Chronic Psychiatric Disorders Research Articles

Evaluation of Clinical Factors Associated with Adverse Drug Events in Patients Receiving Sub-Anesthetic Ketamine Infusions.

IntroductionSub-anesthetic ketamine is frequently used as an analgesic to reduce perioperative opioid consumption and has also been shown to have antidepressant effects. Side effects of ketamine include dizziness, diplopia, nystagmus, and psychomimetic effects. It is unclear what clinical factors may be associated with ketamine-related adverse drug events (ADEs).MethodsWe performed a retrospective review of 95 patients who received sub-anesthetic ketamine infusions at our institution. Data examined associations between ketamine-related ADEs and various clinical characteristics including chronic pain, depression, or psychiatric disorder, patient physical characteristics, chronic opioid use, perioperative opioid use, dose and duration of ketamine infusions, pain scores, and perioperative medications such as serotonergic agents, central nervous system (CNS) depressants, and analgesics.ResultsOverall incidence of ketamine-related ADEs was 29.5% and the incidence of psychomimetic effects was 14.8%. We observed that patients with a history of depression have a lower incidence of ketamine-related ADEs compared to patients without a history of depression (10.3% vs 37.3%; p value = 0.007).ConclusionPatients with depression were found to have a statistically significant reduction in the incidence of ketamine-related ADEs. We found no statistically significant positive associations between ketamine-related ADEs and other clinical factors such as a history of chronic pain, psychiatric disease, patient physical characteristics, perioperative opioid use, dose of ketamine infusion, or co-administration of other CNS depressants.

The impact of psychiatric and medical comorbidity on the risk of mortality: a population-based analysis.

As life expectancy increases, more people have chronic psychiatric and medical health disorders. Comorbidity may increase the risk of premature mortality, an important challenge for health service delivery. Population-based cohort study in Ontario, Canada of all 11 246 910 residents aged ⩾16 and <105 on 1 April 2012 and alive on 31 March 2014. Secondary analyses included subjects having common medical disorders in 10 separate cohorts. Exposures were psychiatric morbidity categories identified using aggregated diagnosis groups (ADGs) from Johns Hopkins Adjusted Clinical Groups software® (v10.0); ADG 25: Persistent/Recurrent unstable conditions; e.g. acute schizophrenic episode, major depressive disorder (recurrent episode), ADG 24: Persistent/Recurrent stable conditions; e.g. depressive disorder, paranoid personality disorder, ADG 23: Time-limited/minor conditions; e.g. adjustment reaction with brief depressive reaction. The outcome was all-cause mortality (April 2014-March 2016). Over 2 years' follow-up, there were 188 014 deaths (1.7%). ADG 25 conferred an almost threefold excess mortality after adjustment compared to having no psychiatric morbidity [adjusted hazard ratio 2.94 (95% CI 2.91-2.98, p < 0.0001)]. Adjusted hazard ratios for ADG 24 and ADG 23 were 1.12 (95% CI 1.11-1.14, p < 0.0001) and 1.31 (95% CI 1.26-1.36, p < 0.0001). In all 10 medical disorder cohorts, ADG 25 carried significantly greater mortality risk compared to no psychiatric comorbidity. Psychiatric disorders, particularly those graded persistent/recurrent and unstable, were associated with excess mortality in the whole population, and in the medical disorder cohorts examined. Future research should examine whether service design accounting for psychiatric disorder comorbidity improves outcomes across the spectrum of medical disorders.

A comparative study of metabolic side effects of risperidone and olanzapine in the treatment of schizophrenia

ABSTRACTBackground: Schizophrenia is one of most serious chronic psychiatric disorder, which affects about 1% of population. Treatment of schizophrenia comprises of typical antipsychotics and or atypical antipsychotics. Typical antipsychotics like haloperidol have extrapyramidal side effects which limit their use in chronic cases. Atypical antipsychotics though have better treatment response, they have metabolic side effects like hypercholesteremia, hypertriglyceridemia and hyperglycaemia. As there is paucity of data in Indian population the present study has been taken up to compare the metabolic side effects of risperidone and olanzapine in the treatment of schizophrenic patients in a tertiary care hospital.Methods: It was a comparative study conducted on 60 patients of Schizophrenia for one year in a tertiary care hospital. The study subjects were randomly assigned into 2 groups of 30 patients each, where group 1 were treated with atypical antipsychotic drug risperidone and group 2 with Olanzapine and both groups received the treatment for one year. Metabolic side effects like hypercholesteremia, hypertriglyceridemia and hyperglycaemia were evaluated and compared over a period of one year.Results: Both risperidone and olanzapine were associated with comparable baseline to endpoint increase in metabolic side effects. However, risperidone treated subjects had significantly less metabolic side effects compared to olanzapine.Conclusions: Apart from total cholesterol and triglycerides, other metabolic side effects were less in risperidone treated patients than olanzapine treated patients.

Discovery and Development of Non-Dopaminergic Agents for the Treatment of Schizophrenia: Overview of the Preclinical and Early Clinical Studies.

Schizophrenia is a chronic psychiatric disorder that affects about 1 in 100 people around the world and results in persistent emotional and cognitive impairments. Untreated schizophrenia leads to deterioration in quality of life and premature death. Although the clinical efficacy of dopamine D2 receptor antagonists against positive symptoms of schizophrenia supports the dopamine hypothesis of the disease, the resistance of negative and cognitive symptoms to these drugs implicates other systems in its pathophysiology. Many studies suggest that abnormalities in glutamate homeostasis may contribute to all three groups of schizophrenia symptoms. Scientific considerations also include disorders of gamma-aminobutyric acid-ergic and serotonergic neurotransmissions as well as the role of the immune system. The purpose of this review is to update the most recent reports on the discovery and development of non-dopaminergic agents that may reduce positive, negative, and cognitive symptoms of schizophrenia, and may be alternative to currently used antipsychotics. This review collects the chemical structures of representative compounds targeting metabotropic glutamate receptor, gamma-aminobutyric acid type A receptor, alpha 7 nicotinic acetylcholine receptor, glycine transporter type 1 and glycogen synthase kinase 3 as well as results of in vitro and in vivo studies indicating their efficacy in schizophrenia. Results of clinical trials assessing the safety and efficacy of the tested compounds have also been presented. Finally, attention has been paid to multifunctional ligands with serotonin receptor affinity or phosphodiesterase inhibitory activity as novel strategies in the search for dedicated medicines for patients with schizophrenia.

Inappropriate Opioid Prescribing in Oregon's Coordinated Care Organizations.

The objective of this study is to identify demographic and clinical characteristics of patients with a pain diagnosis who fill potentially inappropriate opioid prescriptions within the Oregon Medicaid population. Using de-identified Oregon Medicaid claims data (2010-2014), a series of logistic regression models was estimated to identify factors associated with receipt of potential inappropriate opioid prescriptions among patients with acute or chronic pain. Analyses included a total of 204,364 records, representing 118,671 unique patients. The percentage of patients with a pain diagnosis filling at least 1 inappropriate opioid prescription decreased over the study period, falling from 32.5% in 2010 to 22.3% in 2014. Multivariate logistic regression results indicated that white and older enrollees were more likely to fill an inappropriate prescription over the study period. The odds of filling an inappropriate opioid prescription were also greater for patients with chronic health conditions, psychiatric disorders, and substance use disorder. Results were similar for patients diagnosed with either acute or chronic pain, chronic pain only, or acute pain only. Inappropriate opioid prescribing for patients with pain diagnoses decreased over the study period, which stands in stark contrast to other state Medicaid programs. However, in 2014, almost 23% of patients in the Oregon Medicaid program filled at least 1 inappropriate opioid prescription, suggesting additional strategies are needed to further reduce potential inappropriate prescribing. Medicaid programs may consider adopting enhanced prescription drug monitoring program features, enacting pain clinic legislation, and implementing additional prior authorization policies to reduce inappropriate prescribing of opioids.

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate existing clinical evidence of PPAR modulators, highlighting their clinical prospects and challenges. Findings from clinical trials revealed that different agonists of the same PPAR subtype could present different safety profiles and clinical outcomes in a disease-dependent manner. Pemafibrate, due to its high selectivity, is likely to replace other PPARα agonists for dyslipidemia and cardiovascular diseases. PPARγ agonist pioglitazone showed tremendous promises in many non-metabolic disorders like chronic kidney disease, depression, inflammation, and autoimmune diseases. The clinical niche of PPARβ/δ agonists is less well-explored. Interestingly, dual- or pan-PPAR agonists, namely chiglitazar, saroglitazar, elafibranor, and lanifibranor, are gaining momentum with their optimistic outcomes in many diseases including type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and primary biliary cholangitis. Notably, the preclinical and clinical development for PPAR antagonists remains unacceptably deficient. We anticipate the future design of better PPAR modulators with minimal off-target effects, high selectivity, superior bioavailability, and pharmacokinetics. This will open new possibilities for PPAR ligands in medicine.

Differential effects of earthquakes on patients with bipolar disorder versus schizophrenia: Findings from Crete, Greece, 2008-2010.

Electromagnetic radiation influences in many ways humans and animals, while earthquakes are known to be related with electromagnetic phenomena. We recently showed that large earthquakes reduced admissions of psychiatric patients, whereas small earthquakes were associated with increased number of admissions. Our aim was to examine the effect of seismic-related electromagnetic activity on two chronic and severe psychiatric disorders varying in terms of etiology and treatment, i.e. bipolar disorder and schizophrenia. Retrospective data concerning monthly admission rates of patients diagnosed with schizophrenia or bipolar disorder in the Psychiatric Unit of the University Hospital of Heraklion, Crete, Greece between 2008 and 2010 were analyzed in relation to the number of earthquakes with small (≥2) or larger magnitude in the Crete region in Greece. Results showed a marked reduction of acute admissions during a storm of large earthquakes, which was greater in patients with bipolar disorder (91.2%) than schizophrenia patients (52.4%). In addition there was a significant increase of admissions during a period of frequent small earthquakes, primarily among patients with bipolar disorder. The results suggest that electrostatic fields that accompany large earthquakes may have a protective effect on psychiatric disorders, particularly on bipolar disorder. These findings are consistent with the ameliorating effect of electromagnetic fields used in Electroconvulsive therapy (ECT) and Transcranial Magnetic Stimulation (TMS) in patients with bipolar disorder. Future studies focusing on the underlying mechanisms may lead to more specific treatments of psychiatric disorders.

S87GENETIC DIFFERENTIAL DIAGNOSIS IN ULTRA TREATMENT RESISTANT SCHIZOPHRENIA

Genome-wide copy-number association studies offer new opportunities to identify the mechanisms underlying complex diseases, including chronic inflammatory, psychiatric disorders and others. We have used genotyping microarrays to analyse the copy-number variants (CNVs) from 243 Caucasian individuals with Inflammatory Bowel Disease (IBD). The CNV data was obtained by using multiple quality control measures and merging the results of three different CNV detection algorithms: PennCNV, iPattern, and QuantiSNP. The final dataset contains 4,402 CNVs detected by two or three algorithms independently with high confidence. This paper provides a detailed description of the data generation and quality control steps. For further interpretation of the data presented in this article, please see the research article entitled ‘Copy number variation-based gene set analysis reveals cytokine signalling pathways associated with psychiatric comorbidity in patients with inflammatory bowel disease’.

PROGRESS IN THE GENETICS OF SUBSTANCE USE DISORDERS – AN UPDATE

Alcohol use disorder (AUD) is a common and chronic psychiatric disorder characterized by harmful drinking patterns that have substantial negative effects on both personal and public health. Despite its prevalence in society, the underlying pathophysiology of AUD is poorly understood. Although substantial evidence supports a genetic component of the disorder, identification of potential genetic susceptibility factors for AUD has been challenging. Efforts to identify universal genetic risk variants for AUD have included twin, linkage, candidate gene, and genome-wide association studies. Evidence indicates several potential genetic risk variants for AUD, which underscores the complexity and heterogeneity of the disorder. The most consistently identified variants were alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH), the genes of alcohol metabolism. These had protective effects against AUD development. Understanding genetic mechanisms underlying AUD could guide development of targeted pharmacological interventions that would enhance treatment of the disorder.

Crocin ameliorates chronic obstructive pulmonary disease-induced depression via PI3K/Akt mediated suppression of inflammation

Clinical studies have indicated the co-occurrence of chronic obstructive pulmonary disease (COPD) and psychiatric disorders, for example, comorbid depression. However, the underlying mechanism is rarely addressed. The present study aimed to investigate the mechanism of COPD-induced depression and the psychological and physiological effects of crocin, an active constituent of Crocus sativus L. C57BL/6 mice were randomly exposed to cigarette smoke for 7 weeks to establish COPD animal model. Crocin (50 mg/kg), Dexamethasone (2 mg/kg) and IGF-1 (2 mg/kg) were respectively injected to mice once a day. The FEV1/FVC ratio and the mean alveolus area of lung tissue demonstrated the COPD model was successfully established by cigarette smoke. Crocin administration significantly reversed markers of depression [loss of body weight, sucrose preference, and elevation of immobile time in tail-suspension tests (TST) and in forced swimming tests (FST)]. Besides, crocin treatment significantly inhibited the numbers of inflammatory cells (macrophages, neutrophils, and lymphocytes), suppressed the infiltration of peribronchial inflammatory cells, and reduced the concentration of proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and lung tissue. Crocin also reduced proinflammatory cytokines in the hippocampus. In exploring associated mechanisms, we discovered that crocin blunted cigarette smoke-induced IκB phosphorylation and degradation, and NF-κBp65 nuclear translocation. IGF-1, an activator of PI3K, abrogated the effect of crocin against cigarette smoke-induced activation of the NF-κB pathway. Together, these results showed that an inflammatory mechanism might be involved in the pathogenesis of COPD with comorbid depression. Crocin exhibited significant effects through the regulation of PI3K/Akt-mediated inflammatory pathways.

Decreased Cross-Domain Mutual Information in Schizophrenia From Dynamic Connectivity States.

The study of dynamic functional network connectivity (dFNC) has been important to understand the healthy and diseased brain. Recent developments model groups of functionally related brain structures (defined as functional domains) as entities that can send and receive information. A domain analysis starts by detecting a finite set of connectivity patterns known as domain states within each functional domain. Dynamic functional domain connectivity (DFDC) is a novel information theoretic framework for studying the temporal sequence of the domain states and the amount of information shared among domains. In this setting, the information flow among functional domains can be compared to the flow of bits among entities in a digital network. Schizophrenia is a chronic psychiatric disorder which is associated with how the brain processes information. Here, we employed the DFDC framework to analyze a dataset containing resting-state fMRI scans from 163 healthy controls (HCs) and 151 schizophrenia patients (SZs). As in other information theory methods, this study measured domain state probabilities, entropy within each DFDC and the cross-domain mutual information (CDMI) between pairs of DFDC. Results indicate that SZs show significantly higher (transformed) entropy than HCs in subcortical (SC)-SC; default mode network (DMN)-visual (VIS) and frontoparietal (FRN)-VIS DFDCs. SZs also show lower (transformed) CDMI between SC-VIS vs. SC-sensorimotor (SM), attention (ATTN)-VIS vs. ATTN-SM and ATTN-SM vs. ATTN-ATTN DFDC pairs after correcting for multiple comparisons. These results imply that different DFDC pairs function in a more independent manner in SZs compared to HCs. Our findings present evidence of higher uncertainty and randomness in SZ brain function.

The Prevalence of Deficits in Health-Related Physical Fitness in Patients With Chronic Psychiatric Disorders (CPD): Implications for OT

Abstract Date Presented 04/06/19 Compared to the general population, patients with chronic psychiatric disorders (CPD) are more sedentary and have higher rates of somatic comorbidities. This study provides the evidence showing the high prevalence of physical fitness deficits and body composition abnormalities in patients with CPD. The findings suggest the need for OTs to provide holistic care that includes various exercise programs to moderate the client’s deficits in health-related physical fitness. Primary Author and Speaker: Pei-Yun Wang Additional Authors and Speakers: Eric Hwang Contributing Authors: Sung-Lien Chien, Shang-Liang Wu, Hui-Ling Lee

The Efficacy of a Lower-Extremity Exercise Program for Individuals With Chronic Psychiatric Disorders (CPD)

Abstract Date Presented 04/05/19 A lower-extremity strengthening exercise (LESE) program addressing high-intensity interval training was designed to improve the lower limb function of people with chronic psychiatric disorders. This clinical control trial showed that the 16-week LESE program significantly increased clients' lower limb muscle strength and endurance. OTs working with the client population should include lower-extremity exercises as a preparatory task for supporting occupation-based activities. Primary Author and Speaker: Wan-Chi Hsu Additional Authors and Speakers: Eric Hwang Contributing Authors: Pei-Yun Wang, Shang-Liang Wu, Hui-Ling Lee

An In-House Vocational Training (IHVT) Program for Individuals With Chronic Mental Illnesses: The Employment Outcomes Reported by a Multicenter Study

Abstract Date Presented 04/04/19 An IHVT program was designed to improve employment outcomes for people with chronic psychiatric disorders. This client-centered program includes the areas of work-related behaviors, on-the-job skills, and life balance alongside the ongoing vocational counseling. The program outcomes showed satisfactory employment rates (52.9 to 65.6%) and high employment sustainability (greater than 6 months). The IHVT is a promising alternative to traditional vocational training. Contributing Authors: Shang-Liang Wu Additional Authors and Speakers: Eric Hwang Primary Author and Speaker: Hui-Ling Lee

A comparison of somatosensory amplification among fibromyalgia, other forms of chronic pain and psychiatric disorders: A psychiatric perspective

The predictors and independent outcome association of delirium after cardiac surgery are important and yet poorly characterised.We performed a retrospective observational study of cardiac surgery patients between January 2009 and March 2016. We defined delirium using ICD-10 diagnostic codes. Multivariable analysis was conducted to find independent associations between baseline variables, delirium, and key clinical outcomes.We studied 2,447 study patients (28.7% female, median age was 66 [IQR 57–74] years). Delirium was coded for in 12.9% of patients overall, and in 22.9% of those aged >75 years. Increasing age, Charlson co-morbidity index, admission not from home, peripheral vascular disease, respiratory disease, preoperative atrial fibrillation, duration of cardiopulmonary bypass and nature of surgery were all independent predictors of delirium. Delirium was independently and strongly associated with increased risk of reintubation (OR 8.18 [95% CI 5.24–12.78]), tracheostomy (OR 10.44 [95% CI 5.91–18.45]), and increased length of stay by 113.7 [95% CI 99.7–127.7] ICU hours and 6.95 [95% CI 5.94–7.95] hospital days, but not 30-day mortality (OR 0.78 [95% CI 0.38–1.59]; p = 0.5).Delirium is common in cardiac surgery patients and increases with age. Delirium was the strongest predictor of reintubation, need for tracheostomy, and prolongation of intensive care unit (ICU) and hospital length of stay. Delirium prevention and attenuation are a priority in cardiac surgery patients.

Hippocampal PKR/NLRP1 Inflammasome Pathway Is Required for the Depression-Like Behaviors in Rats with Neuropathic Pain

The chronic neuropathic pain-associated psychiatric disorders have seriously disturbed the quality of patients' life, such as depression and anxiety. Neuroinflammation in the hippocampus plays an important role in the neuropathic pain-associated depressive and anxiety disorders, but the underlying mechanism has not been thoroughly elucidated to date. The Nod-like receptor protein (NLRP)-1 inflammasome, which controls the production of pro-inflammatory cytokines, was broadly involved in the neuroinflammation-related diseases. In the present study, we show that the NLRP1 inflammasome is significantly activated in the hippocampus of rats subjected to the chronic constriction injury (CCI)-induced neuropathic pain. Inhibiting the product of NLRP1 inflammasome not only attenuated the depression-like behaviors but also suppressed the production of mature IL-1β in the hippocampus of CCI rats. The double-stranded RNA-dependent protein kinase (PKR, also known as EIF2AK2) has been recently shown to be a pivotal regulator for the activation of inflammasome. In the rats subjected to CCI neuropathic pain, the PKR was simultaneously activated in hippocampus. Functional inhibition of PKR suppressed the NLRP1 inflammasome activation and effectively attenuated the CCI-induced depression-like behaviors. These results indicate that the hippocampal PKR/NLRP1 inflammasome pathway play an important role in the development of the depressive behaviors after chronic neuropathic pain. Thus, interrupting this pathway might provide a novel therapeutic strategy for neuropathic pain-associated depressive disorders.

Effects of lithium and valproate on ERK/JNK signaling pathway in an animal model of mania induced by amphetamine

Bipolar disorder (BD) is a severe and chronic psychiatric disorder, characterized by recurrent mood episodes of depression and mania. Some studies have indicated that there are ERK and JNK pathways alterations in the brain from bipolar patients. The animal model of mania induced by dextroamphetamine (d-AMPH) has been considered an excellent model to study intracellular alterations related to BD. The present study aimed to evaluate the effects of lithium (Li) and valproate (VPA) on the behavioral and ERK1/2/JNK1/2 signaling pathway in an animal model of mania induced by d-AMPH. Wistar rats were first given d-AMPH or saline (Sal) for 14 days, and then, between the 8th and 14th days, the rats were treated with Li, VPA, or Sal. The open-field test was used to evaluate the locomotion and exploration behaviors of rats. The levels of phosphorylated ERK1/2 and JNK1/2 were assessed in the hippocampus and frontal cortex of the rats. Li and VPA reversed the increased of locomotion and exploration induced by d-AMPH. The treatment with VPA or AMPH per se decreased the levels of pERK1 in the hippocampus. The treatment with VPA in the animals submitted to the administration of d-AMPH decreased the levels of ERK1, JNK-1, and JNK-2 phosphorylated in the hippocampus of the animals. The treatment with Li decreased the JNK-1 phosphorylated in the hippocampus of the animals submitted to the animal model of mania induced by d-AMPH. Although the association of VPA plus amphetamine alters some proteins involved in the JNK pathway in the hippocampus, these alterations were very random and seemed that were not related to the d-AMPH-induced manic-like behavior. These results suggest that the manic-like effects induced by d-AMPH and the antimanic effects of mood stabilizers, Li and VPA, are not related to the alteration on ERK1/2 and JNK1/2 pathways.

Altered Activity of SK Channel Underpins Morphine Withdrawal Relevant Psychiatric Deficiency in Infralimbic to Accumbens Shell Pathway.

Drug addiction can be viewed as a chronic psychiatric disorder that is related to dysfunction of neural circuits, including reward deficits, stress surfeits, craving changes, and compromised executive function. The nucleus accumbens (NAc) plays a crucial role in regulating craving and relapse, while the medial prefrontal cortex (mPFC) represents a higher cortex projecting into the NAc that is active in the management of executive function. In this study, we investigated the role of the small conductance calcium-activated potassium channels (SK channels) in NAc and mPFC after morphine withdrawal. Action potential (AP) firing of neurons in the NAc shell was enhanced via the downregulations of the SK channels after morphine withdrawal. Furthermore, the expression of SK2 and SK3 subunits in the NAc was significantly reduced after 3 weeks of morphine withdrawal, but was not altered in the dorsal striatum. In mPFC, the SK channel subunits were differentially expressed. To be specific, the expression of SK3 was upregulated, while the expression of SK2 was unchanged. Furthermore, the AP firing in layer 5 pyramidal neurons of the infralimbic (IL) cortex was decreased via the upregulations of the SK channel-related tail current after 3 weeks of morphine withdrawal. These results suggest that the SK channel plays a specific role in reward circuits following morphine exposure and a period of drug withdrawal, making it a potential target for the prevention of relapse.

Glutamate hypothesis in schizophrenia

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual's life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter-century, an abundance of evidence from pharmacologic challenges, post-mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N-methyl-d-aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment-resistant symptoms, which account for persistent disability.

Prevalence of Post-Traumatic Stress Disorder (PTSD) in Iranian Population Following Disasters and Wars: A Systematic Review and Meta-Analysis

Context: Post-traumatic stress disorder (PTSD) is a chronic psychiatric disorder that occurs as a result of an accident or life-threatening event. The purpose of our study was to examine the prevalence of PTSD in the Iranian population from 2000 to 2015 through a meta-analysis of the published studies to review the epidemiologic evidence of PTSD after disasters and wars and to examine PTSD determinants. Evidence Acquisition: The electronic databases including PubMed, Embase, Web of Science, Magiran, etc. were explored to find related papers. Two authors independently reviewed and extracted data via an extraction sheet, and disagreements were resolved by holding a meeting with a third author. Meta-analysis was performed using “metaprop” command in STATA 11 software. Studies with < 25 participants were excluded from our analysis. Results: Ultimately, 47 studies were included in this meta-analysis. Primary PTSD was investigated in 44 studies and secondary PTSD in six studies. Forty studies investigated natural PTSD and five studies technical PTSD. PTSD related to childbirth, job, earthquake, war, burn, accident, and rape events were investigated in seven, six, nine, nine, two, two, and two studies, respectively, and their pooled prevalence were 25%, 30%, 58%, 47%, 40%, 11%, and 74%, respectively. Conclusion: The results revealed that the burden of PTSD among the Iranian population exposed to wars and disasters is high. PTSD was correlated with a range of factors including demographic and background factors and characteristics of the event exposure.