Blood glucose and ß-hydroxybutyrate predict significant brain injury after hypoxia-ischemia in neonatal mice.

BACKGROUND: The Vannucci procedure is widely used to model cerebral hypoxic-ischemic (HI) injury in neonatal rodents. Identifying minimally invasive biomarkers linked to brain injury would improve stratification of pups to experimental treatments. We hypothesized that extreme blood glucose (BG) and ß-hydroxybutyrate (bHB) levels immediately after HI will correlate with severity of brain injury in this model. METHODS: C57BL6 mice of both sexes underwent the Vannucci procedure with BG and bHB measured immediately after hypoxia. GFAP and α-fodrin were measured to assess injury severity at 4h, P11, P18 and P40. Open field (OF), Y-maze (YM), and Object-location task (OLT) were tested at P40. RESULTS: Clinical seizures-like stereotypies during hypoxia were associated with lower post-hypoxia BG in HI-injured mice. Low BG after HI was related to higher GFAP expression, higher α-fodrin breakdown, lower residual regional volume, and worse working memory. BG was superior to bHB in ROC analysis with BG threshold of <111 mg/dL providing 100% specificity with 72% sensitivity for hippocampal HI-injury. CONCLUSIONS: Post-hypoxic BG is a minimally invasive screening tool to identify pups with significant HI brain injury in the Vannucci model modified for mice improving our ability to stratify pups to experimental treatments to assess effectiveness. IMPACT: End hypoxic-ischemic blood glucose levels are a reliable and inexpensive biomarker to detect hypoxic-ischemic brain injury in mice. Screening with blood glucose levels post-hypoxia allows appropriate stratification of those mouse pups most likely to be injured to experimental treatments improving validity and translatability of the results. These findings provide biological plausibility to the clinical observation that extreme blood glucose levels relate to worse outcomes after hypoxia-ischemia.

On-Screen Visual Feedback Effect on Static Balance Assessment with Perturbations.

In this study, the novel mobile dynamometric platform, OREKA, was utilized to perform an extensive analysis of the centre of pressure behaviour during different tilt motion exercises. This platform is based on a parallel manipulator mechanism and can perform rotations around both horizontal axes and a vertical translation. A group of participants took part in an experimental campaign involving the completion of a set of exercises. The aim was to evaluate the platform's potential practical application and investigate the impact of visual on-screen feedback on centre of pressure motion through multiple balance indicators. The use of the OREKA platform enables the study of the impact on a user's balance control behaviour under different rotational perturbations, depending on the availability of real-time visual feedback on a screen. Furthermore, it presented data identifying postural control variations among clinically healthy individuals. These findings are fundamental to comprehending the dynamics of body balance. Further investigation is needed to explore these initial findings and fully unlock the potential of the OREKA platform for balance assessment methodologies.

Sexual Dimorphism in the Closure of the Hippocampal Postnatal Critical Period of Synaptic Plasticity after Intrauterine Growth Restriction: Link to Oligodendrocyte and Glial Dysregulation.

Intrauterine growth restriction (IUGR) resulting from hypertensive disease of pregnancy (HDP) leads to sexually dimorphic hippocampal-dependent cognitive and memory impairment in humans. In our translationally relevant mouse model of IUGR incited by HDP, we have previously shown that the synaptic development in the dorsal hippocampus including GABAergic development, NPTX2+ excitatory synaptic formation, axonal myelination, and perineural net (PNN) formation were perturbed by IUGR at adolescent equivalence in humans (P40). The persistence of these disturbances through early adulthood and the potential upstream mechanisms are currently unknown. Thus, we hypothesized that NPTX2+ expression, PNN formation, axonal myelination, all events closing synaptic development in the hippocampus, will be persistently perturbed, particularly affecting IUGR female mice through P60 given the fact that they had worse short-term recognition memory in this model. We additionally hypothesized that such sexual dimorphism is linked to persistent glial dysregulation. We induced IUGR by a micro-osmotic pump infusion of a potent vasoconstrictor U-46619, a thromboxane A2-analog, in the last week of the C57BL/6 mouse gestation to precipitate HDP. Sham-operated mice were used as controls. At P60, we assessed hippocampal and hemispheric volumes, NPTX2 expression, PNN formation, as well as myelin basic protein (MBP), Olig2, APC/CC1, and M-NF expression. We also evaluated P60 astrocytic (GFAP) reactivity and microglial (Iba1 and TMEM119) activation using immunofluorescent-immunohistochemistry and Imaris morphological analysis plus cytokine profiling using Meso Scale Discovery platform. IUGR offspring continued to have smaller hippocampal volumes at P60 not related to changes in hemisphere volume. NPTX2+ puncta counts and volumes were decreased in IUGR hippocampal CA subregions of female mice compared to sex-matched shams. Intriguingly, NPTX2+ counts and volumes were concurrently increased in the dentate gyrus (DG) subregion. PNN volumes were smaller in CA1 and CA3 of IUGR female mice along with PNN intensity in CA3 but they had larger volumes in the CA3 of IUGR male mice. The myelinated axon (MBP+) areas, volumes, and lengths were all decreased in the CA1 of IUGR female mice compared to sex-matched shams, which correlated with a decrease in Olig2 nuclear expression. No decrease in the number of APC/CC1+ mature oligodendrocytes was identified. We noted an increase in M-NF expression in the mossy fibers connecting DG to CA3 only in IUGR female mice. Reactive astrocytes denoted by GFAP areas, volumes, lengths, and numbers of branching were increased in IUGR female CA1 but not in IUGR male CA3 compared to sex-matched shams. Lastly, activated microglia were only detected in IUGR female CA1 and CA3 subregions. We detected no difference in the cytokine profile between sham and IUGR adult mice of either sex. Collectively, our data support a sexually dimorphic impaired closure of postnatal critical period of synaptic plasticity in the hippocampus of young adult IUGR mice with greater effects on females. A potential mechanism supporting such dimorphism may include oligodendrocyte dysfunction in IUGR females limiting myelination, allowing axonal overgrowth followed by a reactive glial-mediated synaptic pruning.

Virtual Sensor for Kinematic Estimation of Flexible Links in Parallel Robots.

The control of flexible link parallel manipulators is still an open area of research, endpoint trajectory tracking being one of the main challenges in this type of robot. The flexibility and deformations of the limbs make the estimation of the Tool Centre Point (TCP) position a challenging one. Authors have proposed different approaches to estimate this deformation and deduce the location of the TCP. However, most of these approaches require expensive measurement systems or the use of high computational cost integration methods. This work presents a novel approach based on a virtual sensor which can not only precisely estimate the deformation of the flexible links in control applications (less than 2% error), but also its derivatives (less than 6% error in velocity and 13% error in acceleration) according to simulation results. The validity of the proposed Virtual Sensor is tested in a Delta Robot, where the position of the TCP is estimated based on the Virtual Sensor measurements with less than a 0.03% of error in comparison with the flexible approach developed in ADAMS Multibody Software.

Study of Spirituality in Elderly With Subjective Memory Complaints.

Subjective memory complaints are very common among elderly. They can be due to depression, cognitive decline, or be a part of normal aging process. Spirituality is another important dimension in elderly, and it is believed to help them cope with various adversities. This study was done to find out whether any relation exists between these 2 variables in elderly. A total of 120 elderly individuals, presenting with subjective memory complaints, were divided into 3 groups - controls, elderly with depression, and elderly with mild cognitive impairment (MCI). Spirituality in them was studied by dividing it into the subdomains of self-transcendence, presence of meaning in life, search for meaning in life, and locus of control. Spirituality was the highest in controls, followed by MCI group, and then depression group. Spirituality had a direct negative relationship with severity of depression, while relationship of spirituality with severity of cognitive decline was more complex. Relationship of spirituality with mental health status in elderly patients seemed bidirectional, that is, cause as well as effect relationship.

Serotonin effects in the crab Neohelice granulata: Possible involvement of two types of receptors in peripheral tissues.

In crustaceans, serotonin (5-HT) controls various physiological processes, such as hormonal secretion, color changes, reproduction, and metabolism. Since 5-HT injections cause hyperglycemia, this study was designed to further investigate this action of 5-HT in the crab Neohelice granulate, fed with a high-carbohydrate (HC) or a high-protein (HP) diet. The effects of pre-treatment with mammalian 5-HT receptor antagonists, cyproheptadine and methiothepin, were also investigated. A series of in vivo experiments with (3)H-5-HT was carried out in order to investigate the presence of putative receptors in peripheral tissues. Since gills were the tissue with the highest labeling in in vivo experiments, in vitro studies with isolated anterior and posterior gills were also conducted. Cyproheptadine blocked the hyperglycemic effect of 5-HT in HP-fed crabs. Methiothepin reduced glycogen levels in the anterior gills of HP crabs and partially blocked the 5-HT-like posture. The injection of (3)H-5-HT identified specific binding sites in all the tissues studied and revealed that the binding can be influenced by the type of diet administered to the crabs. Incubation of the anterior and posterior gills with (3)H-5-HT and 5-HT confirmed the specificity of the binding sites. Both antagonists inhibited (3)H-5-HT binding. In conclusion, this study highlights the importance of serotonin in the control of glucose homeostasis in crustaceans and provides evidences of at least two types of 5-HT binding sites in peripheral tissues. Further studies are necessary to identify the structure of these receptors and their signaling pathways.

Effect of starvation and refeeding on amino acid metabolism in muscle of crab Neohelice granulata previously fed protein- or carbohydrate-rich diets.

The present study assesses the effects of starvation and refeeding on 1-[(14)C]-methyl aminoisobutyric acid ((14)C-MeAIB) uptake, (14)C-total lipids, (14)CO(2) production from (14)C-glycine, (14)C-protein synthesis from (14)C-leucine and Na(+)-K(+)-ATPase activity in jaw muscle of Neohelice granulata previously maintained on a carbohydrate-rich (HC) or high-protein (HP) diet. In N. granulata the metabolic adjustments during starvation and refeeding use different pathways according to the composition of the diet previously offered to the crabs. During starvation, (14)CO(2) production from (14)C-glycine, and (14)C-protein synthesis from (14)C-leucine were reduced in HC-fed crabs. In crabs maintained on the HP or HC diet, (14)C-total lipid synthesis increased after 15 days of starvation. In crabs fed HP diet, (14)C-MeAIB uptake and Na(+)-K(+)-ATPase activity decreased in refeeding state. In crabs refeeding HC diet, (14)C-MeAIB uptake and (14)CO(2) production decreased during the refeeding. In contrast, the (14)C-protein synthesis increased after 120h of refeeding. In both dietary groups, (14)C-total lipid synthesis increased during refeeding. Changes in the carbon amino acid flux between different metabolic pathways in muscle are among the strategies used by this crab to face starvation and refeeding. Protein or carbohydrate levels in the diet administered to this crab modulate the carbon flux between the different metabolic pathways.

Effects of acute seizures on cell proliferation, synaptic plasticity and long-term behavior in adult zebrafish.

Acute seizures may cause permanent brain damage depending on the severity. The pilocarpine animal model has been broadly used to study the acute effects of seizures on neurogenesis and plasticity processes and the resulting epileptogenesis. Likewise, zebrafish is a good model to study neurogenesis and plasticity processes even in adulthood. Thus, the aim of this study is to evaluate the effects of pilocarpine-induced acute seizures-like behavior on neuroplasticity and long-term behavior in adult zebrafish. To address this issue, adult zebrafish were injected with Pilocarpine (350 mg/Kg, i.p; PILO group) or Saline (control group). Experiments were performed at 1, 2, 3, 10 or 30 days after injection. We evaluated behavior using the Light/Dark preference, Open Tank and aggressiveness tests. Flow cytometry and BrdU were carried out to detect changes in cell death and proliferation, while Western blotting was used to verify different proliferative, synaptic and neural markers in the adult zebrafish telencephalon. We identified an increased aggressive behavior and increase in cell death in the PILO group, with increased levels of cleaved caspase 3 and PARP1 1 day after seizure-like behavior induction. In addition, there were decreased levels of PSD95 and SNAP25 and increased BrdU positive cells 3 days after seizure-like behavior induction. Although most synaptic and cell death markers levels seemed normal by 30 days after seizures-like behavior, persistent aggressive and anxiolytic-like behaviors were still detected as long-term effects. These findings might indicate that acute severe seizures induce short-term biochemical alterations that ultimately reflects in a long-term altered phenotype.

A Comparison of the Behavioral and Psychological Symptoms of Dementia (BPSD) in Early-Onset and Late-Onset Alzheimer's Disease - A Study from South East Asia (Kashmir, India).

BACKGROUND: A gradual increase in the longevity due to advancement of treatment modalities and a subsequent surge in elderly population in India have led to a growing curiosity in the geriatric age group with Alzheimer's disease (AD). Behavioral and psychological symptoms of dementia (BPSD) represent epiphenomena of AD. However, no comprehensive study has been carried out in South East Asia (Kashmir, India), to assess the behavioral and psychological symptoms in subtypes of AD. OBJECTIVES: The purpose of this study was to assess BPSD in early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). MATERIAL AND METHODS: The study was conducted in the Memory clinic of the postgraduate department of psychiatry, Government Medical College, Kashmir, India from January 2012 to March 2014. The diagnosis of AD patients was done according to NINCDS-ADRDA criteria. A total of 80 patients of AD were screened (40 with age of onset less than 65, and 40 with age of onset greater than 64). Neuropsychiatric inventory (NPI) was the instrument used for evaluating symptoms of BPSD. The data was analyzed using paired t-test. RESULTS: The mean age of presentation of EOAD and LOAD was 63.10 years and 84.28 years, respectively, and the difference between the two was found to be statistically significant. The LOAD group had significantly higher symptom severity for delusions, agitation, anxiety, disinhibition, and nighttime behavioral disturbances (NBD) than the EOAD group (p ≤.0001). CONCLUSION: The behavioral and psychological symptoms are significantly severe in late onset subtype compared to the early onset subtype of Alzheimer's disease in the Kashmiri (Indian) population.

Brain zinc chelation by diethyldithiocarbamate increased the behavioral and mitochondrial damages in zebrafish subjected to hypoxia.

The increase in brain levels of chelatable zinc (Zn) in dysfunctions involving oxygen deprivation has stimulated the treatment with Zn chelators, such as diethyldithiocarbamate (DEDTC). However, DEDTC is a redox-active compound and it should be better evaluated during hypoxia. We use the hypoxia model in zebrafish to evaluate DEDTC effects. The exploratory behavior, chelatable Zn content, activities of mitochondrial dehydrogenases, reactive species levels (nitric oxide, superoxide anion, hydroxyl radical scavenger capacity) and cellular antioxidants (sulfhydryl, superoxide dismutase) of zebrafish brain were assessed after recovery, with or without 0.2 mM DEDTC. The increased brain levels of chelatable Zn induced by hypoxia were mitigated by DEDTC. However, the novel tank task indicated that DEDTC did further enhance the exploratory deficit caused by hypoxia. Furthermore, these behavioral impairments caused by DEDTC were more associated with a negative action on mitochondrial activity and brain oxidative balance. Thus, due to apparent pro-oxidant action of DEDTC, our data do not support its use for neuroprotection in neuropathologies involving oxygen deprivation.

Vitamin D as a marker of cognitive decline in elderly Indian population.

OBJECTIVES: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. MATERIALS AND METHODS: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. RESULTS: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. CONCLUSION: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment.

Prophylaxis of antipsychotic-induced extrapyramidal side effects in east Indians: cultural practice or biological necessity?

OBJECTIVE: Although still controversial, as early as 1989, the World Health Organization recommended that antipsychotic agents should be initiated without routinely adding anticholinergic drugs prophylactically. However, combined treatment with antipsychotics and anticholinergic agents is the norm in India. The goal of this study was to investigate whether Indians are more susceptible to extrapyramidal side effects (EPS) or if the practice of routinely adding an anticholinergic agent to an antipsychotic is overly cautious and wasteful. METHOD: 75 consecutive patients started on conventional antipsychotics were repeatedly evaluated over 2 months on a standardized EPS scale, the abbreviated Simpson-Angus scale. RESULTS: Of 71 subjects who completed the study, 68 (96%) suffered EPS while receiving 2-13 mg/day of haloperidol equivalents, with 70% of EPS present by day 5 and 90% by day 10. The most common symptoms were tremor (49%), cogwheel rigidity (40%), and acute dsytonic reaction (34%). Routine clinical care detected 49% of the EPS, patients volunteered a complaint 19% of the time, and relatives reported EPS in 7% of patients. CONCLUSION: Since patients of Indian origin are prone to suffer EPS when taking conventional antipsychotic drugs, initial prophylaxis with antiparkinson agents should perhaps be more carefully considered on a routine basis. Even among atypicals, agents with the least potential to cause EPS should be favored. In all patients treated with antipsychotics, it is imperative to ask directly about and carefully examine for EPS, because few patients will volunteer their complaints.

Marchiafawa bignami disease possibly related to consumption of a locally brewed alcoholic beverage: Report of two cases.

Marchiafava Bignami disease is a rare toxic disease seen mostly in chronic alcoholics, resulting in progressive demyelination and necrosis of the corpus callosum. Initially it was thought to be specific to individuals in central Italy, consuming large amounts of Chianti red wine; however, alcoholic beverages worldwide are presently implicated. In our case series of two cases, locally made "illicit" liquor (Mahuwa Alcohol) could be the causative factor. In radiological point of view typically the corpus callosum is affected, with involvement of the body, genu, and splenium in order of occurrence. Occasionally the entire callosum may be also involved. Clinical presentation varies from case to case.

Neuropsychiatric symptoms in mild cognitive impairment: An analysis and its impact on caregiving.

BACKGROUND: Neuropsychiatric impairments play a significant role throughout the course of cognitive decline. Many psychological and behavioral symptoms are present in patients of mild cognitive impairment (MCI) similar to that seen in individuals with dementia. AIMS AND OBJECTIVES: To study the relevance of neuropsychiatric symptoms of MCI and the impact it has on caregivers of these patients. MATERIALS AND METHODS: This cross-sectional study was done on 90 patients (30 MCI, 30 dementia and 30 controls) above the age of 50 years. The scales used were Hindi-Mental Status Examination, Global deterioration scale and Neuropsychiatric inventory (NPI). Statistical analysis was done using SPSS 16 software. RESULTS: 73.33% (22) of the subjects in MCI group, 90% (27) of subjects in dementia group and 53.33% (16) of subjects having normal cognition had neuropsychiatric complaints. 73.33% (22) relatives of subjects in the MCI group, 90% (27) relatives of subjects in dementia group and 46.67% (14) relatives of subjects in the normal group (i.e. control group) experienced some distress. The differences in the mean NPI severity, frequency, distress and total scores of the three groups were statistically significant. Severity and frequency of neuropsychiatric symptoms significantly predicted the caregiver's distress. CONCLUSIONS: Neuropsychiatric symptoms increase both in frequency and severity with increasing cognitive decline, and they cause distress both to the patient as well as the caregiver; and hence their early recognition is a must. The NPI appears to be a useful tool in that regard.

Evaluation of spontaneous recovery of behavioral and brain injury profiles in zebrafish after hypoxia.

Cerebral hypoxia-ischemia can lead to motor and sensory impairments which can be dependent on the extent of infarcted regions. Since a better understanding of the neurochemical mechanisms involved in this injury is needed, the use of zebrafish as a cerebral hypoxia model has become quite promising because it could improve the knowledge about hypoxia-ischemia. In the current study, we aimed to investigate the spontaneous recovery of brain and behavioral impairments induced by hypoxia in adult zebrafish. Brain injury levels were analyzed by spectrophotometric measurement of mitochondrial dehydrogenase activity by staining with 2,3,5-triphenyltetrazolium chloride, and behavioral profiles were assessed by the open tank test. The induction of hypoxia substantially decreased mitochondrial activity in the brain and impaired behavior. The spontaneous recovery of fish subjected to hypoxia was assessed after 1, 3, 6, 24, and 48h under normoxia. The quantification of brain injury levels showed a significant increase until 24h after hypoxia, but after 48h this effect was completely reversed. Regarding behavioral parameters, we verified that locomotor activity and vertical exploration were impaired by hypoxia and these effects were reversed after 3h under normoxia. Taken together, these results show that zebrafish exhibited transient cerebral and behavioral impairments when submitted to hypoxia, and 1h under normoxic conditions was insufficient to reverse both effects. Therefore, our data help to elucidate the time window of spontaneous recovery in zebrafish after hypoxia and also the behavioral phenotypes involved in this phenomenon.

Sexuality: desire, activity and intimacy in the elderly.

BACKGROUND: Sexual function and activity in old age have been inadequately studied world over. It is important to know that aging processes are not confined to persons beyond the age of 60 years; many changes in elderly have their antecedents in the middle age. AIMS: This study sought to determine the patterns of sexual activity and function in individuals over 50 years of age. It also sought to discuss barriers such as chronic illness that may interfere with sexual function. MATERIALS AND METHODS: We conducted a study of subjects above the age of 50 years in various outpatient departments (OPDs) of a teaching municipal hospital in Mumbai, by interviewing 60 individuals who attended the OPDs, after taking their informed consent. Socio-demographic and other information on their sexual function and activities were obtained. Data was analyzed using statistical package for social sciences v15. RESULTS: 72% individuals below 60 were sexually active, while only 57% above 60 were active. Others had become completely abstinent at some time in their lives. Statistical analysis revealed significant gender, health and educational status based differences in the sample. CONCLUSION: Our study showed significant presence of sexual desire, activity and function even after the age of 50 years; a decline by the age of 60 and above was a finding that reflected more in women. Chronic illness did affect sexual function and desire.

Indian research on acute organic brain syndrome: Delirium.

Delirium, though quite often referred to psychiatrists for management, does not find many takers for analysis, research and publications. Acute in onset, multiplicity of etiology and manifestations, high risk of mortality delirium is very rewarding in proper management and outcome. Delirium has a limited agenda on teaching programs, research protocols and therapeutic strategies. There is a dearth of Indian studies both in international and national scientific literature. This annotation is based on a Medline search for "delirium India" on Pubmed, which resulted in 54 articles. A search in Indian Journal of Psychiatry for "delirium" resulted in 38 published articles, "delirium tremens" showed up only five articles. The articles are primarily from the Indian Journal of Psychiatry with cross reference to articles on Pubmed or Google search on Indian studies and a few international studies.

Mild cognitive impairment: The dilemma.

Memory complaints are ubiquitous in our aging population. Many older adults fear that today's forgetfulness will usher in tomorrow's dementia. Mild cognitive impairment (MCI) is considered by many as an intermediary stage for dementia. Though the nomenclature has been varied and extensive, the criteria by the American Academy of Neurology and the EADC have been helpful. Prevalence rates varying from 3% to as high as 59% with a conversion rate to dementia varying from 8 to 15% only increases the need for diagnostic tests and markers which are in the form of neuropsychological tests, neuroimaging and other biological markers.Medications indicated for treatment of mild to severe Alzheimer's Disease (AD) are offered to persons with MCI with a varying type of response which does not hold in the long run to newer strategies of exploring disease modifying drugs which hold a better promise. This benefit with management of risk factors like hypertension and diabetes coupled with non-pharmacological approaches like exercise and social networking has thrust upon us the necessity for coordinating our efforts to improve detection and management of MCI.

An open-label multicentric study of the tolerability and response to escitalopram treatment in Indian patients with major depressive disorder.

To evaluate the tolerability and response to escitalopram in Indian patients with major depression, over an 8-week open-label multicentric study was carried out among 18-65 years old Indian patients suffering from DSM IV major depressive disorder with Montgomery-Asberg depression rating scale (MADRS) total score> or =22. Patients received a fixed dose of escitalopram 10 mg daily for 2 weeks, followed by flexible dose of 10 to 20 mg daily for 6 weeks. Patients were evaluated for depression and rated on MADRS score and clinical global impressions-severity (CGI-S) and--improvement (CGI-I) scores. They were monitored for treatment-emergent adverse effects. A total of 119 patients were enrolled and 103 completed the trial. There was a decrease from baseline in the MADRS total score after one week of treatment continuing until 8 weeks. By week 8, 76.9% patients had responded to treatment (> or =50% or more reduction of MADRS total score). A similar pattern of improvement to that seen with the MADRS total score was seen with CGI-S and CGI-I scores. Escitalopram was well tolerated, with only 2 patients (1.7%) withdrawing from the study due to adverse events. There were no serious adverse events.