Naren P. Rao

Neurohemodynamic correlates of 'OM' chanting: A pilot functional magnetic resonance imaging study.

Background: A sensation of vibration is experienced during audible ‘OM’ chanting. This has the potential for vagus nerve stimulation through its auricular branches and the effects on the brain thereof. The neurohemodynamic correlates of ‘OM’ chanting are yet to be explored. Materials and Methods: Using functional Magnetic Resonance Imaging (fMRI), the neurohemodynamic correlates of audible ‘OM’ chanting were examined in right-handed healthy volunteers (n=12; nine men). The ‘OM’ chanting condition was compared with pronunciation of “ssss” as well as a rest state. fMRI analysis was done using Statistical Parametric Mapping 5 (SPM5). Results: In this study, significant deactivation was observed bilaterally during ‘OM’ chanting in comparison to the resting brain state in bilateral orbitofrontal, anterior cingulate, parahippocampal gyri, thalami and hippocampi. The right amygdala too demonstrated significant deactivation. No significant activation was observed during ‘OM’ chanting. In contrast, neither activation nor deactivation occurred in these brain regions during the comparative task – namely the ‘ssss’ pronunciation condition. Conclusion: The neurohemodynamic correlates of ‘OM’ chanting indicate limbic deactivation. As similar observations have been recorded with vagus nerve stimulation treatment used in depression and epilepsy, the study findings argue for a potential role of this ‘OM’ chanting in clinical practice.

Plasma cytokine abnormalities in drug-naïve, comorbidity-free obsessive–compulsive disorder

Growing evidence in the last decade suggest significant role of immune alterations in the pathogenesis of obsessive-compulsive disorder (OCD). Cytokines, mediators of inflammation, alter the neurotransmitter concentration and result in a hyposerotonergic and hyperglutamatergic state implicated in pathogenesis of OCD. However, only few studies have examined cytokine abnormalities in OCD with inconsistent results possibly due to confounding effects of medications and comorbid anxiety-depression. We examined 20 comorbidity free, drug free OCD patients and 20 age and sex matched healthy controls. Clinical severity was assessed using Yale Brown Obsessive Compulsive Scale, Hamilton anxiety rating scale, Hamilton depression rating scale and Clinical Global Impression. Levels of different cytokines, Interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor (TNF)-α and Interferon (IFN)-γ were assessed using Cytometric Bead Array. OCD patients had significantly greater plasma levels of IL-2, IL-4, IL-6, IL-10 and TNF-α levels than controls but not IFN-γ. Reanalysis of data with only drug naïve patients (excluding 4 drug free patients) did not alter the results. Presence of these abnormalities in drug-naïve patients suggests the possible role of cytokines in the pathogenesis of OCD. Study findings have potential clinical utility in development of novel therapeutic options targeting cytokine aberrations in OCD.

Yoga school of thought and psychiatry: Therapeutic potential.

Yoga is a traditional life-style practice used for spiritual reasons. However, the physical components like the asanas and pranayaamas have demonstrated physiological and therapeutic effects. There is evidence for Yoga as being a potent antidepressant that matches with drugs. In depressive disorder, yoga ‘corrects’ an underlying cognitive physiology. In schizophrenia patients, yoga has benefits as an add-on intervention in pharmacologically stabilized subjects. The effects are particularly notable on negative symptoms. Yoga also helps to correct social cognition. Yoga can be introduced early in the treatment of psychosis with some benefits. Elevation of oxytocin may be a mechanism of yoga effects in schizophrenia. Certain components of yoga have demonstrated neurobiological effects similar to those of vagal stimulation, indicating this (indirect or autogenous vagal stimulation) as a possible mechanism of its action. It is time, psychiatrists exploited the benefits if yoga for a comprehensive care in their patients.

Clinical correlates of thalamus volume deficits in anti-psychotic-naïve schizophrenia patients: A 3-Tesla MRI study

Background: Thalamus, the sensory and motor gateway to the cortex, plays an important role in cognitive and perceptual disturbances in schizophrenia. Studies examining the volume of the thalamus in schizophrenia have reported conflicting findings due to the presence of potential confounding factors such as low-resolution imaging and anti-psychotics. The thalamus volume in anti-psychotic-naïve patients determined using high-resolution 3-Tesla magnetic resonance imaging (MRI) has not yet been examined. Materials and Methods: Using 3-Tesla MRI, this study for the first time examined anti-psychotic-naïve schizophrenia patients (n=18; M:F:11:7) in comparison with healthy controls (n=19;M:F:9:10) group-matched for age, sex, handedness, education, and socioeconomic status. The volume of the thalamus was measured using a three-dimensional, interactive, semi-automated analysis with good inter-rater and intra-rater reliability. Psychopathology was assessed using the Scale for Assessment of Negative Symptoms (SANS) and the Scale for Assessment of Positive Symptoms (SAPS). Results: Right, left, and total thalamus volumes of patients were significantly smaller than those of controls after controlling for the potential confounding effect of intracranial volume. Thalamus volumes had significant positive correlation with positive symptoms score (SAPS) and significant negative correlation with negative symptoms score (SANS). Conclusions: Thalamus volume deficits in anti-psychotic-naïve schizophrenia patients support a neurodevelopmental pathogenesis. The contrasting correlation of thalamus volume deficits with psychopathology scores suggests that contrasting pruning aberrations underlie symptom genesis in schizophrenia.

Digit ratio (2D:4D) asymmetry and Schneiderian first rank symptoms: Implications for cerebral lateralisation theories of schizophrenia

Schneiderian first rank symptoms (FRS) in schizophrenia have been hypothesised to be secondary to aberrant cerebral lateralisation over the course of human evolution. The ratio of length of second digit to fourth digit (2D:4D) has been put forward as a potential indicator of cerebral lateralisation. This study examined 2D:4D and its asymmetry in antipsychotic-naïve schizophrenia patients (N=79) in comparison with healthy controls (N=75). Psychopathology was assessed using Scales for Assessment of Positive and Negative Symptoms. FRS assessment was performed as per established descriptions. The digit lengths (2D & 4D) were measured using a digital vernier caliper with good inter-rater reliability. Female schizophrenia patients showed significantly lower 2D:4D than female healthy controls. Mean 2D:4D asymmetry index was significantly lower in male schizophrenia patients than male healthy controls. FRS status had significant effect on left 2D:4D as well as 2D:4D asymmetry index, the patients with FRS having the lowest values. Our study findings support association between Schneiderian FRS and low 2D:4D as well as low 2D:4D asymmetry index. Since 2D:4D is linked with limbic asymmetry, our study findings offer further support to the cerebral lateralisation theories of schizophrenia.

Proton magnetic resonance spectroscopy in depression.

Magnetic Resonance Spectroscopy (MRS) is a unique technique that can directly assess the concentration of various biochemical metabolites in the brain. Thus, it is used in the study of molecular pathophysiology of different neuropsychiatric disorders, such as, the major depressive disorder and has been an area of active research. We conducted a computer-based literature search using the Pubmed database with ‘magnetic resonance spectroscopy’, ‘MRS’, ‘depression’, and ‘major depressive disorder’ as the key words, supplemented by a manual search of bibliographic cross-referencing. Studies in depression report abnormalities in the frontal cortex, basal ganglia, hippocampus, anterior cingulate cortex, and the occipital cortex. These abnormalities improve after treatment with selective serotonin reuptake inhibitor, electroconvulsive therapy, and yoga, and thus, are possibly state-dependent. The findings are consistent with other morphometric and clinical studies and support the proposed pathophysiological theory of dysfunction in the neuronal circuits involving the frontal cortex, limbic cortex, and basal ganglia. Spectroscopy also has potential implications in predicting the response to treatment and formulating individualized pharmacotherapy.

Beneficial effects of add-on raloxifene in schizophrenia

The role of estrogens in schizophrenia has been proposed from the observation of schizophrenia occurring later and with symptom severity being lesser in women. Utility of estrogens in treatment of psychoses, though seen to be useful, comes with inherent risks of neoplasias, given its agonistic action on breast and endometrium. This risk can be overcome with use of selective estrogen receptor modulators, like raloxifene. Raloxifene has been used in schizophrenia, with improvement in symptoms and cognitive functions. We report the use of raloxifene as an adjunctive treatment, with risperidone, in treatment-resistant form of schizophrenia. The patient, a 29-year-old woman, over a 7-month follow-up period, showed significant improvement in socio-occupational functioning, with reduction in symptom severity.

Antithetical asymmetry in schizophrenia and bipolar affective disorder: a line bisection study

OBJECTIVE Evolutionary theories link the pathogenesis of psychosis with anomalous brain asymmetry. Research shows that aberrant lateralization is linked to schizophrenia with elevated rates of left-handedness and reversal of normal cerebral asymmetries. However, lateralization is underexamined in bipolar affective disorder (BPAD) and the available literature suggests the possibility of greater lateralization, which is diametrically opposite to what is observed in schizophrenia. For the first time, we report concurrent analyses of asymmetry in BPAD and schizophrenia using a line bisection task. METHODS We examined 164 subjects (31 patients with BPAD in remission, 30 patients with schizophrenia, and 103 healthy controls) using a two-hand line bisection task with established methodology. Raters with good inter-rater reliability (intraclass correlation coefficient > 0.8) measured deviation from the center. Task performance was compared using analysis of covariance with age, sex, and education as covariates. RESULTS Study groups did not differ significantly on age, sex, and handedness (p > 0.06). Patients (both schizophrenia and BPAD) had significantly more errors in identifying the center than controls (p < 0.001). Patients with schizophrenia bisected fewer lines at center than controls and BPAD subjects (p < 0.001). Using their right hand, schizophrenia patients had significant rightward deviation and BPAD patients had leftward deviation (p = 0.001). A significant interaction between diagnosis and direction of deviation (p = 0.01) was noted, with significant rightward deviation in schizophrenia and a trend toward leftward deviation in BPAD. CONCLUSIONS Study findings suggest attenuation of normal pseudoneglect in schizophrenia and accentuation of normal pseudoneglect in BPAD, indicating lesser lateralization in schizophrenia and possibly greater lateralization in BPAD. From an evolutionary perspective, schizophrenia and BPAD might have antithetical origins.

Neuroanatomical, neurochemical, and neurodevelopmental basis of obsessive-compulsive symptoms in schizophrenia.

The prevalence of the obsessive-compulsive symptoms in schizophrenia (OCSS) appears to be higher than that expected on the basis of comorbidity rates. Review of brain abnormalities in schizophrenia and obsessive-compulsive disorder (OCD) reveals involvement of similar regions namely the frontal lobe, the basal ganglia, the thalamus, and the cerebellum, in both the disorders. Neurodevelopmental etiopathogenesis has been proposed to explain schizophrenia as well as OCD. Significant overlap in neurotransmitter dysfunction (serotonin, glutamate, and dopamine) has been documented between schizophrenia and OCD. The New-onset obsessive-compulsive (OC) symptoms have been reported with the use of atypical antipsychotics in the schizophrenia patients In this background, OCSS is an emerging area of recent interests. This article attempts to review the literature on the neurobiology of OCSS. Neuroimaging, neuropsychological, and neuromotor abnormalities in OCSS discussed in the context of neurodevelopmental etiopathogenesis suggest glutamate abnormalities in OCSS. Atypical antipsychotic induced OCSS points towards the possible roles of glutamate and serotonin. Dopamine may be responsible for the beneficial role of antipsychotics in the treatment of OCD. In summary, we propose that glutamate, serotonin, and dopamine abnormalities may be the probable basis for OCSS.

Volumetric analysis of hippocampal sub-regions in late onset depression: A 3 tesla magnetic resonance imaging study

BACKGROUND While many studies have reported reduced volume of hippocampus in late onset depression (LOD), the status of hippocampus sub-regions (anterior/posterior) is yet to be explored. Evaluating hippocampal sub-regions might facilitate better elucidation of the neurobiological basis of LOD. METHODS Twenty five elderly subjects with LOD (mean age=65.28yr, SD=5.73, 15 females) and 20 healthy controls (mean age=65.35yr, SD=5.67, 7 females) were examined using 3-tesla magnetic resonance imaging (MRI). They were also evaluated with Montgomery Asberg Depression Rating Scale (MADRS) and Hindi Mental State Examination (HMSE). We examined the difference in volume of Hippocampal sub-regions between the LOD group and control group controlling for the age, sex and intracranial volume. RESULTS Left posterior hippocampus volume was significantly smaller in LOD group than the control group (1.01±0.19ml vs 1.16±0.25ml, F=7.50, p=0.009). There was a similar trend for the right posterior hippocampus (1.08±0.19ml vs 1.18±0.27ml, F=3.18, p=0.082). Depression severity (mean MADRS score=20.64±8.99) had a significant negative correlation with volumes of right posterior hippocampus (r=-0.37, p=0.012) and left posterior hippocampus (r=-0.46, p=0.001) in the LOD group. CONCLUSIONS Specific reduction of posterior hippocampus volume and its relationship with depression severity indicates sub region specific hippocampal volumetric abnormalities in LOD. Future studies need to evaluate sub region specific hippocampal volume in LOD longitudinally for better understanding of the pathogenesis of LOD in view of the functional differences between anterior and posterior hippocampus.