A Review of Structural MRI and Diffusion Tensor Imaging in Schizotypal Personality Disorder

Individuals with schizotypal personality disorder (SPD) share genetic, phenomenologic, and cognitive abnormalities with people diagnosed with schizophrenia. To date, 15 structural MRI studies of the brain have examined size, and 3 diffusion tensor imaging studies have examined white matter connectivity in SPD. Overall, both types of structural neuroimaging modalities have shown temporal lobe abnormalities similar to those observed in schizophrenia, while frontal lobe regions appear to show more sparing. This intriguing pattern suggests that frontal lobe sparing may suppress psychosis, which is consistent with the idea of a possible neuroprotective factor. In this paper, we review these 18 studies and discuss whether individuals with SPD who both resemble and differ from schizophrenia patients in their phenomenology, share some or all of the structural brain imaging characteristics of schizophrenia. We attempt to group the MRI abnormalities in SPD into three patterns: 1) a spectrum of severity—abnormalities are similar to those observed in schizophrenia but not so severe; 2) a spectrum of region—abnormalities affecting some, but not all, brain regions affected in schizophrenia; and 3) a spectrum of compensation—abnormalities reflecting greater-than-normal white matter volume, possibly serving as a buffer or compensatory mechanism protecting the individual with SPD from the frank psychosis observed in schizophrenia

Characterization of the Fiber Connectivity Profile of the Cerebral Cortex in Schizotypal Personality Disorder: A Pilot Study

Schizotypal personality disorder (SPD) is considered one of the classic disconnection syndromes. However, the specific cortical disconnectivity pattern has not been fully investigated. In this study, we aimed to explore significant alterations in whole-cortex structural connectivity in SPD individuals (SPDs) by combining the techniques of brain surface morphometry and white matter (WM) tractography. Diffusion and structural MR data were collected from twenty subjects with SPD (all males; age, 19.7 ± 0.9 yrs) and eighteen healthy controls (all males; age, 20.3 ± 1.0 yrs). To measure the structural connectivity for a given unit area of the cortex, the fiber connectivity density (FiCD) value was proposed and calculated as the sum of the fractional anisotropy of all the fibers connecting to that unit area in tractography. Then, the resultant whole-cortex FiCD maps were compared in a vertex-wise manner between SPDs and controls. Compared with normal controls, SPDs showed significantly decreased FiCD in the rostral middle frontal gyrus (crossing BA9 and BA10) and significantly increased FiCD in the anterior part of the fusiform/inferior temporal cortex (P < 0.05, Monte Carlo simulation corrected). Moreover, the gray matter volume extracted from the left rostral middle frontal cluster was observed to be significantly greater in the SPD group (P = 0.02). Overall, this study identifies a decrease in connectivity in the left middle frontal cortex as a key neural deficit at the whole-cortex level in SPD, thus providing insight into its neuropathological basis

The concept of schizotypy — A computational anatomy perspective

AbstractDespite major progress in diagnostic accuracy and symptomatic treatment of mental disorders, there is an ongoing debate about their classification aiming to follow current advances in neurobiology. The main goal of this review is to provide a comprehensive summary of the put forward schizotypy concept that follows the needs for objective assessment of schizophrenia-like personality traits in the general population. We focus on major achievements in the field from the perspective of magnetic resonance imaging-based computational anatomy of the brain. Particular interest is devoted to overlapping brain structure findings in schizotypy and schizophrenia to promote a dimensional view on schizophrenia as extension of phenotype traits in the non-clinical general population

Structural integrity of the uncinate fasciculus in geriatric depression: relationship with age of onset

pre-printBackground: The uncinate fasciculus connects limbic structures, such as the hippocampus and amygdala, with frontal regions. This study utilized diffusion tensor imaging to examine the structural integrity of the uncinate fasciculus in late-life depression. Method: 18 elderly depressed and 19 elderly nondepressed subjects were matched for age and sex; 8 subjects had mid- to late-onset of depression while 10 subjects had early-onset depression. 3T diffusion tensor imaging-based fiber tract mapping delineated the uncinate fasciculus in each hemisphere, which guided measurement of the fractional anisotropy of the uncinate fasciculus in the temporal stem. After controlling for age and sex, differences between diagnostic groups were assessed. Results: After controlling for age and sex, individuals with early onset depression exhibited lower anisotropy of the left uncinate fasciculus than did mid- and late-onset or nondepressed subjects (F2,36 = 4.50, p = 0.02). Analyses of the right uncinate fasciculus were not statistically significant. Conclusions: This provides preliminary evidence that there is a structural connectivity deficit between left frontal and limbic structures in early-onset depression. Further work is needed to determine if this is seen in younger depressed subjects, and if it influences treatment outcomes

Evidence from structural and diffusion tensor imaging for frontotemporal deficits in psychometric schizotypy

BACKGROUND: Previous studies of nonclinical samples exhibiting schizotypal traits have provided support for the existence of a continuous distribution of psychotic symptoms in the general population. Few studies, however, have examined the neural correlates of psychometric schizotypy using structural and diffusion tensor imaging (DTI). METHODS: Healthy volunteers between the ages of 18 and 68 were recruited from the community and assessed using the Schizotypal Personality Questionnaire and received structural and DTI exams. Participants with high (N = 67) and low (N = 71) psychometric schizotypy were compared on gray and white matter volume, and cortical thickness in frontal and temporal lobe regions and on fractional anisotropy (FA) within 5 association tracts traversing the frontal and temporal lobes. RESULTS: Higher levels of schizotypy were associated with lower overall volumes of gray matter in both the frontal and temporal lobes and lower gray matter thickness in the temporal lobe. Regionally specific effects were evident in both white matter and gray matter volume of the rostral middle frontal cortex and gray matter volume in the pars orbitalis. Moreover, relative to individuals who scored low, those who scored high in schizotypy had lower FA in the inferior fronto-occipital fasciculus as well as greater asymmetry (right \u3e left) in the uncinate fasciculus. CONCLUSIONS: These findings are broadly consistent with recent data on the neurobiological correlates of psychometric schizotypy as well as findings in schizotypal personality disorder and schizophrenia and suggest that frontotemporal lobe dysfunction may represent a core component of the psychosis phenotype

Morphometric and connectivity white matter abnormalities in Obsessive Compulsive Disorder

Two psychological mechanisms seem to be associated with the obsessive-compulsive cycle: (1) an emotional mechanism characterized by intense emotional arousal associated with intrusive thoughts of impending danger; (2) a cognitive mechanism exemplified by difficulties with inhibitory control. Several studies found more extensive cognitive deficits in Obsessive Compulsive Disorder (OCD) beyond problems of inhibitory control and emotional regulation, namely: visual-spatial processing and memory. Thus, there is now extensive research showing that alterations of these psychological mechanisms in OCD (i.e., inhibitory control, emotional regulation, working memory, and visual spatial processing) are associated with morphological gray matter alterations in widespread brain regions. More recently, researchers have started looking at white matter abnormalities in OCD. In this article we review the research looking at white matter morphometric and structural connectivity alterations in OCD. Altogether, while some contradictory findings are still present, there is now evidence for widespread white matter morphometric and connectivity abnormalities affecting major white matter tracts (superior longitudinal fasciculus, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, cingulum bundle, semioval center, internal capsule, different regions of the corpus callosum, thalamic radiation, uncinate fasciculus and optic radiation) as well as white matter in regions adjacent to gray matter structures (superior frontal gyrus, dorsolateral prefrontal medial frontal cortex; inferior frontal gyrus, caudate, insulate cortex, parietal cortex, supramarginal and lingual gyri, and thalamus). These white matter alterations may help explaining the diversity of OCD psychological impairments in inhibitory control, emotional regulation, memory and visual spatial processing.The authors have no financial or personal conflicts of interest. The first author was funded by the Brazilian National Counsel for Scientific and Technological Development (CNPq) as a Special Visiting Researcher of the Science Without Borders program (grant number: 401143/2014-7). This study was partially conducted at the Neuropsychophysiology Lab from the Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145- FEDER-007653).info:eu-repo/semantics/publishedVersio

Neurobiological Changes of Schizotypy: Evidence From Both Volume-Based Morphometric Analysis and Resting-State Functional Connectivity

The current study sought to examine the underlying brain changes in individuals with high schizotypy by integrating networks derived from brain structural and functional imaging. Individuals with high schizotypy (n = 35) and low schizotypy (n = 34) controls were screened using the Schizotypal Personality Questionnaire and underwent brain structural and resting-state functional magnetic resonance imaging on a 3T scanner. Voxel-based morphometric analysis and graph theory-based functional network analysis were conducted. Individuals with high schizotypy showed reduced gray matter (GM) density in the insula and the dorsolateral prefrontal gyrus. The graph theoretical analysis showed that individuals with high schizotypy showed similar global properties in their functional networks as low schizotypy individuals. Several hubs of the functional network were identified in both groups, including the insula, the lingual gyrus, the postcentral gyrus, and the rolandic operculum. More hubs in the frontal lobe and fewer hubs in the occipital lobe were identified in individuals with high schizotypy. By comparing the functional connectivity between clusters with abnormal GM density and the whole brain, individuals with high schizotypy showed weaker functional connectivity between the left insula and the putamen, but stronger connectivity between the cerebellum and the medial frontal gyrus. Taken together, our findings suggest that individuals with high schizotypy present changes in terms of GM and resting-state functional connectivity, especially in the frontal lobe

White Matter Integrity, Creativity, and Psychopathology: Disentangling Constructs with Diffusion Tensor Imaging

That creativity and psychopathology are somehow linked remains a popular but controversial idea in neuroscience research. Brain regions implicated in both psychosis-proneness and creative cognition include frontal projection zones and association fibers. In normal subjects, we have previously demonstrated that a composite measure of divergent thinking (DT) ability exhibited significant inverse relationships in frontal lobe areas with both cortical thickness and metabolite concentration of N-acetyl-aspartate (NAA). These findings support the idea that creativity may reside upon a continuum with psychopathology. Here we examine whether white matter integrity, assessed by Fractional Anisotropy (FA), is related to two measures of creativity (Divergent Thinking and Openness to Experience). Based on previous findings, we hypothesize inverse correlations within fronto-striatal circuits. Seventy-two healthy, young adult (18–29 years) subjects were scanned on a 3 Tesla scanner with Diffusion Tensor Imaging. DT measures were scored by four raters (α = .81) using the Consensual Assessment Technique, from which a composite creativity index (CCI) was derived. We found that the CCI was significantly inversely related to FA within the left inferior frontal white matter (t = 5.36, p = .01), and Openness was inversely related to FA within the right inferior frontal white matter (t = 4.61, p = .04). These findings demonstrate an apparent overlap in specific white matter architecture underlying the normal variance of divergent thinking, openness, and psychotic-spectrum traits, consistent with the idea of a continuum

Girls’ Internalizing Symptoms and White Matter Tracts in Cortico-Limbic Circuitry

Dysfunction in cortico-limbic circuitry is implicated in internalizing disorders, but less is known about whether structural abnormalities precede disorder, thus potentially marking risk. I therefore examined associations between white matter tract integrity in cortico-limbic circuitry at age 7, obtained using Diffusion Tensor Imaging, and concurrent and longitudinal patterns of internalizing symptoms, over a 5-year period, in 42 typically developing girls. Using Automated Fiber Quantification, diffusion properties were examined at multiple points along tract length (cf., an average diffusion measure of the entire tract). Concurrent internalizing symptoms were associated with reduced fractional anisotropy in segments of the cingulum bundle and uncinate fasciculus, bilaterally. Moreover, latent profile analysis showed that girls with increasing internalizing symptoms in early and middle childhood had reduced fractional anisotropy in these segments compared to girls with stably low internalizing symptoms. These results point to a putative neural mechanism underlying the course of internalizing symptoms in early childhood