Schizophrenia patients demonstrate variations in response to different therapies that are currently being used for the treatment of disorders, such as augmentation therapy (ECT or mood stabilizer) and combination therapy (with antipsychotics). These therapies are also used to treat schizophrenia patients in Pakistan; however, patients show poor overall response. Therefore, this study was conducted to investigate the association between the patients’ response to treatment and the use of antipsychotic agents, with variability in overall response, within different groups of patients. Methods: We conducted a retrospective study that included schizophrenia subjects (N = 200) belonging to different age groups, ethnicities, and regions from different outpatient and inpatient departments in psychiatric institutes located in different cities of Pakistan. These patients were assessed for their response to treatment therapies and categorized into four groups (non-responders (N-R), slow response (S-R), patients with relapse, and completely recovered patients (C-R)) according to their responses. Results: The final analysis included 200 subjects, of which 73.5% were males. Mean age was 34 ± 10 years. Percentage of N-R was 5%, S-R was 42%, patients with relapse were 24%, and C-R was 1.5%. The generalized linear regression model shows a significant association between medication response and age (p = 0.0231), age of onset (p = 0.0086), gender (p = 0.005), and marital status (p = 0.00169). Variability within the medication responses was a result of the treatment regime followed. Antipsychotic agents were significantly associated with the treatment response (p = 0.00258, F = 4.981) of the patients. Significant variation was also observed in the treatment response (p = 0.00128) of the patients that were given augmentation therapy as well as combination therapy. Conclusion: The data suggests proper monitoring of patients’ behavior in response to treatment therapies to implement tailored interventions. Despite several genetic studies supporting the heritability of schizophrenia, an insignificant association between characteristic features and family history might have been due to the limited sample size, suggesting collaborative work with massive sample sizes.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5–2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.

Cardiomyopathies, a leading cause of heart failure and mortality worldwide, are a diverse group of heart muscle disorders, with dilated cardiomyopathy being the most prevalent subtype. Numerous genetic variants, identified through GWAS and candidate gene studies, are associated with cardiomyopathies. This study aimed to evaluate the association of the rs10757278 SNP polymorphism on chromosome 9p21.3 near the CDKN2A and CDKN2B genes with cardiomyopathy, focusing on its role in genetic susceptibility to ischemic dilated cardiomyopathy. Methods: A case-control study was conducted with 200 participants (100 cardiomyopathy patients and 100 controls). Clinical and echocardiographic parameters were recorded, and genotyping was performed using tetra-arms PCR. Results: Statistical analysis revealed that rs10757278 was significantly associated with cardiomyopathy (Chi-sq=11.679, p=0.00291) in allelic and genotypic distributions. The GG genotype (p=0.00958) increased risk, identifying the G allele as the risk allele. For IDCM, significant associations were observed for GG and AG genotypes (p=0.02613, p=0.00104), with the G allele increasing risk (p=0.0031, OR=3.19, CI=1.51–7.17) and the A allele offering protection (p=0.00961, OR=0.35, CI=0.15–0.177). Conclusion: These findings highlight rs10757278 as a potential biomarker for cardiomyopathy risk profiling. Further large-scale studies are warranted to confirm these results and improve early diagnosis and genetic risk prediction for cardiomyopathies.

Background & Objectives: Apolipoproteins, specifically ApoA-I (a cardioprotective HDL component) and ApoB (associated with cardiovascular risk), are increasingly recognized for their value in diagnosing and predicting heart disease. This study focused on comparing these markers and the ApoB/ApoA-I ratio with traditional lipid profiles to assess their diagnostic and prognostic capabilities. Methods: In this cross-sectional study, 1,200 participants were categorized into three groups: control (n=250), training (n=450), and validation (n=500). Blood samples were analyzed for ApoB, ApoA-I, and conventional lipid profile. Advanced statistical methods, including logistic regression, ROC curve analyses, and propensity score matching, were applied to control for confounding factors and validate findings. Results: The training cohort showed significantly higher ApoB levels (1.20 ± 0.52 g/L) compared to controls (1.0 ± 0.40 g/L, p < 0.001), while ApoA-I levels were significantly lower (1.03 ± 0.34 g/L vs. 1.12 ± 0.34 g/L, p = 0.045). The ApoB/ApoA-I ratio was markedly elevated in the training group (1.46 ± 0.18) versus controls (1.06 ± 0.95, p < 0.001). ApoB proved to be the most reliable predictor of coronary artery disease with an AUC of 0.82, surpassing the ApoB/ApoA-I ratio (AUC 0.70) and ApoA-I (AUC 0.65). Cholesterol and triglycerides demonstrated weaker associations with CAD. Conclusion: ApoB and the ApoB/ ApoA-I ratio are superior markers for assessing CAD risk compared to traditional lipid profile. This investigation lends further support for incorporating apolipoprotein testing into clinical practice, enhancing CAD risk stratification, in particular for the high-risk population.