Project description:Schizotypy is a multidimensional construct that captures a continuum of risk for developing schizophrenia-spectrum psychopathology. Existing 3-factor models of schizotypy, consisting of positive, negative, and disorganized dimensions have yielded mixed evidence of genetic continuity with schizophrenia using polygenic risk scores. Here, we propose an approach that involves splitting positive and negative schizotypy into more specific subdimensions that are phenotypically continuous with distinct positive symptoms and negative symptoms recognized in clinical schizophrenia. We used item response theory to derive high-precision estimates of psychometric schizotypy using 251 self-report items obtained from a non-clinical sample of 727 (424 females) adults. These subdimensions were organized hierarchically using structural equation modeling into 3 empirically independent higher-order dimensions enabling associations with polygenic risk for schizophrenia to be examined at different levels of phenotypic generality and specificity. Results revealed that polygenic risk for schizophrenia was associated with variance specific to delusional experiences (γ = 0.093, P = .001) and reduced social interest and engagement (γ = 0.076, P = .020), and these effects were not mediated via the higher-order general, positive, or negative schizotypy factors. We further fractionated general intellectual functioning into fluid and crystallized intelligence in 446 (246 females) participants that underwent onsite cognitive assessment. Polygenic risk scores explained 3.6% of the variance in crystallized intelligence. Our precision phenotyping approach could be used to enhance the etiologic signal in future genetic association studies and improve the detection and prevention of schizophrenia-spectrum psychopathology.
Project description:BackgroundThere is considerable evidence of dysconnectivity within the default-mode network (DMN) in schizophrenia, as measured during resting-state functional MRI (rs-fMRI). History of childhood trauma (CT) is observed at a higher frequency in schizophrenia than in the general population, but its relationship to DMN functional connectivity has yet to be investigated.MethodsCT history and rs-fMRI data were collected in 65 individuals with schizophrenia and 132 healthy controls. Seed-based functional connectivity between each of 4 a priori defined seeds of the DMN (medial prefrontal cortex, right and left lateral parietal lobes, and the posterior cingulate cortex) and all other voxels of the brain were compared across groups. Effects of CT on functional connectivity were examined using multiple regression analyses. Where significant associations were observed, regression analyses were further used to determine whether variance in behavioral measures of Theory of Mind (ToM), previously associated with DMN recruitment, were explained by these associations.ResultsSeed-based analyses revealed evidence of widespread reductions in functional connectivity in patients vs controls, including between the left/right parietal lobe (LP) and multiple other regions, including the parietal operculum bilaterally. Across all subjects, increased CT scores were associated with reduced prefrontal-parietal connectivity and, in patients, with increased prefrontal-cerebellar connectivity also. These CT-associated differences in DMN connectivity also predicted variation in behavioral measures of ToM.ConclusionsThese findings suggest that CT history is associated with variation in DMN connectivity during rs-fMRI in patients with schizophrenia and healthy participants, which may partly mediate associations observed between early life adversity and cognitive performance.
Project description:Childhood trauma (CT) is a risk factor for schizophrenia spectrum disorders (SSDs), and cognitive impairment is a core feature and a vulnerability marker of SSDs. Studies of the relationship between CT and cognitive impairment in SSDs are inconclusive. In addition, few studies have examined differential effects of CT subtypes, e.g. physical, sexual or emotional abuse/neglect, on cognitive functioning. The present study therefore aimed to examine the effects of CT and CT subtypes on cognitive impairment in SSD. Participants (n = 78) with SSDs completed a comprehensive neuropsychological test battery and the Childhood Trauma Questionnaire Short-Form (CTQ-SF). We compared global cognitive performance as well as scores in seven subdomains (verbal abilities, visuospatial abilities, learning, memory, attention/working memory, executive abilities and processing speed) between participants reporting no CT and those reporting CT experiences using independent samples t-tests as well as linear regression analyses to control for possible confounders. CT subtype physical neglect was associated with attention and working memory after controlling for positive and negative psychosis symptoms, years of education, antipsychotics, gender and age, and adjustment of multiple testing. Our results indicate that the observed heterogeneity in cognitive impairment in SSDs, especially attention/working memory abilities, may in part be associated with childhood physical neglect.
Project description:The association of early life adversities and psychosis symptoms is well documented in clinical populations; however, whether this relationship also extends into subclinical psychosis remains unclear. In particular, are early life adversities associated with increased levels of schizotypal personality traits in non-clinical samples? We conducted a systematic review and meta-analysis of associations between early life adversities and psychometrically defined schizotypal traits in non-clinical samples. The review followed PRISMA guidelines. The search using PubMed, Web of Science and EBSCO databases identified 1,609 articles in total. Twenty-five studies (N = 15,253 participants) met eligibility criteria for the review. An assessment of study quality showed that fewer than half of all studies were rated as methodologically robust. Meta-analyses showed that all forms of childhood abuse (emotional, physical and sexual) and neglect (emotional and physical) were significantly associated with psychometric schizotypy. The association of schizotypy traits with childhood emotional abuse (r = .33: 95%CI .30 to .37) was significantly larger than for all other form of abuse or neglect. Meta-regression analyses showed that the physical abuse-schizotypy relationship was stronger in samples with more women participants; and the sexual abuse-schizotypy relationship was stronger in younger samples. The current review identifies a dose-response relationship between all forms of abuse/neglect and schizotypy scores in non-clinical samples; however, a stronger association emerged for emotional abuse. More research is required to address the relationship of trauma types and specific symptom types. Future research should also address the under-representation of men.
Project description:Childhood trauma, and in particular physical neglect, has been repeatedly associated with lower performance on measures of social cognition (e.g. emotion recognition tasks) in both psychiatric and non-clinical populations. The neural mechanisms underpinning this association have remained unclear. Here, we investigated whether volumetric changes in three stress-sensitive regions-the amygdala, hippocampus and anterior cingulate cortex (ACC)-mediate the association between childhood trauma and emotion recognition in a healthy participant sample (N = 112) and a clinical sample of patients with schizophrenia (N = 46). Direct effects of childhood trauma, specifically physical neglect, on Emotion Recognition Task were observed in the whole sample. In healthy participants, reduced total and left ACC volumes were observed to fully mediate the association between both physical neglect and total childhood trauma score, and emotion recognition. No mediating effects of the hippocampus and amygdala volumes were observed for either group. These results suggest that reduced ACC volume may represent part of the mechanism by which early life adversity results in poorer social cognitive function. Confirmation of the causal basis of this association would highlight the importance of resilience-building interventions to mitigate the detrimental effects of childhood trauma on brain structure and function.
Project description:Schizotypal personality traits show similarity with schizophrenia at various levels of analysis. It is generally agreed that schizotypal personality is multidimensional; however, it is still debated whether impulsive nonconformity should be incorporated into theories and measurement of schizotypy. In addition, relatively little is known about the network structure of the four-dimensional model of schizotypal personality. To estimate the network structure of schizotypy, we used data from participants recruited from the community (N = 11,807) who completed the short version of the Oxford-Liverpool Inventory of Feelings and Experiences, a widespread self-report instrument that assesses the positive, negative, disorganised and impulsive domains of schizotypy. We performed community detection, then examined differences between communities in terms of centralities and compared the strength of edges within and between communities. We found communities that almost perfectly corresponded to the a priori-defined subscales (93% overlap, normalised mutual information = 0.74). Items in the disorganisation community had higher closeness centrality relative to items in the other communities (Cliff's Δs ranged from 0.55 to 0.83) and weights of edges within the disorganisation community were stronger as compared to the negative schizotypy and impulsive nonconformity communities (Cliff's Δs = 0.33). Our findings imply that the inclusion of impulsive nonconformity items does not dilute the classical three-factor structure of positive, negative and disorganised schizotypy. The high closeness centrality of disorganisation concurs with theories positing that cognitive slippage and associative loosening are core features of the schizophrenic phenotype.
Project description:Background and hypothesisSchizotypy provides a framework for understanding the developmental nature of psychotic disorders and a means of identifying "at-risk" individuals early in the lifespan. However, there is a lack of prospective longitudinal research examining the relationship between schizotypy in childhood and later psychotic and other mental disorders. We hypothesized that distinct profiles of schizotypy in childhood would be differentially associated with psychotic and other mental disorders emerging later in adolescence.Study designIn a large population cohort of Australian young people (n = 26 837), we prospectively examined the relationship between person-centered profiles of schizotypy identified in middle childhood (age ~11 years) and adolescent diagnoses (age ~13-18 years) across 7 types of mental disorders using multinomial logistic regression.ResultsMembership in any of 3 childhood schizotypy profiles (true schizotypy, affective schizotypy, or introverted schizotypy) was associated with an increased likelihood of being diagnosed with any type of mental disorder in adolescence; effects were strongest for the true schizotypy group (aOR = 3.07, 95% CI = 2.64, 3.57), followed by the introverted (aOR = 1.94, 95% CI = 1.75, 2.15) and affective (aOR = 1.29, 95% CI = 1.13, 1.47) schizotypy groups. Six of the 7 types of mental disorders measured (including psychotic disorders) were associated with at least 1 schizotypy group.ConclusionsSchizotypy in middle childhood is an important correlate of mental disorders in adolescence; however, it does not appear to be specifically associated with psychotic disorders in this age group.
Project description:Schizotypy and psychotic-like experiences (PLE) form part of the wider psychosis continuum and may have brain structural correlates in nonclinical cohorts. This study aimed to compare the effects of differential schizotypy dimensions, PLE, and their interaction on hippocampal subfields and amygdala volumes in the absence of clinical psychopathology. In a cohort of 367 psychiatrically healthy individuals, we assessed schizotypal traits using the Oxford-Liverpool Inventory of Life Experiences (O-LIFE) and PLE using the short form of the Prodromal Questionnaire (PQ-16). Based on high-resolution structural MRI scans, we used automated segmentation to estimate volumes of limbic structures. Sex and total intracranial volume (Step 1), PLE and schizotypy dimensions (Step 2), and their interaction terms (Step 3) were entered as regressors for bilateral amygdala and hippocampal subfield volumes in hierarchical multiple linear regression models. Positive schizotypy, but not PLE, was negatively associated with left amygdala and subiculum volumes. O-LIFE Impulsive Nonconformity, as well as the two-way interaction between positive schizotypy and PLE, were associated with larger left subiculum volumes. None of the estimators for right hemispheric hippocampal subfield volumes survived correction for multiple comparisons. Our findings support differential associations of hippocampus subfield volumes with trait dimensions rather than PLE, and support overlap and interactions between psychometric positive schizotypy and PLE. In a healthy cohort without current psychosis risk syndromes, the positive association between PLE and hippocampal subfield volume occurred at a high expression of positive schizotypy. Further studies combining stable, transient, and genetic parameters are required.
Project description:Background and hypothesisThe role of early adversity and trauma is increasingly recognized in psychosis but treatments for trauma and its consequences are lacking. Psychological treatments need to understand the prevalence of these experiences, the relationship with specific symptoms and identify potentially tractable processes that may be targeted in therapy. It was hypothesized that greater adversity, and specifically abuse rather than neglect, would be associated with positive symptoms and specifically hallucinations. In addition, negative beliefs would mediate the relationship with positive symptoms.Study design292 Patients with treatment resistant psychosis completed measures of early adversity as well as current symptoms of psychosis.Study resultsEarly adversity in the form of abuse and neglect were common in one-third of the sample. Adversity was associated with higher levels of psychotic symptoms generally, and more so with positive rather than negative symptoms. Abuse rather than neglect was associated with positive but not with negative symptoms. Abuse rather than neglect was associated with hallucinations but not delusions. Abuse and neglect were related to negative beliefs about the self and negative beliefs about others. Mediation demonstrated a general relationship with adversity, negative-self, and other views and overall psychotic symptoms but not in relation to the specific experience of abuse and hallucinations. Females were more likely to be abused, but not neglected, than males.ConclusionsWhilst most relationships were modest, they supported previous work indicating that adversity contributes to people with psychosis experiencing distressing symptoms especially hallucinations. Treatments need to address and target adversity.
Project description:BackgroundThe 11th revision of the World Health Organization's International Classification of Diseases (ICD-11) includes a new disorder, complex posttraumatic stress disorder (CPTSD), the diagnostic applicability of which has not been discussed sufficiently in Chinese culture. The network approach to psychopathology enables investigation of the structure of disorders at the symptom level, which allows for analysis of direct symptom interactions. The main objectives of the present study were to explore CPTSD symptom structure and identify key symptoms in CPTSD among young adults in China.MethodsThe present study collected a large, stratified sample of Beijing university students (1368), ranging from 18 to 25 years old, the majority of whom (65.4%) were female. CPTSD symptoms were assessed using the International Trauma Questionnaire (ITQ). A regularized partial correlation network and Bayesian network were applied to estimate the network structure and the upstream symptoms of CPTSD, respectively.ResultsThe regularized partial correlation network showed that the high central symptoms were feelings of failure and hypervigilance, while the bridge symptom between posttraumatic stress disorder (PTSD) and disturbance in self-organization (DSO) domains was long-term upset. The Bayesian network showed that external avoidance and hypervigilance symptoms were upstream in CPTSD symptoms.ConclusionsHypervigilance is a central symptom that can be predictive of other symptoms of CPTSD. While feeling of failure is also a highly central symptom, it may be influenced by other symptoms. In the diagnosis and intervention of CPTSD, more attention should be given to hypervigilance symptoms.