Effect of nitric oxide on the expression of apelin receptor mRNA in rat caudate nucleus

Objective To investigate the effect of nitric oxide （NO） on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine （L-Arg）, N^G-nitro-L-arginine methyl ester （L-NAME） and normal saline （NS） was separately microinjected into rat caudate nucleus. Expressions of neuronal NO synthase （nNOS） mRNA and apelin receptor mRNA were detected by RT-PCR at 4, 8, 12, 24 and 48 h after microinjection, and their correlation was determined. Results The expressions of nNOS mRNA and apelin receptor mRNA were both significantly increased after microinjection of L-Arg, but significantly decreased after microinjection of L-NAME compared with the NS control group. The nNOS mRNA had a positive correlation with the expression of apelin receptor mRNA after microinjection of L-Arg and L-NAME. Conclusion The activity of NOS in the central nervous system, especially in the caudate nucleus, is one of the key factors for NO to exert many kinds of biological actions, such as modulation of central pain, as a neurotransmitter. The neurobiological action of NO in rat caudate nucleus may be associated with apelin receptors.

Prognostic factors in the surgical treatment of caudate lobe hepatocellular carcinoma

AIM:To evaluate the short-and long-term outcomes of liver resection for caudate lobe hepatocellular carcinoma (HCC).METHODS:We retrospectively analyzed 114 consecutive patients with HCC,originating from the caudate lobe,who underwent resection between January 2001 and January 2007.Univariate and multivariate analyses were performed on several clinicopathologic variables to determine the factors affecting long-term outcome and intrahepatic recurrence.RESULTS:Overall mortality and morbidity were 0% and 18%,respectively.After a median follow-up of 31 mo (interquartile range,11-66 mo),tumor recurrence had occurred in 76 patients (66.7%).The 1-,3-,and 5-year disease-free survival rates were 65.7%,38.1%,and 18.4%,respectively.The 1-,3-,and 5-year overall survival rates were 76.1%,54.7%,and 31.8%,respectively.Univariate analysis showed that subsegmental location of the tumor (45.7% vs 16.2%,P=0.01),liver cirrhosis (12.3% vs 47.9%,P=0.03),surgical margin (18.5% vs 54.6%,P=0.04),vascular invasion (37.9% vs 23.2%,P=0.04) and extended caudate resection (42.1% vs 15.4%,P=0.04) were related to poorer long-term survival.Multivariate analysis showed that only subsegmental location of the tumor,liver cirrhosis and surgical margin were significant independent prognostic factors.CONCLUSION:Hepatectomy was an effective treatment for HCC in the caudate lobe.The subsegmental location of the tumor,liver cirrhosis and surgical margin affected long-term survival.

Resection of hepatic caudate lobe hemangioma:experience with 11 patients

BACKGROUND: Caudate lobectomy is now considered to be the most appropriate surgical treatment for benign tumors in the caudate lobe. But how to resect the caudate lobe safely is a major challenge to current liver surgery and requires further study. This research aimed to analyze the perioperative factors and explore the surgical technique associated with liver resection in hepatic caudate lobe hemangioma. METHODS: Eleven consecutive patients with symptomatic hepatic hemangiomas undergoing caudate lobectomy from November 1990 to August 2009 at our hospital were investigated retrospectively. All patients were followed up to the present. RESULTS: In this series, 9 were subjected to isolated caudate lobectomy and 2 to additional caudate lobectomy (in addition to left lobe and right lobe resection, respectively). The average maximum diameter of tumors was 9.65+/-4.11 cm. The average operative time was 232.73+/-72.16 minutes. Five of the 11 patients required transfusion of blood or blood products during surgery. Ascites occurred in I patient, pleural effusion in the perioperative period in 1, and multiple organ failure in 1 on the 6th day after operation as a result of massive intraoperative blood loss, who had received multiple transcatheter hepatic arterial embolization preoperatively. The alternating left-right-left approach produced the best results for caudate lobe surgery in most of our cases. All patients who recovered from the operation are living well and asymptomatic. CONCLUSIONS: For large hemangioma of the caudate lobe, surgery is only recommended for symptomatic cases. Caudate lobectomy of hepatic hemangioma can be performed safely, provided it is carried out with optimized perioperative management and innovative surgical technique.

Early control of short hepatic portal veins in isolated or combined hepatic caudate lobectomy

BACKGROUND:Caudate lobectomy has long been considered technically difficult.This study aimed to elaborate the significance of early control of short hepatic portal veins(SHPVs) in isolated hepatic caudate lobectomy or in hepatic caudate lobectomy combined with major partial hepatectomy,and to describe the anatomical characteristics of SHPVs.METHODS:The data of 117 patients who underwent either isolated or combined caudate lobectomy by the same team of surgeons from 2005 to 2009 were retrospectively analyzed.From 2005 to 2007(group A,n=55),we carried out early control of short hepatic veins(SHVs) only;from 2008 to 2009(group B,n=62),we carried out early control of both SHVs and SHPVs.The two groups were compared to evaluate which surgical procedure was better.A detailed anatomical study was then carried out on the last 25 consecutive patients in group B to study the number and distribution of SHPVs during surgery.RESULTS:Patients in group B had less intra-operative blood loss,less impairment of liver function,shorter postoperative hospital stay,fewer postoperative complications and required less blood transfusion(P<0.05).The number of SHPVs in the 25 patients was 183,with 7.3±2.7 per patient.The diameters of SHPVs were 1 to 4 mm.On average,3.4 SHPVs/patient came from the left portal vein,2.2 from the bifurcation,1.4 from the right portal vein,and 0.3 from the main portal vein.On average,3.3 SHPVs/patient supplied segment I of the liver,0.4 for segment II,2.1 for segment IV,1.4 for segment V and 0.1 for segment VI.CONCLUSION:Early control of SHPVs in isolated or combined hepatic caudate lobectomy may be a useful method to decrease surgical risk and improve postoperative recovery.

Anatomic isolated caudate lobectomy: Is it possible to establish a standard surgical flow?

AIM To establish the surgical flow for anatomic isolated caudate lobe resection. METHODS The study was approved by the ethics committee of the Second Affiliated Hospital Zhejiang University School of Medicine(SAHZU). From April 2004 to July 2014, 20 patients were enrolled who underwent anatomic isolated caudate lobectomy at SAHZU. Clinical and postoperative pathological data were analyzed. RESULTS Of the total 20 cases, 4 received isolated complete caudate lobectomy(20%) and 16 received isolated partial caudate lobectomy(80%). There were 4 caseswith the left approach(4/20, 20%), 6 cases with the right approach(6/20, 30%), 7 cases with the bilateral combined approach(7/20, 35%), 3 cases with the anterior approach(3/20, 15%), and the hanging maneuver was also combined in 2 cases. The median tumor size was 5.5 cm(2-12 cm). The median intraoperative blood loss was 600 m L(200-5700 m L). The median intra-operative blood transfusion volume was 250 m L(0-2400 m L). The median operation time was 255 min(110-510 min). The median post-operative hospital stay was 14 d(7-30 d). The 1-and 3-year survival rates for malignant tumor were 88.9% and 49.4%, respectively. CONCLUSION Caudate lobectomy was a challenging procedure. It was demonstrated that anatomic isolated caudate lobectomy can be done safely and effectively.

Emergency caudate lobectomy for ruptured hepatocellular carcinoma with multiple primary cancers

We report a case of metachronous multiple primary malignancies involving both rectum and liver with colonic metastasis from hepatocellular carcinoma(HCC) through hematogenous pathway.A 72-year-old woman was admitted to the emergency department with right upper abdominal pain for 4 h.Considering her surgical history of Mile's procedure plus liver resection for rectal cancer with liver metastasis three years ago and the finding of urgent computed tomography scan on admission,the preoperative diagnosis was spontaneous rupture of rectal liver metastasis located in caudate lobe and colonic metastasis from rectal cancer. The patient underwent an emergency isolated caudate lobectomy at a hemorrhagic shock status.Pathology reported a primary HCC in the caudate lobe and colonic metastasis of HCC with tumor embolus in the surrounding vessels of the intestine.No regional lymph node involvement was found.It is hypothesized that HCC may disseminate hematogenously to the ascending colon,thus making it a rare case.

Management of hepatocellular carcinoma rupture in the caudate lobe

AIM: To demonstrate that caudate lobectomy is a valid treatment in cases of hepatocellular carcinoma(HCC) rupture in the caudate lobe based on our experience with the largest case series reported to date.METHODS: A retrospective study of eight patients presenting with spontaneous rupture and hemorrhage of HCC in the caudate lobe was conducted.Two patients underwent ineffective transarterial embolization preoperatively.Caudate lobectomy was performed in all eight patients.Bilateral approach was taken in seven cases for isolated complete caudate lobectomy.Left-sided approach was employed in one case for isolated partial caudate lobectomy.Transarterial chemoembolization was performed postoperatively in all patients.RESULTS: Caudate lobectomy was successfully completed in all eight cases.The median time delay from the diagnosis to operation was 5 d(range: 0.25-9).Median operating time was 200 min(range: 120-310) with a median blood loss of 900 m L(range: 300-1500).Five patient remained in long-term follow-up,with one patient becoming lost to followup at 3 years and two patients currently alive at 7 and 19 mo.One patient required reoperation due to recurrence.Gamma knife intervention was performed for brain metastasis in another case.Two patients survived for 10 and 84 mo postoperatively,ultimately succumbing to multiple organ metastases.CONCLUSION: Caudate lobectomy is the salvage choice for HCC rupture in the caudate lobe.Local anatomy and physiologic features of the disease render caudate lobectomy a technically difficult operation.Postponement of surgical intervention is thus recommended while the rupture remains hemodynamically stable until an experienced surgeon becomes available.Prognosis is confounded by numerous factors,but long-term survival can be expected in the majority of cases.

Caudate lobectomy by the third porta hepatis anatomical method: a study of 16 cases

BACKGROUND: The treatment for primary tumor in the caudate lobe of the liver is difficult because of its unique anatomical location. This study was undertaken to improve operative techniques and results by a new anatomical method of caudate lobectomy. METHODS: Clinical data of 16 patients who had had caudate lobectomy for the liver from January 1996 to November 2004 were retrospectively analyzed. The third porta hepatis anatomical method was performed in all 16 patients. Operative time, intraoperative blood loss, postoperative complications were recorded. The 1-, 3-, and 5-year survival rates of 13 patients with caudate lobe carcinoma were followed up. Anatomical status, operative routes, operative procedures, liver blood supply were evaluated. RESULTS: The operation was successful in the 16 patients. The operative time was 255±70 minutes and blood loss 740±402 ml. None of the patients died from massive bleeding during the operation, nor did complications such as biliary fistula and liver failure occurred. In 13 patients with malignant tumor, 7 died from recurrence and metastasis of the tumor and the other 6 are still alive at the end of follow-up. One patient has survived for 6 years. The 1-, 3-, and 5-year survival rates in the 13 patients were 83.9%, 58.7% and 39.2%, respectively. CONCLUSION: Caudate lobectomy by the third porta hepatis anatomical method can improve operative effect and increase the resection probability for solitary tumor in the caudate lobe.

Robotic isolated partial and complete hepatic caudate lobectomy:A single institution experience

Background:Current reports on robotic hepatic caudate lobectomy are limited to Spiegel lobectomy.This study aimed to compare the safety and feasibility of robotic isolated partial and complete hepatic caudate lobectomy.Methods:Clinical data of 32 patients who underwent robotic resection of the hepatic caudate lobe in our department from May 2016 to January 2020 were retrospectively analyzed.The patients were divided into three groups according to the lobectomy location:left dorsal segment lobectomy(Spiegel lobectomy),right dorsal segment lobectomy(caudate process or paracaval portion lobectomy),and complete caudate lobectomy.General information and perioperative results of the three groups were compared and analyzed.Results:Among the 32 patients,none had conversion to laparotomy,three received intraoperative blood transfusion(9.38%),and none had complications of Clavien-Dindo gradeⅢor higher or died in the perioperative period.Among them,17 patients(53.13%)underwent Spiegel lobectomy,7(21.88%)underwent caudate process or paracaval portion lobectomy,and 8(25.00%)underwent complete caudate lobectomy.The operative time and blood loss in the left dorsal segment lobectomy group were significantly better than those in the right dorsal segment lobectomy and complete caudate lobectomy groups(operative time:P=0.010 and P=0.005;blood loss:P=0.005 and P=0.017,respectively).The postoperative hospital stay in the left dorsal segment lobectomy group was significantly shorter than that in the complete caudate lobectomy group(P=0.003);however,there was no difference in the postoperative hospital stay between the left dorsal segment lobectomy group and right dorsal segment lobectomy group(P=0.240).Conclusions:Robotic isolated partial and complete caudate lobectomy is safe and feasible.Spiegel lobectomy is relatively straightforward and suitable for beginners.

Abscess of the caudate lobe of the liver, a rare disease with a challenging management: a case report

We reported a rare case of abscess of the caudate lobe of the liver in a 60-year old man. We first tried computed tomography （CT） guided percutaneous drainage of the abscess but failed to eradicate the infection. Deterioration of the general condition of the patient necessitated open surgical drainage, which resulted in cure of the abscess. The peculiar anatomical location of caudate lobe abscess introduces a great challenge for the surgeon in plan- ning the appropriate management and paucity of patients with caudate lobe abscess has led to lack of guidelines for management. The non-operative interventional radiology approach has become the therapeutic choice for pyo- genic liver abscess, but is it applicable also for caudate lobe abscess？

Hydrochloric acid enhanced radiofrequency ablation for treatment of large hepatocellular carcinoma in the caudate lobe:Report of three cases

BACKGROUND To report on the use of percutaneous hydrochloric acid(HCl) enhanced radiofrequency ablation(HRFA) for the treatment of large(maximum diameter ≥5 cm) hepatocellular carcinoma(HCC) in the caudate lobe.CASE SUMMARY Between August 2013 and June 2016, three patients with a large HCC(maximum diameter: 5.0, 5.7, and 8.1 cm) in the caudate lobe were treated by transarterial chemoembolization followed by computer tomography(CT) guided RFA using a monopolar perfusion RF electrode, which was enhanced by local infusion of 10%HCl at 0.2 mL/min(total volume, 3 to 12 mL). The output power of HRFA reached 100 W, and the average ablation time was 39 min(range, 15 to 60 min).Two patients each underwent one session of HRFA and one patient two sessions.After treatment, CT/magnetic resonance imaging showed that all the three lesions were completely ablated. There was no major complication. Two patients had asymptomatic bile duct dilatation. One patient died of tongue cancer 24 mo after ablation. The remaining two patients were alive and no area of enhancement is detected in the caudate lobe at 28 and 60 mo after ablation, respectively.CONCLUSION Percutaneous CT-guided HRFA is safe and efficacious in treating large HCC in the caudate lobe.

Choice of approach for hepatectomy for hepatocellular carcinoma located in the caudate lobe:Isolated or combined lobectomy?

AIM:To investigate the significance of the surgical approaches in the prognosis of hepatocellular carcinoma(HCC) located in the caudate lobe with a multivariate regression analysis using a Cox proportional hazard model.METHODS:Thirty-six patients with HCC underwent caudate lobectomy at a single tertiary referral center between January 1995 and June 2010.In this series,left-sided,right-sided and bilateral approaches were used.The outcomes of patients who underwent isolated caudate lobectomy or caudate lobectomy combined with an additional partial hepatectomy were compared.The survival curves of the isolated and combined resection groups were generated by the Kaplan-Meier method and compared by a log-rank test.RESULTS:Sixteen(44.4%) of 36 patients underwent isolated total or partial caudate lobectomy whereas 20(55.6%) received a total or partial caudate lobectomy combined with an additional partial hepatectomy.The median diameter of the tumor was 6.7 cm(range,2.1-15.8 cm).Patients who underwent an isolated caudate lobectomy had significantly longer operative time(240 min vs 170 min),longer length of hospital stay(18 d vs 13 d) and more blood loss(780 mL vs 270 mL) than patients who underwent a combined caudate lobectomy(P < 0.05).There were no perioperative deaths in both groups of patients.The complication rate was higher in the patients who underwent an isolated caudate lobectomy than in those who underwent combined caudate lobectomy(31.3% vs 10.0%,P < 0.05).The 1-,3-and 5-year disease-free survival rates for the isolated caudate lobectomy and the combined caudate lobectomy groups were 54.5%,6.5% and 0% and 85.8%,37.6% and 0%,respectively(P < 0.05).The corresponding overall survival rates were 73.8%,18.5% and 0% and 93.1%,43.6% and 6.7%(P < 0.05).CONCLUSION:The caudate lobectomy combined with an additional partial hepatectomy is preferred because this approach is technically less demanding and offers an adequate surgical margin.

Precautions in caudate lobe resection: Report of 11 cases

AIM： To find the precautions against the safety in caudate lobe resection. METHODS： The clinical data obtained from 11 cases of primary liver cancer in caudate lobe who received hepatectomy successfully were retrospectively analyzed. Four safe procedures were used in resection of primary liver cancer in caudate lobe： （1） selection of appropriate skin incision to obtain excellent exposure of operative field; （2） adequate mobilization of the liver to allow the liver to be displaced upwards to the left or to the right; （3） preparatory placement of tapes for total hepatic vascular exclusion, so that this procedure could be used to control the fatal bleeding of the liver when necessary; （4） selection of the ideal route for hepatectomy based on the condition of the tumor and the combined removal of multiple lobes if necessary. Among the 11 cases, simple occlusion of vessels of porta hepatis was used in caudate Iobectomy for 6 cases, while in the other cases, the vessels were intermittently occluded several times or total hepatic vascular isolation was used in the caudate Iobectomy. Combined partial right hepatectomy was done for 3 cases, combined left lateral Iobectomy for 2 cases and caudate Iobectomy alone for 6 cases. RESULTS： Operation was successful for all the 11 cases. Intermittent inflow occlusion was performed for all patients for 15 min at 5-min intervals. Blockade was performed twice in 3 patients and total hepatic vascular exclusion was performed in one of the three patients. Blockade was performed three times in one patient, including a total hepatic vascular exclusion. Total hepatic vascular exclusion was performed only in one patient. The mean blood loss was 300 mL. Ascites and pleural effusion occurred in 4 patients, jaundice in 1 patient. Six patients died of tumor recurrence in 6, 11, 12, 13, 15, 19 mo after operation, respectively. The other 5 patients have survived more than 16 mo since the operation. CONCLUSION： Caudate Iobectomy for liver cancer in candate lobe can be safely performed with the above procedures.

M-CHOLINOCEPTORS IN CAUDATE NUCLEUS PARTICIPATE IN SmI ORIGINATING DESCENDING MODULATION OF PARAFASCICULARNEURONS IN ACUPUNCTURE ANALGESIA

The present study was undertaken to investigate whether M-cholinoceptors in caudate nucleus (Cd) were implicated in cortical sensorimotor area I (SmI) originating descending modulation of activities in thalamic parafascicular nuclei (Pf) in acupuncture analgesia (AA). It was found that following bilateral microinjection of atropine into Cd head electroacupuncture (EA) (n=12) or glutamate (Glu) applied at SmI (n=12) did not affect the nociceptive responses of Pf neurons (P>0. 05),while in the saline control groups EA (n=11) or Glu at SmI (n=12) obviously inhibited nociceptive responses of Pf neurons (P<0. 05). There were significant differences in the effect of EA or Glu at SmI between atropine and saline groups (ANOVA, P<0. 05). Together with our previous findings demonstrating the participation of SmI originating descending modulation of Pf neurons in AA, the present investigation indicates that M-cholinoceptors are involved in mediating SmI originating descending modulation of Pf neurons in AA.

Feasibility of laparoscopic isolated caudate lobe resection for rare hepatic mesenchymal neoplasms

BACKGROUND Mesenchymal tumors such as perivascular epithelioid cell neoplasm(PEComa)and inflammatory pseudotumor-like follicular dendritic cell sarcoma(IPT-like FDC sarcoma)are relatively uncommon in the liver and are particularly rare in the caudate lobe.The clinical manifestations and available imaging tests lack specificity for hepatic mesenchymal tumors.To the best of our knowledge,no caudate PEComa or IPT-like FDC sarcoma has been completely resected by laparoscopy.The standard laparoscopic technique,surgical approaches,and tumor margins for potentially malignant or malignant caudate mesenchymal tumors are still being explored.AIM To assess both the safety and feasibility of laparoscopic resection for rare caudate mesenchymal neoplasms.METHODS Eleven patients who underwent isolated caudate lobe resection from 2003 to 2017 were identified from a prospective database.Three consecutive patients with rare caudate mesenchymal tumors underwent laparoscopic resection.Patient demographic data,intraoperative parameters,and postoperative outcomes were assessed and compared with the open surgery group.RESULTS All procedures for the three resection patients with caudate mesenchymal tumors were completed using a total laparoscopic technique by two different approaches.The average operative time was 226 min,and the estimated blood loss was 133 mL.The average length of postoperative hospital stay was 6.3±0.3 d for the laparoscopy group and 15.5±2.3 d for the open surgery group(P<0.05).There were no perioperative complications or patient deaths in this series.CONCLUSION Laparoscopic isolated caudate lobe resection for rare mesenchymal neoplasms is a feasible and curative surgical option in selected patients.

Increased activation of the caudate nucleus and parahippocampal gyrus in Parkinson's disease patients with dysphagia after repetitive transcranial magnetic stimulation:a case-control study

Repetitive transcranial magnetic stimulation(r TMS)has been shown to effectively improve impaired swallowing in Parkinson's disease(PD)patients with dysphagia.However,little is known about how r TMS affects the corresponding brain regions in this patient group.In this casecontrol study,we examined data from 38 PD patients with dysphagia who received treatment at Beijing Rehabilitation Medicine Academy,Capital Medical University.The patients received high-frequency r TMS of the motor cortex once per day for 10 successive days.Changes in brain activation were compared via functional magnetic resonance imaging in PD patients with dysphagia and healthy controls.The results revealed that before treatment,PD patients with dysphagia showed greater activation in the precentral gyrus,supplementary motor area,and cerebellum compared with healthy controls,and this enhanced activation was weakened after treatment.Furthermore,before treatment,PD patients with dysphagia exhibited decreased activation in the parahippocampal gyrus,caudate nucleus,and left thalamus compared with healthy controls,and this activation increased after treatment.In addition,PD patients with dysphagia reported improved subjective swallowing sensations after r TMS.These findings suggest that swallowing function in PD patients with dysphagia improved after r TMS of the motor cortex.This may have been due to enhanced activation of the caudate nucleus and parahippocampal gyrus.The study protocol was approved by the Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University(approval No.2018 bkky017)on March 6,2018 and was registered with Chinese Clinical Trial Registry(registration No.Chi CTR 1800017207)on July 18,2018.

Giant hemangioma of the caudate lobe of the liver with surgical treatment:A case report

BACKGROUND Caudate lobe hemangioma of the liver is relatively rare.Due to the unique anatomical location of the caudate lobe,the caudate lobectomy accounts for only 0.5%to 4%of hepatic resection,which is difficult to operate and takes a long time,and even has many postoperative complications.CASE SUMMARY A 34-year-old female presented with a 1 year history of intermittent pain in the right side of the waist without obvious inducement.All laboratory blood tests were within normal limits.Indocyanine green 15 min retention was rated 2.9%,and Child-Pugh was rated A.Computed tomography and magnetic resonance imaging diagnosed giant hemangioma of the caudate lobe with hemangioma of left lobe of liver.After discussion,surgical treatment was performed,which lasted 410 min,with intraoperative bleeding of about 600 mL and postoperative pathological findings of cavernous hemangioma.There were no obvious postoperative complications,and the patient was discharged 10 d after surgery.CONCLUSION Caudate lobectomy is difficult due to its special anatomical location.Under the condition of fully exposing the anatomy of the first porta hepatis,the second porta hepatis,the third porta hepatis,the fourth porta hepatis and middle hepatic vein and combining with the Pringle maneuver,caudate lobectomy can be performed in a precise and safe process.

Anterior transhepatic approach for total caudate lobectomy including spigelian lobe,paracaval portion and caudate process:A Brazilian experience

To the Editor:Nowadays,because of the infiltration of cholangiocarcinoma to the parenchyma and/or bile ducts of the caudate lobe,the inclusion of caudate lobe combined with a major hepatectomy remains the gold standard approach for a resectable hilar cholangiocarcinoma.Since the last years of the 20th century,some authors have begun to report isolated caudate lobe resection for hepatocellular

Proton magnetic resonance spectroscopy of the anterior cingulate gyrus and caudate nucleus in schizophrenia patients versus healthy controls

Proton magnetic resonance spectroscopy （^1 H-MRS） permits the assessment of cerebral neurometabolites, such as N-acetylaspartate, choline, and creatine, in vivo and has been used to study schizophrenia. The present study used ^1H-MRS to compare the spectroscopy change of N-acetylaspartate, creatine, and choline metabolite levels in the anterior cingulate and caudate nucleus of both schizophrenia patients and healthy controls, as well as between the left and right cerebral hemispheres in the schizophrenia patients. Results showed that N-acetylaspartate and creatine metabolite levels in the left anterior cingulate gyrus were significantly lower in the schizophrenia patients than in the healthy controls, indicating hypometabolism. In addition, choline concentration in the left caudate nucleus of schizophrenia patients was significantly lower than in the right caudate nucleus, indicating that it is necessary to study the cerebral lateralization of ^1H-MRS in schizophrenia patients.

Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory

Background: There is emerging evidence that the increased susceptibility to developing alcohol and substance use dis- orders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods: Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results: High-risk subjects showed poorer Working Memory functioning. Caudate volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions: Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood.