The relationship of the methylation status and polymorphism of glucocorticoid receptor gene (NR3C1) with attempted suicide or non-suicidal self-injury patients in schizophrenia.

We aim to investigate the methylation of NR3C1 gene promotor and NR3C1 BclI polymorphism in schizophrenia (SCZ) patients with attempted suicide or non-suicidal self-injury (NSSI). A sample of 112 patients with SCZ was included in the study. Structured Clinical Interview for Diagnostic and Statistical Manual-Fourth Edition Axis I Disorders was used to confirm the diagnosis according to The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. The patients were evaluated by data forms that had sociodemographic, suicidal behavior, and NSSI information. Methylation-specific polymerase chain reaction (PCR) was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR restriction fragment length polymorphism. Our results revealed that although the NR3C1 gene methylation was not statistically significantly different, there was a significant difference in NR3C1 genotype distribution among the SCZ groups with and without attempted suicide. SCZ patients carrying the CC genotype had a lower risk of attempted suicide (Odds Ratio [OR]: 0.421; 95% Confidence Interval [CI]: 0.183-0.970; p = 0.040), while having the GG genotype in SCZ patients was associated with a higher risk of attempted suicide (OR: 3.785; 95% Cl: 1.107-12.945; p = 0.042). Additionally, due to NSSI in SCZ patients, there were no significant differences in NR3C1 gene methylation and NR3C1 genotype distribution among the groups. We propose that the NR3C1 BclI polymorphism may be associated with attempted suicide in Turkish patients diagnosed with SCZ.

IL2RA rs2104286 and IL2 rs2069762 polymorphisms may be associated with bipolar disorder and its clinical findings.

Study results supported that immuno-inflammatory pathways in the brain and environment contribute to the etiopathogenesis of bipolar disorder (BD), a chronic affective disease. Our study aimed to assess the relationship between BD risk and interleukin 2 (IL2) and interleukin 2 receptor subunit alpha (IL2RA) variants in a Turkish population. Genomic DNA from 86 diagnosed BD patients and 100 healthy blood donors was extracted. IL2RA rs2104286, IL2 rs2069762, and IL2 rs2069763 variants were genotyped using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. It was compared to the relationship between the genotype distributions of these variants and clinical characteristics. Results were evaluated statistically. A statistically significant difference in the genotype distribution of the IL2RA rs2104286 variant was found between patients and controls. There was no GG genotype in the patient group. The IL2RA rs2104286 AA genotype was more common in the patient group than the controls, and the AG genotype was higher in the controls compared to the patients (p = 0.001, p = 0.001, respectively). The IL2 rs2069762 and IL2 rs2069763 genotype distributions did not differ between the patient and control groups (p > 0.05). We found that the clinical global impression severity (CGI-S) score was higher in those with IL2 rs2069762 TG and GG genotypes. In this study, we showed for the first time that the genotype distribution of IL2RA rs2104286 and IL2 rs2069762 is associated with BD susceptibility and CGI-S score in a Turkish population.

Genetic polymorphism of IL-17F rs763780 contributes to the susceptibility to bipolar disorder but not to schizophrenia in the Turkish population.

This study aims to investigate the genetic polymorphism in the interleukin-17F (IL-17F) (rs763780, 7488 A/G) gene in bipolar disorder (BD) and schizophrenia (SCZ) patients by comparing it with healthy controls considering clinical parameters. A sample of 107 patients with BD, 129 patients with SCZ, and 100 healthy volunteers were included. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM-D) were administered to BD patients. The Positive and Negative Symptoms Scale (PANSS) was applied to the patients with SCZ. PCR-RFLP was used to determine IL-17F gene polymorphism. Our results demonstrated that the distributions of the IL-17F genotype and the allele frequencies of BD patients were statistically significantly different from the control group. The AA genotype (OR: 0.283; 95% Cl: 0.140-0.573; p<.001) and A allele (OR: 0.333; 95% Cl: 0.171-0.646; p=.001) frequencies were significantly higher in the control group than in the BD group. The IL-17F genotype and the allele frequency distributions of SCZ patients were not statistically significantly different from the control group. When comparing scale scores due to the IL-17F genotype distributions in patients with BD or SCZ, there was no statistically significant difference between the groups of IL-17F genotypes. In summary, whereas the IL-17F polymorphism may be associated with BD, this polymorphism was not related to SCZ.

Treatment of Major Depression with Psychotic Features and Cotard's Syndrome after COVID-19 Infection in a Previously Healthy Patient: A Case Report.

BACKGROUND: COVID-19 pandemic is related to anxiety, depression, and psychotic symptoms either directly due to invasion or inflammation caused by the virus or indirectly due to related psychosocial stress: fear of infection, social isolation, and financial burden. CASE PRESENTATION: We present a 28-year-old female case of post-COVID major depression with psychotic features and Cotard's syndrome with no previous psychiatric history. Her complaints initially described the sadness of mood with early morning worsening, diminished interest in almost all activities, anhedonia, increased anxiety, ideas of worthlessness, hopelessness, guilt, decreased sleep, and appetite. Then, she developed severe depression with psychotic features such as delusions of persecution, poverty, and nihilism. Nihilistic delusions included a description of everything coming to an end. She thought that her organs were no more working. Later, she negated her existence and started believing that she was dead. The patient recovered after a combination of sertraline and olanzapine treatment. CONCLUSION: This case of a COVID-19 patient with psychotic depression and Cotard's delusion highlights the importance of evaluating mental health status and may contribute to our understanding of the potential risk of central nervous system impairment by SARS-CoV-2 infection.

Quantitative detection of methylated SOCS-1 in schizophrenia and bipolar disorder considering SOCS-1 -1478CA/del polymorphism and clinical parameters.

BACKGROUND: We aimed to investigate the quantitative detection of methylated suppressor of cytokine signaling-1 (SOCS-1) in schizophrenia (SCZ) and bipolar disorder (BD), considering SOCS-1 -1478CA/del polymorphism and clinical parameters. METHODS: Our research is a case-control study in which 114 patients with SCZ, 86 patients with BD, and 80 volunteers as a healthy group participated. Bisulfite-converted DNA samples were analyzed using the real-time quantitative methylation-specific PCR (qMS-PCR) method to measure the methylation level of the SOCS-1 gene. In addition, SOCS-1 -1478CA/del gene polymorphism was analyzed with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: When the SOCS-1 promoter methylation levels of SCZ and BD patients were compared with the control group, the methylation levels of SCZ and BD were significantly lower than the control group. An earlier age of illness onset was significantly related to the SOCS-1 promoter hypermethylation in DNA samples of SCZ patients. Again, SOCS-1 promoter hypermethylation was significantly associated with the higher Young Mania Rating Scale (YMRS) score in BD patients. While the SOCS-1 CA/CA genotype frequency was significantly higher in the control group than in the BD group, the del/del genotype was significantly related to a higher frequency of rapid cycling and a lower frequency of family history in the BD patient group. CONCLUSION: In summary, the methylated SOCS-1 quantity in DNA samples of SCZ and BD patients were significantly lower than in control samples. Whereas the SOCS-1 -1478CA/del polymorphism was not related to SCZ, it may be associated with the BD.

Evaluation of Serum Complement Levels and Factors Affecting Treatment Resistance in Patients with Schizophrenia.

Background: There are increasing investigations about the potential role of the complement system in disorders affecting the central nervous system, including schizophrenia. Therefore, we aim to evaluate the levels of complement 3 and complement 4 and the factors affecting treatment resistance in schizophrenia patients. Methods: This cross-sectional study was conducted between January 2020 and January 2021 and included schizophrenia patients resistant to treatment or in remission and healthy controls. The Structured Clinical Interview for Diagnostic and Statistical Manual-5 was used to confirm the diagnosis according to Diagnostic and Statistical Manual -5 criteria. We evaluated the patients with some scales and forms. The complement 3 and complement 4 levels were measured from blood samples. Results: In the treatment-resistant schizophrenia group, complement 3 (P = .001) and complement 4 (P = .001) levels were significantly higher compared to schizophrenia patients in remission and healthy controls. While the Brief Psychiatric Rating Scale (P < .001), the Positive and Negative Syndrome Scale-positive (P < .001), the Positive and Negative Syndrome Scale-negative (P < .001), the Positive and Negative Syndrome Scale-psychopathology (P < .001), the Positive and Negative Syndrome Scale-total (P < .001), and the Clinical Global Impression Scale-Severity (P < .001) scores were significantly higher in treatment-resistant schizophrenia patients, the General Assessment of Functioning (P < .001), and Beck Cognitive Insight Scale (P < .001) scores were significantly lower compared to the other groups. In schizophrenia patients, complement 3 levels were positively correlated with the Positive and Negative Syndrome Scale-negative (P = .046), the Positive and Negative Syndrome Scale-psychopathology (P = .001), the Positive and Negative Syndrome Scale -total (P = .025), and Clinical Global Impression Scale-Severity of Disease (P = .004). Also, complement 4 levels were positively correlated with Brief Psychiatric Rating Scale (P = .004), the Positive and Negative Syndrome Scale-positive (P = .003), the Positive and Negative Syndrome Scale -negative (P = .014), the Positive and Negative Syndrome Scale-psychopathology (P < .001), the Positive and Negative Syndrome Scale-total (P = .002), and Clinical Global Impression Scale-Severity of Disease (P = .001) in patients with schizophrenia. It was determined that a higher C4 level increased the risk of treatment resistance (odds ratio: 1.133, 95% CI: 1.012-1.268; P = .030), while a higher Beck Cognitive Insight Scale score decreased the risk of treatment resistance (odds ratio: 0.317, 95% CI: 0.191-0.526; P < .001). Conclusion: In light of the analyses, it can be said that complement concentration increases in certain stages of schizophrenia, and its imbalance may be associated with symptom severity and treatment resistance.

PERIOD3 (PER3) VNTR Variant Associated with Seasonal Pattern and Family History in Bipolar Disorder.

BACKGROUND: Dysregulation of circadian rhythms has been thought to be associated with psychiatric disorders such as bipolar disorder (BD) and depression. We aimed to evaluate the relationship between clinical specifiers of BD, mainly seasonal pattern (SP), and the variable number tandem repeat (VNTR) variant of the PERIOD3 (PER3) gene (rs57875989) in BD patients by comparing genotype distributions with healthy controls considering clinical parameters. SUBJECTS AND METHODS: A sample of 98 BD patients and 97 healthy volunteers were included in the study. The Clinical Interview for DSM-IV Axis-I Disorders (SCID-I) was administered to all participants. The patients were evaluated with some scales (Sociodemographic and Clinical Data Form, The Young Mania Rating Scale (YMRS), the Hamilton Depression Rating Scale (HAM-D), and The Clinical Global Impression Scale (CGI)) in terms of clinical features and symptom severity. Blood samples were obtained from participants to isolate their DNA. PCR-RFLP was used to determine the PER3 gene variant. RESULTS: The PER3 genotype (4/4, 4/5, 5/5) distribution of BD was found to be significantly different from the control group. There was a statistically significant difference in the PER3 genotype distribution between BD patients with SP and BD patients without SP. Again, the PER3 allele (4, 5) distributions of BD patients with the SP were statistically different from the control group. The BD patients' PER3 genotype distributions with a family history of BD were significantly different from the BD patients without family history or control group. CONCLUSION: It was found that the VNTR variant of the PER3 gene (rs57875989) may be associated with the SP and family history of BD as well as the BD itself. Further studies with the VNTR variant of the PER3 gene (rs57875989) in different ethnic populations are also required to determine these polymorphisms' exact role in BD.

DNA Methylation Pattern of Gene Promoters of MB-COMT, DRD2, and NR3C1 in Turkish Patients Diagnosed with Schizophrenia.

Objective: We aim to evaluate the methylation status of membrane-bound catechol-O-methyltransferase (MB-COMT) promotor, dopamine receptor D2 (DRD2), and nuclear receptor subfamily 3 group C member 1 (NR3C1) gene in pa- tients with SCZ by comparing healthy controls. Methods: A sample of 110 patients with SCZ and 100 age- and sex-matched healthy volunteers was included in the study. The interview was started by filling out data forms that included sociodemographic and clinical information. The Structured Clinical Interview for DSM-IV Axis I Disorders was used to confirming the diagnosis according to DSM-IV-TR criteria. Then the patients were evaluated with the Positive and Negative Symptoms Scale in terms of symp- tom severity. Methylation-specific polymerase chain reaction was used to determine the methylation status of MB-COMT promotor, DRD2 , and NR3C1 gene from DNA material. Results: When we compared the percentages of MB-COMT promotor, DRD2, and NR3C1 gene methylation status in SCZ patients with the healthy control group, the percentages of MB-COMT promotor (OR: 0.466; 95% CI: 0.268- 0.809; p = 0.006), DRD2 (OR: 0.439; 95% CI: 0.375-0.514; p < 0.001), and NR3C1 (OR: 0.003; 95% CI: 0.001- 0.011; p < 0.001) gene methylation status of SCZ was found to be significantly different from the control group. Whereas unmethylation of MB-COMT promotor and NR3C1 genes were associated with SCZ, the partial methylation of the DRD2 gene was related to the SCZ. Conclusion: The MB-COMT promotor, DRD2, and NR3C1 gene methylation status may be associated with the SCZ in the Turkish population.

The Association Between the Duration of Breastfeeding in Infancy and Adult Psychopathology: A Cross-Sectional Study in Turkey.

AIM: To evaluate the association of duration of breastfeeding in infancy and adulthood psychiatric disorders, sexual problems, and clinical features of patients in the Turkish population. METHOD: A sample of 166 patients with depressive disorder, anxiety disorders, obsessive-compulsive disorder, or trauma and stressor-related disorders were consecutively gathered from the outpatient clinic in March-May 2021 in a cross-sectional descriptive study. The patients with a breastfeeding time of fewer than 6 months and equal or more than 6 months were compared in terms of sociodemographic and clinical characteristics, scale scores, and current or lifelong psychiatric disorders. RESULTS: The percentages of the history of psychiatric disorder (p = .009), the number of comorbid psychiatric disorders (p = .020), and the patients diagnosed with current (p = .001) and lifetime (p = .004) panic disorder or lifetime vaginismus (p = .019) were significantly higher in the patients with a breastfeeding time fewer than 6 months compared to the patients with more than 6 months. While the duration of maternal (p = .010) and paternal education (p = .004) was significantly higher, the birth order was significantly lower (p = .010) in the patients with a breastfeeding time of fewer than 6 months compared to the patients with more than 6 months. CONCLUSION: Breastfeeding time of more than 6 months seems favorable in terms of the absence of current or lifetime psychiatric disorder, especially panic disorder and vaginismus, compared to the patients with fewer than 6 months.

COMTVal158Met polymorphism is associated with ecstasy (MDMA)-induced psychotic symptoms in the Turkish population.

OBJECTIVES: To investigate catechol-O-methyltransferase (COMT) Val158Met gene polymorphism in MDMA use disorder (MUD) by comparing genotype distributions between MUD patients and healthy controls considering clinical parameters. METHODS: Eighty-two MUD patients' were consecutively admitted to the outpatient psychiatry clinic in May 2019-January 2020, and 95 healthy volunteers were included in the case-control study. We used the polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) to determine COMT Val158Met polymorphism. RESULTS: The COMT Val158Met genotype distribution and allele frequencies of the MUD patient group were significantly different from the healthy control group. The Met/Met genotype (OR: 2.692; 95% Cl: 1.272-5.698; p=0.008) and Met allele frequencies (OR: 1.716; 95% Cl: 1.118-2.633; p=0.013) were significantly higher in the control group than in MUD patients. When the COMT Val158Met genotype and allele frequency distributions were compared between 2 groups according to the psychotic symptoms in the MUD patient group, the COMT Val158Met genotype distributions were significantly different between the groups of patients. The percentage of patients with the Val/Val genotype was significantly lower in MUD patients with a psychotic symptom than the MUD patients without a psychotic symptom (OR: 2.625; 95% Cl: 1.069-6.446; p=0.033). CONCLUSION: The COMT Val158Met gene polymorphism was found to be related to the MUD-diagnosed Turkish patients and MDMA-induced psychotic symptoms.

Tumor Necrosis Factor-alpha (TNF-α) -238 G/A Polymorphism Is Associated with the Treatment Resistance and Attempted Suicide in Schizophrenia.

Abnormality of the immune system may play an important role in the pathogenesis of schizophrenia (SCZ). We aim to investigate the relationship between clinical features of SCZ and tumor necrosis factor-alpha (TNF-α) -238 G/A, -308 G/A polymorphisms in SCZ patients by comparing genotype distributions of TNF-α gene polymorphisms between patients and healthy controls. A sample of 113 patients with SCZ and 104 healthy volunteers was included in the study. SCID-I was used to confirming the diagnosis according to DSM-IV-TR criteria. We evaluated the patients with some scales and data forms in terms of clinical features, symptom severity, level of insight, suicidal behavior, and treatment response. PCR-RFLP was used to determine TNF-α gene polymorphisms from DNA material. The distributions of TNF-α - 238 G/A and TNF-α - 308 G/A polymorphisms of the patients diagnosed with SCZ were not significantly different from the control group. There was a significant difference in the TNF-α - 238 G/A genotype distributions between treatment-resistant and treatment-responsive SCZ patients. Again, the distributions of TNF-α - 238 G/A genotype of attempted suicide patients in SCZ were significantly different from the non-attempted suicide of SCZ patients. Whereas TNF-α - 238 G/A and -308 G/A polymorphisms were not associated with SCZ, TNF-α - 238 G/A polymorphism may be related to treatment resistance and attempted suicide in SCZ patients in the Turkish population.

Macrophage Migration Inhibitory Factor - 173 G/C Polymorphism is Associated With The Age of Onset and Insight in Schizophrenia in the Turkish Population.

OBJECTIVE: To evaluate the genetic variant in the macrophage migration inhibitory factor (MIF) -173 G/C in patients with schizophrenia (SCZ) by comparing genotype distributions of MIF -173 G/C between patients and healthy controls considering clinical parameters. METHODS: A sample of 118 patients with SCZ and 100 healthy volunteers were included in the study. The patients were evaluated with some scales in terms of clinical features (symptom severity, level of insight, age of onset, and treatment resistance). The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine gene polymorphism. RESULTS: There was a statistically significant difference between the allele frequency (G, C) distributions of SCZ patients with early- and adult-onset. The C allele frequency was significantly higher in SCZ patients with early-onset (p = .033). According to the impairment of insight, we observed statistically significant differences in genotype (GG, GC, CC) distributions between SCZ patients with good and poor insight. SCZ patients with poor insight had a higher GG genotype frequency than SCZ patients with good insight (p = .021). Again, there was a statistically significant difference between genotype groups (GG, GC/CC) regarding the age of illness onset (p = .037) and schedule for assessing the three components of insight (SATCI) score (p = .005). While the age of onset of SCZ was significantly earlier in patients with the GC/CC genotype, SATCI scores of SCZ patients with the GG genotype were significantly lower than SCZ patients with GC/CC genotype. CONCLUSIONS: MIF -173 G/C polymorphism may be associated with the age of illness onset and impairment of insight in SCZ.

Detection of altered methylation of MB-COMT promotor and DRD2 gene in cannabinoid or synthetic cannabinoid use disorder regarding gene variants and clinical parameters.

This study aims to investigate the association between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and methylation status of MB-COMT (membrane-bound catechol-O-methyltransferase) promotor or DRD2 gene considering gene variants and clinical parameters. Based on the DSM-5 criteria, 218 CUD/SCUD patients' diagnoses were confirmed with a positive urine test, and a control group consisting of 102 participants without substance use disorders was included. Methylation-specific PCR was used to identify the methylation of the MB-COMT promotor and DRD2 gene. DRD2-141C Ins/Del and COMT Val158Met gene variants were evaluated by using PCR-RFLP. When the DRD2 and MB-COMT promoter methylation of CUD/SCUD patients were compared with the control group, there was a significant difference between the MB-COMT promoter methylation status of the two groups. When comparing DRD2 gene methylation due to clinical parameters and DRD2 genotype distribution in patients, the methylation status was significantly different between the groups due to the family history. Again, comparing the MB-COMT promotor methylation due to the COMT Val158Met genotype distribution and clinical parameters in patients, the MB-COMT promoter methylation status was significantly different between the groups due to the presence of alcohol usage. In summary, whereas the MB-COMT promoter methylation may be associated with the CUD/SCUD, the methylation of the DRD2 gene was not related to CUD/SCUD.

Global and glucocorticoid receptor gene-specific (NR3C1) DNA methylation analysis in patients with cannabinoid or synthetic cannabinoid use disorder.

This study investigates the relationship between cannabinoid use disorder (CUD) or synthetic cannabinoid use disorder (SCUD) and the global methylation, methylation of NR3C1 gene promotor, and NR3C1 BclI polymorphism, considering clinical parameters. Based on the DSM-5 criteria, 172 SCUD patients' and 44 CUD patients' diagnoses were confirmed with a positive urine test; 88 healthy volunteers were also included in the study. Global DNA methylation was measured using a 5-methylcytosine (5-mC) DNA ELISA Kit. Methylation-specific PCR was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR-RFLP. Our results demonstrated that the mean of 5-mC percentages of SCUD patients differed significantly from those of the control group. When comparing NR3C1 gene methylation and clinical parameters due to NR3C1 genotype distribution in patients, the genotype distribution was significantly different between the groups, due to the former polysubstance abuse. Additionally, there was a significantly positive correlation between the 5-mC percentages of SCUD patients and the reported durations of their disorders. In summary, whereas global DNA methylation may be associated with SCUD, the methylation of the NR3C1 gene and NR3C1 BclI polymorphism were not related to CUD or SCUD.

Comparison of Clinical Features of Bipolar Disorder Patients with and without Psychiatric Comorbidity.

OBJECTIVE: Bipolar disorder (BPD) is a psychiatric condition that often manifests together with Axis-I comorbidity. Comorbidity of psychiatric disorders influences the recognition, prognosis, and treatment of the disorder, posing difficulties for the patient and physician. This study aims at identifying Axis-I comorbidities and their characteristics in patients with BPD. MATERIALS AND METHODS: This retrospective study included 255 patients diagnosed with BPD according to the DSM-IV. Comorbidities were determined using the SCID-I, a semistructured sociodemographic data form developed by the authors, and a mood chart assessing clinical aspects. The patients were divided into 2 groups, those with and without comorbidity, and compared. RESULTS: Out of these 255 patients, 35% was found to have a current and 84.3% a lifelong comorbid psychiatric disorder. About 33.1% of these patients had 1, 11.3% had 2, and 8.8% had more than 2 comorbid disorders. At least one comorbid anxiety disorder was found in 38.7% of the patients. Obsessive and compulsive disorder (OCD) being the most common comorbid psychiatric disorder, followed by social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Comparing the clinical parameters between the 2 groups due to the presence of psychiatric comorbidity in the BD patients, there were statistically significant differences in terms of the number of depressive episodes (P = .041) and mania/hypomania (P = .048), and the need for antipsychotic monotherapy (P = .007) and antidepressants (P = .001) for prophylaxis between the 2 groups. CONCLUSION: Axis-I psychiatric disorders and particularly OCD and anxiety disorders accompanying BPD prevail at a high rate. The presence of comorbid psychiatric disorder in BPD may negatively affect the clinical prognosis of the condition; therefore, this area requires more study and careful investigation.

TNF-α-308 G/A variant may be associated with bipolar disorder in a Turkish population

ABSTRACT Background: Tumor necrosis factor alpha (TNF-α) is a proinflammatory multifunctional cytokine produced by macrophages. A dysregulation of the immune system contribute to the pathogenesis of bipolar disorder (BD). In this study, we aimed to investigate the relationship between the TNF-α gene -308G/A promoter variant and the risk of BD. Methods: A total of 104 BD patients and 94 healthy controls were enrolled in the study. Genomic DNA was isolated and TNF-α -308G/A variant was analyzed using PCR-RFLP method. Results: TNF-α -308G/A variant GG genotype and G allele were more prevalent in BD patients compared to the controls (p = 0.002 and p = 0.017, respectively). The patients carrying GG genotype had a 5.927-fold higher risk of developing BD. Then, we divided patients into two groups as smokers and non-smokers. TNF-α -308G/A variant GA genotype was higher in non-smoker BD patients than smoker patients (p = 0.027). We found that TNF-α -308G/A AA genotype and A allele increased in smoker patients compared to non-smoker patients (p = 0.008, p = 0.002, respectively). Discussion: Our results provided evidence that TNF-α -308G/A variant may contribute to development of BD in a Turkish cohort. In addition, this variant plays a relevant role in the smoker status of BD.

Evaluation of COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in synthetic cannabinoid use disorder patients.

Synthetic cannabinoids (SC) are psychoactive drugs that generally produce more severe clinical outcomes compared to Δ9-tetrahydrocannabinol. This study aimed to evaluate the relationship between clinical features of synthetic cannabinoid use disorder (SCUD) and COMT (rs4680), CNR2 (rs2501432), CNR2 (rs2229579), UCP2 (rs659366), and IL-17 (rs763780) gene variants in SCUD patients by comparing the genotype distributions of gene variants between patients and healthy controls. Based on the DSM-5 criteria, 94 patients with SCUD, confirmed with a positive urine test, and 95 healthy volunteers were included in the study. Self-mutilation, suicidal behavior, psychotic symptoms, drug-induced psychosis, tobacco use disorder (TUD) or alcohol use disorder (AUD) comorbidity, and family history of TUD or AUD were evaluated in all patients. PCR-RFLP was used to identify gene variants from DNA material. The distributions of CNR2 (rs2229579) and UCP2 (rs659366) variants were significantly different in patients diagnosed with SCUD compared to the control group. SC-related psychotic symptoms were associated with the IL-17 (rs763780) variant in SCUD patients who had an onset of SC usage under 18 years of age. While the COMT Val108Met gene variant was related to self-mutilation, the COMT Val158Met variant was associated with attempted suicide. In addition, in SCUD patients, the UCP2 (rs659366) variant was associated with a family history of AUD or TUD. In summary, CNR2 (rs2229579) and UCP2 (rs659366) variants were associated with SCUD. While SC-related psychotic symptoms were related to the IL-17 (rs763780) variant, the COMT variants were associated with self-mutilation or attempted suicide in SCUD patients.

Association of MIF and MBL2 gene polymorphisms with attempted suicide in patients diagnosed with schizophrenia or bipolar disorder.

The aim of this study to investigate the genetic polymorphisms in macrophage inhibitory factor (MIF) and mannose-binding lectin 2 (MBL2) gene in schizophrenia (SCZ) or bipolar disorder (BD) patients with attempted suicide by comparing with a non-attempted SCZ or BD patients and healthy controls. A sample of 108 patients with SCZ, 100 patients with BD and 100 healthy volunteers were included in the study. SCID-I was used to confirm the diagnosis according to DSM-IV-TR criteria. The patients were evaluated by data forms that included sociodemographic, suicidal behavior and symptom severity information. PCR-RFLP was used to determine MIF and MBL2 gene polymorphisms from DNA material. Our results demonstrated that the distributions of MBL2 genotype (AA, AB, BB), combined genotype (AA, AB/BB) and the allele frequencies (A, B) of attempted suicide patients in SCZ were significantly different from the non-attempted SCZ patients. The distributions of the MBL2 genotype of attempted suicide patients in SCZ were significantly different from the control group. The distributions of MIF genotype (GG, GC, CC), combined genotype (GG, GC/CC) and the allele frequencies (G, C) of attempted suicide patients in BD were significantly different from the non-attempted BD patients or control group. In summary MBL2 gene polymorphism may be associated with attempted suicide in SCZ and MIF gene polymorphism might be associated with attempted suicide in BD. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of these polymorphisms in SCZ or BD.