Subcortical Volume Changes in Schizophrenia and Bipolar Disorder: A Quantitative MRI Study

SUMMARY: Volume abnormalities in subcortical structures, including the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus have been observed in schizophrenia (SZ) and bipolar disorder (BD), not all individuals with these disorders exhibit such changes. In addition, the specific patterns and severity of volume changes may vary between individuals and at different stages of the disease. The study aims to compare the volumes of these subcortical structures between healthy subjects and individuals diagnosed with SZ or BD. Volumetric measurements of lateral ventricle, globus palllidus, caudate, putamen, hippocampus, and amygdale were made by MRI in 52 healthy subjects (HS), 33 patients with SZ, and 46 patients with BD. Automatic segmentation methods were used to analyze the MR images with VolBrain and MRICloud. Hippocampus, amygdala and lateral ventricle increased in schizophrenia and bipolar disorder patients in comparison with control subjects using MRIcloud. Globus pallidus and caudate volume increased in patients with schizophrenia and bipolar disorder compared control subjects using Volbrain. We suggested that our results will contribute in schizophrenia and bipolar disorder patients that assessment of the sub-cortical progression, pathology, and anomalies of subcortical brain compositions. In patients with psychiatric disorders, VolBrain and MRICloud can detect subtle structural differences in the brain.

Se han observado anomalías de volumen en las estructuras subcorticales, incluidos el hipocampo, la amígdala, el tálamo, el núcleo caudado, el putamen y el globo pálido, en la esquizofrenia (SZ) y el trastorno bipolar (BD); no todos los individuos con estos trastornos presentan tales cambios. Además, los patrones específicos y la gravedad de los cambios de volumen pueden variar entre individuos y en diferentes etapas de la enfermedad. El estudio tuvo como objetivo comparar los volúmenes de estas estructuras subcorticales entre sujetos sanos e individuos diagnosticados con SZ o BD. Se realizaron mediciones volumétricas del ventrículo lateral, globo pálido, núcleo caudado, putamen, hipocampo y amígdala mediante resonancia magnética en 52 sujetos sanos (HS), 33 pacientes con SZ y 46 pacientes con BD. Se utilizaron métodos de segmentación automática para analizar las imágenes de resonancia magnética con VolBrain y MRICloud. El hipocampo, la amígdala y el ventrículo lateral aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con sujetos de control que utilizaron MRIcloud. El globo pálido y el núcleo caudado aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con los sujetos control que utilizaron Volbrain. Sugerimos que en pacientes con esquizofrenia y trastorno bipolar, nuestros resultados contribuirán a la evaluación de la progresión subcortical, la patología y las anomalías de las composiciones cerebrales subcorticales. En pacientes con trastornos psiquiátricos, VolBrain y MRICloud pueden detectar diferencias estructurales sutiles en el cerebro.

Seroprevalencia de Toxoplasma gondii y su relación con trastornos mentales en adultos / Seroprevalence of Toxoplasma gondii and its Relationship with Mental Disorders in the Adult Population

El Toxoplasma gondii es un parásito que se encuentra, aproximadamente, en el 30 % de la población humana. Durante los últimos años se ha evidenciado que la infección latente puede ser un factor de riesgo para el desarrollo de trastornos mentales; particularmente para la esquizofrenia, ansiedad, trastornos bipolares y trastornos de conducta. La asociación con los trastornos neuropsiquiátricos pueden explicarse por la influencia que tiene el parásito sobre la expresión de múltiples neurotransmisores; entre ellos la dopamina. Se realizó una búsqueda en las bases de datos PubMed y SciELO de 2015 a 2023, se seleccionaron artículos originales y de revisión de revistas científicas internacionales, en idiomas inglés y español con el objetivo de describir la relación entre la seroprevalencia de T. gondii y el desarrollo de trastornos mentales en población adulta. Existe relación entre los trastornos mentales en la población adulta con la infección por Toxoplasma gondii y este aumenta la posibilidad de desarrollar esquizofrenia y depresión en individuos sin historial previo, y que podría exacerbar cuadros psiquiátricos previos con dificultad en el tratamiento. Sin embargo, no todos los datos estadísticos establecen una relación directa, algunos estudios demuestran una asociación, ciertos datos son discordantes, lo que abre una puerta para futuras investigaciones.

Toxoplasma gondii is a parasite that is found in approximately 30 % of the human population. In recent years, it has been shown that latent infection can be a risk factor for the development of mental disorders; particularly schizophrenia, anxiety, bipolar disorders, and conduct disorders. The association with neuropsychiatric disorders can be explained by the influence of the parasite on the expression of multiple neurotransmitters; among them, dopamine has received the most attention. A narrative bibliographic review article was done with the search of original and review articles in international scientific journals, in English and Spanish listing the relationship between the seroprevalence of T. gondii and the development of mental disorders in the adult population. The relationship between mental disorders in the adult population with Toxoplasma gondii infection is present and increases the possibility of developing schizophrenia and depression in individuals with no previous history, including the ability to worsen previous psychiatric conditions, making it difficult for standard management. Not all statistical data establish a direct relationship, some studies show an association and certain data are discordant, which opens a door for future research.

Deterioro funcional y neurocognitivo en pacientes con esquizofrenia deficitaria en Perú y confiabilidad de la estructura bidimensional de la sintomatología negativa / Functional and neurocognitive impairment in deficit schizophrenia patients in Peru and reliability of the bidimensional structure of negative symptomatology

Resumen La mayoría de los estudios sugieren que los pacientes con esquizofrenia deficitaria presentan un deterioro funcional y neurocognitivo más grave en comparación con los pacientes con esquizofrenia no deficitaria. Sin embargo, existen pocos estudios al respecto en América Latina. Examinar las diferencias entre el funcionamiento y el deterioro neurocognitivo en pacientes con y sin esquizofrenia deficitaria; y analizar la validez de la estructura bifactorial de los síntomas negativos en una muestra de pacientes peruanos. Se reclutó a un total de 53 pacientes peruanos con esquizofrenia. Se utilizó la versión en español del Schedule for the Deficit Syndrome (SDS) para diagnosticar el síndrome deficitario, el Functioning Assessment Short Test (FAST) para evaluar el funcionamiento global, y el Screen for Cognitive Impairment in Psychiatry (SCIP) para evaluar el funcionamiento neurocognitivo. La prevalencia de esquizofrenia deficitaria fue del 62,3 %. Los pacientes con esquizofrenia deficitaria presentan un mayor deterioro en la memoria de trabajo (p = 0,003), fluidez verbal (p = 0,002), aprendizaje verbal retardado (p = 0,039) y velocidad de procesamiento (p = 0,004). En cuanto al funcionamiento global, los pacientes con esquizofrenia deficitaria muestran un rendimiento inferior en las dimensiones de autonomía (p = 0,002), laboral (p = 0,001), cognitiva (p = 0,010), finanzas (p = 0,015), relaciones interpersonales (p < 0,001) y tiempo de ocio (p < 0,001). Los pacientes con esquizofrenia deficitaria muestran un mayor deterioro en el funcionamiento global y cognitivo. La replicación de la estructura bidimensional de los síntomas negativos en una muestra peruana contribuye a la hipótesis de la universalidad del modelo de «déficit expresivo¼ y «apatía-abulia¼.

ABSTRACT Many studies suggest that patients with deficit schizophrenia exhibit a more severe functional and neurocognitive impairment than those with non-deficit schizophrenia. However, there are few studies on this topic in Latin America. To examine the differences in functioning and neurocognitive impairment between patients with and without deficit schizophrenia, and to analyze the validity of the bifactorial structure of negative symptoms in a sample of Peruvian patients. A total of 53 Peruvian patients with schizophrenia were recruited. The Spanish version of the Schedule for the Deficit Syndrome (SDS) was used to diagnose the syndrome under study. The Functioning Assessment Short Test (FAST) was employed to assess global functioning, and the Screen for Cognitive Impairment in Psychiatry (SCIP), to evaluate neurocognitive functioning. The prevalence of deficit schizophrenia was 62.3%. Patients with deficit schizophrenia exhibited greater impairment in working memory (p = 0.003), verbal fluency (p = 0.002), delayed verbal learning (p = 0.039), and processing speed (p = 0.004). Regarding global functioning, patients with deficit schizophrenia demonstrated poorer performance in the domains of autonomy (p = 0.002), occupational functioning (p = 0.001), cognitive functioning (p = 0.010), financial functioning (p = 0.015), interpersonal relationships (p < 0.001), and leisure time (p < 0.001). Patients with deficit schizophrenia display greater impairment in global and cognitive functioning. The replication of the bidimensional structure of negative symptoms in a Peruvian sample contributes to the hypothesis of the universality of the "expressive deficit" and "apathy-abulia" model.

Research progress on the improvement mechanism of traditional Chinese medicine compounds and active ingredients in schizophrenia / 中国药房

Schizophrenia has various obstacles in cognition， thinking， emotion， behavior and other aspects； it belongs to the category of “madness” in traditional Chinese medicine （TCM）. Once schizophrenia occurs， multiple factors are often intertwined， and a single therapy is difficult to be effective. At present， TCM compounds and active ingredients have significant effects in the clinical treatment of schizophrenia， which is an important direction for the development of new drugs for schizophrenia. This article summarizes the molecular mechanism of TCM compounds and active ingredients in the treatment of schizophrenia. It is found that Wendan decoction and Yudian decoction can inhibit the apoptosis of hippocampal cells by activating BDNF/TrKB/CREB signaling pathway； quercetin and icariin can promote neural development and regeneration by activating NMDA/ERK signaling pathway； Wendan decoction and icariin can maintain neural cell homeostasis by activating PI3K/AKT signaling pathway； Bushen zhuangyang capsule can enhance learning and memory abilities by activating CaMKⅡ signaling pathway； formulas such as Huatan huoxue tongzhi formula can enhance intercellular information transmission by inhibiting PKC signaling pathway； α-humulene and others can restore nerve cell function by inhibiting NRG1/ErbB4 signaling pathway. TCM compounds and active ingredients can improve schizophrenia by intervening in the above-mentioned signaling pathways.

Correlation of serum glutamate and gamma-aminobutyric acid levels with clinical symptoms in chronic schizophrenia patients and their diagnostic value for cognitive impairment / 国际检验医学杂志

Objective To explore the correlation of serum glutamate(Glu)and gamma-aminobutyric acid(GABA)levels with clinical symptoms in chronic schizophrenia patients,and to assess their diagnostic value for cognitive impairment.Methods A total of 92 patients with chronic schizophrenia and another 80 healthy individuals in Wuhan Mental Health Center/Wuhan Hospital for Psychotherapy from January 2021 to July 2022 were enrolled as study group and control group,respectively.The patients in the study group were divid-ed into the cognitive impairment group(44 cases)and the cognitive normal group(48 cases)according to Montreal Cognitive Assessment Scale(MoCA).Clinical symptoms were assessed by using Positive and Nega-tive Syndrome Scale(PANSS).MoCA was used to evaluate the cognitive function.The levels of Glu and GA-BA in plasma were determined by high-performance liquid chromatography/electrospray tandem mass spec-trometry.The scores of PANSS and MoCA as well as serum levels of Glu and GABA were compared between two groups.Then the correlation of serum Glu and GABA levels with clinical symptoms and the diagnostic value for cognitive impairment in the patients in the study group were investigated.Results The Glu level in the study group was higher than that in the control group,and the GABA level was lower than that in the con-trol group(P＜0.05).The serum Glu levels in both the cognitive impairment group and the cognitive normal group were higher than the normal range,and the Glu level in the cognitive impairment group was higher than that in the cognitive normal group(P＜0.05).The serum GABA levels in both the cognitive impairment group and the cognitively normal group were lower than the normal range,and the GABA level in the cogni-tive impairment group was lower than that in the cognitive normal group(P＜0.05).In the study group,ser-um Glu level was positively correlated with negative,positive,general psychopathological symptom scores,and overall score in PANSS(P＜0.05),while GABA level was negatively correlated with negative,positive,gener-al psychopathological symptom scores,and overall score in PANSS(P＜0.05).The sensitivity of the single and combined detection of serum Glu and GABA for the diagnosis of cognitive impairment in patients with chronic schizo-phrenia was 77.3％,72.7％and 93.2％,respectively,and the specificity was 72.9％,72.9％,and 75.0％,respec-tively,and the area under the curve was 0.778,0.769,and 0.868,respectively.Conclusion Serum Glu level in patients with chronic schizophrenia is higher than that in healthy individuals,while GABA level is lower than that in healthy individuals,and the above two indicators are correlated with PANSS score,which have high value in diagnosing cognitive impairment and could be used as effective biological indicators to help clinical doctors judge patients'cognitive function.

Relationship between serum sTfR and FGF22 levels and clinical symptoms in first-episode schizophrenia patients and their diagnostic value / 国际检验医学杂志

Objective To investigate the expression of soluble transferrin receptor(sTfR)and fibroblast growth factor 22(FGF22)in serum of first-episode schizophrenia(FES)patients,analyze the relationship be-tween the two and the clinical symptoms of FES patients,and analyze their diagnostic value.Methods A total of 97 FES patients diagnosed in the hospital from March 2021 to February 2023 were regarded as the FES group,during the same period,96 healthy volunteers who came to this hospital for physical examination were regarded as the control group.Immunotransmission turbidimetry was applied to detect the level of sTfR,en-zyme linked immunosorbent assay(ELISA)was applied to detect the level of FGF22,Spearman method was applied to analyze the correlation between the levels of sTfR and FGF22 in the serum of FES patients and Pos-itive and Negative Syndrome Scale(PANSS)score and Wisconsin Card Sorting Test(WCST)results,and re-ceiver operating characteristic(ROC)curve was applied to analyze the clinical diagnostic value of levels of sTfR and FGF22 for FES.Results There were no obvious differences between the two groups in terms of gender,age,body mass index,years of education,history of alcohol consumption,and smoking history(P>0.05).Compared with the control group,the serum levels of sTfR and FGF22 in the FES group were obvious-ly lower(P<0.05).The area under the curve(AUC)of sTfR for diagnosing FES alone was 0.835,with the cut off value of 4.606 mg/L,the AUC of FGF22 for diagnosing FES alone was 0.772,with the cut off value of 208.333 μg/L,the AUC of the combination of the two(0.921)was obviously higher than that of sTfR alone(Z=2.613,P=0.009),and that of FGF22 alone(Z=5.140,P<0.001).The PANSS positive symptom score,negative symptom score,pathological symptom score,total score,WCST persistent errors,and incorrect responses in the high sTfR level group and high FGF22 group were lower than those in the low sTfR group and low FGF22 group(P<0.05),while the number of WCST completed classifications and WCST correct re-sponses were higher than those in the low sTfR group and low FGF22 group(P<0.05).The levels of sTfR and FGF22 in the FES group were negatively correlated with PANSS positive symptom score,negative symp-tom score,pathological symptom score,total score,WCST persistent errors,and WCST incorrect responses(P<0.05),and positively correlated with the number of WCST completed classifications and WCST correct responses(P<0.05).Conclusion The levels of sTfR and FGF22 in the serum of FES patients are obviously decreased.Combined detection of sTfR and FGF22 levels is of great significance for the clinical diagnosis of FES.

Research progress in mitochondrial quality control in schizophrenia / 中南大学学报(医学版)

Mitochondria are the main site of energy metabolism within cells,generating a substantial amount of ATP to supply energy to the human body.Research has shown that alterations in mitochondrial structure and function exist in individuals with schizophrenia,suggesting their potential impact on the onset of psychiatric disorders and clinical treatment efficacy.Therefore,understanding the research progress on the genetic mechanisms,pathological processes,image manifestations of schizophrenia and mitochondrial quality control,and summarizing the relevant evidence of mitochondrial-related targets as potential therapeutic targets for schizophrenia,can provide references for further research.

Correlation between the Expression of Serum P2X7R and CTGF Levels and Clinical Symptom Scores and Cognitive Function in Patients with Schizophrenia / 现代检验医学杂志

Objective To investigate the correlation between the expression of purinergic ligand-gated ion channel 7 receptor(P2X7R)and connective tissue growth factor(CTGF)in serum and cognitive function and clinical symptoms in patients with schizophrenia.Methods A total of 160 patients with schizophrenia who were diagnosed and treated in Department of Mental Intensive Care of Wuhan Wudong Hospital from January 2021 to January 2023 were collected as the observation group,and 160 healthy volunteers who underwent physical examinations were collected as the control group for the study.According to the Positive and Negative Symptom Scale(PANSS),patients were evaluated for their clinical and psychiatric symptoms(positive and negative symptoms,general pathological symptoms,and additional symptoms).The patients were grouped into a high score group(PANSS total score≥70 points,n=72)and a low score group(PANSS total score＜70 points,n=88).MATRICS consensus cognitive battery(MCCB)was applied to evaluate the cognitive abilities of patients;enzyme-linked immunosorbent assay(ELISA)was applied to detect serum P2X7R and CTGF levels.Spearman method was applied to analyze the correlation between serum P2X7R,CTGF levels and PANSS scores,and MCCB scores in patients with schizophrenia.Results Compared with the control group,the serum levels of P2X7R(610.71±107.83ng/L vs 384.78±80.62 ng/L)and CTGF(1.85±0.36μg/L vs 1.40±0.21μg/L)in the observation group were increased,with differences of statistical significance(t=21.226,13.658,all P＜0.05).The scores of variety items of MCBB of patients with schizophrenia in the observation group were lower than those in the control group,with differences of statistical significance(t=14.845～24.862,all P＜0.05),the positive symptom score(21.10±3.42score),negative symptom score(23.37±5.03 score),general pathological symptom score(39.48±8.11score),additional symptom score(8.26±1.22 score),and PANSS total score(92.21±12.50score)of schizophrenia patients in the high group were higher than those in the low group(13.65±3.04,15.62±3.91 score,30.14±6.15 score,5.20±0.94score,64.61±5.30score),with differences of statistical significance(t=14.576,10.964,8.280,17.915,18.764,all P＜0.05).The serum levels of P2X7R and CTGF in patients with schizophrenia in the high group were higher than those in the low group,with differences of statistical significance(t=12.233,5.923,all P＜0.05).The levels of serum P2X7R and CTGF in patients with schizophrenia were positively correlated with PANSS score(r=0.464～0.580,all P＜0.05),and negatively correlated with MCCB score[r=-0.603～-0.439,all P＜0.05].Conclusion The serum levels of P2X7R and CTGF in patients with schizophrenia are elevated,they are closely related to the clinical symptoms and cognitive function of patients.

Analysis of therapeutic effect of aripiprazole or risperidone combined with clozapine in the treatment of refractory schizophrenia / 沈阳医学院学报

Objective:To investigate the therapeutic effect of aripiprazole or risperidone combined with clozapine in the treatment of treatment-refractory schizophrenia(TRS).Method:A retrospective analysis was conducted on the clinical data of 90 patients with TRS who received treatment at Tanggu Anding Hospital from May 2021 to May 2022.According to the drug treatment regimen,patients were divided into clozapine group,aripiprazole+clozapine group,and risperidone+clozapine group,with 30 cases in each group.The positive and negative symptom scale(PANSS)score,clinical efficacy,and total incidence of adverse reactions were compared before and after treatment among the three groups.Results:After treatment,the total scores and subscale scores of PANSS in the three groups decreased compared to before treatment(P＜0.05).And after treatment,the total scores and subscale scores of PANSS in aripiprazole+clozapine group and risperidone+clozapine group were lower than those in clozapine group(P＜0.05)and the scores in aripiprazole+clozapine group were lower than those in risperidone+clozapine group(P＜0.05).After treatment,the total effective rates in aripiprazole+clozapine group and risperidone+ clozapine group were higher than those in clozapine group(P＜0.05)and the total effective rate in aripiprazole+clozapine group was higher than that in risperidone+clozapine group(P＜0.05).The total incidence of adverse reactions in the three groups was similar(P＞0.05).Conclusion:The overall efficacy of aripiprazole combined with clozapine in the treatment of TRS is better than that of risperidone combined with clozapine or clozapine alone,and can be promoted as the preferred treatment plan.

Role of histone deacetylase in the sensory gating impairment of offspring during puberty caused by immune activation in pregnant rats / 新乡医学院学报

Objective To investigate the expression of histone deacetylase(HDAC)isoforms in the frontal lobe,hippo-campus and liver of offspring rats delivered by rats with maternal immune activation and their correlation with the efficiency of prepulse inhibition(PPI％).Methods Ten pregnant Sprague-Dawley rats were randomly divided into the model group(n=5)and control group(n=5).The rats in the model group were injected with 10 mg·kg-1 polyinosinic-polycytidylic acid(Poly I:C)via the caudal vein on the 9th day of pregnancy,while rats in the control group were given the same volume of sterile physiological saline.After 3 h,blood was collected from the caudal vein,and the levels of interleukin(IL)-1 β,IL-6 and tumor necrosis factor-α(TNF-α)in the plasma of pregnant rats were detected by enzyme-linked immunosorbent assay to evaluate the immune activation status.The pregnant rats in the two groups were fed until natural delivery,the offspring rats were weaned on the 21st day after birth,and the male offspring rats were fed continuously.A prepulse inhibition test was performed at puberty(the 40th day after birth)to evaluate the spatial recognition memory and sensory gating function of the offspring rats.The expression levels of the HDAC gene family in the hippocampus,frontal lobe and liver of offspring rats were detected by real-time fluorescence quantitative polymerase chain reaction.Results The plasma IL-6,IL-1 β and TNF-α levels in the model group were significantly higher than those in the control group(P＜0.05).When the prepulse stimulation was 75 dB,the PPI％of the offspring rats at puberty in the model group was significantly lower than that in the control group(P＜0.05).When the prepulse stimulation was 80 and 85 dB,there was no significant difference in PPI％between the model group and the control group(P＞0.05).In the frontal lobe,the expression levels of HDAC3,HDAC4,HDAC8,HDAC9,HDAC10 and Sirt mRNA in the offspring rats in the model group were significantly lower than those in the control group(P＜0.05),while the expression level of HDAC5 mRNA was significantly higher than that in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC6,HDAC7 and HDAC11 mRNA between the model group and the control group(P＞0.05).In the hippocampus,the offspring rats in the model group had significantly lower expression levels of HDAC1,HDAC8 and HDAC10 mRNA and significantly higher expression levels of HDAC2 and HDAC5 mRNA than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC3,HDAC4,HDAC6,HDAC7,HDAC9,HDAC11 and Sirt mRNA between the model group and control group(P＞0.05).In the liver tissue,the expression levels of HDAC6 and HDAC10 mRNA of the offspring rats in the model group were significantly lower than those in the control group(P＜0.05);there were no significant differences in the expression levels of HDAC1,HDAC2,HDAC3,HDAC4,HDAC5,HDAC7,HDAC8,HDAC9,HDAC11 and Sirt mRNA between the model group and the control group(P＞0.05).The expression level of HDAC2 mRNA in the hippocampus of offspring rats in the two groups was negatively correlated with PPI％at 75 dB(r=-0.965,P＜0.05),the expression levels of HDAC10 and Sirt mRNA in frontal lobe tissues were positively correlated with PPI％at 75dB(r=0.946,0.925;P＜0.05).Conclusion Pregnancy Poly I:C infection has significant effects on the expression of HDAC family proteins in offspring rats,and which is related to the impairment of early sensory gating,this may provide new ideas for the research in pathogenesis and drug treatment of schizophrenia.