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Modulation of Purkinje cell plasticity in the cerebellum using direct current stimulation: investigating the effects on long-term depression
Full text linkINTRODUCTION: Damage to the cerebellum or its associated pathways can result in cerebellar ataxia, a disorder characterized by impaired coordination and balance. One potential treatment for ataxic patients is transcranial direct current stimulation (tDCS).The mechanism by which tDCS exerts its effects is believed to involve long-term depression (LTD). It is hypothesized that direct current stimulation modulates Purkinje cell plasticity.
OBJECTIVE: Previously, preliminary data was collected to examine the effects of direct current stimulation (DCS) on the Purkinje cell plasticity. It is suggested that E-field application did enhance LTD based on a paired t-test (p-value = 0.018, 8 cells without E-field and 9 cells with E-field). In this study, more cases were obtained to increase the sample size to increase the validity.
METHODS: Cerebellar slices from Sprague Dawley rats (14 to 31 days old, n=25) were prepared for whole-cell patch clamp recordings. To simulate tDCS, an electric field (E-field) was applied. Purkinje cell plasticity was induced both with and without E-field application. LTD was evoked in the molecular layer using tetanus stimulation (5 Hz with train stimulation at 100 Hz). A 100 µA E-field was delivered to the cerebellar slices containing recorded Purkinje cells via parallel silver wires. Data analysis was performed in MATLAB to evaluate the I-V curve, changes in firing rate due to E-field application, and plasticity induction.
RESULTS: LTD was induced in three newly acquired cells without E-field. When combined with data from previous experiments, a total of 11 cells were analyzed to evaluate LTD induction without E-field exposure. The mean LTD responses of these 11 cells were then compared to those of the previously recorded 9 cells, in which LTD was induced under E-field application. Statistical analysis revealed a significant difference between the two groups, with a p-value of 0.0033. This result is consistent with previous findings.
CONCLUSION: The new results support the hypothesis that E-field stimulation modulates Purkinje cell plasticity, offering potential avenues for therapeutic interventions in cerebellar ataxia. Future studies with larger sample sizes and further exploration of E-field parameters are necessary to fully elucidate the mechanisms underlying this enhancement. Additionally, tACS will be delivered to see if it has a strengthened effect on the Purkinje cell plasticity
Sacroiliac Joint Septic Arthritis: A Case Report
Full text linkBackground: Septic arthritis is an infection of a joint typically by bacteria. It classically presents as a warm, erythematous, tender and edematous joint with limited active and passive range of motion. Non-gonococcal septic arthritis most commonly occurs in knee and hip joints, followed by shoulders, wrists, and ankles. Atypical joint infections, such as the sacroiliac joint are extremely uncommon. In this report, we demonstrate a case of a young patient, with no predisposing factors with a unique presentation of sacroiliac septic arthritis.
Case description: 29-year-old female with no pertinent past medical history presented to Roxborough Memorial Hospital with severe 10/10 pain in her left buttock and lower back with intermittent numbness and tingling into the left lower extremity. She had originally presented the day before to the ED and was discharged with pain medication and a muscle relaxer. When she returned home, the pain was so severe, she returned to the hospital. Prior to her original arrival, she was immobilized for 12 hours during a long car ride, after which was when her pain began. In the ED, she was hypotensive, WBC 15.4, lactic acid 2.5. Blood cultures were drawn, and she was started on IV fluids, Unasyn and ceftriaxone for suspected sepsis with an unknown cause. Infectious disease recommended obtaining an MRI lumbosacral spine which showed mild symmetric iliopsoas edema and enhancement. Blood cultures were positive for MSSA bacteremia. Due to persistent pain, she had a repeat MRI 5 days later, showing interval increase in mild edema and enhancement within the left iliac bone and left sacrum adjacent to the sacroiliac joint. There was no evidence of a drainable collection, confirmed by interventional radiology. She was evaluated by orthopedic surgery who confirmed that no surgical intervention was required. She was also evaluated by the osteopathic manipulative medicine (OMM) service for OMT for her low back and sacral pain. She had a PICC line placed for extensive antibiotic therapy at home. She had a repeat MRI 9 days post discharge which showed left-sided sacroiliac joint edema and enhancement, concerning for septic arthritis. At this time, she was unable to walk and was utilizing a wheelchair while out of the house. She was evaluated at the OMM Clinic 1 month later, with significant improvement of her symptoms within the last week before her appointment. She reports that 9 days before, she was switched to daptomycin and noticed significant improvement in her functional ability. She remained using her crutches and began physical therapy 1 week after this appointment. The etiology of her infection remained unclear.
Discussion: This patient’s case describes an unusual presentation of septic arthritis in the sacroiliac joint. This is a rare condition, affecting only 1-2% of individuals with septic arthritis, typically seen in patients who use intravenous drugs, of which our patient had no known history. This patient’s diagnosis remained insidious throughout her early hospitalization, and the etiology remained unclear, as she had no clear risk factors or known causes for the infection
Protein Kinase C Delta Peptide Activator provides protection during hypoxia/reoxygenation and elicits significant anti-cancer effects in vitro
No full textIntroduction
Protein kinase C delta (PKCδ) activation is known to inhibit NOX-2/superoxide (SO) release in polymorphonuclear leukocytes (PMNs) and elicit cardioprotective effects in ischemia-reperfusion (I/R) injury. Augmenting PKCδ activity also promotes tumor suppressive effects via apoptosis. This study examined the cardioprotective and anticancer effects of PKCδ peptide activator (PKCδ+) in endothelial cells and cardiomyocytes, cardiovascular cells particularly susceptible to oxidative damage due to their high concentration of mitochondria.
Methods
Hypoxia/Reoxygenation: Human umbilical vein endothelial cells (HUVECs) and rat cardiomyocytes (H9C2 cells), were cultured at 37°C in EBM-2 medium and DMEM, respectively and pretreated with PKCδ+ (Myr+MRAAEDPM) (0.25-5μM) or untreated control for 37 mins, prior to hypoxia (24hr) and reoxygenation(24hr).
Anti-Cancer: Human breast cancer (MCF7) cells were cultured in RPMI buffer at 37°C and treated with PKCδ+ (0.5-20μM) or untreated control for 37 mins.
Cell viability was assessed by light microscopy and spectrophotometric analysis using a cell counting kit for both experimental groups.. Absorbance data were analyzed using student t-test.
Results
Pretreatment with PKCδ+ (0.25-4μM) improved H9C2 and HUVECs cell viability, with significant improvement of HUVEC viability (1μM, 0.4±0.03; n=5, p\u3c 0.05) vs control (0.26.±0.04, n=5). PKCδ+ dose-dependently promoted MCF7 cell death up to 20μM 0.33±0.03; n=5, p\u3c 0.05 compared to controls (0.49±0.02, n=5).
Conclusions
Lower doses of PKCδ+ provide cardioprotection during hypoxia reoxygenation, while higher doses are more effective at providing anti-cancer effects. Optimizing dosing for tumor suppression and I/R tissue preservation could make PKCδ+ an attractive clinical drug in cases where organ ischemia must be induced temporarily for surgical resection of malignancy.
Discussion
Future studies include dosing optimization and ex-vivo rat tissue I/R studies. Additionally, PKCδ+ may provide cardioprotection in patients undergoing chemotherapy with Doxorubicin (DOX), a cardiotoxic drug that exerts its toxic effects via production of reactive oxygen species (ROS) through various mechanisms. Reducing the cardiotoxic effects of DOX would make its use more effective and desirable in cancer treatment, as it is a potent antineoplastic agent, but its use is currently limited due to its cardiotoxic side effects. Since PKCδ+ also exerts anti-cancer effects, combination with DOX is a promising chemotherapeutic regimen if PKCδ+ can help mitigate DOX-induced cardiotoxicity
Utilization of dexmedetomidine and ketamine in neonatal intensive care units across the US from 2009 to 2023
Full text linkIntroduction
Newborns admitted to neonatal intensive care units (NICUs) often require sedation and analgesia due to critical illness and invasive procedures. Alternatives to narcotics are being used in clinical practice due to improved side effect profiles and decreased risk of dependence. Dexmedetomidine (Precedex), an α₂-adrenergic agonist, and ketamine, an NMDA antagonist, have emerged as attractive alternatives, yet there are limited data on their use in NICUs.
Objective
To assess utilization of dexmedetomidine and ketamine in a large cohort of newborns admitted to US NICUs over time.
Methods
Retrospective cohort study including newborns admitted to a US NICU from 2009-2023 included in the Premier database. We assessed proportions of newborns exposed to each drug overall and by birthweight (BW). We assessed the median first day of exposure and median total days of exposure and assessed visual trends in use over time.
Results
There were 1,721,819 newborns admitted to 818 NICUs from 2009 to 2023. Of these, 8000 (0.5%) received dexmedetomidine and 3515 (0.1%) received ketamine.
For dexmedetomidine, median (IQR) first day of exposure was day 6 (2,27) after birth and total days of exposure was 4 (1,10). Dexmedetomidine use was highest among infants with BW \u3c 500g (4.5% exposed), who received median (IQR) 7 days (2,20). Overall annual proportion of dexmedetomidine exposure increased from 2009 (0.04%) to 2023 (1.30%), with the greatest increase occurring in infants with BW \u3c 500 g (0.38% to 18.29%).
For ketamine, median (IQR) first day of exposure was day 18 after birth and total days of exposure was 1 (1,2). Ketamine use was highest among infants with BW \u3c 1000g (1.5% exposed), though the first day of exposure for this group was considerably later during the second or third month. Overall annual proportion of ketamine usage increased from 2009 (0.16%) to 2023 (0.27%) but showed an inconsistent pattern. No appreciable trend of usage was evidenced within BW groups \u3e500 g.
Discussion
The current study showed dexmedetomidine and ketamine use increased among newborns admitted to US NICUs from 2009 to 2023.
Infants born \u3c 1000g, particularly those \u3c 500g, had the highest exposure rates for both drugs. Dexmedetomidine was prescribed for about a week and used around one month of age for the smallest infants; we speculate this is due to prolonged mechanical ventilation and ongoing clinical instability. Ketamine was typically prescribed for one day and was used earlier for bigger infants and much later in hospitalization for the smallest infants; we speculate this is due to use for short interventions such as procedures.
Given the increasing use of these drugs in NICUs despite a paucity of data on safety and efficacy, further research is needed to guide optimal use in critically ill newborns, particularly those born weighing \u3c 1000g. These data on current utilization patterns can inform prospective safety and comparative effectiveness studies
The All of Us Research Program provides an efficient platform for remote training medical/health science students in science methodology – Showcase: Peripartum cardiomyopathy and its relationship with proxies of socioeconomic status.
No full textBackground: Medicine is a science-based discipline. Scientific method investigates a problem by identifying it, formulating a question and a hypothesis to explain it, testing the hypothesis, and collecting and analyzing data that can potentially reject it. Scientific method also applies to clinical problems providing a systematic approach for diagnosis and treatment. It is an iterative process requiring repetition to achieve proficiency. Iterating processes need time that must integrate with busy schedules within medical school curricula. We explored the “All of Us” NIH-research program to introduce formal training in science methodology to medical students by conducting a retrospective analysis on peripartum cardiomyopathy (PPCM). PPCM is an idiopathic cardiomyopathy with systolic dysfunction occurring during the last month of pregnancy or within months after childbirth in women with previously normal cardiac function. The estimated global PPCM prevalence is 0.05% live births. A retrospective study conducted at the University of Pennsylvania Health System showed that black race and socioeconomic proxies (like neighborhood disadvantage index (NDI)) were independently associated with sustained cardiac dysfunction. The study further demonstrated that among the components of NDI (education, high-rental occupied housing, annual income below poverty line, female-headed household, adult unemployment, adults on public assistance), low-education and high-rental occupied housing were significantly associated with sustained cardiac dysfunction. Here we assessed the effect of educational level on the prevalence of sustained cardiac dysfunction from PPCM across the US using the “All of Us” repository.
Methods: We met with the M4 student and set a schedule to interact virtually during the 4-week research rotation. Once the student enrolled in the program (https://allofus.nih.gov/), she interrogated the relationship between educational level and PPCM prevalence within the “All of Us” repository (retrospective cohort study). We conducted a Chi-square analysis using the All of Us Jupiter Notebook to evaluate if there was a significant association between educational level and PPCM prevalence. Educational level was categorized as college graduate or advanced degree, college one to three, twelve or General Educational Development (GED), less than a high-school degree or equivalent. Statistical significance p\u3c 0.05.
Results: A cohort of 88 patients with PPCM was identified. Using the Chi-square test, we found a significant relationship between PPCM prevalence and educational level. The Chi-square statistic (23.87) was greater than the critical value (7.81) and the p-value (p\u3c 0.001) was less than alpha (0.05). The relative risk (RR) was 4.31 for patients that did not receive a college degree, compared to those who completed college (confidence interval [CI] 2.56-7.26). Among the 88 patients in the PPCM cohort, 80% did not have a college degree.
Conclusion: 1. Low-level education (no college degree) has a significant impact on PPCM prevalence; 2. Identifying socioeconomic factors influencing PPCM prevalence may improve PPCM prevention, early diagnosis, and management; 3. We were able to integrate the research project using the “All of Us” program as an introductory platform for remote formal training in science methodology within the constraints of M4 timeline, demonstrating the program’s flexibility for integrating scientific training into medical education
Superoxide Release in Polymorphonuclear Leukocytes are Attenuated by Naltrindole by a Novel Mechanism Devoid of Opioid Receptors
No full textIntroduction:
Previously, naltrindole (NTI), known as a delta opioid receptor antagonist, produced robust cardioprotective effects (e.g ~ 80% reduction of infarct size) in both ex-vivo (2.5-5 µM) and in-vivo (3.75-7.5 mg/kg; ~ 100-200 µM serum concentration) rat myocardial ischemia-reperfusion (MIR) models compared to control hearts that received H2O-vehicle or naloxone (NX), a broad-spectrum opioid receptor antagonist. Therefore, we planned to test if NTI elicits cardioprotective effects via a novel mechanism of action (MOA) devoid of opioid receptors. To investigate this hypothesis, we conducted experiments using KB-R7943 (KB) as a positive control, known to minimize intracellular calcium (Ca2+) via inhibition of the reverse mode sodium (Na+)/Ca2+ exchanger in phorbol 12-myristate 13-acetate (PMA) induced polymorphonuclear leukocytes (PMNs) superoxide (SO) release. PMNs do not express opioid receptors. NX was used as a negative control. We predict that NTI will diminish PMA-induced PMN SO release similarly to KB, while NX will have no effect compared to vehicle controls without compromising cell viability.
Methods:
PMNs were isolated from anesthetized male Sprague Dawley rats (~ 400g) and incubated (5x106) for 15 min at 37oC in the presence or absence (dH2O vehicle control) of NTI 10-200 µM, KB 5-20 µM, and NX 100-200 µM. PMN SO release was calculated by the change in absorbance at 550 nm over 420 sec via ferricytochrome c reduction after PMA stimulation (100 nM). The cell viability was determined microscopically by 0.2% trypan blue exclusion at the end of the assay. Data were analyzed using ANOVA Fisher’s PLSD post-hoc test.
Results:
NTI significantly decreased PMN SO release at 200 μM (n=10, 0.196±0.06, p\u3c 0.05) and 100 µM (n=7, 0.461±0.08, p\u3c 0.05) compared to control (n=22, 0.731±0.07). KB also showed a significant decrease in PMN SO release at 20 µM (n=7, 0.507±0.07), 10 µM (n=7, 0.552±0.07), and 5 µM (n=5, 0.615±0.11) compared to control (n=10, 0.908±0.07). NX 100/200 µM (n=3, 0.593±0.06) was not significant compared to control. Cell viability was statistically similar (80-90±5%) among all study groups.
Conclusion:
NTI (100 μM, 200 μM) and KB 5-20 µM exhibited concentration-dependent effects in reducing PMN SO release, suggesting that the novel effect of NTI is likely mediated through a reduction in intracellular Ca2+. Moreover, it indicates that NTI diminishes PMN SO release through a mechanism independent of delta opioid receptor antagonism, corroborated by its effects observed in MIR injury experiments when compared to KB and NX.
Future studies will assess the effects of NTI on ROS attenuation in human umbilical vein endothelial cells. We will use different concentrations to investigate optimal concentration-response.
Funding
This study was funded by the Philadelphia College of Osteopathic Medicine, Department of Biomedical Sciences, Division of Research, and the Center for Chronic Diseases of Aging and Young Therapeutics, LLC
Genetic associations with heart failure across ancestries: an analysis of the All-of-Us NIH database.
Full text linkIntroduction
Heart failure (HF) is a complex clinical syndrome characterized by the heart’s inability to pump blood efficiently. This can be significantly influenced by genetic factors. Genetic predisposition varies across ancestries, which can impact disease susceptibility. This study identifies ancestry-specific and shared genetic variants associated with HF. Methods
We analyzed the “All by All” genome-wide association study (GWAS) result tables within the All-of-Us NIH Database using phenotype code CV_424 for HF. Heart failure (HF) patients were stratified into American (AMR), African (AFR), and European (EUR) ancestry groups. The analysis of GWAS identified significant ancestry-specific variants, followed by a meta-analysis to determine shared and unique associations. Rare variant gene associations were also assessed through meta-analysis. Results
Significant variants were identified across ancestries:
AMR:
ZNF608 or LINC02240 (Chr5:125045705, P = 1.948×10⁻9)
ENSG00000293803 or EFNB2 (Chr13:104556816, P = 1.6771×10⁻8)
AFR:
THUMPD2 (Chr2:39751537, P = 3.9006×10⁻9)
ENSG00000297786 or GATA3 (Chr10:8541268, P = 4.6294×10⁻9)
EUR:
ST6GALNAC5 (Chr1:76852538, P = 2.2522×10⁻9)
ENSG00000294728 or UBL3 (Chr13:29995444, P = 3.3422×10⁻9)
SOX2 (Chr3:181688544, P = 1.3921×10⁻8)
FTO (Chr16:53775211, P = 2.9942×10⁻8)
Significant rare genetic variants with loss of function of TTN (P = 7.66×10⁻15) and SLC16A12 (9.07×10⁻7); and synonymous of ZBTB22 (P = 1.31×10⁻6)
Heart Failure Meta-analysis: Common variants at Chr1:76852538- ST6GALNAC5, Chr10:8553206- GATA3, and Chr 16:53775211- FTO, suggest shared genetic influences. Discussion
This study highlights ancestry-specific and shared genetic associations with HF, reinforcing the importance of diverse genomic research. Limitations to this study include the limited sample size, which may affect statistical power. Future directions for this research are functional studies on identified variants and broader population analysis for genetic insights
A Case Report: Goblet Cell Carcinoma of the Appendix
Full text linkIntroduction:
Goblet cell carcinoma (GCC) is a rare subtype of appendiceal neoplasm characterized by both glandular and neuroendocrine features. It accounts for less than 5% of appendiceal tumors, often presenting diagnostic and therapeutic challenges due to its aggressive behavior.
Case Presentation:
This case report discusses a 62-year-old female patient who presented with diffuse abdominal pain and distension. Imaging revealed a large bowel obstruction in the sigmoid colon, pneumatosis of the ascending colon, and pneumoperitoneum. Exploratory laparotomy was significant for large bowel obstruction at sigmoid colon, proximal transverse colon perforation with carcinomatosis involving small bowel, large bowel and ovary. A subtotal colectomy, omentectomy, ileostomy, and a right salpingo-oophorectomy was performed. Histopathological investigation identified GCC of the appendix and subsequent staging was pT4bpN2pM1b. Postoperative recovery was complicated by abdominal fascial dehiscence which healed with the assistance of an ovine biological matrix. Adjuvant chemotherapy was initiated thereafter.
Discussion:
As a complex cancer, GCC requires histopathological evaluation with certain markers including chromogranin A, synaptophysin, and mucin markers to differentiate it from other appendiceal tumors. With rapidly decreasing 5-year survival rate with advancing stage, management will include appendectomy and right hemicolectomy for localized disease, surgical debulking and intraperitoneal chemotherapy/HIPEC for peritoneal carcinomatosis, and systemic chemotherapy for metastatic disease.
Conclusion:
This case offers an understanding of the aggressive nature of this subtype of appendiceal cancer and the importance of histopathological evaluation and the need for a multidisciplinary approach to managing this rare malignancy. Early diagnosis and appropriate surgical management are important in optimizing the outcomes and survival for patients with GCC
Impact of COVID-19 on Emergency Department psychiatric hospitalization patterns in rural South Georgia : a retrospective analysis
Full text linkIntroduction:
The COVID-19 pandemic has significantly impacted healthcare systems worldwide, including psychiatric care in the emergency setting. This study examines psychiatric admission trends before and during the pandemic, analyzing differences in overall admissions, gender distribution, age group variations, and specific psychiatric diagnoses. We aim to determine if the pandemic resulted in significant changes in psychiatric hospitalization patterns in the Colquitt Regional Medical Center (CRMC) emergency department.
Methods:
This retrospective study utilized electronic medical record (EMR) data from CRMC. Admissions from pre-COVID (April 1, 2019 – December 31, 2019) were compared to those during COVID ( April 1, 2020 to December 31, 2020). Statistical analyses included chi-square tests for categorical comparisons, logistic regression for predictive modeling, and Seasonal Autoregressive Integrated Moving Average (SARIMA) time-series modeling for forecasting admission trends. Power analyses were conducted to ensure sufficient statistical strength. Subgroup analyses were also performed to explore potential variations in specific psychiatric diagnoses and other patient demographics.
Results:
A total of 182 psychiatric admissions were recorded pre-COVID compared to 179 during COVID. Chi-square tests showed no significant difference in overall admissions (p = 1.0), but there is a significant difference within gender distribution across age groups (p = 0.026). Younger females (0-18, 19-30) had increased admissions during COVID, whereas female admissions in middle-aged adults (31-45) declined. Male admissions among older adults (61-75) rose during the pandemic.
Regarding diagnoses, Anxiety disorder, unspecified remained the most common psychiatric condition across both periods, with an increase in younger age groups (0-30). Suicidal ideation remained prevalent but did not significantly increase during COVID. Alcohol-related disorders were more common in middle-aged and older adult patients (31-60).
Time-series analysis using SARIMA modeling indicated cyclical fluctuations rather than a steady increase or decrease in psychiatric admissions, with predicted peaks in March and May 2021. The logistic regression model found no significant predictors of admission trends based on gender, age, or diagnosis type.
Discussion:
Contrary to expectations, psychiatric admissions did not rise during COVID-19, though sample size limitations may have influenced results. However, mental health-related hospitalizations changed during COVID, with increased admissions among younger females and older males. The cyclical nature of admissions suggests external seasonal, geographic, or sociocultural factors outside of measured parameters that may influence hospital visits.
Power analysis confirmed that the chi-square test for age group and gender had sufficient statistical power (0.997), reinforcing the significance of observed differences. However, logistic regression did not identify strong predictive factors, indicating that other variables (e.g., policy changes, outpatient mental health access) may better explain admission trends.
Future research with larger sample sizes and multi-center collaborations could provide more robust insights into the potential influence of COVID-19 on psychiatric presentations in rural emergency settings. SARIMA modeling forecasting can also be compared to actual data from 2021 in a future study. It is crucial to understand these patterns to improve resource allocation and enhanced preparedness for heightened psychiatric demand in the emergency department in the midst of a pandemic
Morphological Variation and Change in the Lateral Ventricles and Caudate Nucleus Across Schizophrenia Types: A Metric Analysis
Full text linkSchizophrenia is a complex neurodevelopmental disorder that alters cognitive function, perception, and behavior. The disorder affects one percent of the global population and is characterized by symptoms such as hallucinations, delusions, disorganized speech, cognitive function, and emotional expression (Hany et al., 2024). While previous research involves three-dimensional (3D) renderings of subcortical structures that demonstrate schizophrenic-specific morphology (Narr et al., 2001; Zhang et al., 2023), the variation expressed by different schizophrenia subtypes require greater focus. This research study explores the structural variations in the lateral ventricles and the caudate nucleus across different schizophrenia subtypes, emphasizing potential sexbased differences. This study hypothesized that a neuromorphometric analysis utilizing Magnetic Resonance Imaging (MRI) scans of patients with Schizophrenia Broad and Schizophrenia Strict disorder would show sex-specific variation in the lateral ventricles and caudate nucleus. To test the hypothesis, a representative sample of 200 cases of individuals with different schizophrenia subtypes and a control group were selected from the SchizConnect database, a large-scale database and neuroimaging data portal (schizconnect.org). The cases were organized based on age, sex, and schizophrenia subtype. Three-dimensional renderings of the lateral ventricles and caudate nucleus were created using 3D Slicer, an open-source software for visualization, processing, segmentation, rendering, and analysis of medical images (Fedorov et al., 2012). Specific points were identified for each 3D model, with twenty-four measurements collected and controlled for size. The data were then analyzed using IBM SPSS Statistics (IBM SPSS Statistics Version 30). A General Linear Model Multivariate Analysis of Variance (GLM MANOVA) and a Canonical Discriminant Function Analysis were used to examine the relationship between variation in schizophrenia subtype and sex. The results of the GLM MANOVA test and of the Canonical Discriminant Function Analysis showed statistically significant differences between those diagnosed with Schizophrenia Broad and Schizophrenia Strict. Furthermore, males and females showed variation between the different schizophrenia subtypes. Approximately 87% of the observed variation reflected differences in measurements associated with the left and right lateral ventricles. Thirteen percent of the variation resulted from alterations in caudate nucleus head morphology due to changes in lateral ventricle morphology. The findings of this study highlight that significant structural and sex-specific variations exist among schizophrenia subtypes. More specifically, males displayed the greatest variation when compared to females. Males diagnosed with Schizophrenia Broad have the greatest change in caudate nucleus head morphology, while those diagnosed with Schizophrenia Strict have the greatest change in lateral ventricle morphology. Accurate recognition of these morphological differences is critical to further develop personalized diagnostic and therapeutic approaches to optimize patient outcomes