Abdominal Surgical Site Infection Incidence and Risk Factors in a Mexican Population.

OBJECTIVE: To investigate possible predictors and prevalence of surgical site infections (SSIs) in a group of Mexican patients who underwent open abdominal surgery. METHODS: This retrospective study included all patients (N = 755) who underwent elective or emergency open abdominal surgeries from October 2011 to March 2012. MAIN OUTCOME MEASURE: Sociodemographic and clinical characteristics were collected through preoperative and postoperative examinations by the infection surveillance team. The relationship among variables (age, gender, body mass index, comorbidities, smoking habit, antimicrobial prophylaxis, hair removal, American Society of Anesthesiologists classification, type of operation, duration of operation, and SSI classification) was analyzed by odds ratio and χ tests. MAIN RESULTS: Of the 755 patients, 91 (12%) suffered from SSI. Several variables were associated with SSI: American Society of Anesthesiologists classification (P = .001) and receiving preoperative prophylactic antimicrobials (P < .0001), among other factors. Isolated pathogens were mostly enterobacteria (60%). CONCLUSIONS: Surveillance plays an important role in the control and prevention of SSI. Providers must implement appropriate procedures to reduce SSI after abdominal surgery.

EXPLORATORY ANALYSIS OF POLYGENIC RISK SCORES FOR PSYCHIATRIC DISORDERS: APPLIED TO DUAL DIAGNOSIS.

BACKGROUND: Concurrence of substance use disorders (SUDs) is high in individuals with psychiatric illnesses; more importantly, individuals with both disorders (dual diagnosis) have more severe symptoms. Psychiatric disorders have been proposed to share a genetic susceptibility with SUDs. To explore this shared genetic susceptibility, we analyzed whether any of the polygenic risk scores (PRSs) for psychiatric disorders could be associated to dual diagnosis in patients with schizophrenia (SCZ) or bipolar disorder (BD). METHODS: We included 192 individuals of Mexican ancestry: 72 with SCZ, 53 with BD, and 67 unrelated controls without psychiatric disorders. We derived calculations of PRS for autism spectrum disorders, attention-deficit/hyperactive disorder, BD, major depression, and SCZ using summary genome-wide association statistics previously published. RESULTS: We found that dual diagnosis had a shared genetic susceptibility with major depressive disorder (MDD) and SCZ; furthermore, in individuals with BD, dual diagnosis could be predicted by PRS for MDD. CONCLUSIONS: Our results reinforce the notion that individuals with dual diagnosis have a higher genetic susceptibility to develop both disorders. However, analyses of larger sample sizes are required to further clarify how to predict risks through PRS within different populations.

Identification of gene ontology and pathways implicated in suicide behavior: Systematic review and enrichment analysis of GWAS studies.

Multiple large-scale studies such as genome-wide association studies (GWAS) have been performed to identify genetic contributors to suicidal behaviors (SB). We aimed to summarize and analyze the information obtained in SB GWAS, to explore the biological process gene ontology (GO) of genes associated with SB from GWAS, and to determine the possible implications of the genes associated with SB in Kyoto encyclopedias of genes and genomes (KEGG) biological pathways. The articles included in the analysis were obtained from PubMed and Scopus databases. Enrichment analyses were performed in Enrichr to evaluate the KEGG pathways and GO of the genes associated with SB of GWAS. The findings of biological process GO analysis showed 924 GO involved in genes related with SB; of those, the regulation of glucose import in response to insulin stimulus, regulation of protein localization to plasma membrane, positive regulation of endopeptidase activity, heterotypic cell-cell adhesion, regulation of cardiac muscle cell contraction, positive regulation of protein localization to plasma membrane, and positive regulation of protein localization to cell periphery biological process GO showed significant statistical association. Furthermore, we obtained 130 KEGG pathways involved in genes related with SB, which Aldosterone synthesis and secretion, Rap1 signaling pathway and arrhythmogenic right ventricular cardiomyopathy pathways showed a significant statistical association. These findings give a better perspective of the biological participation of genes associated with SB, which will be important to perform adequate strategies to prevent and treat SB.

Astrogliosis and decreased neural viability as consequences of early consumption of aspartame and acesulfame potassium in male Wistar rats.

Artificial sweeteners are mainly used as substitutes for sucrose derivates. In this study, we analyzed if the chronic consumption of aspartame or acesulfame potassium at an early age, produces histological alterations, astrogliosis and decreased neuronal viability, in hippocampus, prefrontal cortex, amygdala and hypothalamus of male Wistar rats. A histological analysis was performed on male Wistar rats that consumed aspartame or acesulfame potassium during 90 days, initiating the consumption of sweeteners immediately after weaning. The evaluation of neuronal morphology in different areas of the brain was performed with hematoxylin - eosin staining. To measure astrogliosis and neuronal viability, we used the immunohistochemical technique, with the glial fibrillary acidic protein immunomodulators (GFAP) and with neuronal-specific enolase (NSE). The consumption of aspartame or acesulfame potassium promoted morphological changes of neurons including increased pyknotic nuclei and vacuolization in all the brain areas studied. In hippocampus, prefrontal cortex, amygdala and hypothalamus, astrogliosis and reduction of neural viability were observed in sweeteners consumers in comparison with the control group. Chronic consumption of ASP and ACK from early stages of development and during long periods, may promote neural modifications, astrogliosis and decrease neuronal viability in prefrontal cortex, amygdala, hippocampus, and hypothalamus.

Potential drug-drug interaction in Mexican patients with schizophrenia.

OBJECTIVE: The aim of this study was to observe potential drug-drug interactions in the medication of Mexican schizophrenic patients. METHODS: We performed a retrospective and cross-sectional study that was carried out in a psychiatric clinic. Only the prescriptions of patients with schizophrenia whose diagnoses were based on the DSM-IV instrument were included in this study. The Drug Interactions Checker software ( http://www.drugs.com/drug_interactions.html ) was used in this study to analyse potential drug-drug interactions. RESULTS: In total, 86 of 126 patients were at risk of potential drug-drug interactions. Haloperidol and biperiden was the most common drug pair of 232 pairs evaluated. In our study, 13.8% of drug-drug interaction showed a major level of severity, whereas in 83.2%, the interaction was moderate. Finally, central nervous system (CNS) depression and anticholinergic effect were the main possible effects of drug-drug interaction. CONCLUSIONS: Our results revealed a high number of patients with schizophrenia receiving two or more drugs. The potential drug-drug interactions observed in the Mexican population are consistent with the concomitant use of antipsychotics, benzodiazepines, and antidepressants prescribed in schizophrenia that could cause central nervous system (CNS) depression and anticholinergic effect. Drug-drug interaction must be considered when the patient with schizophrenia is medicated.

Coenzyme Q10 supplementation improves metabolic parameters, liver function and mitochondrial respiration in rats with high doses of atorvastatin and a cholesterol-rich diet.

BACKGROUND: The aim of this study was to evaluate the actions of coenzyme Q10 (CoQ10) on rats with a cholesterol-rich diet (HD) and high doses of atorvastatin (ATV, 0.2, 0.56 or 1.42 mg/day). METHODS: Two experiments were done, the first one without coenzyme Q10 supplementation. On the second experiment all groups received coenzyme Q10 0.57 mg/day as supplement. After a 6-week treatment animals were sacrificed, blood and liver were analyzed and liver mitochondria were isolated and its oxygen consumption was evaluated in state 3 (phosphorylating state) and state 4 (resting state) in order to calculate the respiratory control (RC). RESULTS: HD increased serum and hepatic cholesterol levels in rats with or without CoQ10. ATV reduced these values but CoQ10 improved even more serum and liver cholesterol. Triacylglycerols (TAG) were also lower in blood and liver of rats with ATV + CoQ10. HDL-C decreased in HD rats. Treatment with ATV maintained HDL-C levels. However, these values were lower in HD + CoQ10 compared to control diet (CD) + CoQ10. RC was lessened in liver mitochondria of HD. The administration of ATV increased RC. All groups supplemented with CoQ10 showed an increment in RC. In conclusion, the combined administration of ATV and CoQ10 improved biochemical parameters, liver function and mitochondrial respiration in hypercholesterolemic rats. CONCLUSIONS: Our results suggest a potential beneficial effect of CoQ10 supplementation in hypercholesterolemic rats that also receive atorvastatin. This beneficial effect of CoQ10 must be combined with statin treatment in patient with high levels of cholesterol.

[Prevalence and gravity of depression and anxiety in patients with obesity and type 2 diabetes: a study in the population of Tabasco, Mexico]. / Prevalencia y gravedad de la depresión y la ansiedad en pacientes con obesidad y diabetes de tipo 2: estudio en población de Tabasco, México.

AIMS: The aim of this study was to assess the prevalence of anxiety and depression in groups of obese and normal-weight individuals with type 2 diabetes. Also, to analyze the severity of depression in type 2 diabetics by taking into account the body mass index in people with this condition. METHODS: This study included 702 patients with type 2 diabetes, 236 with normal weight, and 231 with obesity. All participants completed a demographic questionnaire, the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale. RESULTS: In patients with obesity, 48.48% (95% CI: 41.82-55.14) were positive for anxiety and 49.78% (95% CI: 43.11-56.44) for depression. A significant correlation existed between the Hamilton Depression Rating Scale and body mass index with a correlation coefficient of 0.11 (p = 0.003). Also, a significant correlation coefficient equal to 0.107 (p = 0.005) between the Hamilton Anxiety Rating Scale and body mass index was found. In addition, when we analyzed depression scores, significant differences were encountered for gender between normal-weight and obesity groups in the range of severe (p = 0.01) and very severe (p = 0.04) cases. CONCLUSION: In view of the existing relationships observed among obesity, depression, anxiety, and gender in type 2 diabetics, we consider that a psychological intervention is necessary for an integral management of these patients.

Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis.

OBJECTIVE: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. METHODS: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. RESULTS: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. CONCLUSIONS: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.

Potential applications of recombinant bifidobacterial proteins in the food industry, biomedicine, process innovation and glycobiology.

Bifidobacterial proteins have been widely studied to elucidate the metabolic mechanisms of diet adaptation and survival of Bifidobacteria, among others. The use of heterologous expression systems to obtain proteins in sufficient quantities to be characterized has been essential in these studies. L. lactis and the same Bifidobacterium as expression systems highlight ways to corroborate some of the functions attributed to these proteins. The most studied proteins are enzymes related to carbohydrate metabolism, particularly glycosidases, due to their potential application in the synthesis of neoglycoconjugates, prebiotic neooligosaccharides, and active metabolites as well as their high specificity and efficiency in processing glycoconjugates. In this review, we classified the recombinant bifidobacterial proteins reported to date whose characterization has demonstrated their usefulness or their ability to produce a product of commercial interest for the food industry, biomedicine, process innovation and glycobiology. Future directions for their study are also discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00957-1.

Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice.

Statins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional changes on hepatocyte mitochondria. In a mouse model we studied the combined administration of a cholesterol-rich diet along with mild and moderate doses of rosuvastatin (1, 2.5 or 5 mg/kg/day) during several days. After the animals were sacrificed, liver mitochondria were isolated for microscopic studies and to analyze the respiratory function. The respiratory control (state-3/state-4) was evaluated in mice who received high doses of rosuvastatin. Rosuvastatin doses higher than 20 mg/kg/day induced premature death in mice with a hypercholesterolemic diet, but not in mice with a cholesterol-free diet. Doses from 2.5 to 5 mg/kg/day also induced morphological and functional alterations in mitochondria but these hypercholesterolemic animals survived longer. Giving 1 mg/kg/day, which is close to the maximal therapeutic dose for humans, did not affect mitochondrial architecture or respiratory function after two months of treatment. We analyzed the effect of rosuvastatin on hepatic tissue because it is where statins are mainly accumulated and it is the main site of endogenous cholesterol synthesis. Our results contribute to understand the side effects of rosuvastatin in hypercholesterolemic mice, effects that could also affect humans who are intolerant to statins.

Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.

Aim: To analyze the association of NKX2.5 gene with congenital heart disease (CHD), and to determine if the variants rs703752, rs3729753 and rs2277923 increase the risk for developing CHD. Materials & methods: PubMed, EBSCO and Web of Science databases were screened to identify eligible studies. Through a comprehensive meta-analysis software, the association between NKX2.5 gene variants and susceptibility of CHD was calculated by pooled odd ratio (ORs) and 95% CI. Results: We observed that the allelic model of rs703752 and rs2277923 increased the risk in the overall population: OR = 1.24; 95% CI: 1.00-1.55; Z p-value = 0.049; OR = 1.18; 95% CI: 0.01-1.37; Z p-value = 0.036; respectively. Conclusion: Our results suggested that the rs703752 and rs2277923 polymorphisms of the NKX2.5 gene are associated with CHD.

Combined Effect of Diosgenin Along with Ezetimibe or Atorvastatin on the Fate of Labelled Bile Acid and Cholesterol in Hypercholesterolemic Rats.

We analyzed the effect of diosgenin, administered with atorvastatin or ezetimibe, on the fate of ³H(G)-taurocholic acid or 26-14C-cholesterol in hypercholesterolemic rats. Male Wistar rats received a hypercholesterolemic diet (HD), HD + atorvastatin (HD+ATV), HD + ezetimibe (HD+EZT), HD + diosgenin (HD+DG), HD+ATV+EZT, or HD+ATV+DG for 40 days. We also included a control normal group (ND). The labelled compounds were administered on day 30. The animals were placed in metabolic cages for daily feces collection. At day 40 the rats were sacrificed. Lipid extracts from blood, liver, spinal cord, testicles, kidneys, epididymis, intestine, and feces were analyzed for radioactivity. Cholesterol activity was the highest in the liver in HD rats. DG diminished one half of this activity in HD+DG and HD+ATV+DG groups in comparison with the HD group. HD+ATV rats showed four to almost ten-fold cholesterol activity in the spinal cord compared with the ND or HD rats. Fecal elimination of neutral steroids was approximately two-fold higher in the HD+DG and HD+ATV+DG groups. Taurocholic acid activity was four to ten-fold higher in HD+DG intestine as compared to the other experimental groups. Taurocholic activity in the liver of HD and HD+DG groups was two and a half higher than in ND. Our results show that the combination of DG and ATV induced the highest cholesterol reduction in the liver and other tissues.

Effects of Resistant Starch Ingestion on Postprandial Lipemia and Subjective Appetite in Overweight or Obese Subjects.

Reports surrounding the role of resistant starch (RS) on postprandial lipemia in humans are scarce. The aim of the present study is to examine the effects of resistant starch on the postprandial lipemic response, subjective measures of appetite, and energy intake in overweight and obese subjects. In a randomized, single-blind, crossover study, 14 overweight/obese participants ate a high-fat breakfast (679 kcal, 58% from fat) and a supplement with native banana starch (NBS), high-amylose maize starch (HMS), or digestible maize starch (DMS) on three separate occasions. All supplements provided were matched by the available carbohydrate content, and the RS quantity in NBS and HMS supplements was identical. Appetite was estimated using visual analogue scale (VAS) and an ad libitum test meal. Postprandial glycemia, triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and insulin excursions did not differ between treatments. Subjective appetite measures of satiety were significantly increased after HMS; however, no effects on energy intake were observed during the ad libitum test meal. These findings suggest that a single acute dose of RS cannot be expected to improve postprandial lipemia in subjects with overweight or obesity on a high-fat meal. However, the potential benefits of long-term supplementation should not be ruled out based on these results.

Erythropoietin: A potential drug in the management of diabetic neuropathy.

Erythropoietin (EPO) is required for promoting the progress of erythroid differentiation. However, the discovery of EPO and the EPO receptor (EPOR) in the nervous system may contribute to new treatment strategies for the use of EPO in neurodegenerative disorders. Diabetic neuropathy is a neurodegenerative disease that affects a large proportion of diabetic patients and results in alterations in functionality, mood and sleep. The pathogenic mechanisms generating diabetic neuropathy involve: Schwannopathy, polyol pathway activity, advanced glycation end-products (AGEs) accumulation, protein kinase C (PKC) activity, increased hexosamine pathway flux, oxidative stress, nitric oxide and inflammation. In this sense, evidence from both clinical and experimental studies indicates that EPO may reverse diabetic neuropathy through an antioxidant action by decreasing pro-inflammatory cytokines, restoring Na+/K+-ATPase activity, and blocking the generation of pro-apoptotic proteins. The aim of this review is to discuss the neuroprotector effect of EPO on pathogenic mechanisms of diabetic neuropathy.

Prevalence and correlations between suicide attempt, depression, substance use, and functionality among patients with limb amputations.

Most patients undergoing limb amputations suffer significant emotional changes. The aim of this study was to estimate the prevalence of suicide attempts and depression in a sample of Mexican patients with limb amputations and, second, to determine whether the patients' functionality correlates with the presence of depression. We studied 40 patients who had undergone a limb amputation. The suicide attempt was evaluated using the Suicide Intent Scale. The depression was assessed using the Hamilton Depression Rating Scale, whereas the functionality of the patients was measured using the Functional Independence Measure. In this sample, 90% were men, whereas only 10% were women. In terms of the suicide behavior, we identified suicide attempts in 27.5% of the patients. The rate of depression was 92.5%. In the Functional Independence Measure, we observed that 57.5% of the patients showed complete dependence. Finally, a significant correlation was found between depression and functionality (r=-0.75, P<0.001). The findings of the present study highlight the high incidence of suicide attempts and depression in Mexican patients with limb amputations. Also, we identified a correlation between the lack of functional independence and depression. Therefore, holistic interventions are necessary in these patients: rehabilitation therapy to increase their functionality, and psychological and pharmacology therapy to decrease suicidal behavior and depression. Finally, more studies using larger samples are necessary to obtain conclusive results.

Peripheral participation of cholecystokinin in the morphine-induced peripheral antinociceptive effect in non-diabetic and diabetic rats.

The effects of cholecystokinin (CCK-8) and the CCK receptor antagonist proglumide, on antinociception induced by local peripheral (subcutaneous) injected morphine in non-diabetic (ND) and streptozotocin-induced diabetic (D) rats, were examined by means of the formalin test. Morphine induced dose-dependent antinociception both in ND and D rats. However, in D rats, antinociceptive morphine potency was about twofold less than in ND rats. Pre-treatment with CCK-8 abolished the antinociceptive effect of morphine in a dose-dependent manner in both groups of rats. Additionally, proglumide enhanced the antinociceptive effect induced by all doses of morphine tested. Both CCK-8 and proglumide had no effect on flinching behaviour when given alone to ND rats. Unlike ND rats, in D rats proglumide produced dose-dependent antinociception and CCK-8 enhanced formalin-evoked flinches, as observed during the second phase of the test. In conclusion, our data show a decrease in peripheral antinociceptive potency of morphine when diabetes was present. Additionally, peripheral CCK plays an antagonic role to the peripheral antinociceptive effect of morphine, additional to the well known CCK/morphine interaction at spinal and supraspinal level.

Characteristics of Mexican children and adolescents who died by suicide: A study of psychological autopsies.

OBJECTIVE: In recent years, suicide in children and adolescents has increased considerably, becoming the second cause of death in this age group. Therefore, the aim of this study was to identify characteristics and factors that could precipitate deaths by suicide in children and adolescents. METHODS: Using the psychological autopsy method, we studied 28 suicide cases of children and adolescents between 10 and 17 years old. Socio-demographic factors, characteristics of the suicide and family history were documented. RESULTS: The proportion of deaths by suicide was the same in females and males (50% each). Most of the suicides were performed at the child/adolescent's home (78.6%) and no history of previous suicide attempts were registered (85.7%). Also, the majority of suicidal individuals came from a dysfunctional family (60.7%). CONCLUSIONS: Our results identified characteristics of children and adolescents that had died by suicide, such as dying at their homes and coming from dysfunctional families. Knowing the characteristics of children and adolescents that had ended their lives by suicide should be considered in future studies to help developing preventive programs and strategies for treating suicidal behaviors in Mexican children and adolescents.

The role of the Cys23Ser (rs6318) polymorphism of the HTR2C gene in suicidal behavior: systematic review and meta-analysis.

The polymorphisms of the serotonin receptor 2C (HTR2C) gene have been proposed to influence suicidal behavior. The aim of our study was to explore the role of the HTR2C gene variant Cys23Ser (rs6318) in the pathogenesis of suicidal behavior through a systematic review and meta-analysis. The search was performed using EBSCO and PubMed databases. To be included in the analysis, the studies had to evaluate suicidal behavior (attempted, ideation, or completed suicide). The results of the meta-analysis were expressed as odds ratios (ORs). Because HTR2C lies on chromosome X, pooled ORs were calculated, respectively, for each of the models used, namely: allelic, homozygous, dominant, and recessive for the female group and allelic for the male group. The meta-analysis comprised 3867 individuals, including 1668 cases and 2199 controls. The HTR2C Cys23Ser (rs6318) polymorphism did not show a significant association with suicidal behavior either in women (OR: 0.75; 95% confidence interval: 0.55-1.00) or in men (OR: 0.89; 95% confidence interval: 0.64-1.23). Similarly, nonsignificant associations were observed for all of the genetic models used in any of the populations/subgroups studied. Our findings suggest that the rs6318 (Cys23Ser) polymorphism is not associated with suicidal behavior. However, because of the study limitations, we suggest more researches should be performed, increasing the sample sizes and statistical power, to determine the association between the rs6318 variant and suicidal behavior.

Decrease in brain-derived neurotrophic factor at plasma level but not in serum concentrations in suicide behavior: A systematic review and meta-analysis.

INTRODUCTION: Suicide is known as a major health concern worldwide. There is evidence for the role of brain-derived neurotrophic factor (BDNF) in suicide behavior. Therefore, this factor has been proposed as a biomarker for suicide behavior. Clinical studies have measured BDNF concentrations at central and peripheral levels. As a consequence, the aim of this study was to assess BDNF levels in blood plasma and serum to see whether there is a difference in concentrations in patients with suicide behavior when compared to those in controls, using a meta-analysis approach. METHODS: We conducted a systematic review and meta-analysis. The search strategy was performed using three databases: PubMed, EBSCO and ScienceDirect. The meta-analysis included a total of nine case-control studies, six measured the BDNF level in serum and three in plasma in suicide behavior. RESULTS: A decrease in BDNF levels in plasma was observed (d = -0.73, 95% CI -1.42 to -0.03 pg/ml). In the case of serum concentrations, no BDNF differences were encountered between cases and controls (d = 0.09, 95% CI -0.31 to 0.13 ng/ml, p(Q) = .92). CONCLUSIONS: According to the results found in the present meta-analysis, the plasma BDNF level could be suggest as a potential biomarker in suicide behavior. However, since the number of studies included in the analysis is limited, a larger number is necessary to determine conclusively the role of BDNF as a biomarker in suicide behavior.

Association of FAAH p.Pro129Thr and COMT p.Ala72Ser with schizophrenia and comorbid substance use through next-generation sequencing: an exploratory analysis

Objective: Individuals with schizophrenia and substance use disorders have a poor prognosis and increased psychiatric symptoms. The present study aimed to explore the association of 106 genes in individuals with schizophrenia and comorbid substance use through a next-generation sequencing (NGS) analysis and different in silico algorithms. Methods: We included 105 individuals diagnosed with schizophrenia and a family history of schizophrenia, of whom 49 (46.67%) presented comorbid substance use. Using NGS, we sequenced 106 genes previously associated with schizophrenia. Logistic regression models were used to assess differences in allele frequencies, and a generalized gene-set analysis was performed at the gene level. Functional annotations were performed using different algorithms and databases. Results: We identified a total of 3,109 variants, of which 25 were associated with schizophrenia and comorbid substance use and were located in regulatory and coding regions. We found low-frequency variants in COMT p.Ala72Ser, independently of p.Val158Met, that were associated with substance use. The endocannabinoid functional variant FAAH p.Pro129Thr was also associated with substance use. Conclusions: Genetic variants of genes related to dopaminergic and cannabinoid neurotransmitter systems were associated with comorbid substance use in schizophrenia. Nevertheless, more studies with larger sample sizes are needed to confirm our findings.