statistical covariates included age, education, and select medications. For women, FT was negatively associated with verbal fluency, semantic memory, and episodic memory, although only verbal fluency was significant at conventional alpha levels. These results support the claim that FT exerts sex-specific influences on cognitive performance.