Association of 11 variants of the dopaminergic and cognitive pathways genes with major depression, schizophrenia and bipolar disorder in the Pakistani population.

Background: The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic and cognitive pathway genes association with these disorders however, no such comprehensive data was available regarding the Pakistani population.Objective: The present study was conducted to analyse the 11 genetic variants of dopaminergic and cognitive system genes in MDD, SHZ, and BD in the Pakistani population.Methods: A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were screened for 11 genetic variants through polymerase chain reaction (PCR) techniques. Univariant followed by multivariant logistic regression analysis was applied to determine the genetic association.Results: Significant risk associations were observed for rs4532 and rs1799732 with MDD; and rs1006737 and rs2238056 with BD. However, after applying multiple test corrections rs4532 and rs1799732 association did not remain significant for MDD. Moreover, a protective association was found for three variants; DRD4-120bp, rs10033951 and rs2388334 in the current cohort.Conclusions: The present study revealed the risk association of single nucleotide polymorphisms (SNPs) rs1006737 and rs2238056 with BD and the protective effect of the DRD4-120bp variant in MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani cohort. Thus, the study is valuable in understanding the genetic basis of MDD, BD and SHZ in the Pakistani population, which may pave the way for future functional studies.

Contributing risk factors of common psychiatric disorders in the Pakistani population.

With an increasing incidence of psychiatric disorders worldwide, there is a need for a better understanding of the population-specific contributing risk factors that are associated with common psychiatric conditions. This study aimed to assess the correlation between socioeconomic, environmental and clinical features associated with major depression (MDD n = 479), bipolar disorder (BD n = 222) and schizophrenia (SHZ n = 146), in the Pakistani population. Multinomial logistic regression and Pearson's correlation were applied to assess the association and correlation between demographic, socioeconomic, environmental, and clinical features of MDD, BD and SHZ. In the present study, MDD was found to be more prevalent than BD and SHZ. The average age at onset (AAO), was observed to be earlier in females with BD and SHZ, in addition, females with a positive family history of MDD, BD and SHZ also had an earlier AAO. The fitted multinomial logistic regression model indicated a significant association of; aggression, tobacco use, drugs abuse, history of head injuries and family history with BD as compared to MDD, while insomnia and suicidality were significantly associated with MDD. Strong positive correlations were observed mainly between age/AAO, AAO/tobacco use and aggression/insomnia in all three cohorts. In conclusion, the present study identifies possible contributing socio-demographic, biological and environmental factors that are correlated and associated with the psychiatric conditions in the Pakistani population.

Association of dopamine ß-hydroxylase polymorphism rs1611115 and serum levels with psychiatric disorders in Pakistani population.

AIM: Dopamine ß-hydroxylase (DBH) is a copper-containing enzyme that has an important role in maintaining the cellular homeostasis between the two neurotransmitters, dopamine (DA) and nor-adrenaline (NA). DBH functional polymorphisms are associated with multiple neuro-psychiatric conditions and are found to alter the DBH protein levels in serum affecting DBH enzymatic activity. The current study was conducted to determine the genetic and serum levels association of DBH rs1611115 functional polymorphism with major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SHZ) in the Pakistani population. METHODS: In total n = 1097 subjects including MDD (n = 427), BD (n = 204), SHZ (n = 134) and healthy controls (n = 332), were screened for the functional polymorphism by polymerase chain reaction-restriction fragment length polymorphism. Univariate logistic regression analysis was applied and the results were adjusted for age and sex. The DBH levels in serum were determined through enzyme-linked immunosorbent assay (ELISA) and the Mann Whitney U test was applied. RESULTS: The minor allele (-1021 C > T) was found to be significantly associated with a higher risk of developing BD and SHZ in both univariable and multivariable analyses. The overall total serum concentration of DBH was comparatively raised in MDD, however, in cross-comparison DBH serum levels were found markedly higher in CC homozygotes compared to TT homozygotes within the BD group. CONCLUSION: The present study suggested a significant association of DBH rs1611115 with BD and SHZ and also the effect of rs1611115 on DBH serum levels in MDD and BD for the first time in the Pakistani population.

Genetic Association of Butyrylcholinesterase with Major Depressive Disorder.

Major depressive disorder (MDD) is characterized as clinical depression, which primarily affects the mood and behaviour of an individual. In the present study butyrylcholinesterase (BChE), a co-regulatory cholinergic neurotransmitter enzyme implicated in several putative neuronal and non-neuronal physiological roles was investigated for its role in MDD. Eighty MDD patients and sixty-one healthy controls were recruited for the study. BChE activity was measured by Ellman's method using serum while DNA samples of the patients were genotyped for BCHE polymorphisms rs3495 (c.*189G > A) and rs1803274 (c.1699G > A) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and tetra-primer Amplification Refractory Mutation System- polymerase chain reaction (ARMS-PCR). The genotyping was further validated by Sanger Sequencing. Biochemical estimation of serum BChE levels revealed a statistically significant decrease of enzyme activity in MDD patients (69.96) as compared to healthy controls (90.97), which was independent of age and gender. BCHE single nucleotide polymorphism rs1803274 genotype GA was found to be associated with the disease under a dominant model (OR 2.32; 95% CI 1.09-4.96; p value = 0.025). Furthermore, risk allele-A frequency was higher in cases (p value = 0.013) than control. Carriers of rs1803274 GA genotype showed reduced mean BChE activity than wild-type allele GG homozygotes (p value = 0.040). Gender-based analysis revealed a protective role of rs3495 in females (χ2 = 6.87, p value = 0.032, RM: OR 0.173, CI = 0.043-0.699 (p value = 0.017). In addition, rs1803274 risk allele-A was observed to be significantly higher in males (χ2 = 4.258, p value = 0.039). In conclusion, the present study is indicative of a role of BChE in the pathophysiology of MDD where genetic polymorphisms were observed to effect BChE activity. Further replication studies in different ethnicities are recommended to validate the current observations.

Filicide In Depressive Psychosis: Case Report Of An Emotionally Unstable Woman Slaughtering Her Two Children.

Filicide is the murder of a child by the parent. It is associated with various psychiatric and nonpsychiatric conditions. We herein present a case report of a filicide by an emotionally unstable mother suffering from depressive psychosis. A thirty years old woman previously treated for depression with psychotic features, having undergone electro-convulsive therapy and on oral medication three years ago was brought by the police for psychiatric assessment. She had slaughtered her two sons of 4 and 7 years of age three days ago without any guilt or remorse. She had low mood, irritability, crying spells, hopelessness and loss of sleep, appetite and sexual desires for the past six months along with the delusions of poverty and infidelity for the past two months. She was a chain smoker. Multiple deliberate self-harm and suicidal attempts were reported in the past two months. She had disturbed family life and multiple conflicts with the husband. Psychometrics revealed BDI score of 32, BPRS score of 39 and PCL-R score of 28. She was diagnosed as a case of depressive psychosis with emotionally unstable personality traits leading to impaired judgment and poor comprehension of the consequences of her actions. This case report highlights the importance of accurately and timely diagnosing and managing a mental health disorder in order to avoid the harm towards self and others.

Comparison Of Effectiveness Of Antipsychotics In Schizophrenia: Second-Generation Versus The Irstgeneration.

BACKGROUND: The choice of the antipsychotic medication is based upon the risks, benefits and the cost. There has been still a debate that which group of antipsychotics is overall better amongst the two so we planned this study with the objective to compare the efficacy of the 1st & 2nd generation antipsychotics for the treatment of schizophrenia. METHODS: This RCT was conducted at in/out patient department of Psychiatry at a tertiary care hospital of Pakistan over the time period of six months. All the patients of schizophrenia between 18-50 years of age of either gender and all the socioeconomic groups were included in the study. Each patient was assessed with the Simpson-Angus Scale (SAS) for the EPS and the Positive and Negative Syndrome Scale (PANSS) for the schizophrenia at the baseline, 6 weeks and 12 weeks after starting the designated medication. RESULTS: The mean age of the 350 patients included in the study was 34.25±16.74 years. One hundred and forty-eight (42.3%) patients were female and 202 (57.7%) were male. The overall response of 1st Generation & 2nd Generation antipsychotics was 51 (140) 36% and 135 (210) 64% respectively (p-value=0.00024). Sixty-three (45%) patients who were taking 1st Generation Antipsychotics had relapse of the disease as compared to the 29 (13.7%) patients who were taking the 2nd Generation antipsychotics. Dryness of mouth, sedation and EPS were the common side effects with the 1st generation antipsychotics while dryness of mouth, cardiac arrhythmias, and sexual dysfunction were the common side effects with the 2nd generation antipsychotics. CONCLUSIONS: This study concluded that the 2nd generation antipsychotics were superior to the 1st generation antipsychotics among the patients of schizophrenia in terms of the success rate, relapse rate and the tolerability.

More anxious than depressed: prevalence and correlates in a 15-nation study of anxiety disorders in people with type 2 diabetes mellitus.

BACKGROUND: Anxiety disorder, one of the highly disabling, prevalent and common mental disorders, is known to be more prevalent in persons with type 2 diabetes mellitus (T2DM) than the general population, and the comorbid presence of anxiety disorders is known to have an impact on the diabetes outcome and the quality of life. However, the information on the type of anxiety disorder and its prevalence in persons with T2DM is limited. AIMS: To assess the prevalence and correlates of anxiety disorder in people with type 2 diabetes in different countries. METHODS: People aged 18-65 years with diabetes and treated in outpatient settings were recruited in 15 countries and underwent a psychiatric interview with the Mini-International Neuropsychiatric Interview. Demographic and medical record data were collected. RESULTS: A total of 3170 people with type 2 diabetes (56.2% women; with mean (SD) duration of diabetes 10.01 (7.0) years) participated. The overall prevalence of anxiety disorders in type 2 diabetic persons was 18%; however, 2.8% of the study population had more than one type of anxiety disorder. The most prevalent anxiety disorders were generalised anxiety disorder (8.1%) and panic disorder (5.1%). Female gender, presence of diabetic complications, longer duration of diabetes and poorer glycaemic control (HbA1c levels) were significantly associated with comorbid anxiety disorder. A higher prevalence of anxiety disorders was observed in Ukraine, Saudi Arabia and Argentina with a lower prevalence in Bangladesh and India. CONCLUSIONS: Our international study shows that people with type 2 diabetes have a high prevalence of anxiety disorders, especially women, those with diabetic complications, those with a longer duration of diabetes and poorer glycaemic control. Early identification and appropriate timely care of psychiatric problems of people with type 2 diabetes is warranted.

Relationship between the Quality of Sleep and Psychiatric Morbidity among the Patients of Head and Neck Tumours.

OBJECTIVE: To assess the difference between mean sleep (PSQI) scores in the patients with head and neck tumours with and without the psychiatric morbidity; and assess the associated socio-demographic factors. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Pakistan Institute of Medical Sciences (PIMS), Islamabad, from May to November 2017. METHODOLOGY: One hundred and seventy patients suffering from the tumours of head and neck region were analysed in this study, which were treated in the E.N.T Department. Pittsburgh Sleep Quality Index (PSQI) was used to record the sleep quality of the study participants. General Health Questionnaire 12 (GHQ-12) was used to look for the presence of psychiatric morbidity among these patients. Mean sleep scores were compared in the patients with and without the presence of psychiatric morbidity. Relationship of the socio-demographic factors was also studied with the presence of poor sleep quality among the study participants. RESULTS: A total of 170 patients filled the PSQI; out of them, 58 (34.1%) had scores lying within the range of normal sleep quality while 112 (65.9%) had insufficient quality of sleep. One hundred and eight (63.5%) patients had significant psychiatric morbidity; whereas, 62 (36.5%) had no psychiatric morbidity on GHQ-12. Mean PSQI score in patients without psychiatric morbidity was (6.2 ±3.2) while in the patients with psychiatric morbidity was 9.4 ±4.6 (p <0.001). CONCLUSION: Patients suffering from head and neck tumours showed high frequency of both poor sleep quality and psychiatric morbidity. Patients with presence of psychiatric morbidity or who had undergone surgical resection of tumour should be routinely screened for the sleep problems.

Frequency of depression in epilepsy: a hospital based study.

BACKGROUND: Depression is the most frequent psychiatric morbidity among epileptic patients adversely affecting their quality of life. It has also been associated with deliberate self harm and suicide. The objectives of this study were to know the frequency of depression in epileptic patients coming to neurology clinic of tertiary care hospital and also to find an association of clinical and demographic variables of epileptic patients with depression. METHODS: Convenient sampling method was used to select patients after informed consent. Depression was diagnosed using semi structured interview based on ICD-10. Data was analyses using SPSS version 10.0, and analysis carried out using descriptive and inferential statistics. Chi-square test of association was applied to see the significance. RESULT: Out of total 100 patients 55% were males, 47% were married and mean age of the patients was 25.5 +/- 4.34 years. About 60% patients were found depressed at the time of interview. Male patients, being married and coming from low socioeconomic stratum were significantly associated with depression. None of the patient was on anti-depressant medication. CONCLUSION: Depression was found to be highly prevalent psychiatric morbidity in epileptic patients. Men, married status, uncontrolled epilepsy and low socioeconomic group more prone to have depression.

A study of reasons of non-compliance to psychiatric treatment.

BACKGROUND: This study was carried out with an objective to find out the frequency of different reasons of non-compliance to treatment in a sample of out door psychiatric patients. METHODS: This study was conducted at Psychiatry department, Pakistan Institute of Medical Sciences, Islamabad, from Aug. 2001 to Jan. 2002. Data from a non-probability sample of two hundred follow up patients with a definite psychiatric illness was collected. A questionnaire designed for this purpose was administered by a consultant psychiatrist to the patients. The data was categorized into different causes of discontinuation of treatment accordingly. RESULTS: The commonest reasons for non-compliance were unawareness of the benefits of treatment (43%), nonaffordability of drugs (33.5%), physical side effects (28.5%), no awareness given by the doctor (03%) and unfriendly attitude of doctors (02%). The commonest illnesses leading to non-compliance were major depressive disorder (31.5%), schizophrenia (19.5%) and bipolar affective disorder (19%). CONCLUSION: Non-compliance is quite common in Pakistan like any other society. Medical practitioners need to be aware of it and address this problem because compliance is directly related to the prognosis of the illness. It is recommended that all efforts should be exerted to improve the compliance of psychiatric patients by eliminating the factors leading to non-compliance.