Publications by authors named "Amirhossein Modabbernia"

54 Publications

Impact of opioid agonist treatment on mental health in patients with opioid use disorder: a systematic review and network meta-analysis of randomized clinical trials.

Am J Drug Alcohol Abuse 2021 05 29;47(3):280-304. Epub 2021 Mar 29.

Institute of Mental Health, Department of Psychiatry, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

: There is a knowledge gap in systematic reviews on the impact of opioid agonist treatments on mental health.: We compared mental health outcomes between different opioid agonist treatments and placebo/waitlist, and between the different opioids themselves.: This meta-analysis of randomized clinical trials (RCTs) was pre-registered at PROSPERO (CRD42018109375). Embase, MEDLINE, PsychInfo, CINAHL Complete, and Web of Science Core Collection were searched from inception to May 2020. RCTs were included if they compared opioid agonists with each other or with placebo/waitlist in the treatment of patients with opioid use disorder and reported at least one mental health outcome after 1-month post-baseline. Studies with psychiatric care, adjunct psychotropic medications, or unbalanced psychosocial services were excluded. The primary outcome was overall mental health symptomatology, e.g. Symptom Checklist 90 total score, between opioids and placebo/waitlist. Random effects models were used for all the meta-analyses.: Nineteen studies were included in the narrative synthesis and 15 in the quantitative synthesis. Hydromorphone, diacetylmorphine (DAM), methadone, slow-release oral morphine, buprenorphine, and placebo/waitlist were among the included interventions. Based on the network meta-analysis for primary outcomes, buprenorphine (SMD (CI95%) = -0.61 (-1.20, -0.11)), DAM (-1.40 (-2.70, -0.23)), and methadone (-1.20 (-2.30, -0.11)) were superior to waitlist/placebo on overall mental health. Further direct pairwise meta-analysis indicated that overall mental health improved more in DAM compared to methadone (-0.23 (-0.34, -0.13)).: Opioid agonist treatments used for the treatment of opioid use disorder improve mental health independent of psychosocial services.
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http://dx.doi.org/10.1080/00952990.2021.1887202DOI Listing
May 2021

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 17. Epub 2021 Feb 17.

Laboratory of Psychiatric Neuroimaging, Departamento e Instituto de Psiquiatria, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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http://dx.doi.org/10.1002/hbm.25364DOI Listing
February 2021

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3-90 years.

Hum Brain Mapp 2021 Feb 11. Epub 2021 Feb 11.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA.

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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http://dx.doi.org/10.1002/hbm.25320DOI Listing
February 2021

Personalized Estimates of Brain Structural Variability in Individuals With Early Psychosis.

Schizophr Bull 2021 Jul;47(4):1029-1038

Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.

Background: Early psychosis in first-episode psychosis (FEP) and clinical high-risk (CHR) individuals has been associated with alterations in mean regional measures of brain morphology. Examination of variability in brain morphology could assist in quantifying the degree of brain structural heterogeneity in clinical relative to healthy control (HC) samples.

Methods: Structural magnetic resonance imaging data were obtained from CHR (n = 71), FEP (n = 72), and HC individuals (n = 55). Regional brain variability in cortical thickness (CT), surface area (SA), and subcortical volume (SV) was assessed with the coefficient of variation (CV). Furthermore, the person-based similarity index (PBSI) was employed to quantify the similarity of CT, SA, and SV profile of each individual to others within the same diagnostic group. Normative modeling of the PBSI-CT, PBSI-SA, and PBSI-SV was used to identify CHR and FEP individuals whose scores deviated markedly from those of the healthy individuals.

Results: There was no effect of diagnosis on the CV for any regional measure (P > .38). CHR and FEP individuals differed significantly from the HC group in terms of PBSI-CT (P < .0001), PBSI-SA (P < .0001), and PBSI-SV (P = .01). In the clinical groups, normative modeling identified 32 (22%) individuals with deviant PBSI-CT, 12 (8.4%) with deviant PBSI-SA, and 21 (15%) with deviant PBSI-SV; differences of small effect size indicated that individuals with deviant PBSI scores had lower IQ and higher psychopathology.

Conclusions: Examination of brain structural variability in early psychosis indicated heterogeneity at the level of individual profiles and encourages further large-scale examination to identify individuals that deviate markedly from normative reference data.
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http://dx.doi.org/10.1093/schbul/sbab005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266574PMC
July 2021

Multivariate Patterns of Brain-Behavior-Environment Associations in the Adolescent Brain and Cognitive Development Study.

Biol Psychiatry 2021 03 24;89(5):510-520. Epub 2020 Aug 24.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Djavad Mowafaghian Centre for Brain Health, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background: Adolescence is a critical developmental stage. A key challenge is to characterize how variation in adolescent brain organization relates to psychosocial and environmental influences.

Methods: We used canonical correlation analysis to discover distinct patterns of covariation between measures of brain organization (brain morphometry, intracortical myelination, white matter integrity, and resting-state functional connectivity) and individual, psychosocial, and environmental factors in a nationally representative U.S. sample of 9623 individuals (aged 9-10 years, 49% female) participating in the Adolescent Brain and Cognitive Development (ABCD) study.

Results: These analyses identified 14 reliable modes of brain-behavior-environment covariation (canonical r = .21 to .49, canonical r = .10 to .39, p < .0001). Across modes, neighborhood environment, parental characteristics, quality of family life, perinatal history, cardiometabolic health, cognition, and psychopathology had the most consistent and replicable associations with multiple measures of brain organization; positive and negative exposures converged to form patterns of psychosocial advantage or adversity. These showed modality-general, respectively positive or negative, associations with brain structure and function with little evidence of regional specificity. Nested within these cross-modal patterns were more specific associations between prefrontal measures of morphometry, intracortical myelination, and functional connectivity with affective psychopathology, cognition, and family environment.

Conclusions: We identified clusters of exposures that showed consistent modality-general associations with global measures of brain organization. These findings underscore the importance of understanding the complex and intertwined influences on brain organization and mental function during development and have the potential to inform public health policies aiming toward interventions to improve mental well-being.
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http://dx.doi.org/10.1016/j.biopsych.2020.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867576PMC
March 2021

Linked patterns of biological and environmental covariation with brain structure in adolescence: a population-based longitudinal study.

Mol Psychiatry 2020 May 22. Epub 2020 May 22.

Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany.

Adolescence is a period of major brain reorganization shaped by biologically timed and by environmental factors. We sought to discover linked patterns of covariation between brain structural development and a wide array of these factors by leveraging data from the IMAGEN study, a longitudinal population-based cohort of adolescents. Brain structural measures and a comprehensive array of non-imaging features (relating to demographic, anthropometric, and psychosocial characteristics) were available on 1476 IMAGEN participants aged 14 years and from a subsample reassessed at age 19 years (n = 714). We applied sparse canonical correlation analyses (sCCA) to the cross-sectional and longitudinal data to extract modes with maximum covariation between neuroimaging and non-imaging measures. Separate sCCAs for cortical thickness, cortical surface area and subcortical volumes confirmed that each imaging phenotype was correlated with non-imaging features (sCCA r range: 0.30-0.65, all P < 0.001). Total intracranial volume and global measures of cortical thickness and surface area had the highest canonical cross-loadings (|ρ| = 0.31-0.61). Age, physical growth and sex had the highest association with adolescent brain structure (|ρ| = 0.24-0.62); at baseline, further significant positive associations were noted for cognitive measures while negative associations were observed at both time points for prenatal parental smoking, life events, and negative affect and substance use in youth (|ρ| = 0.10-0.23). Sex, physical growth and age are the dominant influences on adolescent brain development. We highlight the persistent negative influences of prenatal parental smoking and youth substance use as they are modifiable and of relevance for public health initiatives.
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http://dx.doi.org/10.1038/s41380-020-0757-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981783PMC
May 2020

Parsing out the role of dopamine D4 receptor gene (DRD4) on alcohol-related phenotypes: A meta-analysis and systematic review.

Addict Biol 2020 05 31;25(3):e12770. Epub 2019 May 31.

Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Basic Research and National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Bethesda, MD, USA.

Genetics account for moderate variation of individual differences in developing alcohol use disorder (AUD), but it is unclear which genetic variations contribute to AUD risk. One candidate gene investigated due to its association with AUD is the dopamine D4 receptor gene (DRD4), which contains a 48-base pair variable number tandem repeat (VNTR) in exon 3 of its coding region. To date, no quantitative synthesis of the published literature on the effects of DRD4 VNTR variation on alcohol-related phenotypes has been conducted. MEDLINE, Embase, Web of Science, and PsycInfo were searched for studies that reported on alcohol craving, alcohol consumption, severity of AUD, and case-control (AUD versus no diagnosis of AUD) studies in DRD4L (seven repeats or more) carriers compared with DRD4S (six repeats or less) homozygotes. Random-effects meta-analysis was used for all analyses. A pooled sample size of 655 to 13,360 of 28 studies were included. Compared with DRD4S homozygotes, DRD4L carriers had increased number of drinking days (SMD: 0.205; 95% CI: 0.008 to 0.402), binge drinking days (SMD: 0.217; 95% CI: 0.0532 to 0.380), and severity of AUD (SMD: 0.143; 95% CI: 0.028 to 0.259). There was no difference between DRD4 VNTR genotypes on drinks per drinking day, largest number of drinks per day/occasion, and case-control analysis. It was not possible to conduct a meta-analysis of the craving data, but a systematic review of this literature found mixed results on DRD4 VNTR genotype effect. The present meta-analysis suggests DRD4 VNTR variation may be a risk factor for problematic alcohol use. Our findings are limited, however, by the absence of ancestry data from studies included in our analysis, precluding our ability to adjust for population stratification. Due to the likelihood of type I error in candidate gene approaches, our work highlights the critical need for studies with larger and more inclusive samples that account for sex and genetic ancestry to fully understand this relationship.
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http://dx.doi.org/10.1111/adb.12770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885089PMC
May 2020

Hemorrhage, Seizures, and Dynamic Changes of Familial versus Nonfamilial Cavernous Malformation: Systematic Review and Meta-analysis.

World Neurosurg 2019 Jun 7;126:241-246. Epub 2019 Mar 7.

Division of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Division of Neurosurgery, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science, and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. Electronic address:

Background: Cerebral cavernous malformations (CCMs) may be familial or nonfamilial. This systematic review compared the natural history of CCMs in familial compared with nonfamilial cases.

Methods: We searched MEDLINE, Web of Science, and EMBASE for natural history studies on CCMs up to September 2018. We included studies that followed at least 20 untreated patients. Primary outcomes were hemorrhage, seizures, and neuroimaging changes in familial and nonfamilial cases. Incidence rate per person-year (PY) or lesion-year (LY) of follow-up were used to pool the data using fixed-effects or random-effects models. We used the incidence rate ratio for comparison.

Results: We could not compare hemorrhage rates between familial and nonfamilial cases mainly owing to mixtures of subgroups of patients. The seizure rate was similar in familial and nonfamilial cases with pooled incidence rate of 1.5%/PY (95% confidence interval 1.1%-2.2%). The reseizure rate was higher than the seizure rate (P < 0.001). New lesion development was higher in familial cases (32.1%/PY vs. 0.7%/PY, P < 0.001). Signal change on neuroimaging ranged from 0.2%/LY to 2.4%/LY in familial cases. In familial cases, incidence rate of size change was 8%/PY (95% confidence interval 5.2%-12.2%) and 1.1%/LY (95% confidence interval 0.6%-1.6%).

Conclusions: Familial CCMs show higher dynamic changes than nonfamilial cases. However, the presence of actual dynamic changes needs further assessment in nonfamilial cases. CCMs demonstrate a low incidence of seizure. First-time seizure increases the chance of recurrent seizure. Seizure rate based on the location and type of the lesion should be investigated further.
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http://dx.doi.org/10.1016/j.wneu.2019.02.115DOI Listing
June 2019

Parental Age and Differential Estimates of Risk for Neuropsychiatric Disorders: Findings From the Danish Birth Cohort.

J Am Acad Child Adolesc Psychiatry 2019 06 27;58(6):618-627. Epub 2019 Feb 27.

Icahn School of Medicine at Mount Sinai, New York, NY; Icahn School of Medicine at Mount Sinai, Division of Tics, OCD, and Related Disorders; Friedman Brain Institute and Mindich Child Health and Development Institute. Electronic address:

Objective: Parental age at birth has been shown to affect the rates of a range of neurodevelopmental disorders, but the understanding of the mechanisms through which it mediates different outcomes is still lacking. A population-based cohort was used to assess differential effects of parental age on estimates of risk across pediatric-onset neuropsychiatric disorders: autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and Tourette's disorder/chronic tic disorder (TD/CT).

Method: The study cohort included all singleton births in Denmark from 1980 through 2007 with full information on parental ages (N = 1,490,745) and was followed through December 31, 2013. Cases of ASD, ADHD, OCD, and TD/CT were identified in the Danish Psychiatric Central Register and the National Patient Register. Associations with parental age were modeled using a stratified Cox regression, allowing for changes in baseline diagnostic rates across time.

Results: Younger parental age was significantly associated with increased estimates of risk for ADHD and TD/CT, whereas older parental age was associated with ASD and OCD. Except for OCD, no evidence for differential effects of parental ages on male versus female offspring was observed.

Conclusion: This study provides novel evidence for the association between age at parenthood and TD/CT and OCD and for the first time shows in a population-based sample that parental age confers differential risk rates for pediatric-onset psychiatric disorders. These results are consistent with a model of shared and unshared risk architecture for pediatric-onset neuropsychiatric conditions, highlighting unique contributions of maternal and paternal ages.
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http://dx.doi.org/10.1016/j.jaac.2018.09.447DOI Listing
June 2019

Apgar score and risk of autism.

Eur J Epidemiol 2019 Feb 5;34(2):105-114. Epub 2018 Oct 5.

Department of Psychiatry and Seaver Autism Center, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy PLC, New York, NY, 10029, USA.

Low Apgar score has been associated with higher risk for several neurological and psychiatric disorders, including cerebral palsy and intellectual disability. Studies of the association between Apgar score and autism spectrum disorder (ASD) have been inconsistent. We aimed to investigate (1) the association between low Apgar score at 5 min and risk for ASD, and (2) the modifying effects of gestational age and sex on this association in the largest multinational database of ASD. We included prospective data from 5.5 million individuals and over 33,000 cases of ASD from Norway, Sweden, Denmark and Western Australia who were born between 1984 and 2007. We calculated crude and adjusted risk ratios (RR) with 95% confidence intervals (95% CIs) for the associations between low Apgar score and ASD. All analyses for ASD were repeated for autistic disorder (AD). We used interaction terms and stratified analysis to investigate the effects of sex, gestational age, and birth weight on the association. In fully adjusted models, low Apgar scores (1-3) (RR, 1.42; 95% CI, 1.16-1.74), and intermediate Apgar scores (4-6) (RR, 1.50; 95% CI, 1.36-1.65) were associated with a higher RR of ASD than optimal Apgar score (7-10). The point estimates for low (RR, 1.88; 95% CI, 1.41-2.51) and intermediate Apgar score (RR, 1.54; 95% CI, 1.32-1.81) were larger for AD than for ASD. This study suggests that low Apgar score is associated with higher risk of ASD, and in particular AD. We did not observe any major modifying effects of gestational age and sex, although there seems to be substantial confounding by gestational age and birth weight on the observed association.
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http://dx.doi.org/10.1007/s10654-018-0445-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373297PMC
February 2019

Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses.

Mol Autism 2017 17;8:13. Epub 2017 Mar 17.

Department of Psychiatry and Seaver Autism Center, Icahn School of Medicine at Mount Sinai, New York, USA.

Background: According to recent evidence, up to 40-50% of variance in autism spectrum disorder (ASD) liability might be determined by environmental factors. In the present paper, we conducted a review of systematic reviews and meta-analyses of environmental risk factors for ASD. We assessed each review for quality of evidence and provided a brief overview of putative mechanisms of environmental risk factors for ASD.

Findings: Current evidence suggests that several environmental factors including vaccination, maternal smoking, thimerosal exposure, and most likely assisted reproductive technologies are unrelated to risk of ASD. On the contrary, advanced parental age is associated with higher risk of ASD. Birth complications that are associated with trauma or ischemia and hypoxia have also shown strong links to ASD, whereas other pregnancy-related factors such as maternal obesity, maternal diabetes, and caesarian section have shown a less strong (but significant) association with risk of ASD. The reviews on nutritional elements have been inconclusive about the detrimental effects of deficiency in folic acid and omega 3, but vitamin D seems to be deficient in patients with ASD. The studies on toxic elements have been largely limited by their design, but there is enough evidence for the association between some heavy metals (most important inorganic mercury and lead) and ASD that warrants further investigation. Mechanisms of the association between environmental factors and ASD are debated but might include non-causative association (including confounding), gene-related effect, oxidative stress, inflammation, hypoxia/ischemia, endocrine disruption, neurotransmitter alterations, and interference with signaling pathways.

Conclusions: Compared to genetic studies of ASD, studies of environmental risk factors are in their infancy and have significant methodological limitations. Future studies of ASD risk factors would benefit from a developmental psychopathology approach, prospective design, precise exposure measurement, reliable timing of exposure in relation to critical developmental periods and should take into account the dynamic interplay between gene and environment by using genetically informed designs.
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http://dx.doi.org/10.1186/s13229-017-0121-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356236PMC
May 2017

Prenatal Maternal Smoking and Increased Risk for Tourette Syndrome and Chronic Tic Disorders.

J Am Acad Child Adolesc Psychiatry 2016 09 21;55(9):784-91. Epub 2016 Jul 21.

Division of Tics, Obsessive-Compulsive Disorder (OCD) and Related Disorders, Icahn School of Medicine at Mount Sinai, New York; Friedman Brain Institute and Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai. Electronic address:

Objective: We assessed the role of prenatal maternal smoking in risk for Tourette syndrome and chronic tic disorder (TS/CT) and pediatric-onset obsessive-compulsive disorder (OCD).

Method: In an analysis of 73,073 singleton pregnancies from the Danish National Birth Cohort, we calculated incidence rates (IR) per 1,000 person-year for TS/CT and OCD. We then determined crude and adjusted hazard ratios and 95% CIs associated with prenatal maternal smoking, considering smoking as a dichotomous (yes/no) variable or a stratified variable (no smoking, light smoking, and heavy smoking [≥10 cigarettes/day]). Additional analyses examined the effect of maternal smoking on risk for TS/CT with other comorbid psychiatric conditions.

Results: In final adjusted analyses, heavy smoking was associated with a 66% increased risk for TS/CT (adjusted hazard ratio = 1.66, 95% CI = 1.17-2.35). In addition, heavy smoking was associated with a 2-fold increased risk for TS/CT with comorbid attention-deficit/hyperactivity disorder (ADHD), and both light and heavy smoking were associated with a more than 2-fold increased risk for TS/CT with any non-ADHD psychiatric comorbidity. Our parallel analyses of pediatric-onset OCD were likely underpowered but showed similar relationships.

Conclusion: Prenatal maternal smoking was associated with increased risk for TS/CT as well as TS/CT with comorbid psychiatric conditions, even after adjustment for several important variables, including maternal psychiatric history, socioeconomic status, and partner smoking. Our findings point to a pathway linking prenatal tobacco exposure and altered brain development to TS/CT.
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http://dx.doi.org/10.1016/j.jaac.2016.06.010DOI Listing
September 2016

Attentional bias towards and away from fearful faces is modulated by developmental amygdala damage.

Cortex 2016 08 22;81:24-34. Epub 2016 Apr 22.

UCL Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Wellcome Trust Centre for Imaging Neuroscience, University College London, London, United Kingdom.

The amygdala is believed to play a major role in orienting attention towards threat-related stimuli. However, behavioral studies on amygdala-damaged patients have given inconsistent results-variously reporting decreased, persisted, and increased attention towards threat. Here we aimed to characterize the impact of developmental amygdala damage on emotion perception and the nature and time-course of spatial attentional bias towards fearful faces. We investigated SF, a 14-year-old with selective bilateral amygdala damage due to Urbach-Wiethe disease (UWD), and ten healthy controls. Participants completed a fear sensitivity questionnaire, facial expression classification task, and dot-probe task with fearful or neutral faces for spatial cueing. Three cue durations were used to assess the time-course of attentional bias. SF expressed significantly lower fear sensitivity, and showed a selective impairment in classifying fearful facial expressions. Despite this impairment in fear recognition, very brief (100 msec) fearful cues could orient SF's spatial attention. In healthy controls, the attentional bias emerged later and persisted longer. SF's attentional bias was due solely to facilitated engagement to fear, while controls showed the typical phenomenon of difficulty in disengaging from fear. Our study is the first to demonstrate the separable effects of amygdala damage on engagement and disengagement of spatial attention. The findings indicate that multiple mechanisms contribute in biasing attention towards fear, which vary in their timing and dependence on amygdala integrity. It seems that the amygdala is not essential for rapid attention to emotion, but probably has a role in assessment of biological relevance.
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http://dx.doi.org/10.1016/j.cortex.2016.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4962776PMC
August 2016

Natural history of cavernous malformation: Systematic review and meta-analysis of 25 studies.

Neurology 2016 May 22;86(21):1984-91. Epub 2016 Apr 22.

From the Division of Neurosurgery (S.T.), University of Toronto, Canada; Department of Psychiatry (A.M.), Icahn School of Medicine, Mount Sinai Hospital, New York, NY; Department of Neurosurgery (S.A.-H.), University of Illinois at Chicago; Neurosurgical Service (F.G.B.), Massachusetts General Hospital, Harvard Medical School, Boston; Division of Neurosurgery (R.L.M.), St. Michael's Hospital, Labatt Family Centre of Excellence in Brain Injury and Trauma Research, Keenan Research Centre for Biomedical Science; and the Department of Surgery (R.L.M.), Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Canada.

Objective: We pooled the results of studies on natural history of cavernous malformations (CM) to calculate point estimates and investigate main sources of heterogeneity.

Methods: We searched MEDLINE, EMBASE, and ISI Web of Science for relevant studies published before May 2015. We used fixed or random effects models and meta-regression to pool the data.

Results: Twenty-five studies were entered into the meta-analysis (90-1,295 patients depending on the analysis). Bleeding was defined as symptomatic hemorrhage plus radiologic evidence of hemorrhage. Sources of heterogeneity were identified as mixture of hemorrhage and rehemorrhage, mixture of rehemorrhage before and after 2 years of first bleeding, brainstem vs other locations, and calculation method. The rehemorrhage rate was higher than the hemorrhage rate (incidence rate ratio 16.5, p < 0.001, 95% confidence interval [CI] 9.7-28.0). Rehemorrhage within 2 years of the first hemorrhage was higher than after that (incidence rate ratio 1.8, p = 0.042, 95% CI 1.5-2.0). In two metaregression models, rough estimate of the annual incidence rate of hemorrhage was 0.3% (95% CI 0.1%-0.5%) and 2.8% (2.5%-3.3%) per person year in nonbrainstem and brainstem lesions and rough estimate of annual rehemorrhage rate per person year was 6.3% (3%-13.2%) and 32.3% (19.8%-52.7%) in nonbrainstem and brainstem lesions. Median time to rehemorrhage was 10.5 months. Posthemorrhage full recovery was 38.8%/person-year (28.7%-48.8%). Posthemorrhage full recovery or minimal disability was 79.5%/person-year (74.3%-84.8%). Mortality after bleeding was 2.2%.

Conclusions: The incidence of symptomatic hemorrhage or rehemorrhage is higher in brainstem lesions. First symptomatic hemorrhage increases the chance of symptomatic rehemorrhage, which decreases after 2 years.
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http://dx.doi.org/10.1212/WNL.0000000000002701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4887121PMC
May 2016

Environmental exposure to metals, neurodevelopment, and psychosis.

Curr Opin Pediatr 2016 Apr;28(2):243-9

aDepartment of Psychiatry bSeaver Center for Autism Research and Treatment cDepartment of Preventive Medicine dFriedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York City, New York, USA.

Purpose Of Review: This article presents a new hypothesis about the possible relation between early life exposure to metals and psychosis. We review limitations of available research, and discuss novel approaches to overcome previous methodological barriers.

Recent Findings: Mechanistic studies suggest a possible association between excess lead, manganese, cadmium, arsenic, or copper, and zinc deficiency, and several biochemical disturbances related to psychosis, such as altered neurotransmitters levels, excitotoxicity, and inflammation. Furthermore, studies suggest that some metals (lead, manganese, cadmium excess, and zinc deficiency) are associated with schizophrenia or psychosis-related phenotype. However, previous studies had multiple methodological limitations. Importantly, metal exposure was often measured after disease development and seldom determined during critical developmental periods. Most studies fell short of depicting the exact timing of exposure and the change in exposure over time. Here, we propose several methods to overcome these methodological limitations.

Summary: There is a plausible role of early life exposure to metals in the cause of psychosis. Owing to methodological limitations in exposure measurement, this has not been well characterized. Considering the wide exposure to metals and the high cost of psychosis to society, this hypothesis should be rigorously examined.
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http://dx.doi.org/10.1097/MOP.0000000000000332DOI Listing
April 2016

Impaired Gas Exchange at Birth and Risk of Intellectual Disability and Autism: A Meta-analysis.

J Autism Dev Disord 2016 May;46(5):1847-59

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY, USA.

We conducted meta-analyses of 67 studies on the association between neonatal proxies of impaired gas exchange and intellectual disability (ID) or autism spectrum disorders (ASD). Neonatal acidosis was associated with an odds ratio (OR) of 3.55 [95 % confidence interval (95 % CI) 2.23-5.49] for ID and an OR of 1.10 (95 % CI 0.91-1.31) for ASD. Children with a 5-min Apgar score of <7 had an OR of 5.39 (95 % CI 3.84-7.55) for ID and an OR of 1.67 (95 % CI 1.34-2.09) for ASD. O2 treatment was associated with an OR of 4.32 (95 % CI 3.23-5.78) for ID and an OR of 2.02 (95 % CI 1.45 to 2.83) for ASD. Our meta-analysis demonstrates an increased risk of ID and (to a lesser extent) ASD in children with neonatal hypoxia. Moreover, our findings raise the possibility that concomitant ID might account for the observed association between the gas exchange proxies and ASD.
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http://dx.doi.org/10.1007/s10803-016-2717-5DOI Listing
May 2016

Quality of life in Iranian patients with bipolar disorder: a psychometric study of the Persian Brief Quality of Life in Bipolar Disorder (QoL.BD).

Qual Life Res 2016 07 29;25(7):1835-44. Epub 2015 Dec 29.

Social Determinants of Health Research Center, Qazvin University of Medical Sciences, Shahid Bahounar BLV, Qazvin, 3419759811, Iran.

Purpose: To assess the reliability, validity, and factor structure of the Persian Brief Quality of Life in Bipolar Disorder (QoL.BD) in Iranian patients with bipolar disorder (BD).

Methods: After translation and cross-cultural adaptation of the Brief QoL.BD, we administered the questionnaire to 184 patients diagnosed with BD. To determine factor structure, we performed both exploratory and confirmatory factor analyses. To investigate the reliability, we assessed internal consistency, reproducibility and agreement. Construct validity was assessed by calculating correlations between the Brief QoL.BD and the Short Form-36 (SF-36), Positive And Negative Affect Schedule (PANAS), Hamilton Depression Rating Scale, Young Mania Rating Scale (YMRS) and Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). We also investigated gender differences in interpretations of QoL.BD items.

Results: The results obtained from reliability analysis confirmed internal consistency (Cronbach's alpha was 0.87 and 0.89 for two assessments) and reproducibility and agreement (the intraclass correlation coefficient ranged between 0.74 and 0.94). Validity analyses showed that the items loaded on a single-factor structure. The inter-item correlations varied from 0.31 to 0.68. Significantly lower scores on the Brief QoL.BD were observed in people diagnosed with BD I compared to BD II. Significant correlations were observed between the Brief QoL.BD and SF-36 summary measures, HAMD, YMRS, Q-LES-Q-SF and PANAS subscales. Items in the Brief QoL.BD were interpreted similarly by men and women.

Conclusions: The Brief Persian QoL.BD is a psychometrically sound measure with acceptable validity and reliability and provides a rapid assessment tool for measuring QoL in patients with BD.
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http://dx.doi.org/10.1007/s11136-015-1223-0DOI Listing
July 2016

Memantine for Prophylactic Treatment of Migraine Without Aura: A Randomized Double-Blind Placebo-Controlled Study.

Headache 2016 Jan 6;56(1):95-103. Epub 2015 Dec 6.

Iranian Center of Neurological Research, Tehran University of Medical Sciences, Tehran, Iran.

Background: Uncontrolled studies in human have suggested that memantine might be a suitable option for migraine prophylaxis.

Objective: To assess the efficacy and tolerability of memantine for migraine prophylaxis.

Methods: This was a 12-week randomized double-blind placebo-controlled parallel-group study. Sixty patients with migraine without aura were randomized using a computer-generated list to receive memantine (10 mg/day) or placebo for 12 weeks. The primary outcome was the difference in change from baseline in the monthly attack frequency at week 12 between the two groups (using migraine diary). Secondary efficacy measures were assessed using several clinical, functional, and psychological instruments. We performed both complete case (CC) and intention-to-treat analyses (ITT).

Results: Twenty-five patients in the memantine group and 27 patients in the placebo group completed the study. Patients in the memantine group showed significantly greater reduction (mean change; 3.4; 95%CI, 2.3-4.4) in the monthly attack frequency than the placebo group (mean change, 1.0; 95%CI, 0.3-1.7) (mean difference [MD], 2.3; 95%CI, 1.1-3.5, P < .001). Both CC (MD, 4.9; 95%CI, 2.6-7.2 days), and ITT analyses (MD, 5.2; 95%CI, 2.0-8.5) showed significantly higher reduction in the mean number of migraine days in the memantine group than the placebo group (P < .01). Patients in the memantine group experienced greater reduction in the number of work absence days, severity, and disability score than the patients in the placebo group in both ITT and CC analyses. Changes in quality of life, sleep, depression, and anxiety did not differ between the two groups. Three patients in the memantine group complained of sedation, mild vertigo and nausea, and drowsiness. In the placebo group, one patient complained of nausea and another patient discontinued treatment after 2 weeks due to vertigo.

Conclusion: Memantine might be a tolerable and efficacious option for prophylaxis in patients with migraine without aura. Tolerability, short duration required for titration, and safety profile in pregnancy might give memantine an advantage over other antimigraine medications. The study was registered in the Iranian Registry of Clinical Trials (Registration number: IRCT2013120115616N1).
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http://dx.doi.org/10.1111/head.12732DOI Listing
January 2016

Granulocyte colony-stimulating factor for amyotrophic lateral sclerosis: a randomized, double-blind, placebo-controlled study of Iranian patients.

J Clin Neurol 2015 Apr;11(2):164-71

Iranian Center of Neurological Research, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background And Purpose: The aim of this study was to determine the efficacy and tolerability of granulocyte colony-stimulating factor (G-CSF) in subjects with amyotrophic lateral sclerosis (ALS).

Methods: Forty subjects with ALS were randomly assigned to two groups, which received either subcutaneous G-CSF (5 μg/kg/q12h) or placebo for 5 days. The subjects were then followed up for 3 months using the ALS Functional Rating Scale-Revised (ALSFRS-R), manual muscle testing, ALS Assessment Questionnaire-40, and nerve conduction studies. CD34+/CD133+ cell count and monocyte chemoattractant protein-1 (MCP-1) levels were evaluated at baseline.

Results: The rate of disease progression did not differ significantly between the two groups. The reduction in ALSFRS-R scores was greater in female subjects in the G-CSF group than in their counterparts in the placebo group. There was a trend toward a positive correlation between baseline CSF MCP-1 levels and the change in ALSFRS-R scores in both groups (Spearman's ρ=0.370, p=0.070).

Conclusions: With the protocol implemented in this study, G-CSF is not a promising option for the treatment of ALS. Furthermore, it may accelerate disease progression in females.
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http://dx.doi.org/10.3988/jcn.2015.11.2.164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4387482PMC
April 2015

Melatonin for prevention of metabolic side-effects of olanzapine in patients with first-episode schizophrenia: randomized double-blind placebo-controlled study.

J Psychiatr Res 2014 Jun 24;53:133-40. Epub 2014 Feb 24.

Department of Psychiatry, Shafa Hospital, Guilan University of Medical Sciences, Rasht, Iran. Electronic address:

Unlabelled: We aimed to determine the efficacy of melatonin 3 mg/day in prevention of olanzapine-induced metabolic side-effects. In a randomized double-blind placebo-controlled study, 48 patients with first-episode schizophrenia who were eligible for olanzapine treatment, were randomly assigned to olanzapine plus either melatonin 3 mg/day or matched placebo for eight weeks. Anthropometric and metabolic parameters as well as psychiatric symptoms using The Positive and Negative Syndrome Scale (PANSS) were assessed at baseline, week 4, and 8. Primary outcome measure was the change from baseline in weight at week 8. Data were analyzed using t-test, Mann-Whitney U test, and mixed-effects model. Thirty-six patients had at least one post-baseline measurement. At week eight, melatonin was associated with significantly less weight gain [mean difference (MD) = 3.2 kg, P = 0.023], increase in waist circumference [MD = 2.83 cm, P = 0.041] and triglyceride concentration [MD = 62 mg/dl, P = 0.090 (nearly significant)] than the placebo. Changes in cholesterol, insulin, and blood sugar concentrations did not differ significantly between the two groups. Patients in the melatonin group experienced significantly more reduction in their PANSS scores [MD = 12.9 points, P = 0.014] than the placebo group. No serious adverse events were reported. To summarize, in patients treated with olanzapine, short-term melatonin treatment attenuates weight gain, abdominal obesity, and hypertriglyceridemia. It might also provide additional benefit for treatment of psychosis. The study was registered in the ClinicalTrials.gov (

Registration Number: NCT01593774).
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http://dx.doi.org/10.1016/j.jpsychires.2014.02.013DOI Listing
June 2014

Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

Psychiatry Res 2014 Mar 9;215(3):540-6. Epub 2014 Jan 9.

Psychiatric Research Centre, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran 13337, Iran. Electronic address:

The objective of this study was to assess the efficacy and tolerability of minocycline add-on to risperidone in treatment of negative symptoms of patients with chronic schizophrenia. In a randomized double-blind placebo-controlled study, 40 patients with chronic schizophrenia who were stabilized on risperidone for a minimum duration of eight weeks were recruited. The patients were randomly assigned to minocycline (titrated up to 200 mg/day) or placebo in addition to risperidone (maximum dose of 6 mg/day) for eight weeks. Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale, and Extrapyramidal Syndrome Rating Scale were used. Thirty-eight patients completed the study. Significant time × treatment interaction for negative [F(2.254,85.638)=59.046, P<0.001] general psychopathology [F(1.703,64.700)=6.819, P=0.001], and positive subscales [F(1.655,62.878)=5.193, P=0.012] as well as total PANSS scores [F(1.677,63.720)=28.420, P<0.001] were observed. The strongest predictors for change in negative symptoms were the treatment group (β=-0.94, t=-10.59, P<0.001) followed by the change in PANSS positive subscale (β=-0.185, t=-2.075, P=0.045). Side effect profiles of the two treatment regimens were not significantly different. Minocycline seems to be an efficacious and tolerable short-term add-on to risperidone for treatment of negative and general psychopathology symptoms of schizophrenia.
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http://dx.doi.org/10.1016/j.psychres.2013.12.051DOI Listing
March 2014

Aspirin for treatment of lithium-associated sexual dysfunction in men: randomized double-blind placebo-controlled study.

Bipolar Disord 2013 Sep 8;15(6):650-6. Epub 2013 Aug 8.

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: The aim of the present study was to assess the effect of aspirin on lithium-related sexual dysfunction in men with stable bipolar affective disorder (BAD).

Methods: In a randomized, double-blind, placebo-controlled study, 32 men with stable BAD who had been on lithium maintenance therapy randomly received aspirin (240 mg/day) or placebo for six weeks. The International Index for Erectile Function (IIEF) was used to assess sexual symptoms at baseline, Week 3, and Week 6. Depressive and mania symptoms and plasma lithium concentrations were assessed at baseline and Week 6. Side effects were assessed using a checklist.

Results: Thirty patients (15/group) completed the study. Baseline and endpoint lithium concentrations and mania and depressive symptoms did not differ significantly between the two groups. Significant effects of time × treatment interaction were observed for total score [Greenhouse-Geisser: F(1.410,39.466) = 6.084, p = 0.010] and erectile function [Greenhouse-Geisser: F(1.629,45.602) = 7.250, p = 0.003]. By Week 6, patients in the aspirin group showed significantly greater improvement in the total (63.9% improvement from the baseline) and erectile function domain (85.4% improvement from the baseline) scores than the placebo group (14.4% and 19.7% improvement from the baseline, p-values = 0.002 and 0.001, respectively). By Week 6, 12 (80%) patients in the aspirin group and three (20%) patients in the placebo group met the criteria of minimal clinically important change [χ(2) (1) = 10.800, p = 0.001]. Other IIEF domains also showed significant improvement at the end of the trial. The frequency of side effects was similar between the two groups.

Conclusion: Aspirin effectively improves lithium-related sexual dysfunction in men with stable BAD.
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http://dx.doi.org/10.1111/bdi.12108DOI Listing
September 2013

Riluzole as an adjunctive therapy to risperidone for the treatment of irritability in children with autistic disorder: a double-blind, placebo-controlled, randomized trial.

Paediatr Drugs 2013 Dec;15(6):505-14

Research Center for Behavioral Disorders and Substance Abuse, Hamadan University of Medical Sciences, Hamadan, Iran.

Background: A hyperglutamatergic state has been shown to play a possible role in the pathophysiology of autistic disorders. Riluzole is a glutamate-modulating agent with neuroprotective properties, which has been shown to have positive effects in many neuropsychiatric disorders.

Objective: The aim of this study was to assess the efficacy and tolerability of riluzole as an adjunctive to risperidone in the treatment of irritability in autistic children who were not optimally responding to previous medications.

Study Design: This was a 10-week, randomized, double-blind, parallel-group, placebo-controlled trial.

Participants: The study enrolled male and female outpatients aged 5-12 years with a diagnosis of autistic disorder based on the DSM-IV-TR criteria and a score of ≥12 on the Aberrant Behavior Checklist-Community (ABC-C) irritability subscale who had discontinued other medications because of a lack of efficacy.

Interventions: Subjects received riluzole (titrated to 50 or 100 mg/day based on bodyweight) or placebo in addition to risperidone (titrated up to 2 or 3 mg/day based on bodyweight) for 10 weeks.

Outcome: Patients were assessed at baseline, week 5, and week 10. The primary outcome measure was the difference in the change in the ABC-C irritability subscale score from baseline to week 10 between the two groups. We also compared changes in other ABC-C subscale scores and Clinical Global Impressions-Improvement (CGI-I) scale scores between the two groups.

Results: Forty-nine patients were enrolled in the study, and forty children completed the trial (dropouts: placebo = 4, riluzole = 5). A significantly greater improvement in the study primary outcome (the ABC-C irritability subscale score) was achieved by the riluzole-treated children compared with the placebo group (P = 0.03). Patients in the riluzole group also showed significantly greater improvement on the lethargy/social withdrawal (P = 0.02), stereotypic behavior (P = 0.03), and hyperactivity/non-compliance subscales (P = 0.005), but not on the inappropriate speech subscale (P = 0.20) than patients in the placebo group. Eleven patients in the riluzole group and five patients in the placebo group were classified as responders based on their CGI-I scores [χ(2)(1) = 3.750, P = 0.05]. Children in the riluzole group experienced significantly more increases in their appetite and bodyweight than children in the placebo group by the end of the study.

Conclusion: Riluzole add-on therapy shows several therapeutic outcomes, particularly for improving irritability, in children with autism. However, its add-on to risperidone also results in significantly increased appetite and weight gain.
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http://dx.doi.org/10.1007/s40272-013-0036-2DOI Listing
December 2013

Memantine add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized, double-blind, placebo-controlled study.

J Clin Psychopharmacol 2013 Jun;33(3):336-42

Department of Psychiatry, Kurdistan University of Medical Sciences, Sanandaj, Iran.

We aimed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia. In a double-blind placebo-controlled clinical trial, 40 patients with schizophrenia (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were stabilized on risperidone for a minimum of 8 weeks were randomized to either memantine (20 mg) or placebo in addition to risperidone, 6 mg/d, for eight weeks. Assessment was done using the Positive and Negative Syndrome Scale at baseline, week 4, and week 8. The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms, respectively. All 40 patients had at least one postbaseline measurement, and 38 patients completed the trial. Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point (P < 0.001). The same effect was observed for the total score (P < 0.001) and the general psychopathology subscale score (P = 0.002). There was no significant difference in reduction of positive symptoms score between the 2 groups (P = 0.757). Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups. Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia.
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http://dx.doi.org/10.1097/JCP.0b013e31828b50a7DOI Listing
June 2013

Neuropsychiatric and psychosocial issues of patients with hepatitis C infection: a selective literature review.

Hepat Mon 2013 Jan 7;13(1):e8340. Epub 2013 Jan 7.

Digestive Disease Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, IR Iran ; Psychiatric Research Centre, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, IR Iran.

Context: We briefly reviewed the evidence on the association of hepatitis C (HCV) infection with several aspects of mental and psychosocial health.

Evidence Acquisition: Medline was searched with appropriate keywords. The primary sources were the systematic reviews. If systematic reviews were not available for a subject, then the most relevant and methodologically sound original studies were selected.

Results: HCV infection is associated with poorer health-related quality of life, and physical, mental, and social health. A part of impaired health of these patients is related to cirrhosis, intravenous drug use, co morbid psychiatric disorders, stigmatization, poor social support, alcohol abuse, and interferon treatment. However, HCV itself is also associated with poorer health status particularly in the physical and cognitive domains, which might be related to brain alterations induced by the virus. Interferon treatment is an important cause of depression in HCV patients and sometimes is associated with irritability, manic episode, or acute confusional state. Social health of HCV patients is significantly impaired by stigmatization, poor social support, psychiatric comorbidties, and impaired coping. Psychosocial impairment of HCV patients significantly impairs their treatment adherence. A supportive and nonjudgmental multidisciplinary team is required for optimal management of these patients.

Conclusions: Patients with HCV infection had complex neuropsychiatric and psychosocial problems. These problems are challenges for management of HCV infection, affect the patient's care significantly, and might alter the course of the disease. A multidisciplinary approach, a supportive environment, and a nonjudgmental healthcare team are required for optimal medical and psychosocial management of patients with HCV.
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http://dx.doi.org/10.5812/hepatmon.8340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3582302PMC
January 2013

Saffron, passionflower, valerian and sage for mental health.

Psychiatr Clin North Am 2013 Mar;36(1):85-91

Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran 13337, Iran.

Many cultures have developed folk herbal remedies to treat symptoms of mental illness. An evidence-based view is now being developed for some of these so-called alternative herbal treatments. This article discusses clinically relevant scientific information on medicinal extracts of 4 herbs: saffron, passionflower, valerian, and sage.
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http://dx.doi.org/10.1016/j.psc.2012.12.007DOI Listing
March 2013

A placebo-controlled study of tropisetron added to risperidone for the treatment of negative symptoms in chronic and stable schizophrenia.

Psychopharmacology (Berl) 2013 Aug 21;228(4):595-602. Epub 2013 Mar 21.

Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran, 13337, Iran.

Rational: A growing body of evidence illustrates that 5-HT3 receptor antagonist drugs may be of benefit in the treatment of negative symptoms in schizophrenia.

Objective: The objective of this study was to assess the efficacy and tolerability of tropisetron add-on to risperidone on negative symptoms in patients with chronic stable schizophrenia.

Methods: In a double-blind, placebo-controlled 8-week trial, 40 patients with chronic schizophrenia who were stabilized on risperidone were randomized into tropisetron or placebo add-on groups. Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) every 2 weeks. Furthermore, extrapyramidal and depressive symptoms as well as side effects were assessed. The primary outcome measure was the difference in change from baseline of negative subscale scores between the two groups at week 8.

Results: Tropisetron resulted in greater improvement of the total PANSS scores [F(1.860,70.699) = 37.366, p < 0.001] as well as negative scores [F(2.439,92.675) = 16.623, p < 0.001] and general psychopathology [F(1.767,67.158) = 4.602, p = 0.017], but not positive subscale scores [F(1.348, 51.218) = 0.048, p = 0.893] compared to placebo. In a multiple regression analysis controlling for positive, extrapyramidal, and depressive symptoms, treatment group (standardized β = -0.640) significantly predicted changes in primary negative symptoms. The side effect profile did not differ significantly between the two groups.

Conclusion: Tropisetron add-on to risperidone improves the primary negative symptoms of patients with chronic stable schizophrenia.
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http://dx.doi.org/10.1007/s00213-013-3064-2DOI Listing
August 2013

Transient elastography in hepatitis C virus-infected patients with beta-thalassemia for assessment of fibrosis.

Hepatol Res 2013 Dec 12;43(12):1276-83. Epub 2013 Mar 12.

Digestive Diseases Research Institute, Shariati Hospital, Tehran, Iran.

Aim: We sought to evaluate the performance of transient elastography (TE) for the assessment of liver fibrosis in chronic hepatitis C (CHC) patients with beta-thalassemia.

Methods: Seventy-six CHC patients with beta-thalassemia underwent TE, liver biopsy, T2 -weighted magnetic resonance imaging (MRI) for the assessment of liver iron content (LIC) and laboratory evaluation. The accuracy of TE and its correlation with the other variables was assessed.

Results: TE values increased proportional to fibrosis stage (r = 0.404, P < 0.001), but was independent of T2 -weighted MRI-LIC (r = 0.064, P = 0.581). In multivariate analysis, fibrosis stage was still associated with the log-transformed TE score(standardized β = 0.42 for F4 stage of METAVIR, P = 0.001). No correlation was noted between LIC and TE score (standardized β = 0.064, P = 0.512). The area under the receiver operating characteristic curve for prediction of cirrhosis was 80% (95% confidence interval, 59-100%). A cut-off TE score of 11 had a sensitivity of 78% and specificity of 88.1% for diagnosing cirrhosis. The best cut-off values for "TE-FIB-4 cirrhosis score" comprising TE and FIB-4 and "TE-APRI cirrhosis score" combining TE with aspartate aminotransferase-to-platelet ratio index (APRI) both had 87.5% sensitivity and 91.04% specificity for the diagnosis of cirrhosis.

Conclusion: Regardless of LIC, TE alone or when combined with FIB-4 or APRI, is a diagnostic tool with moderate to high accuracy to evaluate liver fibrosis in CHC patients with beta-thalassemia. However, because splenectomy in a proportion of our subjects might have affected the platelet count, the scores utilizing APRI and FIB-4 should be interpreted cautiously.
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http://dx.doi.org/10.1111/hepr.12088DOI Listing
December 2013

Cytokine alterations in bipolar disorder: a meta-analysis of 30 studies.

Biol Psychiatry 2013 Jul 16;74(1):15-25. Epub 2013 Feb 16.

Department of Psychiatry and Psychiatry Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Background: We conducted a meta-analysis of studies comparing cytokine concentrations between patients with bipolar disorder (BD) and healthy control subjects (HCs).

Methods: We searched ISI Web of Science, MEDLINE, BIOSIS Previews, Scopus, Current Contents Connect, and Biological Abstracts for relevant studies. Based on heterogeneity status, we used fixed-effect or restricted maximal likelihood model to perform meta-analysis.

Results: Thirty studies with a total of 2599 participants (1351 BD and 1248 HCs) were eligible for the analysis. Concentrations of interleukin (IL)-4 (p = .008), IL-6 (p = .073), IL-10 (p = .013), soluble IL-2 receptor (sIL-2R; p < .001), sIL-6R (p = .021), tumor necrosis factor (TNF)-α (p = .010), soluble TNF receptor-1 (sTNFR1; p < .001), and IL-1 receptor antagonist (p value in mania < .001 and euthymia = .021) were significantly elevated in patients compared with HCs. Moreover, IL-1β (p = .059), and IL-6 (p = .073) tended to show higher values in patients. Levels of IL-2 (p = .156), interferon (INF)-γ (p = .741), C-C motif ligand 2 (p = .624), and IL-8 (p = .952) did not significantly differ between patients and HCs. Subgroup analysis based on mitogen stimulation status partially or completely resolved heterogeneity for most of the cytokines. Concentrations of IL-2, IL-4, sIL-6R, and INF-γ were unrelated to medication status. Phasic difference was present for TNF-α, sTNFR1, sIL-2R, IL-6, and IL-1RA, whereas it was absent for IL-4 and IL-10.

Conclusions: This meta-analysis provides evidence for significant elevation of proinflammatory, anti-inflammatory, and regulatory cytokines in BD.
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http://dx.doi.org/10.1016/j.biopsych.2013.01.007DOI Listing
July 2013

Granisetron as an add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study.

J Psychiatr Res 2013 Apr 30;47(4):472-8. Epub 2013 Jan 30.

Razi Psychiatric Hospital, Welfare Sciences University, Iran.

Some 5-HT3 antagonists such as ondansetron have shown beneficial effects on negative symptoms of patients with schizophrenia. We aimed to evaluate the efficacy of granisetron (another 5-HT3 antagonist) add-on therapy in the treatment of negative symptoms of patients with stable schizophrenia. In a randomized, double-blind, and placebo-controlled study, forty stable patients with schizophrenia (DSM-IV-TR), were randomized to either granisetron (1 mg twice daily) or placebo (twice daily) in addition to risperidone up to 6 mg/day for eight weeks. The patients were assessed using positive and negative syndrome scale (PANSS) and extrapyramidal symptom rating scale (ESRS) at baseline, week 4 and 8. Hamilton depression rating scale (HDRS) was used to assess depression at baseline and week 8. Thirty-eight patients completed the trial. Granisetron group showed a significantly greater improvement on negative subscale than the placebo group at endpoint [t(38) = 6.046, mean difference (±95% CI) = 3.2(1.8-3.7), P < 0.001]. The same effect was observed for total score [t(38) = 4.168, mean difference (95% CI) = 3.2(1.6-4.7), P < 0.001]. However the placebo and granisetron groups did not differ in their reduction of positive and general psychopathology symptoms scores. HDRS scores and its changes did not differ between the two groups. The ESRS score at week 4 was significantly lower in the granisetron than the placebo group while the two groups showed similar ESRS score at week 8. Frequency of other side effects was similar between the two groups. In summary, granisetron add-on can safely and effectively reduce the primary negative symptoms of patients with schizophrenia.
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http://dx.doi.org/10.1016/j.jpsychires.2013.01.011DOI Listing
April 2013
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