Studies of Adenosine and GABAA Receptor Functions in Rat Hippocampal Slices

Recent evidence has indicated that adenosine, in addition to potassium and calcium currents, may also affect chloride movement in hippocampal neurones. This project was undertaken to determine the possible role of adenosine on chloride channels and synaptic plasticity in comparison with a selective GABA[A] agonist, muscimol. Extracellular recordings were made from the CA1 pyramidal cell layer of hippocampal slices in response to stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). Adenosine and muscimol induced concentration dependent reductions in the amplitude of orthodromically induced population potentials. In order to eliminate effects of these agents on potassium channels, experiments were performed in the presence of barium, 1mM (in some experiments in the presence of 1 mM tolbutamide). This concentration increased potential size, and reduced the inhibitory effect of adenosine on population spike size, but not synaptic potential size. This profile is consistent with the blockade of potassium channels associated only with the postsynaptic effects of adenosine. However, muscimol responses were unaffected. Adenosine potentiated the ability of muscimol to inhibit evoked potentials in the absence or presence of barium. The potentiation was prevented by the Al selective antagonist 8-cyclopentyltheophylline. The effects of adenosine, as well as muscimol, were reduced by the chloride channel blocker DIDS, which also prevented the adenosine potentiation of muscimol. The results indicate the ability of adenosine to operate chloride channels in hippocampal neurones, and suggest a potentiative interaction between adenosine and muscimol which also involve chloride channels. The second part of this study was to examine neurosteroids which have been reported to be positive modulators of the GABAA receptors. Alphaxalone and 5alpha-pregnan-3alpha-o1-20-one potentiated the inhibitory effect of muscimol on the population spike size at low concentrations (0.5 and 1muM) that had no significant effect on the spike size by themselves. This profile is in agreement with other reports which have described the effect of these neurosteroids as barbiturate-like. Alphaxalone and 5alpha-pregnan-3alpha-o1-20-one also at low concentrations potentiated the inhibitory effect of adenosine alone and in the presence of barium 1 mM which blocked adenosine activated potassium channels. Alphaxalone failed to potentiate the inhibitory effect of adenosine in the presence of bicuculline 1muM. It is concluded that these neurosteroids enhanced the potentiative interaction between adenosine and muscimol in the presence of barium. The results indicate that adenosine's effects are normally enhanced by virtue of the potentiative interaction occurring with endogenous GABA. In addition to this, the results show the chloride channels activated by adenosine to be different from those operated by the GABA[A] receptor. The third part of this project was to investigate the role of GABA[A] and adenosine receptors on long-term depression (LTD) and synaptic plasticity. Unlike long-term potentiation, LTD in the central nervous system remains poorly understood. Muscimol induced a time and concentration-dependent LTD in the amplitude of orthodromic potentials. Increasing the stimulation frequency from 0.01 Hz to 1 Hz for 10 seconds reversed the LTD induced by muscimol. Although adenosine decreased the spike size in a concentration-dependent manner, it failed to induce LTD. Muscimol also induced LTD in the absence of electrical stimulation. Alphaxalone and 5alpha-pregnan-3alpha-o1-20-one at concentrations that did not have any effect themselves on the population spike (0.5 and 1 muM), potentiated the inhibitory effect of muscimol on the population spike size. These neurosteroids at high concentrations (5 and 10 muM) decreased the spike size by themselves. On the other hand, at the low concentrations both steroids were able to potentiate the ability of muscimol to induce LTD. Moreover, muscimol 1 muM which is not able to induce LTD, alphaxalone and 5alpha-pregnan-3alpha-o1-20-one 1 muM maintained the LTD induced by muscimol 10 muM. Bicuculline 5 muM reversed the LTD induced by muscimol 10 muM. To examine the possible role of glutamate receptors in LTD induced by muscimol a number of NMDA and metabotropic receptors agonists and antagonists were used. The NMDA receptor antagonist 2-AP5, the NMDA/metabotropic antagonist 2-AP3 and selective metabotropic antagonist L(+)-AP3 failed to modify the LTD. Quisqualic acid and (1S,3R)- aminocyclopentane dicarboxylic acid (ACPD), a selective agonist at metabotropic receptors, did not induce LTD or short-term depression, whereas kynurenic acid prevented the reversal of the LTD obtained at 1 Hz. It is concluded that LTD can be induced by the selective activation of GABA[A] receptors and the lack of involvement of glutamate receptors in the protocol which is presented in this study confirms the unique role of classical GABA[A] receptors in the effect of muscimol and may indicate a novel type of long-lasting depression. Furthermore, the failure of adenosine to induce LTD taken together with the earlier results, suggests that the adenosine activated chloride channel differs from the GABA[A] receptor chloride channel

Autism Spectrum Disorders in Iran

How to Cite this Article: Mohammadi MR, Salmanian M, Akhondzadeh Sh. Autism Spectrum Disorders in Iran. Iranian Journal of Child Neurology2011;5(4):1-9.ObjectiveAutistic disorder, Asperger syndrome, and PDD-Not Otherwise Specified are subsets of autism spectrum disorders (ASDs), which are characterized by impairments in social communication and stereotyped behavior. This article reviews the prevalence, etiology, diagnosis, and treatment of ASDs in Iran.Materials & MethodsWe searched PubMed, ISI Web of Science, and 4 Iranian databases (IranPsych,IranMedex, Irandoc and Scientific Information Database (SID) to find Iranian studies on  ASDs. The results of 39 investigations, comprising original, review and editorial articles; proceedings; and available dissertations were categorized by prevalence, etiology, diagnosis, and treatment.ConclusionSeveral preliminary investigations have been done to evaluate the prevalence of ASDs, and risk factors and effective variables have been studied with regard to etiology. The diagnostic evaluation of ASDs, especially based on EEG, and several pharmacological and behavioral interventions for ASD have been implemented in Iran. Mental health, stress levels, and personality characteristics were examined in the parents of children with ASDs, which were focused on mothers.ReferencesFirst MB, Frances A, Pincus HA. DSM-IV-TR: Handbook of differential diagnosis. United States of America:American Psychiatric Publishing; 2002.Parker S, Zuckerman B, Augustyn M. Developmental and behavioral pediatrics, 2 th ed. United States of America:Lippincott Williams & Wilkins; 2005.Howlin P. Autism and Asperger syndrome, 2 th ed. United States of America: Routledge; 2005.Mohammadi MR, Akhondzadeh S. Autism Spectrum Disorders: Etiology and Pharmacotherapy. Curr Drug ther2007; 2: 97-103.Newschaffer CJ, Croen LA, Daniels J, Giarelli E, GretherJK, Levy SE, et al. The epidemiology of autism spectrumdisorders. Annu Rev Public Health 2007; 28: 235-258.Zaroff CM, Uhm SY. Prevalence of autism spectrum disorders and influence of country of measurement and ethnicity. Soc Psychiatry Psychiatr Epidemiol 2011;published online.Baron-Cohen S, Scott FJ, Allison C, Williams J, Bolton P, Matthews FE, et al. Prevalence of autism-spectrum conditions: UK school-based population study. Br J Psychiatry 2009;194:500-509.Brugha TS, McManus S, Bankart J, Scott F, Purdon S, SmithJ, et al. Epidemiology of autism spectrum disorders inadults in the community in England. Arch Gen Psychiatry 2011; 68: 459-465.Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ 2009; 58: 1-20.Fombonne E. Epidemiology of pervasive developmental disorders. Pediatr Res 2009; 65: 591-598.Ehlers S, Gillberg C. The epidemiology of Asperger syndrome. A total population study. J Child Psychol Psychiatry 1993; 34: 1327-1350.Kadesjo B, Gillberg C, Hagberg B. Brief report: autismand Asperger syndrome in seven-year-old children: a totalpopulation study. J Autism Dev Disord 1999; 29: 327-331.Williams JG, Higgins JP, Brayne CE. Systematic reviewof prevalence studies of autism spectrum disorders. ArchDis Child 2006; 91: 8-15.Bernier R, Mao A, Yen J. Psychopathology, families, andculture: autism. Child Adolesc Psychiatr Clin N Am 2010;19: 855-867.Shamsi-pour M, Yonesian M, Mansouri A. Epidemiologyof autism: recent challenges in prevalence of autism andits risk factors. Journal of health and knowledge 2010; 5:133.Ghanizadeh A. A preliminary study on screening prevalence of pervasive developmental disorder in school children in Iran. J Autism Dev Disord 2008; 38:759-763.Nejatisafa AA, Kazemi MR, Alaghebandrad J. Autisticfeatures in adult population: evidence for continuity ofautistic symptoms with normality. Advanced in cognitivescience 2003; 5: 34-39.Khoushabi K, Pouretemad HR. Prevalence of pervasive developmental disorders according to gender in a sampleof Iranian children referred to treatment and rehabilitation centers. Journal of Hamedan University of Medical Sciences 2006;13: 58-60.Jannati M. Epidemiology of autism in exceptional studentsin Mashhd. MA thesis in psychology of exceptionalchildren field. Islamic Azad University of Birjand; 2001.Mansouri M, Chalabianlou GR, Malekirad AA, MosadedAA. The comparison of factors affecting the theory of mind development in autistic and normal children. Arak Medical University Journal 2011; 13: 115-125.Salmanian M. Visual memory of shapes and face in children with ASDs as compared to normal children. MS thesis in cognitive psychology. Institute for cognitive science studies; 2010.22. Ghanizadeh A, Mohammadi MR, Sadeghiyeh T, Alavi Shooshtari A, Akhondzadeh S. Symptoms of Childrenwith Autism Spectrum Disorder, a Clinical Sample. Iran J Psychiatry 2009; 4: 165-169. Sasanfar R, Haddad SA, Tolouei A, Ghadami M, Yu D, Santangelo SL. Parental age increases the risk for autismin an Iranian population sample. Mol Autism 2010; 1:2.Abolfazli R, Mirbagheri SA, Zabihi AA, Abouzari M. Autism and Celiac Disease: Failure to Validate the Hypothesis of a Possible Link. Iranian Red Crescent Medical Journal 2009; 11: 442-444.Hamidi Nahrani M, Sedaei M, Fatahi J, Sarough Farahani S, Faghihzadeh S. Auditory brain stem responses in autistic children in comparison with normal children. Audiology 2008; 16: 16-22.Sheikhani A, Behnam H, Mohammadi MR, Noroozian M. Evaluation of Quantitative Electroencephalography in Children with Autistic Disorders in Various Conditions Based on Spectrogram. Iran J Psychiatry 2007; 3: 4-10.Niedermeyer E, Lopes da Silva F. Electroencephalography:Basic principles, clinical applications, and related fields,5th ed. Philadelphia: Lippincott Williams & Wilkins;2005.Sheikhani A, Behnam H, Mohammadi MR, Noroozian M, Mohammadi M. Detection of Abnormalities for Diagnosing of Children with Autism Disorders Using of Quantitative Electroencephalography Analysis. J MedSyst 2010.Noroozian M, Sheikhani A, Behnam H, Mohammadi MR. Abnormalities of Quantitative Electroencephalography inChildren with Asperger Disorder Using Spectrogram and Coherence Values. Iran J Psychiatry 2008; 3: 64-70.Ahmadlou M, Adeli H, Adeli A. Fractality and a wavelet-chaos-neural network methodology for EEG based diagnosis of autistic spectrum disorder. J Clin Neurophysiol 2010; 27: 328-333.Bahari Gharagoz A, Hassanpour A, Amiri SH. Social interactions and repetitive behavior of autistic and trainable mentally retarded children. Developmental Psychology 2010; 7: 39-47.Campbell M, Adams P, Perry R, Spencer EK, Overall JE.Tardive and withdrawal dyskinesia in autistic children: aprospective study. Psychopharmacol Bull 1988; 24: 251-255.Anderson LT, Campbell M, Adams P, Small AM, Perry R, Shell J. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children. J Autism Dev Disord 1989; 19: 227-239.Shattock P, Kennedy A, Rowell F, et al. Role of neuropeptides in autism and their relationships with classical neurotransmitters. Brain Dysfunct 1990; 3: 328-345.Campbell M, Schopler E, Cueva, J, Hallin A. Treatmentof autistic disorder. J Am Acad Child Adolesc Psychiatry1996; 35: 134-143.Tsia LY. Psychopharmacology in autism. Psychosom Med 1999; 61: 651-665.McCracken JT, McGough J, Shah B, et al. Risperidone in children with autism and serious behavioral problems. N Engl J Med 2002; 347: 314 -321.Posey DJ, McDougle CJ. The pharmacotherapy of target symptoms associated with autistic disorder and other pervasive development disorders. Harv Rev Psychiatry 2000; 4: 45-63.Levy SE, Hyman SL. Novel treatments for autistic spectrum disorders. Ment Retard Dev Disabil Res Rev2005; 11: 131-142.Akhondzadeh S, Fallah J, Mohammadi MR, Imani R, Mohammadi M, Salehi B, et al. Double-blind placebo controlled trial of pentoxifylline added to risperidone:effects on aberrant behavior in children with autism. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 32-36.Akhondzadeh S, Tajdar H, Mohammadi MR, Mohammadi M, Nouroozinejad GH, Shabstari OL, et al. A double-blindplacebo controlled trial of piracetam added to risperidonein patients with autistic disorder. Child Psychiatry Hum Dev 2008; 39: 237-245.Rezaei V, Mohammadi MR, Ghanizadeh A, Sahraian A,Tabrizi M, Rezazadeh SA, et al. Double-blind, placebo controlled trial of risperidone plus topiramate in children with autistic disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1269-1272.Akhondzadeh S, Erfani S, Mohammadi MR, Tehrani-Doost M, Amini H, Gudarzi SS, et al. Cyproheptadine in the treatment of autistic disorder: a double-blind placebo controlled trial. J Clin Pharm Ther 2004; 29: 145-150.Mohammadi MR, Asadabadi M, Akhondzadeh S. A double-blind placebo controlled trial of celecoxib added to risperidone in children with autistic disorder. Unpublished paper.Ghanizadeh A. Targeting of glycine site on NMDA receptor as a possible new strategy for autism treatment.Neurochem Res 2011; 36: 922-923.Ghanizadeh A. Targeting neurotensin as a potential novel approach for the treatment of autism. J Neuro inflammation 2010; 7: 58.Bahmanzadegan Jahromi M, Yarmohammadian A,Mousavi H. Efficacy of social skills training in autistic behaviors and social development in children with autism disorder through social stories. New findings inpsychology 2009; 3: 79-93.Dalvand H, Dehghan L, Feizy A, Hosseini SA. The effect of home based Lovaas approach on social interaction,Speech and language, Play and behavior skills, and intensity of autism in young children with Autism. Modern Rehabilitation 2009; 3: 3.Golabi P, Alipour A, Zandi B. the effect of intervention by ABA method on children with autism. Research on exceptional children 2005; 5: 33-54.Arman S, Hakiman S, Golabi P. Three therapeutic methods for autistic children: a clinical trial. Journal of Isfahan Medical School 2005; 23: 44-48.Hatamzadeh A, Pouretemad H, Hassanabadi H. The effectiveness of parent-child interaction therapy for children with high functioning autism. World Conferenceon Psychology, Counselling and Guidance 2010; 5: 994-997.52. Chimeh N, Pouretemad HR, Khoramabadi R. Need assessment of mothers with autistic children. Journal of family research 2007; 3: 697-707.Ghanizadeh A, Alishahi MJ, Ashkani H. Helping families for caring children with autistic spectrum disorders. Arch Iran Med 2009; 12: 478-482.Khoushabi K, Farzad Fard SZ, Kakasoltani B, Pouretemad HR, Nikkhah HR. Coping strategies and stress in mothers with autistic children in comparison with mothers with normal children. Journal of family research 2010; 6: 87-97.Ghobari Bonab B, Estiri Z. A comparative study on personality characteristics and attachment style in mothers of children with and without autism. Research on exceptional children 2006; 6: 787-804.Rajabi Damavandi G, Poushineh K, Ghobari Bonab B. the relationship between personality characteristics and coping strategies in parents of children with ASDs. Research on exceptional children 2009; 9: 133-144.Samadi SA. Parents of children with autism spectrum disorder and children with intellectual disabilities and their stress and general health. Int J Integr Care2009; 9.Khoramabadi R, Pouretemad HR, Tahmasian K,Chimeh N. A comparative study of parental stress in mothers of autistic and non autistic children. Journal of family research 2009; 5: 387-399.59. Poretemad HR, Khoushabi K, Afshari R, Moradi S. Coping strategies and mental health in autistic children mothers. Journal of family research 2006;2: 285-292.Mohammadi A, Pouretemad HR, Khosravi G. Aninitial examination of the effect of guided imagery via music on reduction of stress, depression, and anxiety of mothers with autistic children. Journal of family research 2005; 1: 289-303.Arman S, Zareei N, Farshid nejad AA. Efficacy of group counseling on mothers with autistic children. Research in Behavioral Sciences 2004; 2: 48-52

CHANGE IN FREQUENCY OF ACUTE AND SUBACUTE EFFECTS OF ECSTASY IN A GROUP OF NOVICE USERS AFTER 6 MONTHS OF REGULAR USE

Background: Recent research trends are to specify the relation between patterns of ecstasy use and side effects, possibility of dependency, tolerance and long term neurocognitive damage. The objective of this study was to assess the impact of regular ecstasy use on its acute and subacute effects. Subjects and methods: At the first stage, we recruited 120 subjects. If participants continued regular use of ecstasy in this period, they were asked to participate in the second stage of the research 6 months later. Thirty-five subjects attended the second stage of the study, 5 of which were excluded because they had less than 5 drug experiences during the last 6 months. At last, we recruited 30 novice ecstasy users by means of the snowball technique in Tehran, Iran. The pattern of use and experienced effects of ecstasy was documented at the beginning and after 6 months of regular consumption with a self administered questionnaire. Results: Little or no change was observed in acute effects. Those subacute effects that had considerable increase in frequency were anxiety, depression, aggression, memory impairment, poor concentration and learning problems. Conclusion: Small change in acute effects suggests low possibility of tolerance after at least 6 months of regular use. Our results support long term neurocognitive damage and mood impairment with ecstasy use

Short-term Outcomes of Saffron Supplementation in Patients with Age-related Macular Degeneration: A Double-blind, Placebo-controlled, Randomized Trial

In modern pharmacological medicine, saffron is used for various purposes due to its antioxidant effect. This study evaluated retinal function after treatment with saffron supplementation during a follow-up period of 6 months to provide further insight into the efficacy and safety considerations of this treatment. Sixty patients with wet or dry age-related macular degeneration (AMD) were randomly assigned to receive oral saffron 30 mg/d or placebo supplementation for 6 months. Optical coherence tomography (OCT), electroretinography (ERG), fluorescein angiography, and visual acuity testing were performed at baseline and 3 and 6 months after treatment. The main outcome measures were OCT, ERG amplitude, and implicit time. Six months after treatment, no statistically significant decrease in OCT results was observed between the groups with dry AMD (P = 0.282). However, there was a statistically significant increase in ERG results between the groups at 3 months after treatment (P = 0.027). In addition, there was a significant decrease in OCT results between groups with wet AMD at the follow-up (P = 0.05). Finally, there was a significant increase in ERG findings between the groups with wet AMD at 3 months after treatment (P = 0.01), but these changes decreased at 6 months after treatment (P = 0.213). Daily supplementation with 30 mg of saffron for 6 months may result in a mid-term, significant improvement in retinal function in patients with AMD.Â

Frequency of myasthenic crisis in relation to thymectomy in generalized myasthenia gravis: A 17-year experience

BACKGROUND: Myasthenic crisis is the most serious life-threatening event in generalized myasthenia gravis (MG) patients. The objective of this study was to assess the long-term impact of thymectomy on rate and severity of these attacks in Iranian patients. METHODS: We reviewed the clinical records from 272 myasthenic patients diagnosed and treated in our neurology clinic during 1985 to 2002. Fifty-three patients were excluded because of unconfirmed diagnosis, ocular form of MG, contraindication to surgery, concomitant diseases and loss to follow-up. The Osserman classification was used to assess the initial severity of the disease. Frequency and severity of the attacks were compared between two groups with appropriate statistical tests according to the nature of variables. Multivariate logistic regression analysis was used to assess the predictors of myasthenic crisis in the group of patients without thymoma. RESULTS: 110 patients were in thymectomy group and the other 109 patients were on medical therapy. These two groups had no significant differences with respect to age at onset, gender, Osserman score in baseline and follow up period. 62 patients (28.3% of all 219 patients) had reported 89 attacks of myasthenic crisis. 20 patients of 62 (32%) were in thymectomy group and 42 (68%) were in the other group. There was significant difference between the two groups in number of patients with crisis (P = 0.001; odds ratio = 2.8 with 95% CI of 1.5 to 5.2). In addition, these attacks were more severe in group of non-thymectomized patients as the duration of ICU admission was longer and they needed more ventilatory support during their attacks. Regression model showed thymectomy and lower age at onset as two predictors of decrement in myasthenic crisis rate in non-thymomatous MG patients. CONCLUSIONS: It is suggested that frequency and severity of myasthenic attacks as important endpoints in evaluation of MG patients. Thymectomy seems to have a preventive role on rate and severity of these attacks

Total Antioxidant Capacity and Malondialdehyde in Depressive Rotational Shift Workers

Shift work is associated with sleep deprivation, occupational stress, and increased risk of depression. Depressed patients show increased oxidative stress. During excessive oxidative stress, Malondialdehyde (MDA) increases and total antioxidant capacity (TAC) decreases in body. This cross-sectional study was conducted to determine the serum level of TAC and MDA among depressed rotational shift workers in Shahid Tondooyan Tehran Oil Refinery. 21-item Beck Depression Inventory was used to measure depression level. The level of TAC and MDA was measured by 8 mL fasting blood sample. MDA was determined by thiobarbituric acid reaction. Serum total antioxidants were measured using the ABTS. Results of this study showed that TAC mean and standard deviation concentration was 2.451 (±0.536) mg/dL and MDA was 3.725 (±1.098) mic·mol/L, and mean and standard deviation of depression score and BMI were 14.07 (±3.84) and 24.92 (±3.65) kg/m2, respectively. Depression score had a positive correlation with rotational shift work experience and work experience (r=0.218 and r=0.212), respectively, (P<0.05)

Raloxifene adjunctive therapy for postmenopausal women suffering from chronic schizophrenia: a randomized double-blind and placebo controlled trial

BACKGROUND: Cumulative evidence from epidemiological, preclinical and clinical studies suggests estrogens may have psychoprotective effects in schizophrenic patients. Selective Estrogen Receptor Modulators could have therapeutic benefits in schizophrenia for both sexes without being hazardous to gynecological tissues or having feminizing effects. Few studies have been conducted regarding the effects of raloxifene on postmenopausal women suffering from schizophrenia. We conducted this placebo-controlled trial to compare the add-on effect of raloxifene to risperidone versus risperidone with placebo. METHODS: This was an 8-week, parallel-group, placebo-controlled trial undertaken at two universities affiliated psychiatric Hospitals in Iran. Forty-six postmenopausal women with the definite diagnosis of schizophrenia were enrolled in the study. Patients received risperidone (6 mg/day in 3 divided doses) combined with either placebo (N = 23) or 120 mg/day of raloxifene (N = 23) for 8 weeks. Patients were assessed by a psychiatrist at baseline and at 2 and 8 weeks after the start of medical therapy. Efficacy was defined as the change from baseline to endpoint in score on Positive and Negative Syndrome Scale (PANSS). RESULTS: For PANSS scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.77, p = 0.18]. For positive subscale scores, there was marginal significant interaction between intervention type and time [F (2, 47) = 2.93, p = 0.06] and there was substantial main effect for time [F (2, 47) = 24.39, p = 0.001] within both groups showing reduction in positive subscale scores across the three time periods. In addition, the main effect comparing two types of intervention was significant [F (1, 48) = 3.78, p = 0.02]. On the other hand, for negative subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 1.43, p = 0.23]. For general subscale scores, the main effect comparing two types of intervention was not significant [F (1, 48) = 0.03, p = 0.86]. CONCLUSIONS: According to our findings, raloxifene as an adjunctive treatment to risperidone was only superior in improvement of positive symptoms and it was not effective in treating negative and general psychopathology symptoms. TRIAL REGISTRATION: The trial was registered at the Iranian registry of clinical trials: IRCT201205131556N4

Ritanserin as an adjunct to lithium and haloperidol for the treatment of medication-naive patients with acute mania: a double blind and placebo controlled trial

BACKGROUND: Bipolar disorder is a lifelong episodic condition characterized by mood swings between mania and depression. Several lines of evidence suggest that serotonin is likely to play a pivotal role in the pathophysiology of bipolar disorder. Ritanserin, a 5-HT(2 )receptor antagonist, has been reported to have antipsychotic activity. In this 6-week double blind, placebo controlled study involving moderate to severe manic patients, we assessed the effects of ritanserin plus haloperidol in combination with lithium. METHODS: 45 patients aged between 21–43 were eligible to participate as they met the DSM-IV criteria for a current manic episode, on the basis of a clinical interview by an academician psychiatrist. In addition, a score of at least 20 points on the Young Mania rating Scale was required representing moderate to severe mania. Patients were randomly allocated lithium (1–1.2 mEq/L) + haloperidol (10 mg/day)+ ritanserin (10 mg/day) (Group A) or lithium (1–1.2 mEq/L)+ haloperidol (10 mg/day) + placebo (Group B) for a 6-week, double-blind, placebo-controlled study. Patients were assessed by a third year psychiatry resident at baseline and 3, 7, 14, 21, 28 and 42 days after the medication started. All patients entered the hospital were not previously under any medication. The mean decrease in the Young Mania Rating Scale score from baseline was used as the main outcome measure of response of mania to treatment. The extrapyramidal symptoms were assessed using the Extrapyramidal Symptoms Rating Scale. Side effects were systematically recorded throughout the study and were assessed using a checklist. RESULTS: Young Mania Rating Scale total scores improved with ritanserin. The difference between the two protocols was significant as indicated by the effect of group and the between-subjects factor (F = 5.02, d.f. = 1, P = 0.03). The means Extrapyramidal Symptoms Rating Scale scores for the placebo group were higher than the ritanserin group and the difference was significant in day 42. The difference between the two groups in the frequency of side effects was not significant CONCLUSIONS: The efficacy of ritanserin to obtain a better improvement in patients with mania seems to support the 5-HT hypothesis of bipolar disorder

Cyproheptadine for Prevention of Neuropsychiatric Adverse Effects of Efavirenz: A Randomized Clinical Trial

Cyproheptadine prevention of the neuropsychiatric adverse effects of an antiretroviral regimen including efavirenz has been evaluated in a randomized clinical trial. Twenty-five patients (16 males and 9 females with mean – SD ages of 36 – 9 years) in a cyproheptadine group, and 26 patients (17 males and 9 females with mean – SD ages of 34 – 7 years) in a control group completed the trial. Sexual contact and injection drug use were the main routs of HIV infection in both groups. The patients’ neuropsychiatric adverse effects were evaluated based on the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation, and Somatization Subscale of Symptom Checklist 90 at baseline and 4 weeks after treatment. Cyproheptadine significantly decreased the scores of Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Positive and Negative Syndrome Scale, Beck Depression Scale, Pittsburgh Sleep Quality Inventory, Positive and Negative Suicide Ideation of the patients after 4 weeks in comparison with control group. All of the scores increased in control group following antiretroviral therapy. Although short duration of the patients’ follow-up was a major limitation of the study, the results of the study showed that cyprohepradine is effective in prevention of depression, anxiety, hallucination, aggressive behaviors, emotional withdrawal, poor rapport, poor impulse control, active social avoidance, suicidal ideation, and improved sleep quality of HIV-positive patients after initiation of antiretroviral therapy including efavirenz

Reliability and validity of the Persian version of Food Craving Questionnaire-Trait-Reduced (FCQ-T-r) in overweight and obese women

Introduction: Food Craving Questionnaire (FCQ) is a popular tool in assessing food craving which consisted of a trait (FCQ-T) and state (FCQ-S). The aim of the current study was to provide reliability and validity of the Persian version of FCQ-Trait-reduced (FCQ-T-r 15-items) in overweight and obese women. Material and methods: The subjects were 168 overweight and obese women who were consented to participate. The subjects completed the FCQ-T-r and subsequently, anthropometric, body composition and psychometric assessments performed to assess the inter-correlations and concurrent validity. The confirmatory factor analysis was done to derive the potential factors and internal consistency of the questionnaire was assessed. Two weeks later, FCQ-T-r repeated for 126 subjects to assess test-retest reliability. Results: The confirmatory factor analysis of by varimax rotation, show that three principal components were loaded on expected factors. The Cronbach’s alpha coefficient was 0.90. (0.91, 0.78, and 0.71, for factors). The test–retest analysis shows an acceptable level of reliability ( P=0.001) and Pearson correlation coefficient  of 0.92 between the two administrations. In split-half reliability analysis the Cronbach’s alpha coefficient of the part 1 was 0.80 and for the part 2 was 0.86. The correlation coefficient between part 1 and part 2 was 0.81. Conclusion: This preliminary study provides evidences in favor of reliability and validity of the Persian version of the FCQ-T-r. In general, the results showed a high level of internal consistency for FCQ-T-r, and none of the 15 items had to be deleted to improve α