Inflammation Drives Alzheimer's Disease: Emphasis on 5-lipoxygenase Pathways.

It is a known fact that inflammation affects several physiological processes, including the functioning of the central nervous system. Additionally, impairment of lipid mechanisms/pathways have been associated with a number of neurodegenerative disorders and Alzheimer's Disease (AD) is one of them. However, much attention has been given to the link between tau and beta- amyloid hypothesis in AD pathogenesis/prognosis. Increasing evidences suggest that biologically active lipid molecules could influence the pathophysiology of AD via a different mechanism of inflammation. This review intends to highlight the role of inflammatory responses in the context of AD with the emphasis on biochemical pathways of lipid metabolism enzyme, 5-lipoxygenase (5- LO).

Escitalopram-induced severe akathisia leading to suicide attempt.

Akathisia, a distressing adverse reaction, is usually underdiagnosed or misdiagnosed in patients, who are treated with selective serotonin reuptake inhibitors (SSRIs). Escitalopram-induced akathisia is rarely reported in the literature. We report a case of severe akathisia leading to a suicide attempt in a 25-year-old male induced by 5 mg of escitalopram, that remitted completely after discontinuation of escitalopram and did not reappear later. Patient and their caretakers should be warned of symptoms of akathisia even when a very low dose of SSRI is prescribed.

Quality of life and marital adjustment in remitted psychiatric illness: an exploratory study in a rural setting.

People with mental disorders experience impaired quality of life (QOL). In India, spouses form the most important caregiver for the patient and therefore impact the patients' QOL. However, relatively little is known about marital adjustment, which can definitely influence QOL of patients with mental illness. This study intended to explore marital adjustment and QOL among remitted patients with schizophrenia (SC), depression, and bipolar disorders (BPADs) and to study differences, if any, between the groups. Using a cross-sectional design, consecutive patients (N = 150) with an ICD-10-Diagnostic Criteria for Research diagnosis of SC, depression (recurrent depressive disorder [RDD]), or BPAD, who were currently in remission, were taken up for the study and administered the WHOQOL-BREF for assessing QOL and the Marital Adjustment Inventory for assessing marital adjustment, separately for the husband and the wife. The patients with SC reported poor QOL, whereas a better QOL was seen in those with BPAD and RDD, with significant differences noted between all three groups (p < 0.001). Marital adjustment was perceived to be poor by the patients but not so by the spouses. The greatest marital dissatisfaction was reported by the patients with SC (96%). A positive correlation was observed between the patients' perception of marital adjustment and QOL (p < 0.05). Provision of mental health care should take into consideration patients' possible perception of marital maladjustment and factor these into treatment strategies.

Obesity, diabetes and hypertension associated with antipsychotic use in remitted schizophrenia.

OBJECTIVE: To ascertain the prevalence of diabetes, obesity and hypertension associated with antipsychotic use in remitted patients with schizophrenia. METHODS: This study included a cross sectional survey of diabetes, obesity and hypertension among all remitted patients diagnosed with schizophrenia/schizoaffective disorder (n = 130) on at least 6 months of antipsychotic treatment. RESULTS: A prevalence of 35.4% obesity, 1.5% hypertension and 3.8% (ADA) or 5.4% (WHO) prevalence of diabetes was observed. CONCLUSIONS: The use of antipsychotic drugs in the long run may be associated with a significantly greater risk of developing obesity with moderate influence on development of diabetes and minimal to none on hypertension.

Cheek-biting disorder: another stereotypic movement disorder?

Recurrent cheek biting, a form of self-injurious behavior is a rare entity which presents mostly to dentists and dermatologists. We report a case of recurrent severe cheek biting in an adult male leading to mucosal ulceration. The stereotypic pattern of cheek biting and associated behavior bears striking resemblance to other impulse control disorders.

High dose zolpidem induced fetal neural tube defects.

Use of zolpidem, a short-acting imidazopyridine hypnotic, has not been associated with teratogenic effects in usual clinical doses. We report a case of fetal neural tube defects occurring in a female dependent on zolpidem and consuming high doses in the first trimester of pregnancy. Possible mechanisms by which high dose zolpidem may lead to teratogenicity are discussed. Clinicians are advised to be aware of the risks of high-dose zolpidem abuse in early pregnancy.

Improving tolerability of lithium with a once-daily dosing schedule.

Lithium has been proved to be highly efficacious in the treatment of bipolar affective disorder, though a narrow therapeutic index and a high incidence of troublesome side effects often leads to poor compliance in patients. Therefore, there is a need to explore treatment strategies to improve the efficacy and side effect profile of lithium. We compared the efficacy and side effect profile of a once-daily versus twice-daily dosing schedule of lithium in mania. Eighty-three manic patients according to International Classification of Diseases, 10th Revision, Diagnostic Criteria for Research, giving informed consent were randomly allocated to receive regular lithium carbonate once daily or twice daily. They were assessed using Bech-Rafaelsen Mania Rating Scale, a lithium side effect scale, hemogram, renal function test, lipid profile, and a thyroid function test at baseline and Day 7, Day 21, and Day 42. Repeated-measures analysis of variance for Bech-Rafaelsen Mania Rating Scale scores showed a significant main effect, but interaction of treatment groups over time was not significant. Those subjects receiving twice-daily lithium experienced significantly higher urinary frequency on Day 21 (P = 0.008) and Day 42 (P = 0.035). They also required significantly higher total daily dose of lithium (P = 0.017) and had lower serum lithium levels (P < 0.001). There was a significant positive correlation between urinary frequency at Day 42 with lithium dose. A twice-daily dose of lithium was of similar efficacy as the once-daily schedule but produces higher renal adverse effects that may be dose-related. Therefore, a single daily dose of lithium can be a viable method to reduce the side effects of lithium, which may lead to better patient compliance.

Stevens-Johnson syndrome progressing to toxic epidermal necrolysis with haloperidol and carbamazepine combination.

Carbamazepine and other anticonvulsants are commoner cause of severe adverse cutaneous drug reactions such as erythema multiforme, toxic epidermal necrolysis (TEN), and Stevens-Johnson syndrome (SJS). We report a case of SJS rapidly progressing to TEN with a combination of haloperidol and carbamazepine in a patient with bipolar affective disorder. The pathophysiological mechanism underlying this reaction is discussed.

Stereotyped paroxysmal psychiatric symptoms during oculogyric crisis or 'cognitive dystonia': a case report.

Oculogyric crisis (OGC) is an acute dystonia which can occur after initiation of antipsychotic treatment. Stereotypic paroxysmal psychiatric symptoms have been described along with OGC that resolve spontaneously when the later remits. We report a case of tardive OGC associated with zuclopenthixol in which there were associated paroxysmal auditory pseudohallucinations.

Efficacy of adjunctive high frequency repetitive transcranial magnetic stimulation of left prefrontal cortex in depression: a randomized sham controlled study.

OBJECTIVE: To examine the efficacy of adjunctive left prefrontal high-frequency rTMS treatment in depression patients as compared to sham stimulation. METHOD: 45 right handed moderate to severe depression patients according to ICD-10 DCR criteria were randomized to receive daily sessions of active or sham rTMS (10Hz, 90% of resting MT, 20 trains, 6s duration, 1200 pulses/day) over the right dorsolateral prefrontal cortex for 10 days. Depression and psychosis was rated using Structured Interview Guide for the Hamilton Depression Rating Scale (SIGH-D) and Brief Psychiatric Rating Scale (BPRS) respectively before and after rTMS. RESULT: For SIGH-D scores, repeated measures ANOVA showed a significant effect of treatment over time as shown by interaction effect (Pillai's Trace F [1/38] = 56.75, p<.001, η(2) = .60). For BPRS, repeated measures ANOVA showed a significant interaction effect of treatment over time (Pillai's Trace F [1/38] = 39.87, p<.001, η(2) = .51). In psychotic depression patients, repeated measures ANOVA showed a significant effect of treatment over time for SIGH-D scores (Pillai's Trace F [1/25] = 43.04, p<.001, η(2) = .63) and BPRS scores (Pillai's Trace F [1/25] = 42.17, p<.001, η(2) = .63). CONCLUSION: High-frequency left prefrontal rTMS was well tolerated and found to be effective as add-on to standard pharmacotherapy in nonpsychotic as well as psychotic depression.

Resolution of low voltage electrical injury induced psychosis with olanzapine.

BACKGROUND: The number of electrical injuries are rising in proportion to the increased use of electricity in both domestic and industrial sectors. There are multiple ways in which electricity can cause tissue damage, which can be due to direct effects, electroporation and thermal effects. However, these mechanisms fail to explain the enigmatous occurrences of diffuse and delayed neurological and psychological manifestations, especially those remote to the theoretical current pathway and in absence of any gross neurological abnormalities. Immediate neuropsychological sequelae have been well reported in the literature in the form of transient anxiety, emotional instability and memory disturbances. Among psychiatric manifestations, neurotic disorders like post-traumatic stress disorder, conversion and adjustment disorders have been appreciated many a times as a frequent accompaniment of these injuries. Occasional reports of occurrence of mania have also been recorded. CASE STUDY: This study reports a case of schizophrenia like illness following a low voltage electrical injury. A discussion regarding the ways in which electrical injury and schizophrenia like illness could be related has been put forth. A brief review of the literature regarding the occurrence of psychiatric disorders in such injuries is also presented.

Metabolic syndrome in first episode schizophrenia - a randomized double-blind controlled, short-term prospective study.

BACKGROUND: Although the treatment of schizophrenia, arguably one of the most devastating diseases today, has been immensely helped by the advent of second-generation antipsychotics, they have come at a considerable cost - the metabolic syndrome (MetS). This adverse effect has been described with several antipsychotics to range between 20%-60%, at least double the prevalence in the general population. METHODS: All consecutive patients with first episode schizophrenia at our referral psychiatric hospital were recruited in an extensive prospective randomized, double-blind controlled study including measures of waist circumference (WC), blood pressure (SBP/DBP), triglyceride (TGL), high-density lipoproteins (HDL) and fasting blood sugar (FBS) levels and randomized to receive either, haloperidol, olanzapine or risperidone. The prevalence of MetS was assessed based on two criteria- ATP IIIA and criteria of International Diabetes Federation (IDF). This was compared with a gender, age, exercise and diet matched healthy control group. RESULTS: The analysis of 99 patients showed a prevalence of MetS as 10.1% and 18.2% as assessed by ATP IIIA and IDF criteria respectively. The prevalence of MetS in our sample of patients with schizophrenia is at least five times as high when compared to the matched healthy control group. Olanzapine had maximum prevalence of MetS at 20-25% followed by risperidone at 9-24% and haloperidol at 0-3%. DISCUSSION: Metabolic syndrome is highly prevalent among treated patients with first episode schizophrenia. Early monitoring of patients on atypical antipsychotics can possibly play an important role in early detection and hence prevention of the metabolic syndrome.

Predictors of antipsychotic-induced weight gain in first-episode psychosis: conclusions from a randomized, double-blind, controlled prospective study of olanzapine, risperidone, and haloperidol.

BACKGROUND: Antipsychotic-induced weight gain is one of the most distressing adverse effects being observed in recent times. Most studies have been limited by several confounders. AIM: To evaluate the predictors of antipsychotic-induced weight gain in drug-naive patients with first-episode psychosis treated with olanzapine, risperidone, or haloperidol and compare them with a healthy matched control group. METHODS: Newly diagnosed patients with first-episode schizophrenia treated with antipsychotic medication-olanzapine, risperidone, or haloperidol-and matched healthy controls were followed for 6 weeks. Body mass index (BMI), waist circumference, and weight changes and proportions of subjects with more than 7% weight gain were calculated. The predictors of weight gain were explored. RESULTS: Ninety-nine patients with first-episode schizophrenia and 51 healthy controls were examined. Waist circumference (r = -0.25; P < 0.01) and weight (r = -0.24; P < 0.01) at baseline in addition to the disease process (P < 0.001) as well as antipsychotic use (P < 0.001) were associated with greater increases in weight and BMI. Olanzapine (77%) had greater clinically significant weight gain as compared with risperidone (63%) and haloperidol (22%). Lower BMI at baseline and a diagnosis of undifferentiated schizophrenia were associated with antipsychotic-induced weight gain. CONCLUSIONS: The results confirm clinically significant and substantial weight gain induced by antipsychotic treatment in drug-naive patients with first-episode schizophrenia and identify several risk factors for weight gain such as lower BMI scores, use of olanzapine, and a diagnosis of undifferentiated schizophrenia.

Effect of olanzapine, risperidone, and haloperidol treatment on weight and body mass index in first-episode schizophrenia patients in India: a randomized, double-blind, controlled, prospective study.

OBJECTIVE: The presence of obesity and increases in body mass are important risk factors for cardiovascular disease and diabetes. This study examined the effects of olanzapine, risperidone, and haloperidol on weight, body mass index (BMI), and development of obesity in a drug-naive population compared with a matched healthy control group. METHOD: Consecutive patients during the period from June through October 2006 with DSM-IV schizophrenia at our referral psychiatric hospital were recruited for an extensive prospective study that included anthropometric measures of weight, waist circumference, waist-hip ratio, and BMI. Subjects were randomly assigned to receive haloperidol, olanzapine, or risperidone and compared with a matched healthy control group. The prevalence of obesity, which was the main outcome measure, was assessed on the basis of 2 criteria: revised World Health Organization (WHO) definition for Asians and criteria of the International Diabetes Federation (IDF). Inclusions started in June 2006, and patients were followed for a period of 6 weeks. RESULTS: The analysis of 66 patients showed a prevalence of overweight (WHO criteria) at 22.7% and obesity at 31.8% (IDF criteria). The prevalence of obesity (IDF criteria) in our patients is over 30 times as high as that of the matched healthy control group (p < .001). Subjects in the olanzapine group had the greatest weight gain at 5.1 kg, followed by risperidone at 4.1 kg and haloperidol at 2.8 kg. CONCLUSIONS: Obesity is highly prevalent among patients treated with atypical antipsychotics for schizophrenia. Assessment and monitoring of obesity along with preventive and curative measures should be part of the clinical management of patients treated with antipsychotics. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00534183, www.clinicaltrials.gov.