Kristin R. Laurens

Amygdala Hypoactivity to Fearful Faces in Boys With Conduct Problems and Callous-Unemotional Traits

OBJECTIVE Although early-onset conduct problems predict both psychiatric and health problems in adult life, little research has been done to index neural correlates of conduct problems. Emerging research suggests that a subgroup of children with conduct problems and elevated levels of callous-unemotional traits may be genetically vulnerable to manifesting disturbances in neural reactivity to emotional stimuli indexing distress. Using functional MRI, the authors evaluated differences in neural response to emotional stimuli between boys with conduct problems and elevated levels of callous-unemotional traits and comparison boys. METHOD Seventeen boys with conduct problems and elevated levels of callous-unemotional traits and 13 comparison boys of equivalent age (mean=11 years) and IQ (mean=100) viewed blocked presentations of fearful and neutral faces. For each face, participants distinguished the sex of the face via manual response. RESULTS Relative to the comparison group, boys with conduct problems and elevated levels of callous-unemotional traits manifested lesser right amygdala activity to fearful faces. CONCLUSIONS This finding is in line with data from studies of adults with antisocial behavior and callous-unemotional traits (i.e., psychopaths), as well as from a recent study of adolescents with callous-unemotional traits, and suggests that the neural substrates of emotional impairment associated with callous-unemotional antisocial behavior are already present in childhood.

Neural sources involved in auditory target detection and novelty processing: an event-related fMRI study.

We used event-related functional magnetic resonance imaging (erfMRI) techniques to examine the cerebral sites involved with target detection and novelty processing of auditory stimuli. Consistent with the results from a recent erfMRI study in the visual modality, target processing was associated with activation bilaterally in the anterior superior temporal gyrus, inferior and middle frontal gyrus, inferior and superior parietal lobules, anterior and posterior cingulate, thalamus, caudate, and the amygdala/hippocampal complex. Analyses of the novel stimuli revealed activation bilaterally in the inferior frontal gyrus, insula, inferior parietal lobule, and in the inferior, middle, and superior temporal gyri. These data suggest that the scalp recorded event-related potentials (e.g., N2 and P3) elicited during similar tasks reflect an ensemble of neural generators located in spatially remote cortical areas.

Early intervention and prevention of anxiety disorders in children: results at 2-year follow-up.

The Queensland Early Intervention and Prevention of Anxiety Project evaluated a child- and family-focused group intervention for preventing anxiety problems in children. This article reports on 12- and 24-month follow-up data to previously reported outcomes at posttreatment and at 6-month follow-up. A total of 1,786 7- to 14-year-olds were screened for anxiety problems using teacher nominations and childrens self-report. After diagnostic interviews, 128 children were selected and assigned to either a 10-week school-based child- and parent-focused psychosocial intervention or a monitoring group. Both groups showed improvements immediately at postintervention and at 6-month follow-up; the improvement was maintained in the intervention group only reducing the rate of existing anxiety disorder and preventing the onset of new anxiety disorders. At 12 months, the groups converged, but the superiority of the intervention group was evident again at 2-year follow-up. Severity of pretreatment diagnoses, gender, and parental anxiety predicted poor initial response to intervention, whereas pretreatment severity was the only predictor of chronicity at 24 months. Overall, follow-up results show that a brief school-based intervention for children can produce durable reductions in anxiety problems.

Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia

BACKGROUND The large quantity of systematic reviews of magnetic resonance imaging studies in schizophrenia challenges their meaningful interpretation. This meta-review synthesises the available information from systematic reviews of structural alteration in both chronic and first-episode schizophrenia. METHODS Systematic reviews were identified using electronic databases. Review methodological quality was assessed according to the Assessment of Multiple Systematic Reviews checklist. Data were extracted in duplicate and quality assessed for consistency and precision, guided by Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS Integration of volumetric and voxel-based estimates allowed critical assessment of the magnitude and location of anatomical differences. There is evidence for grey matter reductions of anterior cingulate, frontal (particularly medial and inferior) and temporal lobes, hippocampus/amygdala, thalamus, and insula that may be magnified over time. Other regional alterations appear specific to illness stage or medication status. CONCLUSIONS There is limited high quality evidence supporting grey or white matter changes in schizophrenia, which has previously been obscured by a large volume of conflicting lower quality evidence.

Size matters: Increased grey matter in boys with conduct problems and callous–unemotional traits

Brain imaging studies of adults with psychopathy have identified structural and functional abnormalities in limbic and prefrontal regions that are involved in emotion recognition, decision-making, morality and empathy. Among children with conduct problems, a small subgroup presents callous-unemotional traits thought to be antecedents of psychopathy. No structural brain imaging study has examined this subgroup of children. The present study used voxel-based morphometry to compare whole brain grey matter volumes and concentrations of boys with elevated levels of callous-unemotional conduct problems and typically developing boys and explored four a priori regions of interest. sMRI scans were collected from 23 boys with elevated levels of callous-unemotional conduct problems (mean age = 11 years 8 months) and 25 typically developing boys (mean age = 11 years 6 months) selected from a community sample of children. Data were analysed using optimized voxel-based morphometry. Study-specific probability maps were created and four a priori regions of interest identified (orbitofrontal, anterior cingulate and anterior insular cortices and amygdala). Both grey matter volume and concentration were examined controlling for cognitive ability and hyperactivity-inattention symptoms. Boys with callous-unemotional conduct problems, as compared with typically developing boys, presented increased grey matter concentration in the medial orbitofrontal and anterior cingulate cortices, as well as increased grey matter volume and concentration in the temporal lobes bilaterally. These findings may indicate a delay in cortical maturation in several brain areas implicated in decision making, morality and empathy in boys with callous-unemotional conduct problems.

Childhood adversity in schizophrenia: a systematic meta-analysis

BACKGROUND Childhood adversity is a putative risk factor for schizophrenia, although evidence supporting this suggestion is inconsistent and controversial. The aim of this review was to pool and quality assess the current evidence pertaining to childhood adversity in people with schizophrenia compared to other psychiatric disorders and to non-psychiatric controls. METHOD Included were case-control, cohort and cross-sectional studies. Medline, EMBASE and PsycINFO databases were searched. Study reporting was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist and pooled evidence quality was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS Twenty-five studies met inclusion criteria. Moderate to high quality evidence suggests increased rates of childhood adversity in schizophrenia compared to controls [odds ratio (OR) 3.60, p < 0.00001]. Increased childhood adversity was also reported in schizophrenia compared to anxiety disorders (OR 2.54, p = 0.007), although the effect was not significant in the subgroup analysis of five studies assessing only sexual abuse. No differences in rates of childhood adversity were found between schizophrenia and affective psychosis, depression and personality disorders whereas decreased rates of childhood adversity were found in schizophrenia relative to dissociative disorders and post-traumatic stress disorder (OR 0.03, p < 0.0001). CONCLUSIONS This is the first meta-analysis to report a medium to large effect of childhood adversity in people with schizophrenia and to assess specificity for schizophrenia. Further research is required that incorporates longitudinal design and other potentially causal variables to assess additive and/or interactive effects.

Error-related negativity and correct response negativity in schizophrenia

OBJECTIVES To examine error-related negativity (ERN) and correct response negativity (CRN) in schizophrenia in light of two previous conflicting reports, and to determine their relation to disorganization, psychomotor poverty and reality distortion. METHODS Event-related potentials were recorded from 21 schizophrenic and 21 control participants who performed a simple go/no-go task. Response-locked potentials were computed for errors of commission and for correct-hits. Scores for reality distortion syndrome, psychomotor poverty syndrome and disorganization syndrome were determined for each schizophrenic participant using the Signs and Symptoms of Psychotic Illness (SSPI) scale. RESULTS ERN produced during error trials and CRN produced during correct trials were significantly larger in the control participant group than in the schizophrenic participant group. In the schizophrenic patients, ERN amplitude was negatively correlated with psychomotor poverty syndrome score and CRN amplitude was negatively correlated with disorganization syndrome score. CONCLUSIONS Decreased ERN and CRN in the schizophrenic participant group suggests abnormal internal behavior monitoring in schizophrenic patients. Patients with high disorganization symptoms may employ an abnormal strategy for comparing actual response outcome with desired response outcome, while patients with psychomotor poverty may be less emotionally responsive to errors.

The Role of the Anterior Cingulate Cortex in Conflict Processing: Evidence from Reverse Stroop Interference

A recent theoretical account delineated the role of the anterior cingulate cortex (ACC) in cognitive control as the detection of conflict between competing information streams. Using functional magnetic resonance imaging, we examined the activity of this brain structure during different forms and degrees of conflict between the word and the color dimensions of Stroop stimuli. Overall, our results showed a dissociation between the degree of conflict and ACC activation. More specifically, although ACC activation was very extensive when print color interfered with word reading performance, the level of conflict, as measured by reaction time costs, was only moderate compared to other conditions. These results suggest that either the ACC is differentially sensitive to various types of conflict or its function should be extended to include other cognitive constructs, such as resolution of prior inhibition.

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.

A systematic meta-review grading the evidence for non-genetic risk factors and putative antecedents of schizophrenia

INTRODUCTION Identifying the relative strength of evidence associated with non-genetic risk factors and putative antecedents of schizophrenia will guide research and may inform the design of early detection and intervention strategies. AIMS To present and quality assess current evidence for non-genetic risk factors and putative antecedents derived from well-conducted systematic reviews that report pooled data. METHOD Medline, Embase, CINAHL, Current Contents, and PsycINFO databases were searched systematically, and supplemented by hand searching. Review reporting quality was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, review methodology was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist, and evidence quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS Twenty-four reviews met inclusion criteria. The risk factors with the highest quality evidence, reporting medium effect sizes, were advanced paternal age, obstetric complications, and cannabis use. The strongest evidence among the putative antecedents was identified for motor dysfunction and low IQ. CONCLUSIONS More research is required that applies sound methodological practices, taking into consideration specificity for schizophrenia and possible confounding factors, to robustly identify the non-genetic risk factors and putative antecedents of schizophrenia.