Alexis E. Cullen

Meta-analyses of cognitive and motor function in youth aged 16 years and younger who subsequently develop schizophrenia

BACKGROUND Previous reviews have reported cognitive and motor deficits in childhood and adolescence among individuals who later develop schizophrenia. However, these reviews focused exclusively on studies of individuals with affected relatives or on population/birth cohorts, incorporated studies with estimated measures of pre-morbid intelligence, or included investigations that examined symptomatic at-risk participants or participants 18 years or older. Thus, it remains unclear whether cognitive and motor deficits constitute robust antecedents of schizophrenia. Meta-analyses were conducted on published studies that examined cognitive or motor function in youth aged 16 years or younger who later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and those who did not. METHOD Twenty-three studies fulfilled the following inclusion criteria: (1) written in English; (2) prospective investigations of birth or genetic high-risk cohorts, or follow-back investigations of population samples; (3) objective measures of cognitive or motor performance at age 16 or younger; (4) results provided for individuals who did and who did not develop schizophrenia/SSD later in life; and (5) sufficient data to calculate effect sizes. Four domains of function were examined: IQ; Motor Function; General Academic Achievement; and Mathematics Achievement. RESULTS Meta-analyses showed that, by age 16, individuals who subsequently developed schizophrenia/SSD displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but not in general academic achievement (d=0.25) or mathematics achievement (d=0.21). Subsidiary analysis indicated that the IQ deficit was present by age 13. CONCLUSIONS These results demonstrate that deficits in IQ and motor performance precede the prodrome and the onset of illness.

Neurocognitive performance in children aged 9-12 years who present putative antecedents of schizophrenia

BACKGROUND We previously developed a novel method of identifying children aged 9-12 years who may be at elevated risk of developing schizophrenia and the spectrum disorders because they present a triad of putative antecedents of schizophrenia (ASz). The present study aimed to determine whether ASz children also present neurocognitive deficits that are commonly observed in patients with schizophrenia. METHODS Twenty-eight ASz children and 28 typically-developing (TD) children without the antecedents of schizophrenia completed a battery of neurocognitive tests assessing seven domains of function: General intelligence, scholastic achievement, verbal memory, visual memory, working memory, executive function (EF)-verbal fluency, and EF-inhibition. RESULTS Relative to TD children, the ASz group showed poorer performance on all neurocognitive tests (mean Cohens d effect size=0.52). In linear regression analyses, group status (ASz vs. TD) significantly predicted scores on the general intelligence, verbal memory, working memory, and EF-inhibition domains (p<0.05). The severity of problems on each of the individual antecedents comprising the antecedent triad did not relate strongly to performance on the neurocognitive domains. CONCLUSIONS Children aged 9-12 years who present multiple antecedents of schizophrenia display poorer neurocognition than healthy peers on several domains showing pronounced deficits in schizophrenia, first-episode psychosis, and youth with prodromal symptoms. Longitudinal follow-up is necessary to determine the extent to which poorer neurocognitive performance is specific to those who develop schizophrenia.

A multi-site randomized controlled trial of a cognitive skills programme for male mentally disordered offenders: social-cognitive outcomes

BACKGROUND Cognitive skills programmes have been associated with improvements on psychometric measures and reductions in antisocial behaviour in mentally disordered offenders (MDOs). However, to date there have been no randomized controlled trials (RCTs) of such programmes with this population. In the first RCT of a cognitive skills programme with MDOs we aimed to determine if participation in the Reasoning and Rehabilitation (R&R) programme was associated with improvements in social-cognitive skills and thinking styles. METHOD A total of 84 men with a primary diagnosis of psychotic disorder and a history of violence were recruited from medium-secure forensic units and allocated to receive R&R (n=44) or treatment as usual (TAU; n=40). At baseline and post-treatment interviews, participants completed questionnaires to assess social problem-solving, criminal attitudes, anger experience, blame externalizing and perspective-taking. Researchers were not blind to group status. RESULTS The R&R group demonstrated significant improvements on measures of social problem-solving relative to the TAU group, some of which were maintained at 12 months post-treatment. Only half of those allocated to receive R&R completed the full programme. In post-hoc analyses programme completers showed improvements in social problem-solving at the end of treatment and changes in criminal attitudes at 12 months post-treatment. CONCLUSIONS Among male MDOs, R&R participation was associated with improvements in social-cognitive skills, some of which were maintained for up to 12 months post-treatment. Our finding that programme completers do better may reflect pre-treatment patient characteristics. This study establishes that multi-site RCTs can be conducted in medium-secure forensic units.

Temporal Lobe Volume Abnormalities Precede the Prodrome: A Study of Children Presenting Antecedents of Schizophrenia

Distributed abnormalities of gray matter (GM) and white matter (WM) volume characterize individuals experiencing their first episode of schizophrenia. Regions of abnormality are present already, albeit less extensively, during the prodromal phase of illness. This study aimed to determine whether putatively at-risk children, aged 9-12 years, who present multiple antecedents of schizophrenia (ASz), display GM and WM volume abnormalities relative to typically developing (TD) children presenting no antecedents. Structural magnetic resonance images were acquired for 20 ASz children and 20 TD children matched on age, sex, and IQ. Whole-brain differences in GM and WM volume were determined using voxel-based morphometry. Relative to the TD group, ASz children showed significantly decreased GM volume in the right middle temporal gyrus (MTG) and increased GM volume in the left superior-middle temporal gyri (P < 0.05, cluster correction). WM volume was significantly increased in ASz children relative to TD children in a cluster encompassing the left inferior parietal lobe, occipital lobe, and superior temporal gyrus. Post-hoc analyses indicated that these abnormalities were not limited to ASz children who self-reported auditory hallucinations on questionnaire. Our findings suggest that children aged 9-12 years who present multiple ASz are characterized by abnormalities of GM and WM volume in the temporal lobes, comprising a subset of the regions affected in first-episode schizophrenia and in the prodromal phase of illness. These preliminary findings indicate that structural brain abnormalities associated with schizophrenia may be detected in putatively at-risk, preprodromal children. Prospective studies following the brain development of at-risk children are needed.

Persisting psychotic-like experiences are associated with both externalising and internalising psychopathology in a longitudinal general population child cohort

BACKGROUND Persisting psychotic-like experiences (PLEs) are associated with an increased risk of internalising symptoms in adolescence. Whether this association holds similarly for externalising symptoms, and from mid-childhood, is unclear. This prospective study investigated the extent to which PLE persistence was associated with internalising and externalising psychopathology in a community sample of children aged 9-11years at study commencement. METHODS 8099 children (mean age 10.4years) completed questionnaires assessing PLEs, externalising and internalising symptoms. A subsample of 547 children completed reassessment, on average, two years later. RESULTS Two-thirds (66%) of children reported PLEs at baseline. Approximately two years later, PLEs persisted in 39% of those children. After adjustment for previous psychopathology and other potential confounds, children with persisting PLEs were at higher risk for internalising (odds ratio [OR]=1.94; 95% confidence interval [CI] 1.13-3.34) and externalising (OR=1.97; 95% CI 1.19-3.26) psychopathology than children whose PLEs remitted; and, than children who never presented PLEs. CONCLUSIONS Persistent PLEs from mid-childhood are associated with later internalising and externalising psychopathology in the general population, whereas transitory PLEs may be part of a spectrum of normative childhood development. Interventions that target persistent PLEs may contribute to a reduction in common childhood psychopathology.

A multisite randomized trial of a cognitive skills program for male mentally disordered offenders: violence and antisocial behavior outcomes.

OBJECTIVE Despite a large evidence base indicating that cognitive skills programs can reduce reoffending in individuals without mental illness, there have been no randomized controlled trials (RCTs) to determine their effectiveness in mentally disordered offenders (MDOs). In the first RCT of a cognitive skills program for MDOs, we aimed to investigate whether participation in the Reasoning and Rehabilitation (R&R) program reduced violence and antisocial behavior in this population. METHOD Eighty-four male inpatients with a psychotic disorder and a history of violence were recruited from medium secure forensic hospitals. Participants were randomized to receive the R&R program, consisting of 36 two-hour sessions, or treatment as usual (TAU). Incidents of violence and antisocial behavior (verbal aggression, substance use, and leave violations) were assessed during treatment and at 12-months posttreatment. RESULTS Relative to the TAU group, incident rates of verbal aggression and leave violations during the treatment period were significantly lower in the R&R group; the effect on verbal aggression was maintained at 12-months posttreatment. Half of those randomized to receive R&R did not complete treatment; post hoc analyses were therefore conducted to compare treatment responses in program completers and noncompleters. After controlling for psychopathic traits, incidents of violence, verbal aggression, and leave violations during treatment were significantly lower in program completers, and there were significant effects of program completion on verbal aggression and substance use at 12-months posttreatment. CONCLUSIONS R&R leads to a reduction in incidents of antisocial behavior in MDO populations, with potentially greater impact on those who complete treatment.

The neural diathesis-stress model of schizophrenia revisited: An update on recent findings considering illness stage and neurobiological and methodological complexities

HighlightsDistinct patterns of HPA axis dysregulation in psychosis are observed for basal, stress‐induced and awakening cortisolHPA axis alterations in clinical high risk populations resemble those observed in established psychosis, but are less consistentConfounding factors and challenges in the measurement of stress, cortisol, and symptomatic outcome affect interpretation of resultsGenetic, epigenetic, neurodevelopmental and environmental factors may modulate the effects of HPA axis abnormalities on psychosis progressionHPA axis activity in psychosis appears to be associated with altered neurotransmitter activity, inflammatory processes and brain structure &NA; Over the past decade, our understanding of the role of stress in serious mental illness has become more sophisticated. In this paper, we revisit the neural diathesis‐stress model of schizophrenia that was initially proposed in 1997 and updated in 2008. In light of cumulative research findings, we must now encompass evidence on the premorbid periods of psychosis, and our more nuanced understanding of hypothalamic‐pituitary‐adrenal (HPA) axis function and its association with neurodevelopmental, epigenetic, neurotransmitter, and inflammatory processes, as well as brain structure and function. Giving consideration to the methodological complexities that have become more apparent as research in this area has burgeoned, the various indices of HPA axis function, and the different stages of illness, we review relevant research published since the 2008 update of the model. We conclude by proposing an extended neural diathesis‐stress model that addresses the broader neurobiological context of stress psychobiology in psychosis progression. Implications of this model for best practice, with regards to both future research and treatment strategies, are discussed.

Factors Predicting Dropout From the Reasoning and Rehabilitation Program With Mentally Disordered Offenders

Studies evaluating the implementation of cognitive skills programs with mentally disordered offenders (MDOs) have reported high dropout rates, but little is known about the factors associated with treatment noncompletion. The authors analyzed data from the first randomized controlled trial of the Reasoning and Rehabilitation (R&R) program with MDOs to determine predictors of treatment dropout. Patients with psychotic disorders were recruited from medium-secure hospitals in the United Kingdom. Fifty percent of the 44 participants allocated to receive R&R prematurely terminated treatment. Program dropout was significantly predicted by scores on the Clinical and Risk Management scales of the Historical, Clinical, Risk Management—20, Factor 2 scores of the Psychopathy Checklist—Screening Version, antisocial personality disorder (ASPD), psychopathy, and recent violence. Psychopathy, ASPD, and recent violence emerged as the strongest predictors of dropout in multivariate analyses. Strategies to improve treatment retention should be targeted at MDOs who display high levels of impulsivity, poor behavioral controls, and antisocial or psychopathic traits.

Cognitive impairment among children at-risk for schizophrenia.

Adults with schizophrenia present cognitive impairments, as do individuals at ultra-high risk for the disorder, youth with relatives with schizophrenia spectrum disorders, and children with antecedents of schizophrenia. The present study aimed to determine if impairments in childhood differed depending on the definition of risk and/or on the degree of relatedness to an affected individual, and if impairments were explained by IQ. Four groups of children aged 9-12 years were studied: (1) 13 children with ≥1 first-degree or ≥2 second-degree affected relatives (high familial loading: FHx(H)); (2) 14 with ≥1 affected second-degree relative (lower familial loading: FHx(L)); (3) 32 with well-replicated antecedents of schizophrenia (ASz); and (4) 45 typically-developing (TD) children with neither a positive family history nor antecedents. Compared to TD children, both FHx(H) and ASz children exhibited significantly poorer verbal comprehension, scholastic achievement, and verbal working memory, while FHx(H) children additionally displayed significantly lower full-scale IQ, and verbal memory and executive function impairments. After adjusting statistical analyses for IQ, group differences were attenuated. Relative to TD children, FHx(L) children showed no significant differences in performance. The results imply that impairments in verbal comprehension, scholastic achievement, and verbal working memory may index vulnerability for schizophrenia among children with affected relatives with the disorder and among those with multiple antecedents of the disorder who have no affected relatives. More accurate identification of children at-risk for schizophrenia and the specific deficits that they present provides opportunities for interventions such as cognitive remediation that may impact the development of the illness.

A quasi-experimental pilot study of the Reasoning and Rehabilitation programme with mentally disordered offenders

Cognitive-skills interventions, such as the Reasoning and Rehabilitation (R&R) programme, have been repeatedly shown to have the largest impact on recidivism. However, we have yet to establish the extent to which mentally disordered offenders (MDOs) can benefit from such interventions. Using a quasi-experimental design, we sought to determine: (1) the feasibility of implementing R&R with MDOs, and (2) whether participation was associated with improved psychosocial function. Male patients with psychotic disorders were recruited from two forensic medium secure hospitals, 18 were allocated to receive the full R&R programme, while the control group (N = 17) received treatment-as-usual. All participants completed a battery of questionnaires both before and after treatment. Only three patients failed to complete the full 36-session R&R programme. Those who completed the programme showed significantly improved problem solving ability and increased coping responses. The results suggest that MDOs can benefit from participation in the R&R programme.