Pakistan Journal of Health Sciences

Severity of Coronary Artery Disease in Diabetic and Non-Diabetic Patients Presenting with Non-ST Elevation Myocardial Infarction

Ayesha Bibi — 2025-10-31

Diabetes mellitus accelerates coronary artery disease (CAD) and may worsen outcomes in non–ST–elevation myocardial infarction (NSTEMI). However, data from South Asia comparing lesion complexity and left ventricular function in diabetic vs non-diabetic NSTEMI patients remain limited. Objectives: To compare angiographic complexity (SYNTAX score), lesion severity, and left ventricular ejection fraction (LVEF) between diabetic and non-diabetic NSTEMI patients. Methods: This analytical cross-sectional study was conducted over 2 months (June -August, 2025) and included 83 consecutive NSTEMI patients (41 diabetics, 42 non-diabetics). All underwent coronary angiography for SYNTAX scoring and echocardiography for LVEF. Continuous variables were compared using t-tests with 95% confidence intervals and Cohen’s d, and categorical data were analyzed using Chi-square/Fisher’s exact test with Cramér’s V. Results: Diabetics had significantly higher SYNTAX scores (24.1 ± 5.9 vs 19.2 ± 5.0; mean difference 4.86, 95% CI 2.46–7.25, Cohen’s d = 0.87) and more frequent severe stenosis (61.0% vs 33.3%; p=0.012, Cramér’s V = 0.28). LVEF was significantly lower in diabetics (46.9 ± 7.6% vs 53.7 ± 6.2%; mean difference −6.84, 95% CI −9.87 to −3.81, Cohen’s d = 0.97). Rates of heart failure, arrhythmia, and mortality did not differ significantly (p>0.05). Conclusions: Diabetic NSTEMI patients demonstrate greater anatomic complexity and impaired ventricular function compared to non-diabetics, yet short-term outcomes remain comparable when standardized guideline-directed therapy is applied. These findings underscore the importance of early risk stratification and consideration of adjunctive prognostic markers such as inflammatory indices in this high-risk group.

Epidemiology and Outcomes of Liquefied Petroleum Gas (LPG) Burns at a Regional Burn Center in Karachi: A One-Year Retrospective Review

Samia Tasleem — 2025-10-31

Liquefied petroleum gas (LPG) burns have increased significantly in recent years, posing substantial public health challenges, particularly in resource-constrained environments such as Pakistan. Understanding the epidemiology and clinical profile of LPG burns can guide effective preventive and management strategies. Objectives: To analyze demographic and clinical features of LPG-related burn injuries and assess patient outcomes following treatment. Methods: This retrospective cross-sectional study was conducted at Dr. Ruth K.M. Pfau Civil Hospital’s burn center in Karachi. Records from January 1 to December 31, 2022, were reviewed using convenience sampling. Demographic details, injury mechanisms, accident location, delay before hospital admission, total body surface area (TBSA) burned, anatomical injury sites, treatment interventions, and patient outcomes were analyzed. Results: Among 159 LPG burn patients, 108 (67.9%) were male. Children accounted for 38 (23.9%), while young adults comprised 79 (49.7%). Most patients, 93 (58.5%), belonged to low socioeconomic backgrounds, and 97 (61.0%) worked as laborers. Gas leaks caused most injuries, with 135 (84.9%) patients suffering deep, full-thickness burns involving more than 25% TBSA. Skin grafting was performed in 55 patients (56.7%), tangential excision in 36 (37.1%), and amputation in 6 (6.1%). The overall mortality rate was 62 (38.9%). Conclusions: LPG-related burns at our center are characterized by extensive full-thickness injuries and high mortality. These findings underscore the urgent need for enhanced safety regulations, routine equipment inspection, and targeted community education to prevent LPG burn incidents.

Adjunctive Use of Chlorhexidine and Metronidazole Gels in Periodontal Disease: An Observational Study

Sitwat Sagheer — 2025-10-31

Periodontal inflammation is characterized by gingival bleeding, pocket formation, and compromised oral health. Objectives: To evaluate the periodontal effects of Chlorhexidine (CHX) gel and Metronidazole (MET) gel in individuals with periodontal inflammation. Methods: This observational longitudinal study included a total of 48 participants who were enrolled at the Dental OPD and divided into two groups. Group A received 0.2% CHX gel, and Group B received 0.8% MET gel. Both gels were applied twice daily for 14 days following scaling and root planing. Oral hygiene maintenance and adherence to gel application were monitored through patient diaries and follow-up visits. Clinical parameters, including bleeding on probing (BOP), probing depth (PD), periodontal index score, and oral hygiene index (OHI), were recorded at baseline and after 14 days using a standardized periodontal probe. Results: In the CHX group, BOP significantly reduced from 26.13 ± 8.14 to 15.38 ± 6.36 (p = 0.001), while OHI improved from 22.67 ± 5.55 to 5.71 ± 2.90 (p < 0.001). Similarly, the MET group demonstrated a significant reduction in BOP from 24.67 ± 3.25 to 8.58 ± 3.78 (p < 0.001) and OHI from 24.58 ± 5.11 to 6.71 ± 3.22 (p < 0.001). However, no significant change was observed in probing depth for either group (CHX: p = 0.705; MET: p = 0.705). Conclusions: The use of CHX and MET gels significantly decreases BOP and improves OHI, but no significant change was on probing depth, demonstrating their effectiveness in reducing periodontal inflammation without affecting pocket depth.

Correlation Between Spinopelvic Sagittal Alignment Parameters and Low Back Pain

Muhammad Bilal — 2025-10-31

Low back pain is a common musculoskeletal disorder with a major socioeconomic impact. Understanding its association with spinopelvic alignment may enhance diagnosis and treatment by identifying key biomechanical factors linked to symptom severity. Objectives: To assess the relationship among spinopelvic parameters and low back pain severity. Methods: This retrospective study was conducted at Bahria International Hospital, Rawalpindi, Pakistan, including 150 patients. Full-spine standing X-rays were used to assess sagittal vertical axis, sacral slope, pelvic tilt, pelvic incidence, and lumbar lordosis using Surgimap® software. A visual analog scale was used to measure the severity of the pain, and Pearson correlation analysis was performed to determine associations between spinopelvic parameters and LBP severity. Results: Pelvic tilt showed a positive correlation with lumbar pain, which is significant (r=0.52, p<0.001) and radicular pain (r=0.33, p=0.002). Sagittal vertical axis was also positively correlated with lumbar (r=0.47, p<0.001) and radicular pain (r=0.38, p=0.001). A significant negative correlation of lumber lordosis was exhibited with both lumbar (r=-0.49, p<0.001) and radicular pain (r=-0.41, p<0.001). No significant correlation was found for PI or SS. Conclusions: Pelvic tilt and sagittal vertical axis positively correlate with low back pain severity, whereas lumbar lordosis exhibits a protective role. These findings emphasize the importance of spinopelvic alignment in low back pain pathophysiology.

Comparison of Effectiveness of Intrathecal Tramadol versus Intravenous Tramadol in Prevention of Post-Anesthesia Shivering in Patients Undergoing Lower Limb Orthopedic Surgeries under Subarachnoid Block: A Comparative Study

Sameen Khalid — 2025-10-31

Shivering is a common spinal anesthetic side effect that occurs in 40–60% of people who have had subarachnoid block. Shivering is typified by spontaneous, involuntary, rhythmic fasciculation or skeletal muscular activation that resembles tremors. Hypothalamic thermoreceptors attempt to increase heat synthesis by shivering when they sense this drop in core body temperature due to peripheral heat redistribution. Objectives: To compare anti-shivering effects of intravenous versus intrathecal tramadol in patients receiving subarachnoid block for lower limb orthopedic operations. Methods: This Quasi-experimental study included 130 patients scheduled for elective orthopedic surgery under spinal anesthesia in the Operation Theater, Allied Hospital, Faisalabad. Patients were randomly divided into two groups: Group A (intrathecal tramadol with bupivacaine) and Group B (intravenous tramadol with intrathecal bupivacaine). The frequency of post-anesthesia shivering was recorded in both groups. Results: The mean ± SD of sensory and motor block duration in Group A was 331.72 ± 33.09 and 231.14 ± 11.22 minutes, respectively, while in Group B it was 228.12 ± 12.15 and 157.42 ± 10.02 minutes, respectively (p<0.001). Post-anesthesia shivering occurred in 9 (13.84%) patients in Group A and 23 (35.38%) patients in Group B (p<0.05). Conclusions: Post-anesthesia shivering was significantly higher in patients receiving intravenous tramadol (Group B) compared to those receiving intrathecal tramadol (Group A).

Combination Letrozole and Clomiphene Citrate or Letrozole Alone for Ovulation Induction in Infertile Women with Polycystic Ovarian Syndrome

Shagufta Tabassum — 2025-10-31

Infertility is a devastating health issue with widespread psychological effects. The most common reason for female infertility is polycystic ovary syndrome. The treatment revolves around Clomophene Citrate (CC) and Letrozole individually, but the combination has not been studied in our population. Objectives: To find if the combination of CC and Letrozole has better ovulation efficacy as compared to Letrozole alone. Methods: The foregoing quasi-experimental study was organized in the Department of Gynaecology at Nishtar Hospital of Pakistan. A total of 70 participants fulfilling the inclusion criteria were divided into two equal groups. Group A was prescribed 2.5 mg Letrozole daily, while Group B was given the composite 2.5 mg letrozole + 50 mg CC per day from the 3^rd to the 7^th cycle day for one treatment cycle. Results: The combination group yielded ovulation in 65.7% infertile women, while Letrozole alone in 37.1 % of the cases, making a net difference of 28.6% which is quite significant. The conception was achieved in 17.1% of the combination group cases and 14.2% of the Letrozole alone group, making a net difference of 2.9%. The clinical pregnancy was diagnosed in 14.2% of the combination group cases and 11.1% of the Letrozole alone cases, with a net difference of 3.1%. Conclusions: Our findings endorsed the hypothesis that using combined CC + Letrozole leads to a better ovulation rate than Letrozole alone in women experiencing infertility due to polycystic ovary syndrome (PCOS).

Hyperemesis Gravidarum in the Second Trimester as a Risk Indicator for Preterm Birth

Shumaila Asghar — 2025-10-31

A severe type of nausea and vomiting during the early stages of pregnancy is called hyperemesis gravidarum. Preterm delivery has been reported to be significantly associated with hyperemesis gravidarum. Objectives: To determine the association between preterm birth and hyperemesis gravidarum in female attending an antenatal care clinic in the second trimester. Methods: This Cohort1study was carried out at the Department of Obstetrics and Gynaecology, Sahiwal Teaching Hospital, Sahiwal. A total of 200 female were enrolled and divided into two groups with and without hyperemesis gravidarum. Then female were followed up in OPD until delivery. If female had a delivery before 37 weeks of gestation, then preterm birth was labelled. Data were analyzed in SPSS version 23.0. Results: The mean age of the female was 31.25 ± 5.98 years. In our study, 40 (40%) female were primigravida. The mean gestational age at presentation was 17.47 ± 3.51 weeks, while at delivery it was 37.27 ± 1.94 weeks. In the exposed group, preterm birth was noted in 45 (45%) cases, while in the unexposed group, preterm birth was noted in 15% cases. Thus, there was 1.909 times more risk of preterm birth in females with hyperemesis gravidarum as compared with female without hyperemesis gravidarum, i.e., RR=1.909 (95% CI; 1.483, 2.457, p<0.001). Conclusions: There is more than about two times greater risk of preterm birth in female with hyperemesis gravidarum during the second trimester of their pregnancy.

Efficacy of Topical Testosterone in Hypospadias Patients Presenting with Microphallus

Shahid Khan — 2025-10-31

Hypospadias, a common congenital anomaly in males, is often linked with microphallus, complicating surgery. Preoperative androgen therapy may enhance penile size and outcomes, though most studies focus on intramuscular routes. Limited data exist on topical testosterone, especially locally. Objectives: To assess the effectiveness of topical testosterone in increasing penile length in children with hypospadias and microphallus. Methods: This quasi-experimental study was conducted at the Department of Plastic Surgery, Northwest General Hospital, spanned six months from November 2024 till May 2025. A total of 195 boys aged 1–10 years with hypospadias and microphallus received 5% topical testosterone cream, applied four times daily for 45 days. Stretched penile length was measured before and after treatment. A ≥50% increase defined treatment success. Data were analyzed using SPSS version 25.0; significance was set at p≤0.05. Results: Median penile length increased from 42 mm (IQR: 8 mm) to 60 mm (IQR: 21 mm). Mean length rose from 41.32 mm to 59.18 mm (p < 0.001). A ≥50% increase was seen in 52.3% of patients. No significant link was found between efficacy and age (p = 0.316) or hypospadias type (p=0.118). Conclusions: Topical testosterone effectively increases penile length in children with hypospadias and microphallus, regardless of age or subtype.

Risk Factors and Survival Outcomes Associated with Breast Cancer Recurrence

Syed Saad Gardezi — 2025-10-31

Breast cancer recurrence remains a major clinical challenge, despite advancements in diagnosis and treatment. Identifying reliable clinicopathological predictors is essential for improving long-term outcomes and guiding individualized treatment. Objective: To assess the clinicopathological characteristics and risk factors associated with breast cancer recurrence and evaluate survival outcomes in patients with operable breast cancer. Methods: This retrospective study included 281 patients diagnosed with operable primary breast cancer at a tertiary care center. Data were collected on demographic, histopathological, and treatment-related variables. Recurrence was defined as any documented local, regional, or distant relapse after initial treatment. Statistical analyses included chi-square tests for categorical variables and independent-samples t-tests for continuous variables to assess associations with recurrence. A p-value<0.05 was considered statistically significant. Results: The overall recurrence rate was 31.7 %, with distant metastasis being the most common type. Odds ratios with 95 % confidence intervals for categorical variables (molecular subtype, hormone receptor status, tumor size category, histological grade, Ki-67 index, and lymphovascular invasion) showed no statistically significant associations with recurrence. Likewise, mean differences with 95 % confidence intervals for continuous variables (age, tumor size, Ki-67 index, and disease-free survival) revealed no significant differences between recurrence and non-recurrence groups. Conclusions: No clinicopathological factor was found to be a statistically significant predictor of breast cancer recurrence in this cohort. These findings highlight the limitations of traditional pathological markers and underscore the need to integrate molecular and genomic profiling for more accurate recurrence risk assessment and personalized treatment planning.

Impact of Maternal Obesity on Pregnancy Outcomes: A Hospital-Based Study

Talat Parveen — 2025-10-31

Obesity among pregnant women has emerged as a major global health issue and is closely associated with unfavorable outcomes for both the mother and the newborn. Objectives: To assess how maternal obesity influences pregnancy-related outcomes in both mothers and their newborns at a tertiary care facility. Methods: This hospital-based descriptive cross-sectional research was carried out in the Obstetrics and Gynaecology Department of Bahawal Victoria Hospital, Bahawalpur, during the period from 23-04-2024 to 22-10-2024. A total of 153 pregnant women with obesity (BMI ≥30 kg/m²) and singleton pregnancies beyond 28 weeks of gestation were selected through non-probability consecutive sampling. Women with multiple gestations, fetal anomalies, or chronic illnesses unrelated to obesity were excluded. Data on maternal demographics, obstetric history, and outcomes were collected using a structured proforma. The evaluated outcomes comprised gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), type of delivery, preterm labor, postpartum hemorrhage (PPH), stillbirth, macrosomia, Apgar scores, neonatal intensive care unit (NICU) admissions, and congenital abnormalities. Data analysis was performed using SPSS-26, with a p-value less than 0.05 considered statistically significant. Results: The mean maternal age was 29.99 ± 6.26 years. GDM occurred in 26.8% and PIH in 15.0% of participants. Cesarean delivery was performed in 44.4%, and macrosomia was observed in 23.5% of neonates. Significant associations were noted between parity and PIH (p=0.024), ANC visits and NICU admission (p=0.005), and chronic illness with congenital anomalies (p=0.041). Conclusions: Maternal obesity is associated with increased risks of metabolic, obstetric, and neonatal complications.

Comparison of Thyroid Dysfunction in Patients with Controlled Versus Uncontrolled Diabetes Mellitus: A Comparative Cross-Sectional Study

Khansa Qamar — 2025-10-31

Thyroid dysfunction (TD) and type 2 diabetes mellitus (DM) are the two endocrine conditions most frequently encountered in clinical settings. Objectives: To compare the frequency of thyroid dysfunction in patients with controlled versus uncontrolled DM. Methods: This comparative cross-sectional study was conducted at the Pathology Department of Nishtar Hospital, Multan, from February to July 2025. Diabetic patients aged 30–70 years of both genders were enrolled in the study as uncontrolled diabetes (n=124) and controlled diabetes (n=124). Patients with pre-existing TD, on its treatment, or using medications known to alter thyroid function were excluded. Demographic details, including age, gender, duration of diabetes, and hypertension status, were recorded. TD was categorized into subclinical hypothyroidism, clinical hypothyroidism, subclinical hyperthyroidism, and hyperthyroidism. Descriptive statistics were run through SPSS version 23.0, and the Shapiro-Wilk test for normality. Chi-square test at 5% significance level was used for comparisons, with stratification done to control confounding. Results: Among 248 participants, the mean age was 49.2 ± 10.3 years. Males constituted 48% and 73.4% had hypertension. TD was found in 14.5% of diabetics, more common in uncontrolled (69.4%) than controlled diabetes (30.6%) (p=0.012). Most frequent type was subclinical hypothyroidism (6%), followed by hypo- and hyperthyroidism (3.2% each), and subclinical hyperthyroidism (2%). TD was high in uncontrolled diabetics ≥50 years, females, and hypertensive patients. Conclusions: Thyroid dysfunction was remarkably more common in persons with uncontrolled diabetes, particularly in older age, females, and hypertensives.

Assessment of the Relationship Between Student-Teacher Interactions and Professional Development among Nursing Students in Karachi, Pakistan

Muhmooda Abdul Razzaque — 2025-10-31

Student-teacher interactions (STIs) and professional development (PD) are a crucial part of nursing education. Both contribute to enhancing self-efficacy among nursing students by fostering knowledge, skills, and professional identity. Objectives: To assess the relationship between student-teacher interactions and professional development among nursing students in Karachi, Pakistan. Methods: A cross-sectional analytical study was conducted between November 2024 and January 2025 at two nursing institutions: Dow Institute of Nursing and Midwifery and the College of Nursing, Dr Ruth Pfau Civil Hospital, Karachi. A purposive sample of 235 Bachelor of Science in Nursing (BSN) students was included from the 2nd to 4th years of nursing students. After getting ethical approval and consent from the participants. Data were gathered using a structured, self-developed questionnaire. Data were analyzed using SPSS version 26.0. Results: Out of 235, the mean age (25.9 ± 0.891) of the participants, and a majority were female (n=157, 66.8%), and were studying in their 4th year (n=122, 51.9%). A bulk of participants were not aware of the hidden curriculum. They found a significant positive correlation between STIs and PD (Spearman’s ρ = 0.789, p<0.01) among respondents. Conclusions: This study found a strong relationship between student–teacher interactions and professional development among nursing students in Karachi, Pakistan. It is recommended to conduct longitudinal and qualitative studies to gain deeper insights into student–teacher interactions and their relationship with professional development among nursing students.

Outcome of Topical Dapsone 5% Versus Topical Clindamycin 1% in Treatment of Mild to Moderate Acne Vulgaris

Muhammad Bilal Iftikhar — 2025-10-31

Acne vulgaris is a common inflammatory skin disorder, and increasing resistance to conventional topical antibiotics has highlighted the need for alternative therapies such as dispone. Objective: To compare the outcome of topical dapsone 5% gel versus topical clindamycin 1% gel in the treatment of mild to moderate acne vulgaris. Methods: A Randomized Controlled trial was conducted in the Dermatology Department of Allama Iqbal Memorial Teaching Hospital, Sialkot, from February 2025 to July 2025. A total of 131 patients aged between 18 and 60 years, diagnosed with mild to moderate acne vulgaris based on the Global Acne Grading System (GAGS), were consecutively enrolled. Participants were randomly allocated into two groups (Group A: clindamycin 1% gel twice daily, Group B: dapsone 5% gel once daily). Both regimens were continued for 12 weeks. Mean difference and percentage reduction in GAGS scores, along with adverse events, were noted as outcomes. Results: Both groups had similar baseline characteristics without significant differences (p>0.05). At 12 weeks, mean GAGS scores were significantly lower in the clindamycin group (9.27 ± 2.95) than in the dapsone group (10.57 ± 4.33; p=0.047). Percent reduction in GAGS score was also significantly greater with clindamycin (44.97 ± 14.37) compared to dapsone (38.72 ± 18.52; p=0.033). No adverse events occurred in the Clindamycin 1% gel group, while 5 (7.6%) in the Dapsone 5% gel group reported oily skin, pruritus, or irritation. Conclusions: Clindamycin 1% gel demonstrated superior efficacy and tolerability compared to Dapsone 5% gel in reducing acne severity over 12 weeks.

Impact of Acne Vulgaris on the Quality of Life of Patients Presented to Nishtar Hospital Multan Outpatient Department

Sidra Tahir — 2025-10-31

Acne vulgaris is one of the most prevalent dermatological conditions globally, yet its psychosocial burden is often underestimated in clinical settings. Objectives: To assess the impact of acne vulgaris on quality of life of patients. Methods: This cross-sectional study enrolled 145 patients (aged 14–50 years) with acne vulgaris at the Dermatology OPD, Nishtar Hospital, Multan. Acne severity and quality of life were assessed using GAGS and DLQI, respectively. Statistical tests included chi-square, ANOVA, and logistic regression, with significance set at p < 0.05. Results: Of 145 patients, 81 (55.9%) were female and 64 (44.1%) male. Based on GAGS, 45 (31.0%) had mild, 63 (43.4%) moderate, and 37 (25.5%) severe acne; mean GAGS score was 23.12 ± 9.89. DLQI assessment revealed no impact in 13 (9.0%), mild in 33 (22.8%), moderate in 26 (17.9%), very large in 48 (33.1%), and huge in 25 (17.2%); mean DLQI was 11.79 ± 8.43. DLQI scores increased with acne severity: mild 8.40 ± 9.34, moderate 11.44 ± 7.53, severe 16.49 ± 6.54 (F=10.71, p<0.001). Very large DLQI impact was seen in 11.1%, 33.3%, and 59.5% of mild, moderate, and severe cases, respectively. Independent predictors of high DLQI impact included age 31–50 years, unemployment, and low socioeconomic status (χ²=38.70, df = 8, p<0.001). Conclusions: This study demonstrates that the severity of acne vulgaris is significantly associated with greater impairment in dermatology-specific quality of life. Independent predictors of poor quality of life include age, gender, occupation, and socioeconomic status.

Maternal Dietary Diversity in Pakistan: Influences of Education, Poverty, and Food Insecurity from a Cross-Sectional Survey

Ijaz Habib — 2025-10-31

Maternal nutrition strongly influences pregnancy outcomes. In Pakistan, poor dietary diversity and food insecurity remain key drivers of malnutrition, particularly in disadvantaged areas. Objectives: To assess dietary diversity, household food insecurity, and nutritional status among pregnant women in Kurram District, Pakistan, and examine their associations with maternal education and poverty. Methods: A community-based cross-sectional baseline survey, nested within a non-randomized, cluster-controlled trial (ISRCTN94319790), was conducted in Upper Kurram from January to April 2018, using multi-stage cluster sampling (80 clusters from 12 health facilities) and consecutive home-based enrolment of 1,209 pregnant women (15–49 years). Data were collected via structured questionnaires (HFIAS, MDD-W), standardized anthropometry, and analyzed in Stata 14. Results: Mean age was 27.9 ± 5.8 years; 68.9% of women and 24% of husbands were uneducated. Most households were non-poor (87.6%), and 77.4% were food secure (mean HFIAS 4.2 ± 5.2). Dietary diversity was low, with only 13.2% achieving MDD-W ≥5; diets were dominated by cereals (98.4%), low in fruits, vegetables, and animal-source foods. Mean BMI was 24.9 ± 4.5; 4.5% were underweight, 29.8% overweight, and 11.0% obese. In bivariate analyses, food insecurity was more common among women with no formal education, the poorest households, and those consuming <5 food groups (all p<0.001). Conclusions: Findings reveal a double burden of malnutrition, with overweight and obesity coexisting with poor dietary diversity. Food insecurity was strongly linked to poverty, low education, and limited dietary diversity. Interventions addressing education, poverty, and dietary diversity are critical to improve maternal nutrition in similar low-resource settings.

Substance P and Its Role in Anxiety Disorders

Riffat Mehboob — 2025-10-31

Anxiety disorders are the most prevalent mental illnesses in the world with an almost 19 percent prevalence among adults in the United States. Similar to major depressive disorder, they are associated with stress and pain and include disturbances in neurotransmitters like serotonin, dopamine, norepinephrine, and GABA and abnormalities in the activity of the amygdala and prefrontal cortex that leads to anxiety symptoms.[1-3] Exposure to stress results in increased endogenous Substance P (SP) in the central nervous system especially in the amygdala thus intensifying anxiety-related responses. This has led to a rising research interest on the role of SP in the development and control of anxiety disorders.[4]

However, studies investigating psychiatric conditions often encounter methodological difficulties. Variables such as participant age, sex, and inclusion of subclinical populations can influence observed correlations and restrict the generalizability of findings. Moreover, findings of unexpected positive correlations between subclinical symptoms and gray matter volume challenge traditional interpretations, highlighting the importance of cautious analysis and interpretation of neuroimaging results.[1,4]

Experimental evidence supports the involvement of SP in stress-induced anxiety. Animal studies have shown that emotional stress triggers SP release in the amygdala; for example, immobilization stress in rats leads to a prolonged elevation of SP in the medial amygdala (MeA), while mild stress causes only a short-lived increase. Notably, blocking neurokinin-1 receptors (NK-1R) in the MeA prevents the development of stress-induced anxiety-like behaviors, confirming the critical role of SP signaling in anxiety. Similarly, localized SP microinjections into specific brain regions have been shown to produce anxiogenic effects.[4,5]

Moreover, SP triggers the sympathetic nervous system and hypothalamic-pituitary-adrenal (HPA) axis, leading to a high level of norepinephrine and cortisol, which accentuate the symptoms of anxiety even more. Simultaneously with the findings in MDD, NK-1R antagonists are shown to have anxiolytic effects thus supporting the primary place of the SP/NK-1R signaling in the pathophysiology of anxiety disorders.[5,6]