Retinal vascular abnormalities in schizophrenia and bipolar disorder: A window to the brain.

OBJECTIVES: The examination of retinal microvascular abnormalities through fundus photography is currently the best available non-invasive technique for assessment of cerebral vascular status. Several studies in the last decade have reported higher incidences of adverse cerebrovascular events in Schizophrenia (SCZ) and bipolar disorder (BD). However, retinal microvasculature abnormalities in SCZ and BD have remained under-explored, and no study has compared this aspect of SCZ and BD till date. METHODS: Retinal Images of 100 SCZ patients, BD patients, and healthy volunteers each were acquired by trained individuals using a non-mydriatic camera with a 40-degree field of view. The retinal images were quantified using a valid semi-automated method. The average of left and right eye diameters of the venules and arterioles passing through the extended zone between 0.5 and 2 disc diameters from the optic disc were calculated. RESULTS: The groups differed significantly with respect to average diameters of both retinal venules (P < 0.001) and retinal arterioles (P < 0.001), after controlling for age and sex. Both SCZ and BD patients had significantly narrower arterioles and wider venules compared to HV. There were also significant differences between SCZ and BD patients; patients with BD had narrower arterioles and wider venules. CONCLUSION: Considering the affordability and easy accessibility of the investigative procedure, retinal microvascular examination could serve as a potential screening tool to identify individuals at risk for adverse cerebrovascular events. The findings of the current study also provide a strong rationale for further systematic examination of retinal vascular abnormalities in SCZ and BD.

Examination of retinal vascular trajectory in schizophrenia and bipolar disorder.

AIM: Evidence suggests microvascular dysfunction (wider retinal venules and narrower arterioles) in schizophrenia (SCZ) and bipolar disorder (BD). The vascular development is synchronous with neuronal development in the retina and brain. The retinal vessel trajectory is related to retinal nerve fiber layer thinning and cerebrovascular abnormalities in SCZ and BD and has not yet been examined. Hence, in this study we examined the retinal vascular trajectory in SCZ and BD in comparison with healthy volunteers (HV). METHODS: Retinal images were acquired from 100 HV, SCZ patients, and BD patients, respectively, with a non-mydriatic fundus camera. Images were quantified to obtain the retinal arterial and venous trajectories using a validated, semiautomated algorithm. Analysis of covariance and regression analyses were conducted to examine group differences. A supervised machine-learning ensemble of bagged-trees method was used for automated classification of trajectory values. RESULTS: There was a significant difference among groups in both the retinal venous trajectory (HV: 0.17 ± 0.08; SCZ: 0.25 ± 0.17; BD: 0.27 ± 0.20; P < 0.001) and the arterial trajectory (HV: 0.34 ± 0.15; SCZ: 0.29 ± 0.10; BD: 0.29 ± 0.11; P = 0.003) even after adjusting for age and sex (P < 0.001). On post-hoc analysis, the SCZ and BD groups differed from the HV on retinal venous and arterial trajectories, but there was no difference between SCZ and BD patients. The machine learning showed an accuracy of 86% and 73% for classifying HV versus SCZ and BD, respectively. CONCLUSION: Smaller trajectories of retinal arteries indicate wider and flatter curves in SCZ and BD. Considering the relation between retinal/cerebral vasculatures and retinal nerve fiber layer thinness, the retinal vascular trajectory is a potential marker for SCZ and BD. As a relatively affordable investigation, retinal fundus photography should be further explored in SCZ and BD as a potential screening measure.

Association between urban upbringing and functional brain connectivity in schizophrenia.

Background: Environmental factors considerably influence the development of the human cortex during the perinatal period, early childhood, and adolescence. Urban upbringing in the first 15 years of life is a known risk factor for schizophrenia (SCZ). Though the risk of urban birth and upbringing is well-examined from an epidemiological perspective, the biological mechanisms underlying urban upbringing remain unknown. The effect of urban birth and upbringing on functional brain connectivity in SCZ patients is not yet examined. Methods: This is a secondary data analysis of three studies that included 87 patients with SCZ and 70 healthy volunteers (HV) aged 18 to 50 years. We calculated the developmental urbanicity index using a validated method in earlier studies. Following standard pre-processing of resting functional magnetic resonance imaging (fMRI) scans, seed-return on investment (ROI) functional connectivity analysis was performed. Results: The results showed a significant association between urban birth and upbringing on functional connectivity in SCZ patients and HV (P < 0.05). In SCZ patients, connections from the right caudate, anterior cingulate cortex, left and right intracalcarine cortices, left and right lingual gyri, left posterior parahippocampal cortex to the cerebellum, fusiform gyri, lateral occipital cortex, and amygdala were significantly associated with the urbanicity index (P < 0.05). Conclusions: These study findings suggest a significant association between urban birth and upbringing on functional brain connectivity in regions involved in reward processing and social cognition in SCZ. Assessment of social cognition could have implications in developing an in-depth understanding of this impairment in persons with SCZ.

Effect of antipsychotic dose reduction on cognitive function in schizophrenia.

Cognitive deficits are predictors of social functioning but remain an unmet therapeutic challenge. While lowering the antipsychotics carries a risk of relapse, it possibly has a beneficial effect on cognitive function. However, this has not been examined in a real-world setting. A prospective naturalistic 6-month follow-up study (n = 71) was conducted with patients between 18 and 45 years in their first five years of illness and the maintenance phase of the treatment. Brief Assessment of Cognition in Schizophrenia (BACS) was administered to assess cognitive functions. Patients were divided into three groups based on the change in dose of antipsychotics. The data were analyzed using linear mixed-effects modeling (LMEM) to examine the group differences. At the end of six months, those with decreased antipsychotic dose had significant improvement in BACS total score, token test, and symbol coding compared to those with no change in the dose of antipsychotic. Reducing the dose of antipsychotics during the maintenance phase was associated with improved cognitive functions without an increased risk of relapse. Antipsychotic dose reduction may be better than discontinuation as the relapse risk is higher with the discontinuation strategy. Clinicians must balance the improvements in cognitive functions and relapse risk.

Relation between frontal pole volumes and cognitive insight in Schizophrenia.

OBJECTIVE: Cognitive insight comprising self-reflection and self-certainty is an important determinant of functional outcomes in Schizophrenia. The neural correlates of cognitive insight in Schizophrenia are underexamined. The frontal pole (FP) is implicated in metacognitive function in healthy individuals, but its role is not well examined in Schizophrenia. We had earlier reported the relationship between Frontal pole volumes and cognitive insight in a small sample of only male patients. Hence, we studied this relationship in an independent sample of schizophrenia patients and healthy controls. METHODS: We examined 41 healthy volunteers (HV) and 57 patients with Schizophrenia (SCZ). We used a previously validated manual morphometric method to perform FP parcellation on images obtained from a 3 T scanner and calculated the volumes. Cognitive insight was measured using Beck's Cognitive insight scale (BCIS). To assess the relationship between FP volumes and BCIS scores, multiple linear regression analyses were performed. RESULTS: In the overall sample, age, years of education, and intracranial volume were significant predictors of BCIS scores. Within the SCZ group, age and left FP volume were significant predictors of BCIS composite scores and age, ICV for BCIS-self certainty. There was no significant relationship between age and FP volumes in either SCZ or HV group. DISCUSSION: The current study in an independent sample further supports the critical role of the frontal pole in cognitive insight, earlier reported by us. As cognitive insight has a vital role in functional outcome, our findings have potential clinical implications.

Effect of Intranasal Oxytocin on Resting-state Effective Connectivity in Schizophrenia.

OBJECTIVES: Evidence from several lines of research suggests the critical role of neuropeptide oxytocin in social cognition and social behavior. Though a few studies have examined the effect of oxytocin on clinical symptoms of schizophrenia, the underlying neurobiological changes are underexamined. Hence, in this study, we examined the effect of oxytocin on the brain's effective connectivity in schizophrenia. METHODS: 31 male patients with schizophrenia (SCZ) and 21 healthy male volunteers (HV) underwent resting functional magnetic resonance imaging scans with intra-nasal oxytocin (24 IU) and placebo administered in counterbalanced order. We conducted a whole-brain effective connectivity analysis using a multivariate vector autoregressive granger causality model. We performed a conjunction analysis to control for spurious changes and canonical correlation analysis between changes in connectivity and clinical and demographic variables. RESULTS: Three connections, sourced from the left caudate survived the FDR correction threshold with the conjunction analysis; connections to the left supplementary motor area, left precentral gyrus, and left frontal inferior triangular gyrus. At baseline, SCZ patients had significantly weaker connectivity from caudate to these three regions. Oxytocin, but not placebo, significantly increased the strength of connectivity in these connections. Better cognitive insight and lower negative symptoms were associated with a greater increase in connectivity with oxytocin. CONCLUSIONS: These findings provide a preliminary mechanistic understanding of the effect of oxytocin on brain connectivity in schizophrenia. The study findings provide the rationale to examine the potential utility of oxytocin for social cognitive deficits in schizophrenia.

Deep learning model using retinal vascular images for classifying schizophrenia.

Contemporary psychiatric diagnosis still relies on the subjective symptom report of the patient during a clinical interview by a psychiatrist. Given the significant variability in personal reporting and differences in the skill set of psychiatrists, it is desirable to have objective diagnostic markers that could help clinicians differentiate patients from healthy individuals. A few recent studies have reported retinal vascular abnormalities in patients with schizophrenia (SCZ) using retinal fundus images. The goal of this study was to use a trained convolution neural network (CNN) deep learning algorithm to detect SCZ using retinal fundus images. A total of 327 subjects [139 patients with Schizophrenia (SCZ) and 188 Healthy volunteers (HV)] were recruited, and retinal images were acquired using a fundus camera. The images were preprocessed and fed to a convolution neural network for the classification. The model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The CNN achieved an accuracy of 95% for classifying SCZ and HV with an AUC of 0.98. Findings from the current study suggest the potential utility of deep learning to classify patients with SCZ and assist clinicians in clinical settings. Future studies need to examine the utility of the deep learning model with retinal vascular images as biomarkers in schizophrenia with larger sample sizes.

Association between retinal vascular measures and brain white matter lesions in schizophrenia.

OBJECTIVE: Recent studies have examined retinal vascular abnormalities in schizophrenia as retinal vascular imaging is a non-invasive proxy to cerebral microvasculature. However, relation between retinal vascular abnormalities and brain structure is not well examined in schizophrenia. Hence in this study, for the first time, we examined the relationship between retinal vascular measures and brain white matter lesions in schizophrenia. We examined brain white matter lesions as they are considered a predictive marker for future adverse cerebrovascular event. METHODS: We acquired retinal vascular images of both eyes using a non-mydriatic camera and calculated retinal vascular diameter, tortuosity, trajectory and fractal dimension using validated methods. All patients underwent Magnetic Resonance Imaging of bran and we computed white matter hypo-intensities using Freesurfer software. We performed a linear regression analysis to examine the relationship between white matter hypo-intensities and retinal vascular measures controlling for age, sex, fasting blood sugar, creatinine, whole-brain volume, and antipsychotic dose. RESULTS: The regression model was significant in Schizophrenia patients (R=0.983;R2 =0.966;-F=10.849;p = 0.008) but not in healthy volunteers (R=0.828;R2 =0.686;F=0.182; p = 0.963). Among the retinal vascular measures, arterial tortuosity (ß = 0.963;p-0.002), tortuosity (ß = -1.002;p = 0.001) and fractal dimension (ß = -0.688;p = 0.014) were significant predictors of white matter lesions. DISCUSSION: The current study's findings support the conclusion that retinal vascular fractal dimension and tortuosity are associated with changes in cerebral white matter and may be considered proxy markers for cerebral microvasculature in schizophrenia. Considering the relationship between white matter lesions and stroke, these observations could have important clinical implications to screen schizophrenia patients for risk of adverse cerebrovascular event.

The frontal pole and cognitive insight in schizophrenia.

Absence of insight owing to impaired self-reflection and lack of touch with reality is a hallmark of schizophrenia. Functional imaging studies in healthy individuals have implicated the frontal pole (FP), sub-division of the prefrontal cortex in self-reflective processes. Despite the significance of self-referential processing in the pathogenesis of schizophrenia, the relationship between FP volume and cognitive insight in this disorder is underexplored. We examined the relationship between cognitive insight and volume of FP using precise manual morphometry of high resolution magnetic resonance images in 19 schizophrenia patients (SCZ) and 21 healthy-volunteers (HV). The manual morphometry technique was replicated from a previous study based on a cytoarchitectonically and functionally valid definition of FP and cognitive insight was measured using Beck's cognitive insight scale. Left frontal pole volume was a significant predictor of self-reflection sub-score of Beck's cognitive insight scale (ß=0.68; t = 2.86; p = 0.01). A significant inverse relationship between age and bilateral FP volumes was noted in HV (left FP - r=-0.45; p = 0.04; right FP - r=-0.57; p = 0.008) but not in SCZ (p>0.05). Our findings provide anatomical substrates to devise intervention strategies targeting cognitive insight, thereby improving treatment adherence and functional outcomes.

Add on yoga treatment for negative symptoms of schizophrenia: A multi-centric, randomized controlled trial.

The efficacy of antipsychotic medications in the treatment of negative symptoms of schizophrenia is modest at best. Preliminary studies suggest the beneficial effects of add on Yoga, a traditional Indian practice, in the treatment of schizophrenia. Hence, in this study, we examined the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia in a randomized, wait-list controlled design from two clinical institutes in south India. 89 patients (age - 34.20 ± 8.06 years; education - 14.22 ± 2.69 years; 28 females) were randomized into the add-on yoga or treatment as usual (TAU - wait-list control) group. Patients had a mean illness duration of 10.97 ± 7.24 years with an age at onset of 23.34 ± 5.81 years. Central block randomization was followed to ensure concealed allocation. Participants randomized to the yoga treatment group attended 12 supervised yoga training sessions over two weeks and practiced yoga sessions at home for the subsequent 10 weeks. 64 patients completed the trial. An intent to treat analysis was conducted with 89 participants using a linear mixed model. Improvement in negative symptoms was our primary outcome measure. The two groups were matched on demographic variables and baseline psychopathology severity. Participants in the add-on yoga group had significantly greater improvement in negative symptoms (SANS baseline: 49.13 ± 2.30; 12-weeks follow up: 31.55 ± 2.53) compared to the TAU group (SANS baseline: 51.22 ± 2.40; 12-weeks follow up: 45.30 ± 2.93; t = 3.36; p = 0.006; Cohen's d-0.65). The current study findings suggest the efficacy of yoga as an add-on treatment for negative symptoms of schizophrenia. The effectiveness of yoga practice as a regular clinical intervention for patients needs to be explored in future studies by integrating yoga services along with other clinical services.

Association between retinal vascular caliber and brain structure in schizophrenia.

OBJECTIVE: Several lines of research in the last decade have indicated the potential utility of retina as a window to the brain. Emerging evidence suggests abnormalities in retinal vascular caliber in schizophrenia. However, the relationship between retinal vascular measures and brain structure has not been examined in schizophrenia to date. Hence, we examined the relationship between retinal vasculature measured using fundus photography and brain structure measured using magnetic resonance imaging. METHOD: We recruited 17 healthy volunteers and 20 patients with schizophrenia. Using a non-mydriatic camera, we captured the images for left and right eyes separately and retinal vascular calibers were calculated using a semi-automated software package. Whole-brain anatomical T1 MPRAGE images were acquired using a 3-Tesla MRI scanner. Whole-brain and regional volume and cortical thickness were calculated using the Freesurfer software package. We used FreeSurfer's QDEC interface to compute vertex-by-vertex for analysis of the volume and cortical thickness. The relation between brain volume, cortical thickness, and retinal vascular caliber was examined using partial correlation and regression analysis. RESULTS: There was a significant negative correlation between average CRVE and global cortical mean thickness in schizophrenia but not in healthy. In schizophrenia patients, there was a significant negative correlation between average CRVE and cortical thickness in frontal regions - left rostral middle frontal, left superior frontal, and right caudal middle frontal gyri and posterior brain regions - left lateral occipital gyrus and left posterior cingulate cortex. DISCUSSION: The findings of the study suggest potential utility of retinal venular diameter as a proxy marker to abnormal neurodevelopment in schizophrenia.

Glutamate metabolites in treatment resistant schizophrenia: A meta-analysis and systematic review of 1H-MRS studies.

Nearly a third to half of schizophrenia patients are non-responsive to first-line antipsychotics and are labelled treatment resistant schizophrenia (TRS). Neurochemical abnormalities in TRS may not be dopaminergic but possibly glutamate (Glu) related. Studies that have examined glutamatergic abnormalities using proton magnetic resonance spectroscopy (1H-MRS) in TRS, have showed inconsistent results. Hence, we conducted a meta-analysis of 1H-MRS studies comparing levels of Glu-and its metabolites in the brains of TRS and non-treatment resistant schizophrenia (nTRS) patients. Four eligible studies were included in the analysis. Summary effect size for the group difference between TRS (n = 101, including Ultra-TRS) and nTRS (n = 61) in Glu-levels in the anterior cingulate cortex (ACC) as measured with Hedges's g was 0.21 (95% CI: -0.42 to 0.85; p = 0.5) suggesting absence of significant difference. However, on leave one out analysis, one iteration showed significant difference in Glu-levels between the groups (Hedges's g = 0.46; p = 0.02) with higher Glu-levels in TRS implying significant effect of a single study on the effect size. The higher ACC Glu-in TRS was not associated with symptom severity or antipsychotic administration, indicating a possible trait abnormality. The limited number of datasets comparing Glu-metabolites in other brain regions are narratively described. Our analysis is limited by the significant heterogeneity between studies. Further longitudinal, prospective studies are needed to confirm higher Glu-metabolite levels in ACC in TRS and explore this potential trait abnormality.

"To co-operate or not?" Risky co-operative behavior in Schizophrenia and the effect of vasopressin.

Risky co-operation is when an individual chooses to co-operate in a social situation despite the possibility of the partner refusing to co-operate. Although this is a deviation from rational behavior, it may have helped humans in societal adaptation. Risky co-operation holds significance in social functioning. However, the status of risky cooperative behavior in schizophrenia, a disorder with impaired social cognition, is yet to be investigated. Moreover, the underlying neurobiology is unexplored. 27 individuals with schizophrenia and 30 healthy volunteers performed an iterative stag hunt game, an ecologically valid, neuroeconomics game to measure risky cooperative behavior. The patients and healthy volunteers were matched on age and sex. An independent group of patients (n = 30) later performed the stag hunt game with intranasal vasopressin or saline in a counterbalanced crossover study design. Patients with schizophrenia, compared to healthy controls, switched from high-risk situations to a low-risk situation at lower payoff, suggesting impaired co-operation in a risky situation. Group differences were significant even after controlling for general risk- taking tendency and subjective mood state. In part-II of the study, there was no statistically significant difference in risky co-operative behavior with vasopressin. The results suggest impaired risky co-operative behavior in schizophrenia, which could influence the functional outcome. The study also provides a testable, ecologically valid paradigm for risky co-operative behavior in schizophrenia. Though single dose vasopressin did not influence the risky co-operative behavior, long term study with repeated administration is needed for a definitive conclusion.

A proof of concept machine learning analysis using multimodal neuroimaging and neurocognitive measures as predictive biomarker in bipolar disorder.

BACKGROUND: Concomitant use of complementary, multimodal imaging measures and neurocognitive measures is reported to have higher accuracy as a biomarker in Alzheimer's dementia. However, such an approach has not been examined to differentiate healthy individuals from Bipolar disorder. In this study, we examined the utility of support vector machine (SVM) technique to differentiate bipolar disorder patients and healthy using structural, functional and diffusion tensor images of brain and neurocognitive measures. METHODS: 30 patients with Bipolar disorder-I and 30 age, sex matched individuals participated in the study. Structural MRI, resting state functional MRI and diffusion tensor images were obtained using a 1.5 T scanner. All participants were administered neuropsychological tests to measure executive functions. SVM, a supervised machine learning technique was applied to differentiate patients and healthy individuals with k-fold cross validation over 10 trials. RESULTS: The composite marker consisting of both neuroimaging and neuropsychological measures, had an accuracy of 87.60 %, sensitivity of 82.3 % and specificity of 92.7 %. The performance of composite marker was better compared to that of individual markers on classificatory. CONCLUSIONS: We were able to achieve a high accuracy for machine learning technique in distinguishing BD from HV using a combination of multimodal neuroimaging and neurocognitive measures. Findings of this proof of concept study, if replicated in larger samples, could have potential clinical applications.

Examination of social decision making in patients with schizophrenia using ultimatum game.

Intact decision-making skills in the social context are essential for optimal functioning in the community. Despite its significance, social decision making in schizophrenia (SCZ) has not been adequately examined. Hence, we examined social decision making in SCZ using the Ultimatum Game(UG), a neuroeconomic paradigm that involves financial transactions between a proposer and a responder to split a sum of money between them. Thirty male patients with a diagnosis of schizophrenia as per DSM-IV (age = 30 ± 7.08) and thirty age-matched healthy male volunteers (HV;age = 28.48 ± 3.74) participated in the study. All participants functioned as responders and had to either accept or reject offers made by an anonymous proposer. We also examined whether the gender or emotional expression of the proposer influenced acceptance rates. SCZ had significantly lower acceptance rates than HV for slightly unequal offers (t = 3.94, p = < 0.0001). However, there was no significant difference between SCZ and HV for other offers. Gender and emotional expression of the proposer did not significantly influence the outcome. These results suggest aberrant social decision making and increased inequity aversion in patients with SCZ. The difficulty in incorporating social components while engaging in financial interactions could have important implications for rehabilitation, functional recovery, and successful community living in SCZ.

Comparison of first-episode and multiple-episode bipolar disorder: A surface-based morphometry study.

It is still unclear whether the structural abnormalities in Bipolar disorder (BD) are static or progressive. We aimed to compare differences in cortical thickness, surface area, and volume between patients with BD and healthy volunteers (HV) and to examine whether there are differences between patients who have had a single manic episode and those with multiple episodes. We recruited 30 patients with Type I BD and 30 age and sex matched HV. All participants underwent structural magnetic resonance imaging. Cortical volume, thickness, and surface area were measured using the QDEC tool from the Freesurfer software with age and intracranial volume as covariates. Study groups were comparable across age, sex distribution, and intracranial volume. Patients had significantly lower surface area in bilateral cuneus, right postcentral gyrus, and rostral middle frontal gyri; and lower cortical volume in the left middle temporal gyrus, right postcentral gyrus, and right cuneus. BD patients with multiple episodes had lower cortical measures while those with single episode had cortical measures comparable to HV. Findings indicate that the pathophysiological processes in BD are possibly progressive in nature. Our findings underscore the potential importance of early diagnosis and intervention in preventing deterioration and improving functional recovery.

Relation between retinal vascular abnormalities and working memory impairment in patients with schizophrenia and bipolar disorder.

Emerging evidence indicates abnormal retinal micro-vasculature in schizophrenia (SCZ) and bipolar disorder (BD) and its relation to cognitive functions. However, the association of these abnormalities with the cognitive deficits in these disorders has not been examined till date. Hence, we explored this aspect in patients with SCZ, BD, and healthy volunteers (HV). We examined 34 with SCZ, 39 with BD, and 45 HV. Retinal images were acquired using nonmydriatic fundus camera. The retinal images were analyzed, and average diameters of retinal arterioles and venules were calculated. Working memory was assessed using computerized one-back test from Cogstate® battery. There was significant difference between groups in retinal venules and arterioles caliber (p < 0.001). Both SCZ and BD patients had wider venules and narrower arterioles. They had significantly lower working memory accuracy (p = 0.008) and higher log mean speed (p < 0.001). There was significant positive correlation between one-back test accuracy and retinal arteriolar caliber (r = 0.22; p = 0.01) and between log mean speed score and retinal venular caliber (r = 0.20; p = 0.02). Findings suggest association between working memory and retinal vascular caliber, a potential pointer towards understanding the vascular pathology in cognitive deficits in SCZ and BD. Future studies need to examine whether retinal vascular could be a biomarker for SCZ and BD.

Investigating spontaneous brain activity in bipolar disorder: A resting-state functional magnetic resonance imaging study.

BACKGROUND: Despite several neuroimaging studies in the past few years, the exact pathophysiology responsible for the development of bipolar disorder (BD) is still not completely known. Importantly, to the best of our knowledge, no study from India has examined resting state (RS) connectivity abnormalities in BD using regional homogeneity (ReHo). Hence, we examined spontaneous brain activity in patients with BD using RS functional magnetic resonance imaging (RS-fMRI). AIM: The aim of the study is to examine the spontaneous brain activity in patients with BD-I using ReHo approach and RS-fMRI compared to age- and gender-matched healthy control (HC). MATERIALS AND METHODS: A total of 20 patients with BD and 20 age-, gender-, and education-matched HCs participated in the study. The fMRI data were obtained using 1.5T scanner. RS-fMRI abnormalities were analyzed using ReHo method. RESULTS: Compared to healthy adults, significantly increased ReHo in the BD group was found in the right precuneus, right insula, right supramarginal gyrus, left superior frontal gyrus, right inferior frontal gyrus, right precentral gyrus, and right paracentral lobule. No region had significantly lower ReHo values in BD patients compared to controls. CONCLUSION: These results suggested that abnormal local synchronization of spontaneous brain activity is present in the frontoparietoinsular region which may be related to the pathophysiology of BD.

Retinal vascular fractal dimension in bipolar disorder and schizophrenia.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SCZ), are associated with greater vascular co-morbidities and adverse vascular events. Owing to shared developmental origins and morphology, retinal vasculature is a proxy assessment measure of the cerebral vasculature. Although retinal vascular fractal dimension (Df), a measure of vascular geometry and complexity of branching, has been shown to be directly associated with cerebrovascular pathology, it has not been examined in SCZ and BD. METHODS: We studied 277 participants (92 healthy volunteers, 98 SCZ, and 87 BD) from 18 to 50 years of age. Images were acquired by trained personnel using a non-mydriatic fundus camera and the retinal vascular Df was calculated by the box-counting method using an automated algorithm. The average Df across the left and right eyes were calculated. RESULTS: Both SCZ and BD had significantly increased Df compared to HV despite controlling for possible confounding factors. However, there was no significant difference between SCZ and BD. These findings suggest abnormal retinal vascular Df in psychoses. LIMITATIONS: The study design was cross-sectional, and patients were on medications. Confound of lifestyle factors such as diet and exercise, if any, was not controlled. Sub-group analysis between BD-I and BD-II was not performed in view of the small sample. CONCLUSIONS: Considering the easy accessibility, affordability, and non-invasive nature of the examination, retinal vascular Df could serve as a surrogate marker for cerebral vascular abnormality and could potentially identify BD and SCZ patients at risk of developing adverse vascular events.

Retinal vascular tortuosity in schizophrenia and bipolar disorder.

The micro-vasculature of retina and brain share common morphological, physiological, and pathological properties. Retina being easily accessible, retinal vascular examination provides an indirect assessment of cerebral vasculature. Considering the high prevalence of vascular morbidity in SCZ and BD a few studies have examined retinal vascular caliber and have reported increased retinal venular caliber in schizophrenia (SCZ). Retinal vascular tortuosity could serve as a better structural measure than caliber as it is static and less susceptible to pulse period variations. However, to date, no study has examined retinal vascular tortuosity in SCZ and bipolar disorder (BD). Hence, we examined retinal vascular tortuosity in comparison with healthy volunteers (HV). We included 255 subjects (78 HV, 79 SCZ, and 86 BD) in the age range of 18 to 50 years. Trained personnel acquired images using a non-mydriatic fundus camera. To measure the average retinal arteriolar tortuosity index (RATI) and retinal venular tortuosity index (RVTI), we used a previously validated, semi-automatic algorithm. The results showed significant differences across the three groups in RATI but not in RVTI; both BD and SCZ had significantly increased RATI compared to HV. There was also a significant difference between SCZ and BD, with BD having higher RATI. If shown to be of predictive utility in future longitudinal studies, it has the potential to identify patients at risk of development of adverse vascular events. As retinal vascular imaging is non-invasive and inexpensive, it could serve as a proxy marker and window to cerebral vasculature.