Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the major psychiatry disorder, which the exact cause remains unknown. However, it is well known that dopamine-mediated neurotransmission imbalance is associated with this pathology and the main target of antipsychotics is the dopamine receptor D₂. Recently, it was described alteration in levels of two dopamine signaling related proteins in schizophrenic prefrontal cortex (PFC): Neuronal Calcium Sensor-1 (NCS-1) and DARPP-32. NCS-1, which is upregulated in PFC of schizophrenics, inhibits D₂internalization. DARPP-32, which is decreased in PFC of schizophrenics, is a key downstream effector in transducing dopamine signaling. We previously demonstrated that antipsychotics do not change levels of both proteins in rat's brain. However, since NCS-1 and DARPP-32 levels are not altered in wild type rats, we treated wild type PC12 cells (PC12 WT) and PC12 cells stably overexpressing NCS-1 (PC12 Clone) with antipsychotics to investigate if NCS-1 upregulation modulates DARPP-32 expression in response to antipsychotics treatment.</p> <p>Results</p> <p>We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.</p> <p>Conclusions</p> <p>Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.</p

Is the PANSS used correctly? a systematic review

<p>Abstract</p> <p>Background</p> <p>The PANSS (Positive and Negative Syndrome Scale) is one of the most important rating instruments for patients with schizophrenia. Nevertheless, there is a long and ongoing debate in the psychiatric community regarding its mathematical properties.</p> <p>All 30 items range from 1 to 7 leading to a minimum total score of 30, implying that the PANSS is an interval scale. For such interval scales straightforward calculation of relative changes is not appropriate. To calculate outcome criteria based on a percent change as, e.g., the widely accepted response criterion, the scale has to be transformed into a ratio scale beforehand. Recent publications have already pointed out the pitfall that ignoring the scale level (interval vs. ratio scale) leads to a set of mathematical problems, potentially resulting in erroneous results concerning the efficacy of the treatment.</p> <p>Methods</p> <p>A Pubmed search based on the PRISMA statement of the highest-ranked psychiatric journals (search terms "PANSS" and "response") was carried out. All articles containing percent changes were included and methods of percent change calculation were analysed.</p> <p>Results</p> <p>This systematic literature research shows that the majority of authors (62%) actually appear to use incorrect calculations. In most instances the method of calculation was not described in the manuscript.</p> <p>Conclusions</p> <p>These alarming results underline the need for standardized procedures for PANSS calculations.</p

Oscillatory Cortical Network Involved in Auditory Verbal Hallucinations in Schizophrenia

Auditory verbal hallucinations (AVH), a prominent symptom of schizophrenia, are often highly distressing for patients. Better understanding of the pathogenesis of hallucinations could increase therapeutic options. Magnetoencephalography (MEG) provides direct measures of neuronal activity and has an excellent temporal resolution, offering a unique opportunity to study AVH pathophysiology.Twelve patients (10 paranoid schizophrenia, 2 psychosis not otherwise specified) indicated the presence of AVH by button-press while lying in a MEG scanner. As a control condition, patients performed a self-paced button-press task. AVH-state and non-AVH state were contrasted in a region-of-interest (ROI) approach. In addition, the two seconds before AVH onset were contrasted with the two seconds after AVH onset to elucidate a possible triggering mechanism.AVH correlated with a decrease in beta-band power in the left temporal cortex. A decrease in alpha-band power was observed in the right inferior frontal gyrus. AVH onset was related to a decrease in theta-band power in the right hippocampus.These results suggest that AVH are triggered by a short aberration in the theta band in a memory-related structure, followed by activity in language areas accompanying the experience of AVH itself

Interhemispheric EEG coherence is reduced in auditory cortical regions in schizophrenia patients with auditory hallucinations

Central auditory processing has been reported to be impaired in schizophrenia patients who experience auditory hallucinations, and interhemispheric transfer in auditory circuits may be compromised. In this study, we used EEG spectral coherence to examine interhemispheric connectivity between cortical areas known to be important in the processing of auditory information. Coherence was compared across three subject groups: schizophrenia patients with a recent history of auditory hallucinations (AH), schizophrenia patients who did not experience auditory hallucinations (nonAH), and healthy controls (HC). Subjects listened to pure tone and word stimuli while EEG was recorded continuously. Upper alpha and upper beta band coherence was calculated from six pairs of electrodes located over homologous auditory areas in the left and right cerebral hemispheres. Significant between-group differences were found on four electrode pairs (C3-C4, C5-C6, Ft7-Ft8 and Cp5-Cp6) in the upper alpha band. Relative to both the HC and nonAH groups, coherence was lower in the AH patients, consistent with the hypothesis that interhemispheric connectivity is reduced in these patients

Antioxidant treatment of the glutathione deficiency in bipolar disorder with n-acetyl cysteine: a double blind randomized placebo controlled trial

We present an approach which we call PSyKAl that is designed to achieve portable performance for parallel finite-difference, finite-volume, and finite-element earth-system models. In PSyKAl the code related to the underlying science is formally separated from code related to parallelization and single-core optimizations. This separation of concerns allows scientists to code their science independently of the underlying hardware architecture and for optimization specialists to be able to tailor the code for a particular machine, independently of the science code. We have taken the free-surface part of the NEMO ocean model and created a new shallow-water model named NEMOLite2D. In doing this we have a code which is of a manageable size and yet which incorporates elements of full ocean models (input/output, boundary conditions, etc.). We have then manually constructed a PSyKAl version of this code and investigated the transformations that must be applied to the middle, PSy, layer in order to achieve good performance, both serial and parallel. We have produced versions of the PSy layer parallelized with both OpenMP and OpenACC; in both cases we were able to leave the natural-science parts of the code unchanged while achieving good performance on both multi-core CPUs and GPUs. In quantifying whether or not the obtained performance is good we also consider the limitations of the basic roofline model and improve on it by generating kernel-specific CPU ceilings

Cognitive dysfunction and real world disability in clinically stable patients with bipolar disorder and schizophrenia: a cross sectional study from India

&lt;p&gt;&lt;b&gt;Introduction&lt;/b&gt;: Cognitive deficits in various domains have been shown in patients with schizophrenia and bipolar disorder in the western population. The purpose of the present study was to compare the neurocognitive function in a cohort of Indian patients with that of normal controls.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; Performance on tests of attention, visual and verbal memory in 25 patients with schizophrenia in remission and 25 euthymic bipolar disorder patients was compared to 25 normal controls. Correlation analysis was used to look for relationship between illness factors, cognitive function and disability. We also correlated the effect sizes of cognitive deficits in the patient groups.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Both patient groups performed significantly worse than normal controls on most cognitive tests. The resulting effect sizes ranged from 0.37 to 0.98 (mean = 0.83) across tests for schizophrenia patients and from 0.08 to 0.85 (mean = 0.63) for bipolar disorder patients. There was a correlation between memory dysfunction and functional disability.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Discussion:&lt;/b&gt; Patients with bipolar disorder displayed cognitive deficits that were milder but qualitatively similar to those of patients with schizophrenia. This finding is similar to studies done in the western population. The cognitive deficits were significantly associated with real-world functional disability. However, employment rates remained high in the patient population suggesting that factors such as family support reduce disability due to major mental illnesses in developing countries like India.M&lt;/p&gt