AbstractDespite extensive research and prodigious advances in neuroscience, our comprehension of the nature of schizophrenia remains rudimentary. Our failure to make progress is attributed to the ...extreme heterogeneity of this condition, enormous complexity of the human brain, limitations of extant research paradigms, and inadequacy of traditional statistical methods to integrate or interpret increasingly large amounts of multidimensional information relevant to unravelling brain function. Fortunately, the rapidly developing science of machine learning appears to provide tools capable of addressing each of these impediments. Enthusiasm about the potential of machine learning methods to break the current impasse is reflected in the steep increase in the number of scientific publication about the application of machine learning to the study of schizophrenia. Machine learning approaches are, however, poorly understood by schizophrenia researchers and clinicians alike. In this paper, we provide a simple description of the nature and techniques of machine learning and their application to the study of schizophrenia. We then summarize its potential and constraints with illustrations from six studies of machine learning in schizophrenia and address some common misconceptions about machine learning. We suggest some guidelines for researchers, readers, science editors and reviewers of the burgeoning machine learning literature in schizophrenia. In order to realize its enormous promise, we suggest the need for the disciplined application of machine learning methods to the study of schizophrenia with a clear recognition of its capability and challenges accompanied by a concurrent effort to improve machine learning literacy among neuroscientists and mental health professionals.
Abstract Background This study aimed to identify how the activity of large-scale brain networks differs between mood states in bipolar disorder. The authors measured spontaneous brain activity in ...subjects with bipolar disorder in mania and euthymia and compared these states to a healthy comparison population. Methods 23 subjects with bipolar disorder type I in a manic episode, 24 euthymic bipolar I subjects, and 23 matched healthy comparison (HC) subjects underwent resting state fMRI scans. Using an existing parcellation of the whole brain, we measured functional connectivity between brain regions and identified significant differences between groups. Results In unbiased whole-brain analyses, functional connectivity between parietal, occipital, and frontal nodes within the dorsal attention network (DAN) were significantly greater in mania than euthymia or HC subjects. In the default mode network (DMN), connectivity between dorsal frontal nodes and the rest of the DMN differentiated both mood state and diagnosis. Limitations The bipolar groups were separate cohorts rather than subjects imaged longitudinally across mood states. Conclusions Bipolar mood states are associated with highly significant alterations in connectivity in two large-scale brain networks. These same networks also differentiate bipolar mania and euthymia from a HC population. State related changes in DAN and DMN connectivity suggest a circuit based pathology underlying cognitive dysfunction as well as activity / reactivity in bipolar mania. Altered activities in neural networks may be biomarkers of bipolar disorder diagnosis and mood state that are accessible to neuromodulation are promising novel targets for scientific investigation and possible clinical intervention.
Atorvastatin Improves Left Ventricular Systolic Function and Serum Markers of Inflammation in Nonischemic Heart Failure
Srikanth Sola, Muhammad Q. S. Mir, Stamatios Lerakis, Neeraj Tandon, Bobby V. ...Khan
Little is known about the role of statins in patients with nonischemic heart failure (HF) due to systolic dysfunction. We randomized 108 patients with nonischemic HF and a left ventricular ejection fraction (LVEF) ≤35% to either atorvastatin 20 mg/day or placebo for a 12-month period. Left ventricular systolic function and markers of inflammation were determined. Atorvastatin 20 mg/day was associated with an improvement in LVEF and serum markers of inflammation, suggesting that it might have a role in the management of nonischemic HF.
This study examined the effect of statin therapy on vascular markers of inflammation and echocardiographic findings in patients with nonischemic forms of cardiomyopathy.
Despite advances in therapy, morbidity and mortality from heart failure (HF) remain high. We wished to determine whether treatment with atorvastatin affects left ventricular (LV) systolic function and markers of inflammation in patients with nonischemic HF.
A total of 108 patients with nonischemic HF and a left ventricular ejection fraction (LVEF) ≤35% were randomized to either atorvastatin 20 mg/day or placebo in a double-blinded fashion for a 12-month period. The LVEF and LV end-diastolic diameter (LVEDD) and left ventricular end-systolic diameter (LVESD) were determined by echocardiography. Serum markers of inflammation and oxidation were also measured.
The LVEF increased from 0.33 ± 0.05 to 0.37 ± 0.04 (p = 0.01) in the atorvastatin group over the 12-month follow-up period, whereas those patients in the placebo group experienced a decline in ejection fraction during the same time period. In addition, LVEDD was reduced from 57.1 ± 5.9 mm to 53.4 ± 5.1 mm (p = 0.007) and LVESD was reduced from 42.4 ± 3.8 mm to 39.1 ± 3.8 mm (p = 0.02) in the cohort of patients treated with atorvastatin; these dimensions increased in the placebo group. There was an increase in erythrocyte superoxide dismutase (E-SOD) activity, and there were significant reductions in serum levels of high sensitivity C-reactive protein, interleukin-6 (IL-6), and tumor necrosis factor-alpha receptor II (TNF-α RII) in the atorvastatin group.
The use of atorvastatin in patients with nonischemic HF improves LVEF and attenuates adverse LV remodeling. The effects on soluble levels of several inflammatory markers with atorvastatin suggest, in part, mechanisms by which statins might exert their beneficial effects in nonischemic HF.
Withania somnifera popularly known as Aswagandha or Indian Ginseng/Poison Gooseberry have thousands years of history of use in Indian traditional medicine. Besides, finding place root of the plant as ...Indian Ginseng, Ayurveda also uses root of this plant as general health tonic, adaptogenic, nootropic, immunomodulatory etc. With its widespread and growing use, it becomes prudent to scientifically evaluate and document both the efficacy and safety of this plant in humans.
Aswagnadha root is rapidly gaining popularity abroad for use as medicine. Current article attempts to primarily review the human efficacy and safety of Aswagandha generated through clinical trials.
A systematic search both for indexed and non-indexed literature was made for W. somnifera using various search engines and databases and the details of research articles pertaining to all clinical trials/human studies, animal studies addressing safety issues of CNS, CVS, general toxicity, mutagenicity, genotoxicity, reproductive safety and herb-drug interactions were reviewed and compiled comprehensively from full texts.
A total of 69 (39 pre-clinical and 30 clinical) studies documenting efficacy and safety aspects were identified and the desired information of these studies is comprehensively presented in this review. Retrieved thirty(30) human studies demonstrated reasonable efficacy of root preparations in subclinical hypothyroidism (1), schizophrenia (3), chronic stress (2), insomnia (2), anxiety (1), memory and cognitive improvement (2), obsessive-compulsive disorder (1), rheumatoid arthritis (2), type-2 diabetes (2), male infertility (6), fertility promotion activity in females (1), adaptogenic (3), growth promoter in children (3) and chemotherapy adjuvant (1).
Reasonable safety of root preparations of Aswagandha has been established by these retrieved 30 human trials. No serious adverse events or any changes in haematological, biochemical or vital parameters were reported in these human studies. Only mild and mainly transient type adverse events of somnolence, epigastric pain/discomfort and loose stools were reported as most common (>5%); and giddiness, drowsiness, hallucinogenic, vertigo, nasal congestion (rhinitis), cough, cold, decreased appetite, nausea, constipation, dry mouth, hyperactivity, nocturnal cramps, blurring of vision, hyperacidity, skin rash and weight gain were reported as less common adverse events.
Pre-clinical chronic toxicity studies conducted up to 8 months also found root extracts to be safe. No mutagenicity or genotoxicity was reported for the root; only mild CNS depression and increase in thyroxine (T4) levels were reported with rootby some studies. Further, there was no in vitro and in vivo inhibition seen for CYP3A4 and CYP2D6, the two major hepatic drug metabolizing enzymes.
Root of the Ayurvedic drug W. somnifera (Aswagandha) appears a promising safe and effective traditional medicine for management of schizophrenia, chronic stress, insomnia, anxiety, memory/cognitive enhancement, obsessive-compulsive disorder, rheumatoid arthritis, type-2 diabetes and male infertility, and bears fertility promotion activity in females adaptogenic, growth promoter activity in children and as adjuvant for reduction of fatigue and improvement in quality of life among cancer patients undergoing chemotherapy. Properly designed, randomized-controlled, large-size, prospective trials with standardized preparations are needed to ascertain efficacy of Aswagandha root in previously studied and other new indications.
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ABSTRACT Background The corpus callosum has been implicated in the pathogenesis of schizophrenia and bipolar disorder. However, it is unclear whether corpus callosum alterations are related to the ...underlying familial diathesis for psychotic disorders. We examined the corpus callosum and its subregion volumes and their relationship to cognition, psychotic symptoms, and age in probands with schizophrenia (SZ), psychotic bipolar disorder (PBD), and schizoaffective disorder; their first-degree relatives; and healthy control subjects. Methods We present findings from morphometric and neurocognitive analyses of 1381 subjects (SZ probands, n = 224; PBD probands, n = 190; schizoaffective disorder probands, n = 142; unaffected relatives, n = 483 SZ relatives, n = 195; PBD relatives, n = 175; schizoaffective disorder relatives, n = 113; control subjects, n = 342). Magnetization prepared rapid acquisition gradient-echo T1 scans across five sites were obtained using 3-tesla magnets. Image processing was done using FreeSurfer Version 5.1. Neurocognitive function was measured using the Brief Assessment of Cognition in Schizophrenia scale. Results Anterior and posterior splenial volumes were significantly reduced across the groups. The SZ and PBD probands showed robust and significant reductions, whereas relatives showed significant reductions of intermediate severity. The splenial volumes were positively but differentially correlated with aspects of cognition in the probands and their relatives. Proband groups showed a significant age-related decrease in the volume of the anterior splenium compared with control subjects. Among the psychosis groups, the anterior splenium in probands with PBD showed a stronger correlation with psychotic symptoms, as shown by the Positive and Negative Syndrome Scale. All five subregions showed significantly high familiality. Conclusions The splenial volumes were significantly reduced across the psychosis dimension. However, this volume reduction impacts cognition and clinical manifestation of the illnesses differentially.
Abstract Introduction Smaller hippocampal volumes similar to those found in schizophrenia (SZ) are frequently observed to a lesser extent in non-psychotic first-degree relatives of patients with the ...illness, compared to control subjects. In this study, subdivisions of the hippocampal formation and their association with verbal and visual learning and memory were assessed in persons at familial high risk (FHR) for SZ. Methods MRI scans were acquired using a 3 T Siemens scanner of young adult (ages 19–32) FHR subjects (N = 46) and controls with no family history of illness (i.e., at low genetic risk LRC; N = 31) were processed using FreeSurfer 5.0. Subfields of the hippocampal formation were evaluated using the van Leemput method (Van Leemput et al., 2010). Learning and memory measures were collected by standardized neurocognitive tests. Results Controlling intracranial volume, significantly reduced left (p < 0.025), and right hippocampus (p < 0.024) volumes were observed in FHR subjects. Among the subfields, the left (p < 0.01) and right subicula (p < 0.005) were significantly reduced in the FHR group. Immediate verbal recall of stories was significantly impaired and was significantly correlated with the left and right subicula within the FHR group. Conclusions Reduced subiculum volume and its association with verbal memory refines further the association with left and right hippocampus reported in previous FHR studies of schizophrenia. Further research is needed to determine the specific genetic and environmental risk factors that may be related to hippocampal subfield alterations.
Recent efforts in the prevention of schizophrenia have focused on defining psychosis-risk syndromes and evaluating treatments that can prevent transition to psychosis in these ultra-high risk groups. ...In this review, different kinds of prevention approaches are enumerated and necessary conditions for a disease-prevention strategy are summarized. The broad overlap as well as the significant difference between a schizophrenia prodrome and a 'psychosis-risk syndrome is discussed and the present status of approaches to identify individuals at increased risk for developing psychosis and schizophrenia are critically examined along with evaluations on therapeutic interventions to reduce these risks. Finally, to conclude, recommendations for current best clinical practice and key questions for the future are suggested.
Medicinal plants belong to the oldest known health care products that have been used by human beings all over the world and are major components of the formulations used in indigenous system of ...medicine practiced in many countries. Besides, finding place as health supplements, nutraceuticals, cosmetics, herbal tea etc. there has been a global insurgence of interest, including India, leading to enormous research/activities in the area of medicinal plants.
The article is aimed to provide the effort and initiatives of ICMR towards research on medicinal plants and its contributions on consolidation of Indian research on medicinal plants that are very relevant and important in the national context.
The various initiatives undertaken by ICMR on research on traditional medicines/medicinal plants in the past are reviewed and documented in this article.
The multi-disciplinary, multicentric research initiatives of ICMR have resulted in validation of traditional treatment Kshaarasootra (medicated Ayurvedic thread) for anal fistula, Vijayasar (heart wood of Pterocarpus marsupium Roxb.) for diabetes mellitus, encouraging micro- and macrofilaricidal activity of Shakotak (stem bark of Streblus asper Lour.) in experimental studies an iridoid glycosides fraction isolated from root/rhizomes of Picrorhiza kurroa Royle ex Benth. (designated as Picroliv) for viral hepatitis. Other developmental and compilation of research works on Indian medicinal plants have resulted in publications of the thirteen volumes of quality standards, comprising of 449 Indian medicinal plants; three volumes of 90 phytochemical reference standards; fifteen volumes of review monographs on 4167 medicinal plant species; and one publication each on perspectives of Indian medicinal plants for management of liver disorders, lymphatic filariasis and diabetes mellitus (details available at http://www.icmr.nic.in/mpsite).
The ICMR efforts assume special significance in the light of multifaceted use of medicinal plants, and the need of better drugs and remedies for various diseases. Further, the indigenous system of medicine, and the plant drugs, could promise to provide both concepts of therapy, as well as therapeutic agents in the areas, where modern system of medicines has few answers. The developement of quality standards and review monographs also help the regulators, pharmacopoeial bodies and drug industry towards generation of quality herbal drugs or traditional medicine preparations. These initiatives are also in favour of the World Health Organisation advocating herbal medicines as a valid alternative system of therapy in the form of phytomedicines or herbal drugs or herbal drug preparations or herbal medicinal products.
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