Comorbidities of Major Depressive Disorder and Bipolar Disorders in Patients with Substance Use Disorder in Iran Psychiatric Hospital: A Cross-sectional Study.

Background: Mood disorders are the most common psychiatric comorbidities in substance users. Mood disorders and substance use disorders are 2 intertwined processes in which treating one aid in treating the other. Depression and substance use disorder are now regarded as major mental health issues due to their widespread incidence. The study was designed to investigate the prevalence of major depressive disorder (MDD) and bipolar I and II disorders in patients with substance use disorder. Methods: The participants of this cross-sectional study were 320 patients with substance use disorder based on the DSM-5 (diagnostic and statistical manual of mental disorders 5th edition) criteria in Iran Psychiatric Hospital in 2020, who were assessed using the SCID-5-CV (Structured Clinical Interview for DSM-5 disorders-clinician version), and the demographic and clinical variables questionnaire considering familial and substance use history. The chi-square, Fisher, independent t test, and logistic regression were used to analyze the data. Results: Of the patients, 32.8% (n = 105) had mood disorders. The most common mood disorder was MDD (16.9%, n = 54), followed by bipolar I (12.5%, n = 40) and bipolar II (2.8%, n = 9) disorders. Methamphetamine was the most commonly used substance (47.5%, n = 152). Also, 62.5% (n = 200) of participants consumed 2 or more substances simultaneously. The chance of having a mood disorder in married and divorced patients was 2.12 and 2.04 times more than in single patients, respectively. Conclusion: The lifetime prevalence of bipolar I disorder in patients with substance use disorders is several times more than the general population, thus psychiatrists should pay more attention to mood comorbidities diagnosis and treatment in substance users.

The Comparison Between Positive and Negative Symptoms Severity in Prolonged Methamphetamine-induced Psychotic Disorder and Schizophrenia.

Introduction: This study aims to compare the positive and negative symptoms of schizophrenia in patients who had psychotic symptoms more than one month after discontinuation of methamphetamine abuse. These factors were analyzed by the positive and negative syndrome scale (PANSS) questionnaire. Methods: Sixty participants were selected from patients referred to Iran Psychiatric Hospital with psychotic symptoms (delusions or hallucinations, disorganized behavior, and speech). The control group was 30 patients with schizophrenia based on a semi-structured interview according to DSMIV-TR (SCID). Thirty patients with a prolonged methamphetamine-induced psychotic disorder were also placed in the case group. For both groups of patients, questionnaires of PANSS, Brief Psychiatric Rating Scale (BPRS), and Global Assessment Of Functioning (GAF) were filled out after obtaining the companions' consent. The scale scores were compared between groups. We used the Mann-Whitney and the Chi-square test to evaluate the mean values of PANSS, BPRS, and GAF scores between the two groups. Results: here was an insignificant difference in positive and general pathology scores between the two groups, but the total score of negative symptoms in the schizophrenia group was significantly higher than in the group of prolonged methamphetamine psychotic disorders (P=0.034). Average scores of uncooperativeness (0.008), difficulty in abstract thinking (0.004), motor retardation (0.002), unusual thought content (0.001), and hostility (0.011) in the schizophrenia group were significantly higher than those in the prolonged methamphetamine psychosis. Conclusion: The results showed that most of the disturbances in patients with schizophrenia might be more influenced by the expression of cognitive disabilities than those with methamphetamine psychosis. The difference in negative symptom scores suggests that schizophrenia and prolonged methamphetamine psychotic disorder can be two different disorders. Highlights: General and positive symptoms scores don't have significant differences.Negative symptoms are much more in schizophrenia.Uncooperativeness, unusual thought content and, motor retardation have more scores in schizophrenia. Plain Language Summary: In clinical practice, Schizophrenia and prolonged methamphetamine-induced psychotic disorder have some similar mental presentations. Additionally, in scientific literature, there is scarce evidence about these similarities. In this regard, this research was designed to investigate the aforementioned obscurity. Determination of similarities and differences between them helps us to address these disorders in terms of treatment and follow-up and awareness of their prognosis of them. This research is a case-control study in which we examine positive and negative psychotic symptoms in schizophrenia and prolonged methamphetamine-induced psychotic disorder. Researchers investigated psychotic symptoms with positive and negative syndrome scale (PANSS), brief psychiatric rating scale (BPRS), and global assessment of functioning (GAF) questionnaires. Moreover, results demonstrate general and positive symptoms scores don't have many differences but negative symptoms are much more in patients with schizophrenia than in patients with a prolonged methamphetamine-induced psychotic disorder. Also, other features like uncooperativeness, unusual thought content, motor retardation, difficulty in abstract thinking, and hostility have higher scores in schizophrenia than the others. In conclusion, this research showed that these disorders are two distinct disorders with some similarities in positive symptoms but not in all features. So, some studies can be designed about why there are similarities between them?

Comparison of Online Sexual Activity Among Iranian Individuals With and Without Substance Use Disorder: A Case-Control Study.

The most important practical concerns in addiction medicine are the non-substance addiction and related addictive behaviors among individuals with substance use disorder. On the other hand, technological advances, and easy access have increased the frequency of online sexual activities (OSAs) as one of these behaviors. This study aimed to compare the prevalence of OSAs, based on the Internet Sex Screening Test (ISST) scores, among 60 patients with substance use disorder referred to Iran Psychiatric Hospital and 60 non-dependent individuals. The results showed significant negative correlations between the ISST scores and age, age at the onset of substance use, and substance use duration. There was a significant difference between the ISST scores of the case and control groups (P = 0.001). Patients who start using substances at an early age and have a great duration of substance use are more likely to engage in other addictive behaviors such as OSAs. Therefore, it is critical to consider OSAs and other addictive behaviors in patients with substance use disorder to provide better care for this vulnerable community.

Medication Adherence and Drug Attitude Amongst Male Patients with the Methamphetamine-Induced Psychotic Disorder After Discharge: A Three Months Follow Up Study.

Medication adherence and attitudes toward psychiatric medication affect treatment outcome. The objective of this study was to evaluate the effect and interaction of psychotic symptoms, sociodemographic factors, and attitudes concerning medication use with a three-month follow-up among methamphetamine-induced psychotic male patients. In this prospective, descriptive study, 42 male patients diagnosed with a methamphetamine-induced psychotic disorder were selected on the last day of their admission period in Iran Psychiatry Hospital, Tehran, Iran. Each patient was evaluated using the Persian version of the Drug Attitude Inventory (DAI-10), Medication Possession Ratio (MPR), Positive and Negative Syndrome Scale (PANSS), as well as a sociodemographic questionnaire immediately, one month and three months after discharge. There was a significant difference in MPR between the first and third months. Moreover, the frequency of patients with a positive attitude toward their medications increased over time. Indeed, all participants stated a positive attitude at the last follow-up based on the DAI-10 cutoff. Based on our findings, medication adherence of male patients with methamphetamine-induced psychotic disorder should be an essential aspect of treatment after discharge from psychiatry inpatient wards, more specifically, through the first months.

Cognitive network reconstruction in individuals who use opioids compared to those who do not: Topological analysis of cognitive function through graph model and centrality measures.

Introduction: Cognitive dysfunction related to opioid use disorder (OUD) requires investigation of the interconnected network of cognitive domains through behavioral experiments and graph data modeling. Methods: We conducted n-back, selective and divided attention, and Wisconsin card sorting tests and reconstructed the interactive cognitive network of subscales or domains for individuals who use opioids and controls to identify the most central cognitive functions and their connections using graph model analysis. Each two subscales with significant correlations were connected by an edge that incorporated in formation of interactive networks. Each network was analyzed topologically based on the betweenness and closeness centrality measures. Results: Results from the network reconstructed for individuals who use opioids show that in the divided attention module, reaction time and number of commission errors were the most central subscales of cognitive function. Whereas in controls, the number of correct responses and commission errors were the most central cognitive measure. We found that the subscale measures of divided attention module are significantly correlated with those of other tests. These findings corroborate that persons who use opioids show impaired divided attention as higher reaction time and errors in performing tasks. Divided attention is the most central cognitive function in both OUD subjects and controls, although differences were observed between the two groups in various subscales. Discussion: Although equal proportions of males and females may be used in future studies, divided attention and its subscales may be the most promising target for cognitive therapies, treatments and rehabilitation as their improvement can enhance overall cognitive domain performance.

Assessment of psychiatrists' approaches regarding disclosure of psychiatric disorders to their patients: a qualitative study.

Background: Diagnosis disclosure is the result of a shift in medical approaches from traditional paternalism to participatory and patient-centered decision making. Disclosure of psychiatric diagnosis remained uncommon and controversial. Giving information about psychiatric illnesses is very complicated, and it is affected by several factors. While clinical guidelines provide a clear pathway for treating patients, in practice, the treatment of patients is influenced by cultural and social factors. The aim of the current study was a qualitative assessment of psychiatrists' approaches regarding the disclosure of psychiatric disorders to their patients. Methods: The current study was conducted with a qualitative approach. The participants were purposefully selected psychiatrists from three medical universities in Tehran, Iran. The data gathered using the semi-structured interview method. Sixteen interviews with 14 psychiatrists were conducted. Data were analyzed using thematic analysis. Results: Psychiatrists decide to disclose the diagnosis based on several factors. We summarized these factors in a central theme, passive situational decision making based on paternalism and displacement of responsibility. It has two subthemes, including "passive and situational decision making" and "paternalism and displacement of responsibility." Each theme presented by detailed quotations. Conclusion: The results of this study showed that psychiatrists did not actively disclose the diagnosis name to patients. Diagnosis disclosure was influenced by several factors, such as the certainty about the diagnosis and the severity of the disease. This passive approach does not respect the patient's rights. The paternalistic nature of this approach mandates psychiatrists to consider themselves as the responsible perosn for their patients' welfare.

Validity and reliability of the Persian version of "drug-related knowledge and attitude questionnaire" among Iranian medical students.

BACKGROUND: Promoting drug-related knowledge and improving relevant attitudes among students are of crucial importance toward the prevention of drug misuse. Objective: This study aimed to assess the validity and reliability of the "drug-related knowledge and attitude questionnaire" among Iranian medical students. Methods: The participants of this cross-sectional study were students of Iran University of Medical Sciences. The "drug-related knowledge and attitude questionnaire" and a socio-demographic questionnaire were used to gather the data. Content validity was assessed by a panel of 11 experts, and face validity was evaluated by 10 participating students. Item-total correlation and Cronbach's alpha coefficients were used as internal consistency estimates. Results: The face and content validity of the questionnaire were satisfactory. The overall content validity index was .82. Cronbach's alpha was .679, indicating an acceptable degree of internal consistency and homogeneity between the items. Overall, most of the students had adequate knowledge about the harmful effects of addictive substances (48.11 ± 3.26). Conclusions: The "drug-related knowledge and attitude questionnaire" has favorable validity and reliability to assess the knowledge and attitude of Iranian students toward drug misuse and may be used in clinical and epidemiological studies. Besides, our findings can provide a suitable starting point for the implementation of effective psychoeducational interventions aimed at the improvement of the students' knowledge and attitudes toward drug misuse.

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.

DNA hypermethylation of serotonin transporter gene promoter in drug naïve patients with schizophrenia.

INTRODUCTION: Dysfunctional serotonin signaling has been linked to the pathogenesis of autism, obsessive compulsive disorder, mood disorders and schizophrenia. While the hypo-activity of serotonin signaling is involved in the pathogenesis of depression, anxiety and obsessive compulsive disorder; LSD, an agonist of serotonin type 2 receptor (5-HTR2A) induces psychosis. Therefore, anxiety and depressive disorders are treated by SSRIs which inhibit serotonin transporter (5-HTT) while psychotic disorders are controlled by drugs that block serotonin and/or dopamine receptors. Since genetic polymorphisms and epigenetic dysregulation of 5-HTT are involved in the pathogenesis of mental diseases, we analyzed DNA methylation of 5-HTT promoter in post-mortem brains and saliva samples of patients with schizophrenia (SCZ) and bipolar disorder (BD) to evaluate its potential application as a diagnostic and/or therapeutic biomarker in SCZ and BD. METHODS: Whole genome DNA methylation profiling was performed for a total of 24 samples (including two saliva samples) using the Illumina 27K (for 12 samples) and 450K DNA methylation array platform (for another 12 samples), followed by bisulfite sequencing to identify candidate CpGs for further analysis. Quantitative methylation specific PCR (qMSP) was used to assess the degree of CpG methylation of 5-HTT promoter in 105 post-mortem brains (35 controls, 35 SCZ and 35 BD) and 100 saliva samples (30 controls, 30 SCZ, 20 BD and 20 first degree relatives of SCZ or BD). The U133 2.0 Plus Human Transcriptome array for a total of 30 post-mortem brain samples (each group 10) followed by quantitative real-time PCR was used to study 5-HTT expression in 105 post-mortem brain samples. RESULTS: The qMSP analysis for 5-HTT promoter region showed DNA hypermethylation in post-mortem brain samples of SCZ patients (~30%), particularly in drug free patients (~60%, p=0.04). Similarly, there was a trend for DNA hypermethylation in antipsychotic free BD patients (~50%, p=0.066). qMSP analysis of DNA extracted from the saliva samples also exhibited hypermethylation of 5-HTT promoter in patients with SCZ (~30%, p=0.039), which was more significant in drug naïve SCZ patients (>50%, p=0.0025). However, the difference was not significant between the controls and unaffected first degree relatives of patients with SCZ (p=0.37) and versus patients using antipsychotic drugs (p=0.2). The whole genome transcriptome analysis of post-mortem brain samples showed reduced expression of 5-HTT in SCZ compared to the control subjects (~50%, p=0.008), confirmed by quantitative real-time PCR analysis (~40%, p=0.035) which was more significant in drug free SCZ patients (~70%, p=0.022). CONCLUSION: A correlation between reduction in 5-HTT expression and DNA hypermethylation of the 5-HTT promoter in drug naïve SCZ patients suggests that an epigenetically defined hypo-activity of 5-HTT may be linked to SCZ pathogenesis. Furthermore, this epigenetic mark in DNA extracted from saliva can be considered as one of the key determinants in a panel of diagnostic and/or therapeutic biomarkers for SCZ.

DNA hypomethylation of MB-COMT promoter in the DNA derived from saliva in schizophrenia and bipolar disorder.

The failure in the discovery of etiology of psychiatric diseases, despite extensive genetic studies, has directed the attention of neuroscientists to the contribution of epigenetic modulations, which play important roles in fine-tuning of gene expression in response to environmental factors. Previously, we analyzed 115 human post-mortem brain samples from the frontal lobe and reported DNA hypo methylation of the membrane-bound catechol-O-methyltransferase (MB-COMT) gene promoter, associated with an increased gene expression, as a risk factor for schizophrenia (SCZ) and bipolar disorder (BD). Since most epigenetic modifications are tissue specific and the availability of brain tissue to identify epigenetic aberrations in living subjects is limited, detection of epigenetic abnormalities in other tissues that represent the brain epigenetic marks is one of the critical steps to develop diagnostic and therapeutic biomarkers for mental diseases. Here, hypothesizing that; those factors that lead to the brain MB-COMT promoter DNA hypo-methylation may also cause concurrent epigenetic aberrations in peripheral tissues, we analyzed MB-COMT promoter methylation in DNA derived from the saliva in SCZ, BD and their first-degree relatives (20 cases each) as well as 25 control subjects. Using bisulfite DNA sequencing and quantitative methylation specific PCR (qMSP), we found that similar to the brain, MB-COMT promoter was hypo-methylated (∼50%) in DNA derived from the saliva in SCZ and BD compared to the control subjects (p = 0.02 and 0.037, respectively). These studies suggest that DNA methylation analysis of MB-COMT promoter in saliva can potentially be used as an available epigenetic biomarker for disease state in SCZ and BD.

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.