Evaluating the association of vitamin D3, parathyroid hormone, and C-reactive protein serum levels in patients with an acute psychotic episode: a cross-sectional study in tertiary centre in Iran.

BACKGROUND: The high impact of vitamin D on brain development and its relationship with inflammatory markers in the clinical course of psychiatric disorders have compelled researchers to investigate the potential association between vitamin D levels, C-reactive protein (CRP) levels, and the incidence of mental disorders. In the present study, we aimed to compare the serum levels of vitamin D and its related markers, including calcium, phosphorus, and parathyroid hormone (PTH), along with CRP, in 3 groups of patients with acute psychotic episodes, including schizophrenia, bipolar disorder, and methamphetamine-induced psychosis, with a standard control group of the Iranian population. METHODS: This descriptive cross-sectional study was conducted at a psychiatric hospital in Tehran, Iran, and involved a total of 185 subjects. The subjects included four groups: acute phase of schizophrenia (n = 49), acute manic episodes of bipolar disorder (n = 43), methamphetamine-induced psychotic disorder (n = 46), and control group (n = 47). Among 138 patients in acute psychotic episodes, 33 patients were in their first episode of psychosis, while 105 patients were in acute exacerbation of their chronic psychotic disorders. The Brief Psychiatric Rating Scale (BPRS) was measured by an expert attending psychiatrist for all patients. Then, serum levels of calcium, phosphorus, parathormone, vitamin D, and CRP were assessed in all study groups. RESULTS: Among our 185 study subjects, it was observed that individuals with higher education levels and those who were married had a lower prevalence of mental disorders. In all patient groups, the serum levels of CRP were significantly higher, and PTH levels were significantly lower than in the control group (p < 0.001). The serum levels of calcium, phosphorus, and vitamin D were not statistically significantly different between the patient and control groups of the study. In chronic psychotic patients, CRP levels were significantly higher (p < 0.031), and vitamin D levels were significantly lower (p < 0.044) compared to first-episode psychotic patients. CONCLUSION: This study suggests that CRP levels are significantly higher and PHT level is significantly lower in acute psychotic patients. Moreover, vitamin D levels were significantly lower in chronic psychotic patients compared to first-episode psychotic patients.

Risk factors for attention-deficit/hyperactivity disorder: a case-control study in 5 to 12 years old children.

BACKGROUND AND AIMS: Attention deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder known by a pattern of diminished sustained attention and increased impulsivity or hyperactivity. This study aimed to evaluate the risk factors associated with ADHD. METHODS: This case-control study included 297 ADHD children aged 5-12 years admitted to Tehran Institute of Psychiatry, Iran (2012-2013). They were compared with 297 non-ADHD (as controls matched to cases 1:1) who were of the same age (±1 years) selected from outpatients in general pediatric medical centers in Tehran. ADHD Rating Scale IV (ADHD-RS-IV)-Home Version was used to confirm ADHD. Data were analyzed using conditional binary logistic regression. RESULTS: Mean±SD age were 8.18±3.11 and 8.11±2.9 years in the case and control groups, respectively (P=0.61). Mean±SD birth weight (BW) was higher in ADHD patients compared with the controls (3245.09±0.66 vs 3026.56±0.45 gr, P=0.045). The results showed that odds of ADHD in children with high BW (>3500g) was 3.36 (1.96-5.78) times the odds of ADHD in normal BW children (2500-3500g) controlling for other risk factors. ADHD risk in low BW children (<2500 g) was not statistically different compared with normal BW children [OR:1.74 (0.7-3.7)]. Experience of neonatal disease, fewer offspring, lower level of mothers' education, and preterm delivery were also risk factors for higher odds of ADHD. CONCLUSION: Based on our sample, preterm birth, neonatal disease, high BW, lower level of mother's education, and fewer offspring were ADHD risk factors.

Lower folate levels in methamphetamine-induced psychosis: A cross-sectional study.

BACKGROUND: Folate deficiency is shown to be associated with schizophrenia. Folate profile in patients with psychosis due to stimulant use has not been investigated. We aim to determine whether there is an association between serum folate level and the presence of psychosis in patients with methamphetamine (METH) use disorder. METHODS: Forty patients diagnosed with METH-use disorder were included in this cross-sectional study. Serum folate levels were measured using enzyme immunoassay technique and compared between psychotic and non-psychotic subgroups (N = 25 and 15, respectively). We designed a logistic regression model to measure the extent of any association and also to adjust for potential confounders. RESULTS: We detected lower serum folate level in the psychotics [3.4 (IQR = 5.3)] compared to non-psychotic METH users [8.9 (IQR = 2.5)], p = 0.01. The model demonstrated that every 1-unit increase in serum folate decreases the odds of presence of psychosis by 27% (R2 = 53.5%, CI 12-64%, p = 0.006). The observed difference was not associated with the duration of METH use, patient's age at first METH use, or concurrent use of other substances. CONCLUSIONS: Our findings suggest that low folate level in psychotic METH users does not correlate with previously established risk factors for meth-induced psychosis such as duration of use, age of onset of using, and poly-drug use. We assume that low folate levels may play a crucial role in the pathophysiology of psychosis.

No molecular evidence of Borna disease virus among schizophrenia and bipolar disorder patients in Iran.

BACKGROUND AND OBJECTIVES: Viruses have been suggested as one of the risk factors for psychiatric disorders. Among infectious agents Borna disease virus (BDV) has been known as a neurotropic virus which is able to cause neurological disorders in different animals. Recently there were controversial findings about BDV association with pathogenesis of human psychotic disorders. MATERIALS AND METHODS: Here we performed a nested reverse transcription polymerase chain reaction for detection of BDV P40 RNA in peripheral blood mononuclear cell samples of schizophrenia (SC), bipolar disorder (BD) patients and healthy controls (HCs). RESULTS: Only one out of 120 (0.8 %) psychiatric patients and two samples (2.7%) in 75 HCs showed positive results. There were no significant molecular evidence of BDV infection in 120 psychotic patients (60 SC and 60 BD) and 75 matched HCs. CONCLUSION: Our findings showed no association between BDV infection and pathogenesis of these psychiatric disorders. This is an interesting issue given both the as yet un-clarified role of BDV in human mental disorders and addressing patients in the so far under-investigating Middle East era.

29 Year Old Man with Multiple Sclerosis and Schizophrenia: A Case Report.

Multiple sclerosis (MS) is the most common debilitating neurological disease that affects adults, whether young adults or middle-aged. Although, most attention is toward the neurological signs of the disease, the neuropsychiatric signs are not uncommon. This case report presents a 29 year old male with a record of obsessive-compulsive disorder (OCD) without psychotic disorder, which coincides with the diagnosis MS, has been stricken to auditory hallucinations and reference delusion. The patient received some antipsychotic drugs such as Haloperidol and Perphenazine irregularly, but any psychotic signs of the patient were never in control. During this period he had several active episodes of MS disease, wherein the symptoms had subsided due to hospitalization and received corticosteroids pulse. The first time the patient was submitted to the emergency unit of Rasoul Akram Hospital, there was the possibility of schizophrenia which was confirmed in subsequent visits. The signs of the patient were not controllable for a long time and finally fully controlled by a combination of Aripiprazole (abilizol), Risperidone and Sertraline, and currently, for almost 3 years, both psychotic symptoms and MS disease have been under control. Our patient seems to catch the MS disease and schizophrenia simultaneously. There was no relation between MS and psychosis episodes and the MS attacks. Since the onset the patient had several acute MS attacks of MS, and hospitalization several times. These findings and characteristics regarding our patient made him completely different from other reported cases of MS along with neuropsychiatric signs which may help doctors in diagnosis and managment of similar cases.

Integration of suicide prevention program into primary health care network: a field clinical trial in Iran.

BACKGROUND: Suicide prevention is one of the priorities in policies of Iranian Ministry of Health and Medical Education (MHME). The suicide prevention program had two main parts of identifying and treatment of the depressed and suicide high risk individuals by Primary Health Care (PHC) network. The main aim of this study was to evaluate the results of integration of the program into PHC network in two cities with moderate to high rate of suicide with diverse socio-cultural backgrounds. METHODS: This work as a field trial study was conducted in Nahavand and Savojbolagh from April 2010 to March 2011 (12 months). A screening tool was designed. Required capacities such as treatment, referral and registration system were provided six months before the main study. The intervention phase (for one year) including the treatment process and five consultation sessions was conducted to identify depressed people and individuals with high risk of suicide. The data were analyzed by Chi square test. RESULTS: After one year of intervention, the rate of committing suicide became 4.98 and 3.36 per one hundred thousand population in Nahavand and Savojbolagh, respectively (16 and 1.6 per 100,000 in the year of before intervention respectively, 2009-2010). The female: male ratio of committing suicide was 2:1 in Nahavand and 1:1 in Savojbolagh. The most common method of committing suicide was drug intoxication in both cities. The identified cases by health workers at rural setting were 33 to 44 per 1000, in which 1.3 cases per 1000 population had been approved by general physicians. CONCLUSION: This study approved the feasibility and efficacy of integration of suicide prevention program into PHC. The increased rate of suicide in Savojbolagh could be related to low rate of screening and lack of treatment facilities (hospitalization and electroconvulsive therapy (ECT), and part-time psychiatrist. Increasing the PHC capacities could improve the health network efficiency to identify and manage depressed and at risk of suicide individuals. Screening tool/s and method have to be improved to provide better results.

Depot Typical Antipsychotics versus Oral Atypical Antipsychotics in Relapse Rate Among Patients with Schizophrenia: A Five -Year Historical Cohort Study.

OBJECTIVE: The present study aimed to review the relapse rate in patients with schizophrenia treated with orally taken atypical agents (serotonin dopamine antagonists, SDAs) and depot preparation of conventional (typical) antipsychotics. METHODS: In this historical cohort study, mean relapse per month (MRM) index, duration between initiation of antipsychotic treatment and the first relapse episode, and the time gap between successive relapses were compared between 84 patients on SDAs-except clozapine (group 1) and 81 others on depot typical antipsychotics (group 2). RESULTS: The two groups were comparable regarding mean (±SD) MRM index [0.033 (±0.004) in group1 and 0.044 (±0.05) in group 2; p = 0.345]. Mean (±SD) duration of time between initiation of maintenance treatment and the first relapse was 15.5 (±13.67) months in group 1 and 16.40 (±15.31) months in group 2, (p = 0.876). Mean (±SD) duration of remission periods between successive relapses were 17.92 (±14.2) and 15.8 (±16.9) months for group 1 and group 2, respectively (Mann-Whitney test, (p = 0.048). CONCLUSION: Orally taken atypical antipsychotics were able to keep the duration of remission periods between successive relapses more prolonged compared to depot conventional preparations. This could be added to their other remarkable benefits especially if the patient is expected to experience multiple relapses. DECLARATION OF INTEREST: None.

Evaluation of gene expression changes of serotonin receptors, 5-HT3AR and 5-HT2AR as main stress factors in breast cancer patients.

Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.

Dopamine receptor gene (DRD1-DRD5) expression changes as stress factors associated with breast cancer.

Breast cancer is the most common cancer among females worldwide and a most prevalent malignancy in Iranian women. Chronic stress may make an important contribution to cancer, especially in the breast. Numerous studies showed roles of neurotransmitters in the occurrence and progression of cancers which are mediated by their various types of receptors. This study was conducted to evaluate alterations in the expression profile of dopamine receptor genes in peripheral blood mononuclear cells (PBMC) as stress factors in breast cancer patients and the human breast cancer cell line (MCF-7). Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total mRNA was extracted from PBMC and MCF-7 cells and RT-PCR was performed to confirm the presence of five dopamine receptors (DRD1-DRD5). Expression changes of dopamine receptor genes were evaluated by real time PCR. We observed that DRD2-DRD4 in PBMCs of breast cancer patients were increased compared to healthy individuals. In addition, all dopamine receptor subtypes but DRD1 were expressed in MCF-7 cells. Therefore, alterations of these receptors as stress factorsshould be assessed for selecting appropriate drugs such as D2-like agonists for treatment of breast cancer after performing complimentary tests. Determining the expression profile of dopamine receptor genes thus seems promising.

Hypomethylation of the serotonin receptor type-2A Gene (HTR2A) at T102C polymorphic site in DNA derived from the saliva of patients with schizophrenia and bipolar disorder.

Several lines of evidence indicate that dysfunction of serotonin signaling and HTR2A receptor are involved in the pathogenesis of schizophrenia (SCZ) and bipolar disorder (BD). DNA methylation of HTR2A at T102C polymorphic site influences HTR2A expression and aberrant DNA methylation of HTR2A promoter was reported in postmortem brain of patients with SCZ and BD. Hypothesizing that the brain's epigenetic alteration of HTR2A may also exist in peripheral tissues that can be used as a diagnostic/therapeutic biomarker, we analyzed HTR2A promoter DNA methylation in DNA extracted from the saliva of patients with SCZ and BD, and their first degree relatives versus normal controls. Bisulfite sequencing was used to screen DNA methylation status of the HTR2A promoter CpGs and qMSP was used to quantify the degree of cytosine methylation at differentially methylated sites. Most of the cytosines of the HTR2A promoter were unmethylated. However, CpGs of the -1438A/G polymorphism site, -1420 and -1223 were >95% methylated. The CpG at T102C polymorphic site and neighboring CpGs were ∼70% methylated both in the patients and controls. qMSP analysis revealed that the cytosine of the T102C polymorphic site was significantly hypo-methylated in SCZ, BD, and their first degree relatives compared to the controls. Cytosine methylation of HTR2A at T102C polymorphic site in DNA derived from the saliva can potentially be used as a diagnostic, prognostic, and/or therapeutic biomarker in SCZ and BD. However, these preliminary observations need to be replicated in other populations with a larger sample size to be considered for clinical applications.

Advanced paternal age is a risk factor for schizophrenia in Iranians.

BACKGROUND: Since 1958 many, but not all studies have demonstrated that paternal age is a risk factor for schizophrenia. There may be many different explanations for differences between studies, including study design, sample size, collection criteria, heterogeneity and the confounding effects of environmental factors that can for example perturb epigenetic programming and lead to an increase in disease risk. The small number of children in Western families makes risk comparisons between siblings born at different paternal ages difficult. In contrast, more Eastern families have children both at early and later periods of life. In the present study, a cross-sectional population study in an Iranian population was performed to compare frequency of schizophrenia in younger offspring (that is, older paternal age) versus older offspring. METHODS: A total of 220 patients with the diagnosis of schizophrenia (cases) from both psychiatric hospitals and private clinics and 220 individuals from other hospital wards (controls), matched for sex and age were recruited for this study. Patients with neurological problem, substance abuse, mental retardation and mood disorder were excluded from both groups. RESULTS: Birth rank comparisons revealed that 35% vs 24% of the cases vs the controls were in the third or upper birth rank (P = 0.01). Also, the mean age of fathers at birth in case group (30 ± 6.26 years) was significantly more than the control group (26.45 ± 5.64 years; P = 0.0001). The age of 76 fathers at birth in case group was over 32 versus 33 fathers in control group. Individuals whose fathers' age was more than 32 (at birth) were at higher risk (2.77 times) for schizophrenia versus others (P < 0.0001, 95% CI 1.80 to 4.27). The maternal age at parturition of the case versus controls groups was 26.1 ± 5.41 vs 25.07 ± 4.47 (P = 0.02). Logistic regression analysis suggests that maternal age is less likely to be involved in the higher risk of schizophrenia than advanced parental age. DISCUSSION: This study demonstrates a relationship between paternal age and schizophrenia in large families of an Iranian population. Arguments have been put forth that DNA bases changes or epigenetic changes in sperm account for the increased risk associated with older fathers. However, it would not be surprising that both de novo germline mutations and epigenetic changes contribute to disease occurrence because DNA replication and DNA methylation are closely linked at both the macromolecular level (that is, methylation closely follows replication), and at the metabolic level (both processes require folate), and susceptible to modulation by the environment. Further research on samples such as those collected here are needed to sort out the contributions of de novo mutations versus epigenetic changes to schizophrenia.

Expression changes of serotonin receptor gene subtype 5HT3a in peripheral blood mononuclear cells from schizophrenic patients treated with haloperidol and Olanzapin.

Serotonin receptors are involved in pathophysiology of schizophrenia and may mediate other neurotransmitter effects. We investigated serotonin receptors gene expression in peripheral blood mononuclear cells (PBMC) of naïve schizophrenic patients, before and after treatment. Also serotonin receptor gene expression was compared in two treatment groups including Haloperidol and Olanzapine. The PBMC was separated from whole blood by Ficoll-hypaque. The total cellular RNA was extracted and the cDNA was synthesized. This process was followed by real-time PCR using primer pairs specific for 5HT(3a) serotonin receptor mRNA and beta-actin as internal control. The results showed the presence of subtype of serotonin receptor in lymphocytes. Serotonin gene expression showed significant changes in Olanzapine treatment group which correlated with Clinical Global Impression (CGI) score improvement. In conclusion, the present study has shown that human PBMC express serotonin receptors 5HT(3a). Moreover, clinical symptom improvement of Olanzapin may be demonstrated by a change in serotonin receptor gene expression.

The frequency of sexual abuse and depression in a sample of street children of one of deprived districts of Tehran.

The purpose of this study was to determine the frequency of sexual abuse and depression among street children who live in a deprived district of Tehran. The researchers used the K-SADS questionnaire and a clinical interview were used to evaluate depression and sexual abuse in 87 street children in Tehran. Eighteen (20.9%) of the children had been sexually abused. Depressed children were 3.2 times more likely to be sexually abused than non-depressed children. Furthermore, 26 girls (86.7%) and 27 boys (48.2%) suffered from depression. The frequency of depression demonstrated a significant association with the father's or breadwinner's history of imprisonment or unemployment. Interventional programs providing education and support should be implemented for street children.

The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR.

There is interrelationship between the immune and nervous systems that is accomplished by the molecular mediators. Dopamine is one of the most important neurotransmitters. Five different dopamine receptor genes (DRD1, DRD2, DRD3, DRD4, and DRD5) have been recognized and cloned. The expression of the dopamine receptors is well characterized in the brain but little work has been done to examine their expression in other organ tissues. In certain diseases of the immune and nervous systems, alterations in dopamine receptors gene expression in different cells have been reported. This suggests that dopamine and its receptors have important role in pathophysiology of above-mentioned diseases.In the present study, using Real Time Polymerase Chain Reaction (PCR) technique, we investigated dopamine receptors genes expression in PBMC of normal individuals. The PBMC was separated from normal whole blood by Ficoll-hypaque; the total cellular RNA was then extracted and the cDNA was synthesized. This process followed by real time-PCR using primer pairs specific for five dopamine receptors mRNAs and beta-actin as internal control. The results showed the presence of all types of dopamine receptors in lymphocytes of normal individuals. The specificities of the obtained PCR products for the respective dopamine receptors fragments were confirmed by sequenced analysis capillary system. In conclusion, the present study has shown that human lymphocytes express five dopamine receptors DR1-DR5. However, the conclusive evidence on the possible function of these receptors in lymphocytes remains unknown. Because lymphocytes express all of the five neuronal dopamine receptors, it is quite reasonable to consider them as a model of dopaminergic neuron.