Progressive structural brain changes during development of psychosis

Background:

Ultra-high risk (UHR) for psychosis has been associated with widespread structural brain changes in young adults. The onset of these changes and their subsequent progression over time are not well understood.

Methods:

Rate of brain change over time was investigated in 43 adolescents at UHR for psychosis compared with 30 healthy controls. Brain volumes (total brain, gray matter, white matter [WM], cerebellum, and ventricles), cortical thickness, and voxel-based morphometry were measured at baseline and at follow-up (2 y after baseline) and compared between UHR individuals and controls. Post hoc analyses were done for UHR individuals who became psychotic (N = 8) and those who did not (N = 35).

Results:

UHR individuals showed a smaller increase in cerebral WM over time than controls and more cortical thinning in the left middle temporal gyrus. Post hoc, a more pronounced decrease over time in total brain and WM volume was found for UHR individuals who became psychotic relative to controls and a greater decrease in total brain volume than individuals who were not psychotic. Furthermore, UHR individuals with subsequent psychosis displayed more thinning than controls in widespread areas in the left anterior cingulate, precuneus, and temporo-parieto-occipital area. Volume loss in the individuals who developed psychosis could not be attributed to medication use.

Conclusion:

The development of psychosis during adolescence is associated with progressive structural brain changes around the time of onset. These changes cannot be attributed to (antipsychotic) medication use and are therefore likely to reflect a pathophysiological process related to clinical manifestation of psychosis.     

White Matter Development in Adolescence: Diffusion Tensor Imaging and Meta-Analytic Results

Background

In light of the evidence for brain white matter (WM) abnormalities in schizophrenia, study of normal WM maturation in adolescence may provide critical insights relevant to the neurodevelopment of the disorder. Voxel-wise diffusion tensor imaging (DTI) studies have consistently demonstrated increases in fractional anisotropy (FA), a putative measure of WM integrity, from childhood into adolescence. However, the WM tracts that show FA increases have been variable across studies. Here, we aimed to assess which WM tracts show the most pronounced changes across adolescence.

Methods

DTI was performed in 78 healthy subjects aged 8–21 years, and voxel-wise analysis conducted using tract-based spatial statistics (TBSS). In addition, we performed the first meta-analysis of TBSS studies on WM development in adolescence.

Results

In our sample, we observed bilateral increases in FA with age, which were most significant in the left superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and anterior thalamic radiation. These findings were confirmed by the meta-analysis, and FA increase in the bilateral SLF was the most consistent finding across studies. Moreover, in our sample, FA of the bilateral SLF showed a positive association with verbal working memory performance and partially mediated increases in verbal fluency as a function of increasing age.

Conclusions

These data highlight increasing connectivity in the SLF during adolescence. In light of evidence for compromised SLF integrity in high-risk and first-episode patients, these data suggest that abnormal maturation of the SLF during adolescence may be a key target in the neurodevelopment of schizophrenia.     

Hippocampal subdivision and amygdalar volumes in patients in an at-risk mental state for schizophrenia

Background

Accumulating evidence from postmortem and magnetic resonance imaging (MRI) studies suggests that abnormalities of medial temporal lobe structures are critically involved in the pathogenesis of schizophrenia. It is still unclear, however, whether certain abnormalities are already present in individuals at ultra high-risk (UHR) for transition into psychosis. Recent studies involving patients at UHR showed contradictory results for hippocampal volume, and only 1 study reported that amygdalar volume was unchanged between healthy patients and those at UHR. Furthermore, no subregions of the hippocampus have been investigated in people at UHR.

Methods

We recruited 29 UHR patients, 23 first-episode patients and 29 age-and sex-matched healthy controls. We measured hippocampal and amygdalar volumes from MRI scans by use of BRAINS2 to manually trace the regions of interest. The hippocampi were divided in 2 regions: head and corpus/tail.

Results

Patients at UHR had significantly smaller volumes of the hippocampus corpus and tail bilaterally, but not of the head, compared with healthy controls. Group differences for the right hippocampus corpus and tail volume remained significant after we controlled for whole brain volume and other covariates. We found that UHR patients who later developed psychosis had smaller right hippocampus corpus and tail volumes than did those who did not develop psychosis. First-episode patients had significantly smaller left amygdalar volumes than did healthy individuals or those at UHR.

Limitations

Our study had a small sample size, and we were unable to control for the effects of medication.

Conclusion

Our findings suggest that parts of the hippocampal–amygdalar complex are involved in the pathogenesis of schizophrenia. Reduction of hippocampus corpus and tail volumes may be indicative of the prodromal phase of schizophrenia and represent risk factors for transition into psychosis. Further investigations are needed to determine whether structural changes of the left amygdala play a role during transition from the prodromal phase to the first manifest episode of schizophrenia.     

Comparing Fractional Anisotropy in Patients With Childhood-Onset Schizophrenia,Their Healthy Siblings,and Normal Volunteers Through DTI

Background:

Diffusion tensor imaging is a neuroimaging method that quantifies white matter (WM) integrity and brain connectivity based on the diffusion of water in the brain. White matter has been hypothesized to be of great importance in the development of schizophrenia as part of the dysconnectivity model. Childhood-onset schizophrenia (COS), is a rare, severe form of the illness that resembles poor outcome adult-onset schizophrenia. We hypothesized that COS would be associated with WM abnormalities relative to a sample of controls.

Methods:

To evaluate WM integrity in this population 39 patients diagnosed with COS, 39 of their healthy (nonpsychotic) siblings, and 50 unrelated healthy volunteers were scanned using a diffusion tensor imaging (DTI) sequence during a 1.5 T MRI acquisition. Each DTI scan was processed via atlas-based analysis using a WM parcellation map, and diffeomorphic mapping that shapes a template atlas to each individual subject space. Fractional anisotropy (FA), a measure of WM integrity was averaged over each of the 46 regions of the atlas. Eleven WM regions were examined based on previous reports of WM growth abnormalities in COS.

Results:

Of those regions, patients with COS, and their healthy siblings had significantly lower mean FA in the left and right cuneus as compared to the healthy volunteers (P < .005). Together, these findings represent the largest DTI study in COS to date, and provide evidence that WM integrity is significantly impaired in COS. Shared deficits in their healthy siblings might result from increased genetic risk.Key words: DTI, COS, siblings, cuneus, FA     

Complementary diffusion tensor imaging study of the corpus callosum in patients with first-episode and chronic schizophrenia

Background

Abnormalities in the corpus callosum have long been implicated in schizophrenia. Previous diffusion tensor imaging (DTI) studies in patients with different durations of schizophrenia yielded inconsistent results. By comparing patients with different durations of schizophrenia, we investigated if white matter abnormalities of the corpus callosum emerge at an early stage in the illness or result from pathological progression.

Methods

We recruited patients with first-episode schizophrenia, patients with chronic schizophrenia and age-, sex-and handedness-matched healthy controls. We used 2 DTI techniques (voxel-based and fibre-tracking DTI) to investigate differences in corpus callosum integrity among the 3 groups.

Results

With both DTI techniques, significantly decreased fractional anisotropy values were identified in the genu of corpus callosum in patients with chronic schizophrenia, but not first-episode schizophrenia, compared with healthy controls.

Limitations

This study was cross-sectional, and the sample size was relatively small.

Conclusion

Abnormalities in the genu of the corpus callosum might be a progressive process in schizophrenia, perhaps related to disease severity and prognosis.     

Depressive Symptoms and Brain Metabolite Alterations in Subjects at Ultra-high Risk for Psychosis: A Preliminary Study

Objective

Recent neuroimaging studies have suggested that brain changes occur in subjects at ultra-high risk (UHR) for psychosis while experiencing prodromal symptoms, among which depression may increase the risk of developing a psychotic disorder. The goal of this study is to examine brain metabolite levels in the anterior cingulate cortex, the left dorsolateral prefrontal cortex and the left thalamus in subjects at UHR for psychosis and to compare brain metabolite levels between the UHR subjects with comorbid major depressive disorder and healthy controls.

Methods

Proton magnetic resonance spectroscopy was used to examine brain metabolite levels. Twenty UHR subjects and 20 age- and intelligence quotient (IQ)-matched healthy controls were included in this study.

Results

Overall, no significant differences were observed in any metabolite between the UHR and healthy control group. However, UHR subjects with major depressive disorder showed significantly higher myo-inositol (Ins) levels in the left thalamus, compared to the healthy control.

Conclusion

Our results demonstrate that increased thalamic Ins level is associated with prodromal depressive symptoms. Further longitudinal follow-up studies with larger UHR sample sizes are required to investigate the function of Ins concentrations as a biomarker of vulnerability to psychosis.     

Reduced prepulse inhibition in adolescents at risk for psychosis: a 2-year follow-up study

Background

Reduced prepulse inhibition (PPI) of the auditory startle reflex is a hallmark feature of attention-processing deficits in patients with schizophrenia and other psychotic disorders. Recent evidence suggests that these deficits may also be present before the onset of psychosis in individuals at ultra-high risk (UHR) and become progressively worse as psychosis develops. We conducted a longitudinal follow-up study to observe the development of PPI over time in UHR adolescents and healthy controls.

Methods

Two-year follow-up data of PPI measures were compared between UHR adolescents and a matched control group of typically developing individuals.

Results

We included 42 UHR adolescents and 32 matched controls in our study. Compared with controls, UHR individuals showed reduced PPI at both assessments. Clinical improvement in UHR individuals was associated with an increase in PPI parameters.

Limitations

A developmental increase in startle magnitude partially confined the interpretation of the association between clinical status and PPI. Furthermore, post hoc analyses for UHR individuals who became psychotic between assessments had limited power owing to a low transition rate (14%).

Conclusion

Deficits in PPI are present before the onset of psychosis and represent a stable vulnerability marker over time in UHR individuals. The magnitude of this marker may partially depend on the severity of clinical symptoms.     

Reduced Binding Potential of GABA-A/Benzodiazepine Receptors in Individuals at Ultra-high Risk for Psychosis: An [18F]-Fluoroflumazenil Positron Emission Tomography Study

Background:

Altered transmission of gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter, may contribute to the development of schizophrenia. The purpose of the present study was to investigate the presence of GABA-A/benzodiazepine (BZ) receptor binding abnormalities in individuals at ultra-high risk (UHR) for psychosis in comparison with normal controls using [¹⁸F]-fluoroflumazenil (FFMZ) positron emission tomography (PET). In particular, we set regions of interest in the striatum (caudate, putamen, and nucleus accumbens) and medial temporal area (hippocampus and parahippocampal gyrus).

Methods:

Eleven BZ-naive people at UHR and 15 normal controls underwent PET scanning using [¹⁸F]-FFMZ to measure GABA-A/BZ receptor binding potential. The regional group differences between UHR individuals and normal controls were analyzed using Statistical Parametric Mapping 8 software. Participants were evaluated using the structured interview for prodromal syndromes and neurocognitive function tasks.

Results:

People at UHR demonstrated significantly reduced binding potential of GABA-A/BZ receptors in the right caudate.

Conclusions:

Altered GABAergic transmission and/or the imbalance of inhibitory and excitatory systems in the striatum may be present at the putative prodromal stage and play a pivotal role in the pathophysiology of psychosis.Key words: GABA, schizophrenia, ultra-high, risk for psychosis, caudate, PET, fluoroflumazenil     

Event-related potentials and changes of brain rhythm oscillations during working memory activation in patients with first-episode psychosis

Background

Earlier contributions have documented significant changes in sensory, attention-related endogenous event-related potential (ERP) components and θ band oscillatory responses during working memory activation in patients with schizophrenia. In patients with first-episode psychosis, such studies are still scarce and mostly focused on auditory sensory processing. The present study aimed to explore whether subtle deficits of cortical activation are present in these patients before the decline of working memory performance.

Methods

We assessed exogenous and endogenous ERPs and frontal θ event-related synchronization (ERS) in patients with first-episode psychosis and healthy controls who successfully performed an adapted 2-back working memory task, including 2 visual n-back working memory tasks as well as oddball detection and passive fixation tasks.

Results

We included 15 patients with first-episode psychosis and 18 controls in this study. Compared with controls, patients with first-episode psychosis displayed increased latencies of early visual ERPs and phasic θ ERS culmination peak in all conditions. However, they also showed a rapid recruitment of working memory–related neural generators, even in pure attention tasks, as indicated by the decreased N200 latency and increased amplitude of sustained θ ERS in detection compared with controls.

Limitations

Owing to the limited sample size, no distinction was made between patients with first-episode psychosis with positive and negative symptoms. Although we controlled for the global load of neuroleptics, medication effect cannot be totally ruled out.

Conclusion

The present findings support the concept of a blunted electroencephalographic response in patients with first-episode psychosis who recruit the maximum neural generators in simple attention conditions without being able to modulate their brain activation with increased complexity of working memory tasks.     

Does neuroanatomy account for superior temporal dysfunction in early psychosis? A multimodal MRI investigation

Background

Neuroimaging studies of ultra-high risk (UHR) and first-episode psychosis (FEP) have revealed widespread alterations in brain structure and function. Recent evidence suggests there is an intrinsic relationship between these 2 types of alterations; however, there is very little research linking these 2 modalities in the early stages of psychosis.

Methods

To test the hypothesis that functional alteration in UHR and FEP participants would be associated with corresponding structural alteration, we examined brain function and structure in these participants as well as in a group of healthy controls using multimodal MRI. The data were analyzed using statistical parametric mapping.

Results

We included 24 participants in the FEP group, 18 in the UHR group and 21 in the control group. Patients in the FEP group showed a reduction in functional activation in the left superior temporal gyrus relative to controls, and the UHR group showed intermediate values. The same region showed a corresponding reduction in grey matter volume in the FEP group relative to controls. However, while the difference in grey matter volume remained significant after including functional activation as a covariate of no interest, the reduction in functional activation was no longer evident after including grey matter volume as a covariate of no interest.

Limitations

Our sample size was relatively small. All participants in the FEP group and 2 in the UHR group had received antipsychotic medication, which may have impacted neurofunction and/or neuroanatomy.

Conclusion

Our results suggest that superior temporal dysfunction in early psychosis is accounted for by a corresponding alteration in grey matter volume. This finding has important implications for the interpretation of functional alteration in early psychosis.     

White matter tractography in early psychosis: clinical and neurocognitive associations

Background

While many diffusion tensor imaging (DTI) investigations have noted disruptions to white matter integrity in individuals with chronic psychotic disorders, fewer studies have been conducted in young people at the early stages of disease onset. Using whole tract reconstruction techniques, the aim of this study was to identify the white matter pathology associated with the common clinical symptoms and executive function impairments observed in young people with psychosis.

Methods

We obtained MRI scans from young people with psychosis and healthy controls. Eighteen major white matter tracts were reconstructed to determine group differences in fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD) and then were subsequently correlated with symptomatology and neurocognitive performance.

Results

Our study included 42 young people with psychosis (mean age 23 yr) and 45 healthy controls (mean age 25 yr). Compared with the control group, the psychosis group had reduced FA and AD in the left inferior longitudinal fasciculus (ILF) and forceps major indicative of axonal disorganization, reduction and/or loss. These changes were associated with worse overall psychiatric symptom severity, increases in positive and negative symptoms, and worse current levels of depression. The psychosis group also showed FA reductions in the left superior longitudinal fasciculus that were associated with impaired neurocognitive performance in attention and semantic fluency.

Limitations

Our analysis grouped 4 subcategories of psychosis together, and a larger follow-up study comparing affective and nonaffective psychoses is warranted.

Conclusion

Our findings suggest that impaired axonal coherence in the left ILF and forceps major underpin psychiatric symptoms in young people in the early stages of psychosis.     

Temperament and character in individuals at ultra-high risk for psychosis and with first-episode schizophrenia: Associations with psychopathology,psychosocial functioning,and aspects of psychological health

Objective

The psychobiological model of temperament and character indicates that personality traits are heritable and, during development, constantly influence one’s susceptibility to schizophrenia. Our objective was to evaluate temperament and character in subjects at ultra-high risk (UHR) for psychosis and individuals with first-episode schizophrenia.

Methods

UHR for psychosis subjects (n = 50), first-episode schizophrenia patients (n = 33), and normal controls (n = 120) were compared on temperament and character dimensions, and correlation analysis of each personality dimension with psychopathologies, global and social functioning, and self-esteem. General and social self-efficacy reports were conducted. UHR subjects were followed-up for 24 months and the baseline personality dimensions were compared between the converted and non-converted groups.

Results

Both clinical groups showed abnormal personality traits in terms of temperament (higher harm avoidance, lower reward dependence and persistence) and character (lower self-directedness and cooperativeness). Psychosocial functioning and psychological health components were found to be correlated with some personality dimensions. The conversion rate of overt psychotic disorder was 25.0% at the 24-month follow-up. Baseline cooperativeness dimension was a significant predictive dimension for conversion into overt psychosis in the UHR group during the follow-up period.

Conclusion

Patients with first episode schizophrenia have a pervasively altered personality profile from normal controls. More importantly, this altered personality profile already emerged in putative prodromal, UHR individuals. The present findings indicate that certain personality traits can play a protective or vulnerable role in developing schizophrenia.     

Basic Self-Disturbance Predicts Psychosis Onset in the Ultra High Risk for Psychosis “Prodromal” Population

Introduction

Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to a disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. In this study, we investigated the presence of basic self-disturbance in an “ultra high risk” (UHR) for psychosis sample compared with a healthy control sample and whether it predicted transition to psychotic disorder.

Methods

Forty-nine UHR patients and 52 matched healthy control participants were recruited to the study. Participants were assessed for basic self-disturbance using the Examination of Anomalous Self-Experience (EASE) instrument. UHR participants were followed for a mean of 569 days.

Results

Levels of self-disturbance were significantly higher in the UHR sample compared with the healthy control sample (P < .001). Cox regression indicated that total EASE score significantly predicted time to transition (P < .05) when other significant predictors were controlled for. Exploratory analyses indicated that basic self-disturbance scores were higher in schizophrenia spectrum cases, irrespective of transition to psychosis, than nonschizophrenia spectrum cases.

Discussion

The results indicate that identifying basic self-disturbance in the UHR population may provide a means of further “closing in” on individuals truly at high risk of psychotic disorder, particularly of schizophrenia spectrum disorders. This may be of practical value by reducing inclusion of “false positive” cases in UHR samples and of theoretical value by shedding light on core phenotypic features of schizophrenia spectrum pathology.     

Disruption of brain white matter microstructure in women with anorexia nervosa

Background

The etiology of anorexia nervosa is still unknown. Multiple and distributed brain regions have been implicated in its pathophysiology, implying a dysfunction of connected neural circuits. Despite these findings, the role of white matter in anorexia nervosa has been rarely assessed. In this study, we used diffusion tensor imaging (DTI) to characterize alterations of white matter microstructure in a clinically homogeneous sample of patients with anorexia nervosa.

Methods

Women with anorexia nervosa (restricting subtype) and healthy controls underwent brain DTI. We used tract-based spatial statistics to compare fractional anisotropy (FA) and mean diffusivity (MD) maps between the groups. Furthermore, axial (AD) and radial diffusivity (RD) measures were extracted from regions showing group differences in either FA or MD.

Results

We enrolled 19 women with anorexia nervosa and 19 healthy controls in our study. Patients with anorexia nervosa showed significant FA decreases in the parietal part of the left superior longitudinal fasciculus (SLF; p_FWE < 0.05), with increased MD and RD but no differences in AD. Patients with anorexia nervosa also showed significantly increased MD in the fornix (p_FWE < 0.05), accompanied by decreased FA and increased RD and AD.

Limitations

Limitations include our modest sample size and cross-sectional design.

Conclusion

Our findings support the presence of white matter pathology in patients with anorexia nervosa. Alterations in the SLF and fornix might be relevant to key symptoms of anorexia nervosa, such as body image distortion or impairments in body–energy–balance and reward processes. The differences found in both areas replicate those found in previous DTI studies and support a role for white matter pathology of specific neural circuits in individuals with anorexia nervosa.     

Hippocampal and caudate volume reductions in antipsychotic-naive first-episode schizophrenia

Background

Enlarged ventricles and reduced hippocampal volume are consistently found in patients with first-episode schizophrenia. Studies investigating brain structure in antipsychotic-naive patients have generally focused on the striatum. In this study, we examined whether ventricular enlargement and hippocampal and caudate volume reductions are morphological traits of antipsychotic-naive first-episode schizophrenia.

Methods

We obtained high-resolution 3-dimensional T₁-weighted magnetic resonance imaging scans for 38 antipsychotic-naive first-episode schizophrenia patients and 43 matched healthy controls by use of a 3-T scanner. We warped the brain images to each other by use of a high-dimensional intersubject registration algorithm. We performed voxel-wise group comparisons with permutation tests. We performed small volume correction for the hippocampus, caudate and ventricles by use of a false discovery rate correction (p < 0.05) to control for multiple comparisons. We derived and analyzed estimates of brain structure volumes. We grouped patients as those with (n = 9) or without (n = 29) any lifetime substance abuse to examine the possible effects of substance abuse.

Results

We found that hippocampal and caudate volumes were decreased in patients with first-episode schizophrenia. We found no ventricular enlargement, differences in global volume or significant associations between tissue volume and duration of untreated illness or psycho-pathology. The hippocampal volume reductions appeared to be influenced by a history of substance abuse. Exploratory analyses indicated reduced volume of the nucleus accumbens in patients with first-episode schizophrenia.

Limitations

This study was not a priori designed to test for differences between schizophrenia patients with or without lifetime substance abuse, and this subgroup was small.

Conclusion

Reductions in hippocampal and caudate volume may constitute morphological traits in antipsychotic-naive first-episode schizophrenia patients. However, the clinical implications of these findings are unclear. Moreover, past substance abuse may accentuate hippocampal volume reduction. Magnetic resonance imaging studies addressing the potential effects of substance abuse in antipsychotic-naive first-episode schizophrenia patients are warranted.     

White matter microstructure in patients with obsessive-compulsive disorder

Background

Previous diffusion tensor imaging (DTI) studies in patients with obsessive–compulsive disorder (OCD) have reported inconsistent findings, and it is not known whether observed findings are related to abnormalities in axonal structure or myelination.

Methods

In this DTI study, we investigated fractional anisotropy, as well as axial and radial diffusivity, in 21 patients with OCD and 29 healthy controls.

Results

We found decreased fractional anisotropy in the body of the corpus callosum in the OCD group, which was underpinned by increased radial diffusivity.

Limitations

The cross-sectional design was the main limitation.

Conclusion

Our findings of increased radial diffusivity provide preliminary evidence for abnormal myelination in patients with OCD.     

Associated factors of quality of life in first-episode schizophrenia patients

Objective

Improving quality of life is an important goal in the treatment of schizophrenia. In previous research, quality of life has been reported to be compromised in patients with schizophrenia. The aim of this study was to investigate whether quality of life may be impaired in first-episode schizophrenia patients and to identify the associated factors of quality of life in first-episode schizophrenia.

Methods

Forty-eight patients with first-episode schizophrenia and 20 normal controls were recruited. Quality of life was measured by using the Quality of Life scale (QLS). General and social self-efficacy, perceived social support were measured by using the self-report scales. The clinical assessments and comprehensive neurocognitive battery were also administered.

Results

First-episode group showed significantly decreased QLS total and QLS subscale scores compared to normal controls group. The key associated factors of quality of life in patients with first-episode schizophrenia were the negative symptoms and social self-efficacy.

Conclusion

This finding implies that compromised quality of life may be already emerged in schizophrenia in their first-episode and the psychosocial interventions should be targeting the negative symptoms and the psychosocial protective factors including self-efficacy in addition to simply ameliorating the positive symptoms to foster social reintegration and recovery of first-episode patients.     

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 > 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.Key words: schizotypy, MRI/DTI, healthy subjects     

A primary study of diffusion tensor imaging-based histogram analysis in vascular cognitive impairment with no dementia

Purpose

This study performed diffusion tensor imaging (DTI) histogram analysis and voxel-based analysis (VBA) to detect white matter (WM) damage in patients with vascular cognitive impairment with no dementia (VCIND) and to determine correlations between DTI histogram-derived measures and cognitive dysfunction in these patients.

Materials and methods

Among patients with subcortical ischemic vascular disease, 18 patients with VCIND were selected along with 18 age- and sex-matched cognitive-normal subjects. Both groups underwent magnetic resonance and DTI scans, and fractional anisotropy (FA) changes in VBA between the two groups were assessed. Further, mean diffusivity (MD) and FA histograms of WM and normal-appearing WM (NAWM) in each subject were evaluated.

Results

Compared to control, the VCIND group showed lower FA values throughout the brain. FA and MD histogram patterns of WM and NAWM were significantly different between the groups. Significant differences were found in all DTI histogram-derived measures, except in the mean FA peak height of WM and mean MD peak location of NAWM. Neuropsychological results (z-scores) were found to be significantly correlated with mean FA peak location, average MD, mean MD peak location of WM, and mean FA peak height, average MD, mean MD peak location of NAWM.

Conclusions

Results of VBA and diffusion tensor imaging-based histogram analysis suggest that VCIND patients have more severe damage in WM and NAWM than the control. Thus, the severity of damage in WM and NAWM may be related with cognitive dysfunction in VCIND patients, and DTI histogram analysis can help in further understanding VCIND.     

A randomized controlled trial of cognitive behavioral therapy for individuals at clinical high risk of psychosis

Background

Symptomatic and functional outcomes in schizophrenia are associated with the duration of untreated psychosis. However, no candidate biomarkers have been adopted in clinical settings. Multichannel near-infrared spectroscopy (NIRS), which can easily and noninvasively measure hemodynamics over the prefrontal cortex, is a candidate instrument for clinical use.

Aims

We intended to explore prefrontal dysfunction among individuals at different clinical stages, including ultra-high-risk (UHR), first-episode psychosis (FEP), and chronic schizophrenia (ChSZ), compared to healthy subjects.

Method

Twenty-two UHR subjects, 27 patients with FEP, 38 patients with ChSZ, and 30 healthy subjects participated. We measured hemodynamic changes during a block-designed letter fluency task using multichannel NIRS instruments.

Results

We found that the activations of the bilateral ventrolateral prefrontal cortex, and the fronto-polar and anterior parts of the temporal cortical regions in the UHR group were lower than those of the controls, but similar to those of the FEP and ChSZ groups. However, the activations in the bilateral dorsolateral prefrontal cortex regions decrease with advancing clinical stage.

Conclusions

To the best of our knowledge, this is the first study directly comparing differences in hemodynamic changes with respect to the 3 clinical stages of psychosis. Furthermore, this study also demonstrates different patterns of impairment according to the progression of clinical stages using NIRS instruments. NIRS measurements for UHR and FEP individuals may be candidate biomarkers for the early detection of the clinical stages of psychosis.