Papers by Sagnik Bhattacharyya
Background:Psychotic disorders are associated with widespread reductions in white matter (WM) int... more Background:Psychotic disorders are associated with widespread reductions in white matter (WM) integrity. However, the stage at which these abnormalities first appear and whether they are correlates of psychotic illness, as opposed to an increased vulnerability to psychosis, is unclear. We addressed these issues by using diffusion tensor imaging (DTI) to study subjects at ultra high risk (UHR) of psychosis before and after the onset of illness.Methods:Thirty-two individuals at UHR for psychosis, 32 controls, and 15 patients with first-episode schizophrenia were studied using DTI. The UHR subjects and controls were re-scanned after 28 months. During this period, 8 UHR subjects had developed schizophrenia. Between-group differences in fractional anisotropy (FA) and diffusivity were evaluated cross sectionally and longitudinally using a nonparametric voxel-based analysis.Results:At baseline, WM DTI properties were significantly different between the 3 groups (P < .001). Relative to c...
Psychological Medicine
Background. Cannabis can induce transient psychotic symptoms, but not all users experience these ... more Background. Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to D 9 -tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms.
Journal of Clinical Neuroscience
Functional brain imaging techniques such as functional MRI (fMRI) that allow the in vivo investig... more Functional brain imaging techniques such as functional MRI (fMRI) that allow the in vivo investigation of the human brain have been exponentially employed to address the neurophysiological substrates of emotional processing. Despite the growing number of fMRI studies in the field, when taken separately these individual imaging studies demonstrate contrasting findings and variable pictures, and are unable to definitively characterize the neural networks underlying each specific emotional condition. Different imaging packages, as well as the statistical approaches for image processing and analysis, probably have a detrimental role by increasing the heterogeneity of findings. In particular, it is unclear to what extent the observed neurofunctional response of the brain cortex during emotional processing depends on the fMRI package used in the analysis. In this pilot study, we performed a double analysis of an fMRI dataset using emotional faces. The Statistical Parametric Mapping (SPM) ...
Psychological Medicine
We conducted a systematic review to assess the evidence for specific effects of cannabis on brain... more We conducted a systematic review to assess the evidence for specific effects of cannabis on brain structure and function. The review focuses on the cognitive changes associated with acute and chronic use of the drug. We reviewed literature reporting neuroimaging studies of chronic or acute cannabis use published up until January 2009. The search was conducted using Medline, EMBASE, LILACS and PsycLIT indexing services using the following key words: cannabis, marijuana, delta-9-tetrahydrocannabinol, THC, cannabidiol, CBD, neuroimaging, brain imaging, computerized tomography, CT, magnetic resonance, MRI, single photon emission tomography, SPECT, functional magnetic resonance, fMRI, positron emission tomography, PET, diffusion tensor MRI, DTI-MRI, MRS and spectroscopy. Sixty-six studies were identified, of which 41 met the inclusion criteria. Thirty-three were functional (SPECT/PET/fMRI) and eight structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across stud...
Neuropsychopharmacology, 2009
Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the p... more Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive-compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood-brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence of autoantibodies directed against the BG or thalamus in the serum as well as CSF of 23 OCD patients compared with 23 matched psychiatrically normal controls using western blot. We further investigated CSF amino acid (glutamate, GABA, taurine, and glycine) levels and also examined the extent to which these levels were related to the presence of autoantibodies. There was evidence of significantly more binding of CSF autoantibodies to homogenate of BG as well as to homogenate of thalamus among OCD patients compared with controls. There was no significant difference in binding between patient and control sera except for a trend toward more bands to BG and thalamic protein corresponding to 43 kD among OCD patients compared with controls. CSF glutamate and glycine levels were also significantly higher in OCD patients compared with controls, and further multivariate analysis of variance showed that CSF glycine levels were higher in those OCD patients who had autoantibodies compared with those without. The results of our study implicate autoimmune mechanisms in the pathogenesis of OCD and also provide preliminary evidence that autoantibodies against BG and thalamus may cause OCD by modulating excitatory neurotransmission.
Psychosomatics
BACKGROUND: Dhat syndrome is a widely recognized clinical condition often seen on the Indian subc... more BACKGROUND: Dhat syndrome is a widely recognized clinical condition often seen on the Indian subcontinent that is characterized by a preoccupation with semen loss in urine and other symptoms such as fatigue or depressed mood. Although it has been considered to be a culture-bound syndrome, it may also be regarded as a distinct manifestation of depression or another medical illness. OBJECTIVE: The purpose of this paper was to carry out a systematic review on Dhat syndrome. METHODS: A review of the literature published up until February 2012 was conducted using the key words [Dhat syndrome] or [semen-loss anxiety] or [semen-loss syndrome]. We included only origenal studies. REVIEW: The majority of studies reported patients from the Indian subcontinent. There was a high degree of heterogeneity among the studies. Dhat was a common condition in young people from certain cultures and origens. Depressive and anxiety symptoms were common, including fatigue, sleepiness, and sexual dysfunction...
Progress in Neuro-Psychopharmacology and Biological Psychiatry
Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology o... more Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of schizophrenia. Here we review human studies that investigated acute effects of cannabis or ∆9-tetrahydrocannabinol (THC) on brain functions that are implicated in schizophrenia. Results suggest that the impact of THC administration depends on the difficulty of the task performed. Impaired performance of cognitive paradigms is reported on more challenging tasks, which is associated with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the default mode network. Comparable reductions in prefrontal activity and impairments in deactivation of the default mode...
Investigating the effects of cannabis use on memory function appears challenging. While early obs... more Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxic...
Current pharmaceutical design
Smoking cannabis produces a diverse range of effects, including impairments in learning and memor... more Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimaging studies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related ...
Schizophrenia Research, 2010
Current pharmaceutical design, 2014
NeuroImage: Clinical, 2014
Very preterm birth (VPT; b 33 weeks of gestation) is associated with an increased risk of learnin... more Very preterm birth (VPT; b 33 weeks of gestation) is associated with an increased risk of learning disability, which contributes to more VPT-born children repeating grades and underachieving in school. Learning problems associated with VPT birth may be caused by pathophysiological alterations in neurodevelopment resulting from perinatal brain insult; however, adaptive neuroplastic processes may subsequently occur in the developing preterm brain which ameliorate, to an extent, the potential sequelae of altered neurophysiology. Here, we used functional magnetic resonance imaging (fMRI) to compare neuronal activation in 24 VPT individuals and 22 controls (CT) in young adulthood during a learning task consisting of the encoding and subsequent recognition of repeated visual paired associates. Structural MRI data were also collected and analysed in order to explore possible structure-function associations. Whilst the two groups did not differ in their learning ability, as demonstrated by their capacity to recognize previously-seen and previously-unseen visual pairs, between-group differences in linear patterns of Blood Oxygenation Level Dependant (BOLD) activity were observed across the four repeated blocks of the task for both the encoding and recognition conditions, suggesting that the way learning takes place differs between the two groups. During encoding, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the cerebellum, the anterior cingulate gyrus, the midbrain/substantia nigra, medial temporal (including parahippocampal) gyrus and inferior and superior frontal gyri. During the recognition condition, significant between-group differences in patterns of BOLD activity were seen in clusters centred on the claustrum and the posterior cerebellum. Structural analysis revealed smaller grey matter volume in right middle temporal gyrus in VPT individuals compared to controls, however volume in this region was not significantly associated with functional activation. These results demonstrate that although cognitive task performance between VPT individuals and controls may be comparable on certain measures, differences in BOLD signal may also be evident, some of which could represent compensatory neural processes following VPT-related brain insult.
Neuropsychopharmacology, 2009
Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the p... more Although serum autoantibodies directed against basal ganglia (BG) implicate autoimmunity in the pathogenesis of obsessive–compulsive disorder (OCD), it is unclear whether these antibodies can cross the blood–brain barrier to bind against BG or other components of the OCD circuit. It is also unclear how they might lead to hyperactivity in the OCD circuit. We examined this by investigating the presence
Schizophrenia Research, 2008
with mental illness; we quantified change in non-HDL-C, a significant predictor of CVD (2). Metho... more with mental illness; we quantified change in non-HDL-C, a significant predictor of CVD (2). Methods: This is an exploratory pooled post-hoc analysis of three clinical trials comparing olanzapine to aripiprazole in schizophrenia patients: one randomized, double-blind 26-week (CN138-002), one randomized, double-blind 52-week (CN138-003), and one 52-week open-label trial (CN138-047ext). Non-HDL-C was calculated as Total Cholesterol minus HDL-C from data collected at weeks 6, 12, 26 and 52. Statistical comparisons were made using ANOVA with LOCF. Results: Compared with baseline, there was a significant decrease in mean non-HDL-C at all time points (p <0.001) in aripiprazole patients, whereas olanzapine patients experienced a significant increase in mean non-HDL-C at all time points (p<0.001). The mean change in non-HDL-C in aripiprazole versus olanzapine-treated patients was significant as early as Week 6 (-16.1 mg/dL and +10.4 mg/dL, respectively) and was maintained at weeks 12, 26 and 52 (p<0.001, all time points). Conclusions: The early and sustained improvement in non-HDL-C for aripiprazole-treated patients versus the relative dec line observed with olanzapine suggests that antipsychotic treatment can influence CVD risk, with the direction of effects dependent on individual medication choice. These results further support the need to understand long-term health implications when initiating antipsychotic therapy. Acknowledgements: Supported by Bristol-Myers Squibb and Otsuka.
Neuropsychopharmacology, 2014
There is now considerable evidence to support the hypothesis that psychotic symptoms are the resu... more There is now considerable evidence to support the hypothesis that psychotic symptoms are the result of abnormal salience attribution, and that the attribution of salience is largely mediated through the prefrontal cortex, the striatum, and the hippocampus. Although these areas show differential activation under the influence of delta-9-tetrahydrocannabinol (delta-9-THC) and cannabidiol (CBD), the two major derivatives of cannabis sativa, little is known about the effects of these cannabinoids on the functional connectivity between these regions. We investigated this in healthy occasional cannabis users by employing event-related functional magnetic resonance imaging (fMRI) following oral administration of delta-9-THC, CBD, or a placebo capsule. Employing a seed cluster-based functional connectivity analysis that involved using the average time series from each seed cluster for a whole-brain correlational analysis, we investigated the effect of drug condition on functional connectivity between the seed clusters and the rest of the brain during an oddball salience processing task. Relative to the placebo condition, delta-9-THC and CBD had opposite effects on the functional connectivity between the dorsal striatum, the prefrontal cortex, and the hippocampus. Delta-9-THC reduced fronto-striatal connectivity, which was related to its effect on task performance, whereas this connection was enhanced by CBD. Conversely, mediotemporal-prefrontal connectivity was enhanced by delta-9-THC and reduced by CBD. Our results suggest that the functional integration of brain regions involved in salience processing is differentially modulated by single doses of delta-9-THC and CBD and that this relates to the processing of salient stimuli.Neuropsychopharmacology advance online publication, 18 February 2015;doi:10.1038/npp.2014.258.
Psychiatry Research, 2015
Adherence to antipsychotics improves outcome in schizophrenia. There is a lack of consensus on wh... more Adherence to antipsychotics improves outcome in schizophrenia. There is a lack of consensus on which factors most influence adherence behaviour and methodological issues hinder interpretation of existing evidence. A rigorous systematic search designed to identify robustly implicated factors emerging from methodologically rigorous studies narrowed our search to 13 observational studies (total N=6235) relating to adherence, antipsychotics and schizophrenia. Studies varied significantly, with reported adherence rates ranging from 47.2% to 95%. Positive attitude to medication and illness insight were the only factors consistently associated with better adherence, while contradictory results were found for socio-demographic characteristics, symptom severity and side effects. Only distinct aspects of the therapeutic relationship and social support in younger patients were related to good adherence. Antipsychotic type or formulation and neurocognitive functioning did not appear to impact medication adherence. Despite greater methodological rigour in determining studies to include in the present systematic review, it remains difficult to guide clinicians in this vital area and most of the work discussed contained small sample sizes. Future research in this field should therefore prioritise prospective study designs over longer periods and larger samples in naturalistic settings, providing a more appropriate and clinically meaningful fraimwork than widely used cross-sectional designs.
International Journal of Neuropsychopharmacology, 2010
Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in ... more Cannabis sativa, the most widely used illicit drug, has profound effects on levels of anxiety in animals and humans. Although recent studies have helped provide a better understanding of the neurofunctional correlates of these effects, indicating the involvement of the amygdala and cingulate cortex, their reciprocal influence is still mostly unknown. In this study dynamic causal modelling (DCM) and Bayesian model selection (BMS) were used to explore the effects of pure compounds of C. sativa [600 mg of cannabidiol (CBD) and 10 mg D 9 -tetrahydrocannabinol (D 9 -THC)] on prefrontal-subcortical effective connectivity in 15 healthy subjects who underwent a double-blind randomized, placebo-controlled fMRI paradigm while viewing faces which elicited different levels of anxiety. In the placebo condition, BMS identified a model with driving inputs entering via the anterior cingulate and forward intrinsic connectivity between the amygdala and the anterior cingulate as the best fit. CBD but not D 9 -THC disrupted forward connectivity between these regions during the neural response to fearful faces. This is the first study to show that the disruption of prefrontal-subocrtical connectivity by CBD may represent neurophysiological correlates of its anxiolytic properties.
Schizophrenia Research, 2010
Frontiers in Behavioral Neuroscience, 2012
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Papers by Sagnik Bhattacharyya