Cognitive Function Disturbances Research Articles

Abnormal Temporal Window of Integration in Auditory Sensory Memory in Schizophrenia.

Mismatch negativity (MMN) is automatically elicited by incoming sound deviation compared to the neural representation of preceding homogenous sounds stored in the brain's auditory sensory memory. This study aimed to assess time-functional deviation sensitivity in auditory sensory memory associated with a temporal window of integration (TWI) of 160-170 msec in patients with schizophrenia. To this end, we measured the magnetic counterpart of the MMN (MMNm) in 20 patients with schizophrenia on medication and 20 healthy age-matched adults as a control group responding to an omitted tone segment incorporated into a complex sound of 176 ms duration corresponding to the TWI duration. Overall, the magnitude of the MMNm was smaller in the patients with schizophrenia than in the healthy control group. The peak latency of the MMNm was prolonged in the latter omitted segments for both groups, but to a greater extent in patients with schizophrenia. These results indicate that deviation detection is impaired in the later part of the TWI, corresponding to the duration of auditory sensory memory in patients with schizophrenia. Thus, the specific impairment of MMN in response to duration deviants (duration MMN), as previously reported, might result from a damaged mechanism in the later part of the TWI of sensory memory, suggesting that a decline in sensory memory causes distorted perception or disturbances in cognitive function in patients with schizophrenia.

Cognitive impairment and therapeutic response in resistant depression

Therapeutic response in depression is a major challenge since more than one third of patients are not in remission after two attempts of antidepressant treatment and will present a treatment-resistant depression. In order to better adapt therapeutic strategies for treatment-resistant patients, predictive indicators and markers of therapeutic response still need to be identified. In parallel, patients with depression exhibit disturbances in cognitive functioning. This study aims to describe and compare cognitive performances collected at inclusion of patients presenting treatment-resistant depression who will be responders at 6 months to those of non-responders, and to evaluate the predictive value of cognitive indicators on clinical therapeutic response at 6 months after a therapeutic modification. Observational study. Patients were evaluated at the clinical (HDRS and BDI-II) and cognitive levels using standardized tools assessing memory, executive functions, attention, and social cognition, prior to a change in antidepressant treatment. Six months after inclusion, they were reassessed and classified into two groups based on the presence or absence of therapeutic response, defined by a 50% improvement on HDRS and BDI-II. The cognitive scores collected at inclusion were then compared. Additionally, univariate logistic regression models were used. Thirty patients were included in this study. Only 13 could be evaluated at 6 months. Among these patients, four had responded to the new treatment while nine were non-responders. Both groups of patients presented deviant cognitive performances compared to norms on tests evaluating executive functions and attention. Statistical analyses did not reveal any difference between the cognitive performances of responders and non-responders at 6 months. Regression analyses showed no association between cognitive scores and therapeutic response at 6 months. Executive functioning plays a significant role in treatment-resistant depression. In order to improve the understanding and identification of subtypes of depression, cognitive indicators should be systematically integrated into future research.

The effect of surgical technique on the long-term results of treatment of brain aneurysms

To study the long-term outcomes of surgical treatment of cerebral aneurysms (CA) after using different methods of excluding the aneurysm from the bloodstream. We analyzed the long-term results of surgical treatment of 311 patients for CA (on average after 3.5 years). Two hundred and one patients were operated after CA rupture, 110 for an unruptured aneurysm. Microsurgical or endovascular methods were used to isolate the aneurysm from the bloodstream. Upon admission to the hospital for surgical treatment, a clinical diagnostic examination was performed to confirm the diagnosis and determine the timing and type of intervention. In the long-term period, a clinical neurological study, including an assessment of disability with the Barthel index and the modified Rankin scale, cognitive functions (MoCA test) and the psycho-emotional sphere (HADS) was carried out. In the long-term period of aneurysm surgery, symptoms of disability were identified in 49 patients (16%), severe and complete limitation of self-care in 17 (8%), and cognitive impairment in 212 (68%). Endovascular embolization performance of an aneurysm was associated with a higher proportion of favorable functional outcomes compared with the use of a microsurgical method (10% versus 17%), as well as preservation of cognitive functions (9% and 17%, respectively). Blood clots fibrinolysis was associated with severe disability and dependence in the long-term period (p=0.04). Patients treated with extra-intracranial shunting (EICS) demonstrated better cognitive functions; fibrinolysis, on the contrary, was a predictor of dementia (p=0.02). There was no relationship between symptoms of anxiety and depression in the long-term period and surgical treatment method. Disability, dependence and disturbance of cognitive functions in the long-term period of CA surgical treatment are higher in patients after microsurgical clipping compared to endovascular embolization. Performance of blood clots fibrinolysis is associated with severe disability and dementia in patients with massive basal aneurysmal subarachnoid hemorrhage. Performing EICS is associated with a favorable prognosis for the recovery of cognitive functions.

APPLICATION OF COGNITIVE BEHAVIOUR THERAPY (CBT) AND FAMILY PSUCHOEDUCATION (FPE) IN PATIENTS AT RISK OF SUICIDE

Schizophrenia is a severe mental illness that causes disturbances in cognitive function, emotion, language, behavior and movement. One of the effects of severe mental disorders is suicide. Data shows that every 40 seconds, someone loses their life by suicide. The negative state of mind of patients at risk of suicide is usually a cognitive distortion. The purpose of this scientific paper is to provide an overview of the application of cognitive behavior therapy (CBT) and family psychoeducation to patients at risk of suicide using the Tidal model approach. Nursing actions were performed on 6 patients at risk of suicide. The method used is case series. The results show that giving cognitive behavior therapy (CBT) and family psychoeducation with the Tidal model approach can reduce suicide scores, reduce signs and symptoms and increase the ability of families and patients at risk of suicide with schizophrenia. Cognitive behavior therapy (CBT) and family psychoeducation are recommended to be carried out by psychiatric nurses to overcome the risk of suicide

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

The Combination of Cooling Techniques in a Tropical Environment Improves Precision Performance in Young International Fencers

The performance of intense exercise in a tropical climate is associated with limited exercise capacity due to thermal strain. This limitation is exacerbated in sports requiring full protective equipment. Research evidence suggests disturbances in cognitive function due to thermal discomfort and/or protective equipment (e.g., helmets), and thus sports that require skills in decision-making, fast reaction times, precision, and/or inhibition can be greatly affected. The objective of this study was to investigate the effects of countermeasures on the psychological and physiological responses in young international fencers wearing full protective equipment during an ecological fencing task. Nine young international fencers performed an aiming task in tropical conditions (1) without cooling interventions and (2) with cumulative cooling interventions (i.e., pre+percooling and head+torso). Participants completed a battery of cognitive (i.e., simple and choice reaction times, Stroop test), affective (i.e., PANAS), and perception (i.e., thermal environment, Feeling Scale, rating of perceived exertion) tests in each session, and their heart rate, skin temperature, and fencing performances (i.e., execution time and total score) were checked at several time points. Although the results revealed no differences in the perception of the thermal environment or the cognitive and affective scores, the cooling interventions seemed to improve movement precision during the fencing task and limit the decrease in pleasurable feelings related to the physical task. This study suggests that attentional resources are more available with cumulative cooling interventions, which leads to better performance during an ecological fencing task in tropical conditions.

Sex difference in cognitive behavioral alterations and barrel cortex neuronal responses in rats exposed prenatally to valproic acid under continuous environmental enrichment.

Autism spectrum disorder is a developmental disorder that can affect social interactions and sensory-motor behaviors. The present study investigates the effect of environmental enrichment (EE) on behavioral alterations and neuron responses associated with the barrel cortex of young adult female and male rats exposed prenatally to valproic acid (VPA). Pregnant female rats were pretreated with either saline or VPA (500 mg/kg, IP) on day 12.5 of gestation. Male and female pups were exposed to either EE or standard-setting (non-enrichment) conditions for 1 month (between postnatal day [PND] 30 and 63-65) and were divided into non-EE (control), EE, VPA, and VPA + EE groups. Three-chamber sociability and social novelty, acoustic startle reflex, and texture discrimination tests were conducted on PND 62. Responses of barrel cortex neurons of male pups were evaluated using the extracellular single-unit recording technique on PND 63-65. Results showed that the performance of rats of both sexes in social interactions, texture discrimination tasks, and acoustic startle reflex significantly decreased in the VPA groups compared with the control rats (P <0.05). In this regard, EE attenuated the altered deficit performance observed in the VPA animals compared with the VPA-EE animals (P <0.05). The performance of females was better than males in the discrimination tasks and acoustic startle reflex. In contrast, males were better than females in the three-chamber social interaction test. Additionally, the excitatory receptive field response magnitude of the barrel cortex neurons in the VPA + EE group increased compared with the VPA group (P <0.05). The results suggest that continuous EE can attenuate cognitive function disturbances in autistic-like rats and, at least at the behavioral level, the effects depend on sex.

A disorder in executive functions crosses traditional diagnostic borders of the schizophrenia-bipolar spectrum

IntroductionOur series of studies in the spectrum of psychosis (schizophrenia, bipolar affective disorder, schizoaffective disorder) is based on the concept of the RDoC system.ObjectivesIn this study, we were interested in knowing whether cross-diagnostic disturbances in cognitive functions can be found in the spectrum and whether they predict clinical symptoms.MethodsIn the study, N = 66 schizophrenic (M = 38.2 ± 9.37 years, 26 women), N = 30 bipolar (M = 47.4 ± 9.35 years, 19 women), N = 33 schizoaffective (M = 39.8 years± 11.3 years, 21 women) and N = 28 healthy subjects (M = 36.5 ± 9.9 years, 14 women) participated. All subjects underwent the Wisconsin Card Sorting Test (WCST), Raven Test, Digit Span Test, Visual Patterns Test, Letter and Semantic Fluency tests, Metaphor and Irony Comprehension, Directed Forgetting, Stop Signal Test, and Lexical Decision Task. In addition, symptom rating scales were administered (PANSS, SANS, YMRS, MADRS).ResultsBased on our results, the performance of the WCST-deficient group lagged behind the WCST-non-deficient group and the healthy control group in most executive control tests. Importantly, this effect was independent of diagnosis, so it appeared in all three patient groups. Members of the deficit group had a higher rate of negative symptoms.ConclusionsDisruption of executive functions is a transdiagnostic feature of the schizophrenia-bipolar spectrum, which could be associated with any diagnosis.DisclosureNo significant relationships.

Adipokines Level and Cognitive Function-Disturbance in Homeostasis in Older People with Poorly Managed Hypertension: A Pilot Study.

Aim: To explore the network relationship between cognitive function, depressive symptom intensity, body composition, proxies of cognitive reserve, trophic factor, adipokines and myokines, physical performance and blood pressure in a group of older people with poorly managed hypertension (PMHTN) compared to a normotensive (NTN) group. Materials and methods: History of hypertension and blood pressure level were examined in older participants. Thirty-one subjects diagnosed with PMHTN (history of hypertension diagnosis and values of sBP or dBP over 140/90 mmHg) and eighteen NTN (lack of history of hypertension and sBP and dBP lower than 140/90 mmHg) participated. Participants completed physical and cognitive function assessments: including the Mini–Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF) and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning: age, years of education, cognitive and travel activity were assessed using a questionnaire. Visceral fat was determined by bioimpedance testing and gait velocity and agility assessed using an Up and Go test. To summarize the strength and direction (negative or positive) of a relationship between two variables, Spearman’s rank correlation coefficient was used. Then, network graphs were created to illustrate the relationship between variables. Node strength (number of edges per node), neighbourhood connectivity (the average connectivity of all the neighbours of a node), stress (the number of shortest paths passing through each node) were compared in network from PMHTN group to network from NTN group. Results: Neighbourhood connectivity and stress were significantly higher in of the PMHTN network compared to NTN (6.03 ± 1.5 vs. 4.23 ± 2.5, p = 0.005 and 118.21 ± 137.6 vs. 56.87 ± 101.5, p = 0.02, accordingly). Conclusion: In older subjects with poorly managed hypertension, dyshomeostasis was observed, compared to normotensive subjects.

Milnacipran for the Treatment of Fibromyalgia.

This is a comprehensive review of the literature regarding the use of milnacipran in treating fibromyalgia. A chronic pain disorder with other system disturbances, fibromyalgia is often resistant to many therapeutic approaches. This review presents the background, evidence, and indications for using milnacipran as a treatment option for this condition. The definition of fibromyalgia has evolved over many years as it is a relatively tricky syndrome to measure objectively. Today, it is characterized by chronic, widespread pain accompanied by alterations in sleep, mood, and other behavioral aspects. A variety of therapeutic regimens currently used to treat the syndrome as a singular approach are rarely effective.Milnacipran is one of three drugs currently approved by the FDA for the treatment of fibromyalgia. It acts as a serotonin and norepinephrine reuptake inhibitor, which results in decreased pain transmission. Milnacipran remains an effective treatment option for fibromyalgia in adults and needs to be further evaluated with existing therapeutic approaches. Fibromyalgia is a broad-spectrum disorder primarily characterized by chronic pain coupled with disturbances in cognitive functioning and sleep. The progression of this syndrome is often debilitating and significantly affects the quality of life. Milnacipran is one of three FDA-approved drugs used to alleviate the symptom burden and is comparatively more therapeutic in specific domains of fibromyalgia. A more holistic approach is needed to treat fibromyalgia effectively and further research, including direct comparison studies, should be conducted to fully evaluate the usefulness of this drug.

Assessment of cognitive function following a course of electroconvulsive therapy

IntroductionECT is a potentially life-saving treatment for patients with severe or treatment resistant depression. Cognitive function disturbances following ECT are generally transient, but could be of longer duration in some casesObjectivesTo assess the cognitive side effects in patients with affective disorders treated with a course of electroconvulsive therapy (ECT).MethodsCognitive functions of patients who undergo ECT was assessed prior to start of treatment, midway of the course of treatment and after end of the course of treatment using Montreal Cognitive Assessment (MoCA). We did a retrospective analysis of MoCA scores of 15 patients who received bilateral ECT in 2017-2018. In order to assess the efficacy of ECT in the treatment of their illness, we did a retrospective analysis of Montgomery Asberg Depression Rating Scale (MADRS) scores of 18 patients who received bilateral ECT in 2017-2018ResultsOnly 7% of the patients who underwent ECT in our sample did have significant cognitive decline as per their MoCA scores. 28% of patients achieved complete remission in their depressive symptomes. 22% of patients continued on maintenance treatment. 95% of patients showed significant improvement in their symptoms following treatment with ECT where there symptoms reduced to either mild or minimal depressive symptoms.ConclusionsCognitive side effect was not a significant side effect in our sample of patients. We did see an improvement in cognitive function in a significant number of the sample of patients as they progressed with treatment, which coincided with improvement in their affective symptoms.

The role of sleep disturbances in cognitive function and depressive symptoms among community-dwelling elderly with sleep complaints.

The relationships between sleep problems, cognitive impairments, and depression have been established in the aging population. However, less is known about the role of late-life onset insomnia and sex involved in these dyad or tripartite relationships. This study aimed to consider onset age of insomnia and sex in the relationship between sleep parameters, cognition and depression among older adults with current insomnia complaints. A multistep sampling method was adopted to recruit participants with current insomnia complaints in China in 2018. Sleep measures include onset age of insomnia (64 years old or before vs during/after 65), three factors from insomnia severity index (ISI; nighttime, daytime, and perception), excessive daytime sleepiness, and sleep duration. Outcome measures were mini-mental state examination (MMSE) and center for epidemiologic studies depression scale (CESD). The average age of older adults was 75 (SD = 7.1). Among them, 62% participants are female. In general, older aged, female, late-life onset insomnia as well as interaction of sex * onset age of insomnia were significantly associated with poorer cognition. Yet, age, sex, and onset age of insomnia were not significant indicators for depression. For female participants, later onset of insomnia, nighttime symptoms of insomnia, excessive daytime sleepiness and depression were risk factors for cognitive decline. Nevertheless, only daytime sleepiness, together with depression, were found positively associated with male participants' cognitive decline. There were robust associations between daytime sleepiness, depressive symptoms, and poor cognitive performance. More importantly, late-life onset insomnia was particularly indicative for poor cognitive performance among female older adults. Future study should emphasize the specific mechanism involved in changes of sleep patterns in the development of cognitive impairment among older adults. Sex differences in the relationship between onset age of insomnia and cognition also require further attention.

The Impact of a Structured Exercise Programme upon Cognitive Function in Chronic Fatigue Syndrome Patients.

Background: Cognitive function disturbance is a frequently described symptom of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In this study, the effects of a structured exercise programme (SEP) upon cognitive function in ME/CFS patients was examined. Methods: Out of the 53 ME/CFS patients initiating SEP 34 (64%) completed the 16 week programme. Cognitive function was assessed using a computerized battery test consisting of a Simple Reaction Time (SRT) (repeated three times) and Choice Reaction Time (CRT) measurements, a Visual Attention Test (VAT) and a Delayed Matching to Sample (DMS) assessment. Results: Statistically significant improvement was noted in the third attempt to SRT in reaction time for correct answers, p = 0.045, r = 0.24. Moreover, significant improvement was noted in VAT reaction time, number of correct answers and errors committed, p = 0.02, omega = 0.03, p = 0.007, r = 0.34 and p = 0.004, r = 0.35, respectively. Non-significant changes were noted in other cognitive tests. Conclusions: A substantial number of participants were unwilling or unable to complete the exercise programme. ME/CFS patients able to complete the SEP showed improved visual attention both in terms of reaction time and correctness of responses and processing speed of simple visual stimuli.

Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations

Disturbances of cognitive functions occur rapidly during acute metabolic stress. However, the underlying mechanisms are not fully understood. Cortical gamma oscillations (30–100 Hz) emerging from precise synaptic transmission between excitatory principal neurons and inhibitory interneurons, such as fast-spiking GABAergic basket cells, are associated with higher brain functions, like sensory perception, selective attention and memory formation. We investigated the alterations of cholinergic gamma oscillations at the level of neuronal ensembles in the CA3 region of rat hippocampal slice cultures. We combined electrophysiology, calcium imaging (CamKII.GCaMP6f) and mild metabolic stress that was induced by rotenone, a lipophilic and highly selective inhibitor of complex I in the respiratory chain of mitochondria. The detected pyramidal cell ensembles showing repetitive patterns of activity were highly sensitive to mild metabolic stress. Whereas such synchronised multicellular activity diminished, the overall activity of individual pyramidal cells was unaffected. Additionally, mild metabolic stress had no effect on the rate of action potential generation in fast-spiking neural units. However, the partial disinhibition of slow-spiking neural units suggests that disturbances of ensemble formation likely result from alterations in synaptic inhibition. Our study bridges disturbances on the (multi-)cellular and network level to putative cognitive impairment on the system level.

Biochemical Mechanisms and Translational Relevance of Hippocampal Vulnerability to Distant Focal Brain Injury: The Price of Stress Response.

Focal brain injuries (in particular, stroke and traumatic brain injury) induce with high probability the development of delayed (months, years) cognitive and depressive disturbances which are frequently comorbid. The association of these complications with hippocampal alterations (in spite of the lack of a primary injury of this structure), as well as the lack of a clear dependence between the probability of depression and dementia development and primary damage severity and localization served as the basis for a new hypothesis on the distant hippocampal damage as a key link in the pathogenesis of cognitive and psychiatric disturbances. According to this hypothesis, the excess of corticosteroids secreted after a focal brain damage, in particular in patients with abnormal stress-response due to hypothalamic-pituitary-adrenal axis (HPAA) dysfunction, interacts with corticosteroid receptors in the hippocampus inducing signaling pathways which stimulate neuroinflammation and subsequent events including disturbances in neurogenesis and hippocampal neurodegeneration. In this article, the molecular and cellular mechanisms associated with the regulatory role of the HPAA and multiple functions of brain corticosteroid receptors in the hippocampus are analyzed. Functional and structural damage to the hippocampus, a brain region selectively vulnerable to external factors and responding to them by increased cytokine secretion, forms the basis for cognitive function disturbances and psychopathology development. This concept is confirmed by our own experimental data, results of other groups and by prospective clinical studies of post-stroke complications. Clinically relevant biochemical approaches to predict the risks and probability of post-stroke/post-trauma cognitive and depressive disturbances are suggested using the evaluation of biochemical markers of patients' individual stress-response. Pathogenetically justified ways for preventing these consequences of focal brain damage are proposed by targeting key molecular mechanisms underlying hippocampal dysfunction.

An organic mental disorder and comorbid affective spectrum disturbances: a forensic-psychiatric assessment

To identify the influence of combined pathology, an organic personality disorder and affective disturbances, on the regulation of subjects' legally significant behavior in forensic-psychiatric examination in criminal and civil proceedings. Two groups of patients with the diagnosis of organic personality disorder (ICD-10 F07) established in the course of forensic-psychiatric examination were studied. The first group included 82 criminally prosecuted men (mean age 40.7±15.8); the second group comprised 50 women (mean age 65.1±15.4) and 28 men (mean age 60.2±14.4), who underwent forensic-psychiatric examination in civil litigation over declaring their contracts null and void. All patients had affective disorders. Standard expertise procedure and data analysis were used. The modifying influence of a set of psychogenic factors is of great significance in the course of forensic-psychiatric examination of individuals diagnosed with organic personality disorder: in criminal proceedings these are determined by the fact of being prosecuted, and in civil proceedings by the problems of adaptation, deterioration of one's social status, and the somatic ill-being. The unfavorable dynamics of organic mental disorder in these cases manifested itself in decompensation of personality, cognitive disturbances or addition of comorbid depressive disorders (68.3 and 31.7%, respectively). In 48.7% of patients, the addition of affective pathology to organic disorders significantly increased the extent of disturbance of cognitive functions, insight and prognostic capacity, volitional control of activity, which determined the incapacity of patients to understand the significance of their own actions and control them at the time of entering into contract.

Cognitive Function Differences based on Hemispheric Lesions of First-Ever Ischemic Stroke Patients

Ischemic stroke is one of stroke subtype often correlated with disturbance of cognitive function. We conduct an observational study with cross-sectional design of 70 ischemic stroke patients. Objective of this study is to evaluate cognitive differences based on hemispheric lateralization lesions. We used Montreal Cognitive Assessment – Indonesian version (MoCA-Ina) to assess cognitive function resulting on 70 patients, consist of 48 subjects (68.57 %) of left hemispheric stroke and 22 subjects (31.43%) of right hemispheric stroke. As much as 68 subjects (97.14 %) are categorized as having cognitive disturbance. Mean differences of MoCA-Ina was assessed using Mann-Whitney test resulting no significant differences between left vs right hemisphere groups (18.94 + 3.26 vs 19.82 + 3.13; p= 0.320). Further study would warrant lesions lateralizations could affects cognitive performance of ischemic stroke patients.

Reversal of mecamylamine-induced effects in healthy subjects by nicotine receptor agonists: Cognitive and (electro) physiological responses.

Establishing a pharmacological challenge model could yield an important tool to understand the complex role of the nicotinic cholinergic system in cognition and to develop novel compounds acting on the nicotinic acetylcholine receptor. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study examined the effects of the nicotinic antagonist mecamylamine on a battery of cognitive and neurophysiological test with coadministration of a placebo, nicotine or galantamine in order to reverse the cognitive impairment caused by mecamylamine. Thirty-three healthy subjects received a single oral dose of 30mg of mecamylamine (or placebo) in combination with either 16mg of oral galantamine or 21mg of transdermal nicotine (or its double-dummy). Mecamylamine 30mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short- and long-term memory was impaired and the reaction velocity during the test was slower when compared to placebo. Mecamylamine 30mg produced a decrease in posterior α and β power in the surface electroencephalogram, effects that were reversed by nicotine coadministration. Memory and motor coordination tests could be partially reversed by the coadministration of nicotine. Mecamylamine administration induced slowing of the electroencephalogram and produced decrease in performance of tests evaluating motor coordination, sustained attention and short- and long-term memory. These effects could be partially reversed by the coadministration of nicotine, and to a lesser extent by galantamine.

Mechanisms Underpinning the Polypharmacy Effects of Medications in Psychiatry.

BackgroundBipolar disorder is a mental health condition with progressive social and cognitive function disturbances. Most patients’ treatments are based on polypharmacy, but with no biological basis and little is known of the drugs’ interactions. The aim of this study was to analyze the effects of lithium, valproate, quetiapine, and lamotrigine, and the interactions between them, on markers of inflammation, bioenergetics, mitochondrial function, and oxidative stress in neuron-like cells and microglial cells.MethodsNeuron-like cells and lipopolysaccharide-stimulated C8-B4 cells were treated with lithium (2.5 mM), valproate (0.5 mM), quetiapine (0.05 mM), and lamotrigine (0.05 mM) individually and in all possible combinations for 24 h. Twenty cytokines were measured in the media from lipopolysaccharide-stimulated C8-B4 cells. Metabolic flux analysis was used to measure bioenergetics, and real-time PCR was used to measure the expression of mitochondrial function genes in neuron-like cells. The production of superoxide in treated cells was also assessed.ResultsThe results suggest major inhibitory effects on proinflammatory cytokine release as a therapeutic mechanism of these medications when used in combination. The various combinations of medications also caused overexpression of PGC1α and ATP5A1 in neuron-like cells. Quetiapine appears to have a proinflammatory effect in microglial cells, but this was reversed by the addition of lamotrigine independent of the drug combination.ConclusionPolypharmacy in bipolar disorder may have antiinflammatory effects on microglial cells as well as effects on mitochondrial biogenesis in neuronal cells.

Performance of OCD Patients on WCST in Context of Comorbid Depression

Introduction: Over the years it has been observed that disturbances in cognitive functions including attention, executive functions, visuospatial functions, verbal and non-verbal memory, in OCD (obsessive compulsive disorder) patients are mediated by co morbid neuropsychiatric conditions. It has been observed that comorbid depression in OCD patients is associated with executive function deficits. Wisconsin Card Sorting Test (WCST) is one of the most widely used tests to assess the executive function deficits. Methods: 160 patients fulfilling the DSM-IV criteria for OCD & depression were selected and categorized in 2 sample groups namely OCD with depression (OCDD, n=80) & OCD without depression (OCWD, n=80). Yale Brown Obsessive Scale (Y-BOCS) scale was used for assessment of OCD & Hamilton rating scale of depression (HAM-D) was used for further grading the severity of depression into mild, moderate & severe. The executive function deficits in patients of the three categories of depression with OCD were tested with WCST & intergroup comparisons were made. Results: Both the OCDD & OCWD groups were matched for age, gender, marital status, educational qualification, age of onset of illness & duration of illness. The overall mean age of the patients presenting to the OPD was 32.63 years. The patients in groups OCD with moderate & severe depression completed less categories & committed more perseverative errors as compared to patients in groups OCD without depression & OCD with mild depression. Conclusion: The observations of this study suggest that patients with OCD have impairment in executive functions which are further worsened by the presence of comorbid depression. Assessment of neurocognitive functions of patients with OCD should always include assessment of comorbid depression which will help in providing a patient tailored treatment.