Modelling the overlap and divergence of autistic and schizotypal traits on hippocampal subfield volumes and regional cerebral blood flow.

Psychiatric disorders show high co-morbidity, including co-morbid expressions of subclinical psychopathology across multiple disease spectra. Given the limitations of classical case-control designs in elucidating this overlap, new approaches are needed to identify biological underpinnings of spectra and their interaction. We assessed autistic-like traits (using the Autism Quotient, AQ) and schizotypy - as models of subclinical expressions of disease phenotypes and examined their association with volumes and regional cerebral blood flow (rCBF) of anterior, mid- and posterior hippocampus segments from  structural MRI scans in 318 and arterial spin labelling (ASL) in 346 nonclinical subjects, which overlapped with the structural imaging sample (N = 298). We demonstrate significant interactive effects of positive schizotypy and AQ social skills as well as of positive schizotypy and AQ imagination on hippocampal subfield volume variation. Moreover, we show that AQ attention switching modulated hippocampal head rCBF, while positive schizotypy by AQ attention to detail interactions modulated hippocampal tail rCBF. In addition, we show significant correlation of hippocampal volume and rCBF in both region-of-interest and voxel-wise analyses, which were robust after removal of variance related to schizotypy and autistic traits. These findings provide empirical evidence for both the modulation of hippocampal subfield structure and function through subclinical traits, and in particular how only the interaction of phenotype facets leads to significant reductions or variations in these parameters. This makes a case for considering the synergistic impact of different (subclinical) disease spectra on transdiagnostic biological parameters in psychiatry.

Nonclinical psychotic-like experiences and schizotypy dimensions: Associations with hippocampal subfield and amygdala volumes.

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.

Subclinical schizotypal vs. autistic traits show overlapping and diametrically opposed facets in a non-clinical population.

BACKGROUND: The overlap of autism spectrum disorder (ASD) and psychosis or schizophrenia spectrum disorders (SSD) has exposed problems central to conceptualising and understanding co-morbidity in psychiatric disorders. METHODS: In the present study, we demonstrate that a deep phenotyping approach aids clarification of both overlapping and diametrically opposed features of ASD and SSD on the level of trait facets. RESULTS: We first show overlap of negative and disorganised (but not positive) features of schizotypy with autistic traits in a sample of n = 376 German non-clinical subjects using multiple psychometric measures of schizotypy (MSS multidimensional schizotypy scale, OLIFE Oxford-Liverpool Inventory of Feelings and Experiences, and SPQ-B schizotypal personality questionnaire - brief) and the AQ autism spectrum quotient, with control measures for affective spectrum pathology (BDI). Findings were then replicated in a French-Swiss sample (n = 264) using MSS, OLIFE, AQ, and in addition the Community Assessment of Psychic Experiences (CAPE). Additional principal component analysis confirmed our finding of the co-existence of both overlapping (loss of function, social communication deficit, and negative schizotypy) as well as diametrically opposed features (AQ attention to detail, positive schizotypy) across the two spectra. Results were validated with Horn's parallel analyses, affirming two component solutions, and PCA using sample-specific, factor-analysis-derived schizotypy scores. CONCLUSIONS: Providing a framework for multi-dimensional transdiagnostic characterisation of ASD vs. SSD phenotypes we point out overlapping vs. discriminating facets. In addition to the use of novel multidimensional schizotypy scales, it also shows transcultural consistency of findings, and highlights a particular role for the attention to detail AQ subscale.

Associations of subclinical autistic-like traits with brain structural variation using diffusion tensor imaging and voxel-based morphometry.

BACKGROUND: Previous case-control studies of autistic spectrum disorder (ASD) have identified altered brain structure such as altered frontal and temporal cortex volumes, or decreased fractional anisotropy (FA) within the inferior fronto-occipital fasciculus in patients. It remains unclear whether subclinical autistic-like traits might also be related to variation in these brain structures. METHODS: In this study, we analyzed magnetic resonance imaging (MRI) data of 250 psychiatrically healthy subjects phenotyped for subclinical autistic-like traits using the Autism Spectrum Quotient (AQ). For data analysis, we used voxel-based morphometry of T1-MRIs (Computational Anatomy Toolbox) and tract-based spatial statistics for diffusion tensor imaging data. RESULTS: AQ attention switching subscale correlated negatively with FA values in the bilateral uncinate fasciculus as well as the bilateral inferior fronto-occipital fasciculus. Higher AQ attention switching subscale scores were associated with increased mean diffusivity and radial diffusivity values in the uncinate fasciculus, while axial diffusivity values within this tract show a negative correlation. AQ attention to detail subscale correlated positively with gray matter volume in the right pre- and postcentral gyrus. CONCLUSIONS: We demonstrate that individuals with higher levels of autism-spectrum-like features show decreased white matter integrity in tracts associated with higher-level visual processing and increased cortical volume in areas linked to movement sequencing and working memory. Our results resemble regional brain structure alterations found in individuals with ASD. This offers opportunities to further understand the etiology and pathogenesis of the disorder and shows a subclinical continuum perspective.

Distress severity in perceptual anomalies moderates the relationship between prefrontal brain structure and psychosis proneness in nonclinical individuals.

In the general population, psychosis risk phenotypes occur independently of attenuated prodromal syndromes. Neurobiological correlates of vulnerability could help to understand their meaningfulness. Interactions between the occurrence of psychotic-like experiences (PLE) and other psychological factors e.g., distress related to PLE, may distinguish psychosis-prone individuals from those without risk of future psychotic disorder. We aimed to investigate whether (a) correlates of total PLE and distress, and (b) symptom dimension-specific moderation effects exist at the brain structural level in non-help-seeking adults reporting PLE below and above the screening criterion for clinical high-risk (CHR). We obtained T1-weighted whole-brain MRI scans from 104 healthy adults from the community without psychosis CHR states for voxel-based morphometry (VBM). Brain structural associations with PLE and PLE distress were analysed with multiple linear regression models. Moderation of PLE by distress severity of two types of positive symptoms from the Prodromal Questionnaire (PQ-16) screening inventory was explored in regions-of-interest after VBM. Total PQ-16 score was positively associated with grey matter volume (GMV) in prefrontal regions, occipital fusiform and lingual gyri (p < 0.05, FDR peak-level corrected). Overall distress severity and GMV were not associated. Examination of distress severity on the positive symptom dimensions as moderators showed reduced strength of the association between PLE and rSFG volume with increased distress severity for perceptual PLE. In this study, brain structural variation was related to PLE level, but not distress severity, suggesting specificity. In healthy individuals, positive relationships between PLE and prefrontal volumes may indicate protective features, which supports the insufficiency of PLE for the prediction of CHR. Additional indicators of vulnerability, such as distress associated with perceptual PLE, change the positive brain structure relationship. Brain structural findings may strengthen clinical objectives through disentanglement of innocuous and risk-related PLE.

Untangling the complex relationships between symptoms of schizophrenia and emotion dynamics in daily life: Findings from an experience sampling pilot study.

The unfolding of emotions over time (i.e., emotion dynamics) has been characterized by baseline, intraindividual variability and regulatory tendency (return time to baseline after deflection). Mounting evidence suggests that compared to healthy individuals, individuals with schizophrenia are characterized by a more negatively valenced baseline and a higher intraindividual variability. However, the regulatory tendency has not been investigated in schizophrenia so far. We hypothesize that the severity of positive symptoms is linked to increased emotional variability and that the severity of negative symptoms is associated with an increased regulatory tendency. Fifteen individuals diagnosed with schizophrenia took part in this pilot experience sampling study and reported their emotional state ten times a day. The dynamics of valence and arousal and their relationship with symptomatology were estimated with the DynAffect model. Regulatory tendency in valence and arousal was positively associated with negative symptom severity and negatively associated with positive symptom severity. However, the severity of positive symptoms was not credibly associated with the variability of valence. The study only partly corroborates findings on increased stress reactivity in schizophrenia, which might be due to the small sample size. However, results suggest that negative symptoms could stem from over-regulated emotion dynamics, which may impede goal-directed behavior.

Cognitive emotion regulation in patients with schizophrenia: Evidence for effective reappraisal and distraction.

Negative emotions trigger psychotic symptoms, according to a growing body of evidence. Thus, there is a need for effective emotion regulation in schizophrenia. Reappraisal is an effective, cognitive emotion regulation strategy in healthy individuals. However, it is an open research question whether individuals with schizophrenia have difficulties in successfully applying reappraisal. This study experimentally tests the efficacy of reappraisal compared to distraction in patients with schizophrenia and non-clinical controls. An experimental design with group as between-subject factor (non-clinical controls versus patients with schizophrenia) and emotion regulation during anxiety induction as within-subject factor (reappraisal, distraction, no regulation). Seventeen patients with schizophrenia and 27 healthy participants were instructed to respond to anxiety-inducing stimuli by either using reappraisal, distraction or by just watching. Both reappraisal and distraction were effective in down-regulating anxiety, compared to no regulation. The main effect of group and the interaction of emotion regulation condition and group were not significant indicating that the efficacy of both cognitive emotion regulation strategies was independent of group. Patients with schizophrenia are able to apply reappraisal successfully under experimental conditions. Conclusions are limited by the small sample size of this pilot study. Clinical implications for cognitive behavioral therapy for psychosis are discussed.