P. John

In vitro and in vivo neurogenic potential of mesenchymal stem cells isolated from different sources

Regenerative medicine is an evolving interdisciplinary topic of research involving numerous technological methods that utilize stem cells to repair damaged tissues. Particularly, mesenchymal stem cells (MSCs) are a great tool in regenerative medicine because of their lack of tumorogenicity, immunogenicity and ability to perform immunomodulatory as well as anti-inflammatory functions. Numerous studies have investigated the role of MSCs in tissue repair and modulation of allogeneic immune responses. MSCs derived from different sources hold unique regenerative potential as they are self-renewing and can differentiate into chondrocytes, osteoblasts, adipocytes, cardiomyocytes, hepatocytes, endothelial and neuronal cells, among which neuronal-like cells have gained special interest. MSCs also have the ability to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation. In this review we focus on neural differentiation potential of MSCs isolated from different sources and how certain growth factors/small molecules can be used to derive neuronal phenotypes from MSCs. We also discuss the efficacy of MSCs when transplanted in vivo and how they can generate certain neurons and lead to relief or recovery of the diseased condition. Furthermore, we have tried to evaluate the appropriate merits of different sources of MSCs with respect to their propensity towards neurological differentiation as well as their effectiveness in preclinical studies.

Complexity analysis of EEG in patients with schizophrenia using fractal dimension

We computed Higuchis fractal dimension (FD) of resting, eyes closed EEG recorded from 30 scalp locations in 18 male neuroleptic-naïve, recent-onset schizophrenia (NRS) subjects and 15 male healthy control (HC) subjects, who were group-matched for age. Schizophrenia patients showed a diffuse reduction of FD except in the bilateral temporal and occipital regions, with the reduction being most prominent bifrontally. The positive symptom (PS) schizophrenia subjects showed FD values similar to or even higher than HC in the bilateral temporo-occipital regions, along with a co-existent bifrontal FD reduction as noted in the overall sample of NRS. In contrast, this increase in FD values in the bilateral temporo-occipital region was absent in the negative symptom (NS) subgroup. The regional differences in complexity suggested by these findings may reflect the aberrant brain dynamics underlying the pathophysiology of schizophrenia and its symptom dimensions. Higuchis method of measuring FD directly in the time domain provides an alternative for the more computationally intensive nonlinear methods of estimating EEG complexity.

Exploration of dimensions of psychopathology in neuroleptic-naı̈ve patients with recent-onset schizophrenia/schizophreniform disorder

Previous studies have suggested that schizophrenic psychopathology segregates into three orthogonal dimensions, viz., psychosis, negative and disorganization. Most of these reports were based on studies on medicated patients with varying degrees of chronicity. The present study aimed at exploring the dimensionality of psychopathology rated on the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) in a sample of 43 neuroleptic-naïve patients with recent-onset schizophrenia/schizophreniform disorder. Principal Components Analysis (PCA) of SANS and SAPS global ratings, excluding inattention but including inappropriate affect as a separate global rating, revealed that the symptoms segregated into three dimensions, viz., negative (affective flattening, alogia, avolition anhedonia and inappropriate affect), psychosis (delusions and hallucinations) and disorganization (positive formal thought disorder and bizarre behavior). Cumulatively these three dimensions explained 74.07% of the variance. The results suggest that the three dimensions of schizophrenic psychopathology are valid even in neuroleptic-naïve, recent-onset patients with schizophrenia/schizophreniform disorder. PCA of the SANS and SAPS individual items revealed similar findings, but psychotic symptoms loaded under two components, thus yielding a four-factor solution; however, this observation needs to be confirmed in a larger sample of neuroleptic-naïve schizophrenic patients.

Comparative Study of Psychiatric Morbidity among the Displaced and Non-Displaced Populations in the Andaman and Nicobar Islands following the Tsunami

OBJECTIVE The objective of this study was to compare the psychiatric morbidity between the displaced and non-displaced populations of the Andaman and Nicobar Islands during the first three months following the 2004 earthquake and tsunami. METHODS The study was conducted at the 74 relief camps in the Andaman and Nicobar Islands. Port Blair had 12 camps, which provided shelter to 4,684 displaced survivors. There were 62 camps on Car-Nicobar Island, which provided shelter to approximately 8,100 survivors who continued to stay in their habitat (non-displaced population). The study sample included all of the survivors who sought mental health assistance inside the camp. A psychiatrist diagnosed the patients using the ICD-10 criteria. RESULTS Psychiatric morbidity was 5.2% in the displaced population and 2.8% in the non-displaced population. The overall psychiatric morbidity was 3.7%. The displaced survivors had significantly higher psychiatric morbidity than did the non-displaced population. The disorders included panic disorder, anxiety disorders not otherwise specified, and somatic complaints. The existence of an adjustment disorder was significantly higher in the non-displaced survivors. Depression and post-traumatic stress disorder (PTSD) were distributed equally in both groups. CONCLUSIONS Psychiatric morbidity was found to be highest in the displaced population. However, the incidence of depression and PTSD were distributed equally in both groups. Involvement of community leaders and survivors in shared decision-making processes and culturally acceptable interventions improved the community participation. Cohesive community, family systems, social support, altruistic behavior of the community leaders, and religious faith and spirituality were factors that helped survivors cope during the early phase of the disaster.

Fronto-temporal dysfunction in schizophrenia: A selective review

Schizophrenia is conceptualized as a disorder of aberrant neurodevelopment, with evident stigmata such as minor physical anomalies (MPA), neurological soft signs (NSS), and abnormalities of brain structure and function, proposed as disease endophenotypes. We have examined the neurobiology of schizophrenia using neurodevelopmental markers, structural MRI (sMRI), EEG spectral power, and coherence as well as neuropsychological testing in neuroleptic-naïve, recent-onset schizophrenia (NRS) subjects. It has been our focus to link the positive and negative symptom dimensions of schizophrenia with their underlying neural correlates specifically reflecting fronto-temporal circuitry dysfunction. We found that MPAs and NSSs constituted independent neurodevelopmental markers of schizophrenia and would afford greater predictive validity when used as a composite endophenotype. In an exploratory factor analytic study of the dimensionality of psychopathology, we noted that the symptoms segregated into three dimensions, viz., positive, negative, and disorganization, even in NRS subjects. Executive function tests as well as EEG spectral power and coherence studies revealed that the symptom dimensions of schizophrenia could be linked to specific neural correlates. In an attempt to study the relationship between the symptom dimensions and brain structure and function using MRI, we have proposed neuroanatomical definitions with cytoarchitectonic meaning for parcellation of the prefrontal sub-divisions. Using sMRI, we have found specific corpus callosal abnormalities that possibly link the temporo-parietal association cortices with the positive symptom dimension. Recently, we also found evidence for neurodevelopmental deviance in schizophrenia possibly involving the frontal pole (FP)-driven cortical network, in a sMRI study linking FP volume and total brain volume with age in NRS subjects and age-, gender- and education-matched healthy subjects. Overall, our findings highlight the potential significance of linking the homogeneous symptom dimensions of schizophrenia with dysfunctional connectivity in the fronto-temporal region.

Assessing Neurocognition via Gamified Experimental Logic: A Novel Approach to Simultaneous Acquisition of Multiple ERPs.

The present study describes the development of a neurocognitive paradigm: “Assessing Neurocognition via Gamified Experimental Logic” (ANGEL), for performing the parametric evaluation of multiple neurocognitive functions simultaneously. ANGEL employs an audiovisual sensory motor design for the acquisition of multiple event related potentials (ERPs)—the C1, P50, MMN, N1, N170, P2, N2pc, LRP, P300, and ERN. The ANGEL paradigm allows assessment of 10 neurocognitive variables over the course of three “game” levels of increasing complexity ranging from simple passive observation to complex discrimination and response in the presence of multiple distractors. The paradigm allows assessment of several levels of rapid decision making: speeded up response vs. response-inhibition; responses to easy vs. difficult tasks; responses based on gestalt perception of clear vs. ambiguous stimuli; and finally, responses with set shifting during challenging tasks. The paradigm has been tested using 18 healthy participants from both sexes and the possibilities of varied data analyses have been presented in this paper. The ANGEL approach provides an ecologically valid assessment (as compared to existing tools) that quickly yields a very rich dataset and helps to assess multiple ERPs that can be studied extensively to assess cognitive functions in health and disease conditions.

Psychological impact of the tsunami on elderly survivors.

OBJECTIVE The study aimed at comparing the psychiatric morbidity in geriatric versus nongeriatric (NG) adults during the initial 3 months following the December 2004 tsunami involving the Andaman and Nicobar Islands, India. METHODS This observational study was undertaken during the relief operation of tsunami. There were 12,784 survivors sheltered across 74 relief camps with 4,684 displaced survivors in Port Blair, and 8,100 nondisplaced survivors in Car Nicobar Island. All persons who accessed mental health assistance within the camps constituted the study sample. Diagnoses were made by qualified psychiatrists using the International Classification of Diseases, Tenth Revision. There were 438 adult patients, of which 75 (17%) were geriatric (60 years or older) and 363 (83%) were NG (aged 19-59 years). RESULTS The geriatric sample had greater levels of adjustment disorder than NG group. The two groups differed in terms of displacement as the elderly preferred to stay in their own locality. A comparison between displaced geriatric and NG groups showed that major depression was less common in the geriatric sample. However, in the nondisplaced group, geriatric subgroup showed a higher incidence of posttraumatic stress disorder. Within the geriatric sample, there were higher levels of adjustment disorder in the nondisplaced group whereas the displaced group suffered more depressive episodes and unspecified anxiety disorders. CONCLUSION Greater levels of adjustment disorder in geriatric group may indicate grief reaction and survivor guilt, especially in nondisplaced group. In addition, lower occurrences of depressive episodes in nondisplaced geriatric sample may indicate that the elderly need to be rehabilitated in their own habitats after major disasters.

A study of structural and functional connectivity in early Alzheimer's disease using rest fMRI and diffusion tensor imaging.

Alzheimers disease (AD) is a progressive neurodegenerative condition where in early diagnosis and interventions are key policy priorities in dementia services and research. We studied the functional and structural connectivity in mild AD to determine the nature of connectivity changes that coexist with neurocognitive deficits in the early stages of AD.

Single-Trial EEG Classification Using Logistic Regression Based on Ensemble Synchronization

In this paper, we propose an ensemble synchronization measure across all EEG channel pairs of a cluster based on Frobenius norm of the phase synchronization matrix, in a 0-1 scale enabling a direct comparison between clusters with different number of channels. Using this metric, we studied the intrahemispheric EEG synchronization in the lower gamma band (30-40 Hz) during 1229 single trials of an audio-visual integration cross modal task (CMT) recorded from five patients with schizophrenia and five healthy control subjects. Using ensemble synchronization measure and response latency of single trials recorded during the CMT as features for logistic regression, we could classify each single trial of EEG as belonging to a patient with schizophrenia or a healthy control subject with 73% accuracy, with an area under receiver operating characteristics curve of 0.83. We also propose a likelihood rating to denote the possibility of a subject belonging to the schizophrenia group.

Differential relationship of frontal pole and whole brain volumetric measures with age in neuroleptic-naive schizophrenia and healthy subjects

Brodmanns area (BA) 10, which occupies the frontal pole (FP) of the human brain, has been proven to play a central role in the executive control of cognitive operations. Previous in vivo morphometric studies of the FP have been limited by the lack of an accepted boundary of its posterior limit. We studied the FP gray matter volume in 23 healthy subjects who were age-, sex-, and education-matched to 23 neuroleptic-naïve recent-onset schizophrenia subjects in the age span 20-40 years, using a cytoarchitectonically and functionally valid landmark-based definition of its posterior boundary that we proposed recently (John, J.P., Yashavantha, B.S., Gado, M., Veena, R., Jain, S., Ravishankar, S., Csernansky, J.G., 2007. A proposal for MRI-based parcellation of the frontal pole. Brain Struct. Funct. 212, 245-253. 2007). Additionally, we examined the relationship between FP volume and age in both healthy and schizophrenia subjects to examine evidence for a possible differential relationship between these variables across the samples. A major finding of the study was the absence of a group-level difference in frontal pole gray volumes between the healthy and schizophrenia participants. However, a more complex finding emerged in relation to age effects. The healthy participants showed an inverse relationship of FP gray volume with age, even after taking total brain volume differences into account. But this age effect was completely absent in the schizophrenia group. Moreover, all the volumetric measures in schizophrenia subjects showed substantially higher range, variance, skewness and kurtosis when compared to those of healthy subjects. These findings have implications in understanding the possible role of FP in the pathophysiology of schizophrenia.