Short communicationNeural substrates of a schizotypal spectrum in typically-developing children: Further evidence of a normal-pathological continuum
Introduction
Schizophrenia is a severe neuropsychiatric condition characterized by unusual sensory/perceptual experiences (hallucinations, delusions), cognitive and linguistic disorganization, odd behavior, social withdrawal, and mood disturbance (DSM-5; [2]). Recent advances in psychiatry recognize that neurodevelopmental (NDD) and neuropsychiatric disorders (NPD) reflect quantitative, dimensional traits that are distributed throughout the general population [7]. Indeed, it has been demonstrated that the schizophrenia phenotype may be represented along a normal-pathological continuum [20], [33]. Even severe symptoms such as hallucinations and delusions are relatively common in the general population [20] with prevalence rates of hallucinations ranging from 10% [53] to over 70% [40], [56]. Forty-three percent of respondents who were not under psychiatric care reported at least some auditory hallucinations [44]. The presence of many key symptoms of schizophrenia, therefore, do not always indicate psychiatric morbidity, but rather, reflect the broad spectrum of human experiences [20], [27].
Schizotypy refers to multiple personality dimensions that represents an endophenotype along the psychosis continuum. Schizotypy is found in the general population [27], and includes unusual sensory/perceptual experiences, magical thinking, cognitive disorganization, social anxiety, and withdrawal [43]. Along the schizotypal personality dimension, those at the higher end are at increased risk of schizophrenia [4].
The psychosis continuum may extend beyond the behavioral manifestations of the phenotype; common neural substrates appear to underlie severe, prodromal, and mild symptom expression [33]. For example, similar neural structural and functional variations have been observed in unaffected family members of clinically-affected probands with psychotic disorders [9]. Establishing brain-behavior links in both clinically-significant behaviors and those that occur as part of typical development is a particularly important step in understanding the continuities and discontinuities that exist between normal and pathological behavior.
A range of brain atypicalities, including enlarged ventricle volumes [10] and compromised white matter structure [23], have been noted in schizophrenia. However, findings of grey matter (GM) abnormalities are reported most consistently in the schizophrenia literature. A recent meta-review has implicated GM abnormalities in schizophrenia with remarkable reliability [48]. Findings from 32 systematic reviews confirm high consistency across studies, pointing to GM reductions of the anterior cingulate cortex, middle and superior temporal gyri, various frontal regions, amygdala, hippocampus, thalamus, and insula [29].
Some of these GM abnormalities are independent of severity, chronicity, and medication status, and may constitute an endophenotype for schizophrenia [41], [54]. Indeed, several recent meta-analytic and empirical studies have confirmed that individuals who are at risk, or exhibit only mild, sub-clinical psychotic-like behavior show similar GM volume reductions as do patients with schizophrenia. These findings were observed in siblings of individuals with schizophrenia [5], [8], [32], [38]; “at-risk” individuals who show subthreshold psychotic symptoms [39], [57]; and individuals with schizotypal personality disorder [13], [18].
Although findings confirm that GM abnormalities are detectable before the onset of schizophrenia, the functional significance of these GM abnormalities is not well characterized. In individuals with schizophrenia, reduced GM volume in the temporal lobes has been linked to positive symptoms such as hallucinations and delusions [35], [36], [37], [50], whereas GM reduction in the frontal regions has been associated with negative symptoms (e.g., withdrawal) [37], [45], [58]. Overall, schizotypal symptoms have been linked to similar GM abnormalities (for a comprehensive overview please see [15], and [30]).
To date, only four neuroimaging studies have examined schizotypal and other psychosis-spectrum symptoms in healthy individuals, and these have yielded inconsistent results. One study [12] reports that adults who scored high (above the median) on the Schizotypal Personality Questionnaire (SPQ; [42]) had less GM volume and cortical thickness in the frontal lobes (rostral middle frontal gyrus) and less GM and cortical thickness in the temporal lobes, relative to those scoring low (below the median) in schizotypy. Similarly, Ettinger et al. [14] report that adults’ scores on the Rust Inventory of Schizotypal Cognitions [46] were negatively associated with GM volume in the medial prefrontal area including the superior and orbital medial frontal gyri, the anterior cingulum, and the insula, middle and superior temporal cortex. In contrast, others [31], [34] report positive associations between psychotic and schizotypal symptoms and GM volume. For example, when comparing the highest (N = 38) and lowest (N = 38) subjects on a measure of positive psychotic symptoms, that the high-scoring group had greater GM volumes in the medial posterior cingulate cortex and the precuneus. These psychotic symptoms were linearly (positively) correlated with GM in the cingulum and precuneus. Nenadic et al. [34] reported positive correlations between dimensions of the schizotypal and psychotic symptoms (using Schizotypal Personality Questionnaire and the Community Assessment of Psychic Experiences) and GM volumes, in the inferior frontal cortices (bilateral), right superior frontal, right supplementary motor area (SMA), and the left inferior parietal cortex. After correcting for multiple comparisons, however, the only positive association remaining was between the negative schizotypy symptoms and the right precuneus.
In summary, previous work has identified a behavioral continuum of psychotic and schizotypal traits that span from typically functioning healthy individuals, to those exhibiting prodromal psychotic states, up to fully-developed schizophrenia. Recent work suggests this continuum may extend to the neuroanatomic level, as manifested in GM abnormalities. However, the directionality of the associations between psychotic and schizotypal dimensions and GM volumes in healthy individuals have thus far been inconsistent, with some [14], [12] reporting negative associations between GM volumes and schizotypy scores in healthy adults, while others [31], [34] report positive associations. Two of these previous studies have dichotomized the construct, by examining the median split or extreme groups of the schizotypal continuum. Furthermore, these studies have been limited to adults and have combined male and female participants, despite known age and sex differences in brain morphology and psychosis risk. Finally, although schizotypy is a multidimensional construct [27], previous studies have treated it largely as unitary construct, focusing only on the overall scores, thereby potentially obscuring differential patterns of relationships between different trait dimensions and particular brain substrates. The aim of our study was to examine the relationship between dimensions of psychotic and schizotypal behavior and brain structures in typically developing children. Indeed, this is the first study of its kind to examine brain-behavior links in the psychosis/schizotypy continuum in healthy children using a dimensional measure designed for children.
Here we examine normal variations in GM content in a cohort of typically-developing children. We focus on structures that have been consistently implicated in fully developed schizophrenia and studies that have explored relationship between schizotypy in healthy and at risk individuals. We relate the volumetric indices of these structures to a continuously distributed measure of cognitive, sensory-perceptual, emotional, social, and behaviour functioning in typical children, using a recently developed measure of the schizotypy/psychosis continuum normed on a nationally-representative sample. We also explore gender-specific patterns of these brain-behaviour links.
Section snippets
Subjects
Twenty-eight children (14 males, 14 females) ranging in age from 6 to 17 years, participated in this study. Families were recruited from a rural, demographically stable community in central Pennsylvania. All families were screened for the presence of psychological and psychiatric illnesses in first-degree relatives. Children were within the normal range of intellectual functioning (See Table 1).
Measures
The Psychiatric and Schizotypal Inventory for Children (PSI-C; [16] Evans et al. under review) is a
Results
Males and females did not differ on either the PSI-C total scores nor on the Cognitive Disorganization/Impulsivity, Unusual Sensory-Perceptual/Magical Thinking, and Social Anxiety/Withdrawal subscales (all p-values > 0.20). In this sample the Cronbach alpha was 0.88, 0.63 and 0.75 for Cognitive Disorganization/Impulsivity, Unusual Sensory-Perceptual/Magical Thinking, and Social Anxiety/Withdrawal factors, respectively.
The findings revealed several significant and sexually-dimorphic associations
Discussion
In this study, we examined the links between psychotic and schizotypal traits and structural grey matter (GM) volume in regions previously implicated in schizophrenia, schizotypal personality disorder, at-risk populations, and healthy adults. Most notably, GM volume in the left medial temporal gyrus was strongly linked to and unusual sensory-perceptions/magical thinking and cognitive disorganization/impulsivity in males. For females, unusual sensory-perceptions/magical thinking was negatively
Conclusion
This is the first study to extrapolate the links between neural correlates that are implicated in psychotic disorders to the dimensions of the psychosis-like phenotype in typically-developing children without familial risk for any NDD/NPD. These findings have implications for understanding the full range of psychotic-like behaviour as it manifests in the typical population.
Funding
This research was supported by the Bucknell-Geisinger Research Initiative (BGRI) awarded to DWE and GJM.
References (58)
- et al.
Voxel-based morphometry—the methods
Neuroimage
(2000) - et al.
Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder
Schizophr. Res.
(2002) - et al.
Intergenerational transmission of subthreshold autistic traits in the general population
Biol. Psychol.
(2005) - et al.
Multimodal voxel-based meta-analysis of structural and functional magnetic resonance imaging studies in those at elevated genetic risk of developing schizophrenia
Psychiatry Res.: Neuroimaging
(2014) - et al.
Quantification of frontal and temporal lobe brain-imaging findings in schizophrenia: a meta-analysis
Psychiatry Res.
(2003) - et al.
The cognitive functions of the caudate nucleus
Prog. Neurobiol.
(2008) - et al.
The continuity of psychotic experiences in the general population
Clin. Psychol. Rev.
(2001) - et al.
Reduction of caudate nucleus volumes in neuroleptic-naive female subjects with schizotypal personality disorder
Biol. Psychiatry
(2006) - et al.
A review of diffusion tensor imaging studies in schizophrenia
J. Psychiatr. Res.
(2007) - et al.
Brain-behaviour relationships in people at high genetic risk of schizophrenia
Neuroimage
(2006)
Basal ganglia shape abnormalities in the unaffected siblings of schizophrenia patients?
Biol. Psychiatry
The Oxford-Liverpool inventory of feelings and experiences: further description and extended norms
Schizophr. Res.
Neuroanatomical deficits in drug-naive adult patients with generalized social anxiety disorder: a voxel-based morphometry study
Psychiatry Res.
Does function follow form?: : Methods to fuse structural and functional brain images show decreased linkage in schizophrenia
Neuroimage
The concept of schizotypy — a computational anatomy perspective
Schizophr. Res.: Cognit.
Evidence of a dimensional relationship between schizotypy and schizophrenia: a systematic review
Neurosci. Biobehav. Rev.
Brain structural correlates of schizotypy and psychosis proneness in a non-clinical healthy volunteer sample
Schizophr. Res.
Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia
Schizophr. Res.
The neuroanatomy of psychotic diathesis: a meta-analytic review
J. Psychiatr. Res.
Neuroanatomical abnormalities before and after onset of psychosis: a cross-sectional and longitudinal MRI comparison
Lancet
Systematic meta-review and quality assessment of the structural brain alterations in schizophrenia
Neurosci. Biobehav. Rev.
Cognitive and brain function in schizotypal personality disorder
Schizophr. Res.
A multivariate perspective on schizotypy and familial association with schizophrenia: a review
Clin. Psychol. Rev.
Reliability of the amplitude of low-frequency fluctuations in resting state in chronic schizophrenia
Psychiatry Res.
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study
Psychiatry Res.
The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others’ emotions
Brain Behav.
Diagnostic and Statistical Manual of Mental Disorders
The role of schizotypy in the study of the etiology of schizophrenia-spectrum disorders
Schizophr. Bull.
Cited by (7)
Subcortical surface shape in youth at familial high risk for schizophrenia
2017, Psychiatry Research - NeuroimagingCitation Excerpt :Additionally, our investigation revealed a correlation between left amygdala regional shape displacement and schizotypy score in HC only. In an analysis of typically developing HC female children, left amygdala gray matter volume correlated with schizotypy scores such that increased social anxiety and withdrawal was associated with decreased volume (Evans et al., 2016). Furthermore, in a study among adolescents with mild intellectual impairments, those with higher schizotypy scores had more gray matter loss in the left amygdala than those with low schizotypy scores (Moorhead et al., 2009).
Empathy and schizotypy following acquired brain damage
2021, British Journal of Clinical PsychologyDevelopmental trajectories of cortical thickness in relation to schizotypy during adolescence
2020, Schizophrenia BulletinSchizotypal traits are associated with sleep spindles and rapid eye movement in adolescence
2019, Journal of Sleep Research