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Abstract Background Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis. Methods We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity. Results The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN. Conclusion MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group.

Background Few previous studies have established Snaith–Hamilton Pleasure Scale (SHAPS) cut-off values using receiver operating characteristic curve analysis and applied these values to compare predictors of anhedonia between clinical and nonclinical groups. Aims To determine the optimal cut-off values for the SHAPS and use them to identify predictors of anhedonia in clinical and nonclinical groups in Taiwan. Method This cross-sectional and correlational study used convenience sampling to recruit 160 patients from three hospitals and 412 students from two universities in northern Taiwan. Data analysis included receiver operating characteristic curve, univariate and multivariate analyses. Results The optimal SHAPS cut-off values were 29.5 and 23.5 for the clinical and nonclinical groups, respectively. Moreover, two-stage analysis revealed that participants in the clinical group who perceived themselves as nondepressed, and participants in the nonclinical group who did not skip classes and whose fathers exhibited higher levels of care and protection were less likely to attain the cut-off values. Conversely, participants in the nonclinical group who reported lower academic satisfaction and were unwilling to seek help from family or friends were more likely to attain the cut-off values. Conclusions Our findings highlight the importance of optimal cut-off values in screening for depression risk within clinical and nonclinical groups. Accordingly, the development of comprehensive, individualised programmes to monitor variation trends in SHAPS scores and relevant predictors of anhedonia across different target populations is crucial.

Abstract Microbiota-gut-brain axis signaling plays a pivotal role in mood disorders. The communication between the host and the gut microbiota may involve complex regulatory networks. Previous evidence showed that host-fecal microRNAs (miRNAs) interactions partly shaped gut microbiota composition. We hypothesized that some miRNAs are correlated with specific bacteria in the fecal samples in patients with major depressive disorder (MDD), and these miRNAs would show enrichment in pathways associated with MDD. MDD patients and healthy controls were recruited to collect fecal samples. We performed 16S ribosome RNA sequence using the Illumina MiSeq sequencers and analysis of 798 fecal miRNAs using the nCounter Human-v2 miRNA Panel in 20 subjects. We calculated the Spearman correlation coefficient for bacteria abundance and miRNA expressions, and analyzed the predicted miRNA pathways by enrichment analysis with false-discovery correction (FDR). A total of 270 genera and 798 miRNAs were detected in the fecal samples. Seven genera (Anaerostipes, Bacteroides, Bifidobacterium, Clostridium, Collinsella, Dialister, and Roseburia) had fold changes greater than one and were present in over 90% of all fecal samples. In particular, Bacteroides and Dialister significantly differed between the MDD and control groups (p-value

Background/Purpose: Orexin-A levels are reportedly increased in antipsychotic (APD)-treated patients with schizophrenia compared to healthy controls and have been associated with metabolic abnormalities. It is not clear whether the orexin-A elevation is related specifically to the drug (APDs) effect, which should be clarified by including a drug-free group for comparison, or related to drug-induced metabolic abnormalities. Methods: Blood orexin-A levels and metabolic profiles were compared between 37 drug-free, 45 aripiprazole-treated, and 156 clozapine-treated patients with schizophrenia. The association between orexin-A and metabolic outcomes were examined. We explored the effects of APDs treatment and metabolic status on orexin-A levels by linear regression. Results: Patients under APDs treatment had increased orexin-A levels compared to drug-free patients, with aripiprazole-treated group having higher orexin-A levels than clozapine-treated group. Higher orexin-A levels reduced the risks of metabolic syndrome (MS) and type 2 diabetes mellitus, indicating a relationship between orexin-A levels and metabolic problems. After adjusting the effect from metabolic problems, we found APD treatment is still associated with orexin-A regulation, with aripiprazole more significantly than clozapine. Conclusion: With the inclusion of drug-free patients rather than healthy controls for comparison, we demonstrated that orexin-A is upregulated following APD treatment even after we controlled the potential effect from MS, suggesting an independent effect of APDs on orexin-A levels. Furthermore, the effect differed between APDs with dissimilar obesogenicity, i.e. less obesogenicity likely associated with higher orexin-A levels. Future prospective studies exploring the causal relationship between APDs treatment and orexin-A elevation as well as the underlying mechanisms are warranted.

BackgroundSchizophrenia is considered one of the major risk factors for mortality from SARS-CoV-2 infection. Early antiviral treatment is important to decrease the risk of mortality. Currently, Paxlovid (nirmatrelvir-ritonavir) has been widely used in SARS-CoV-2 patients with risk factors. However, drug–drug interactions with anti-psychotics are prominent and complicated.Case presentationWe report a clozapine-treated patient with SARS-CoV-2 infection who developed neutropenia after coadministration with Paxlovid. In this case, clozapine was used for over 15 years, without neutropenia development. However, severe neutropenia (absolute neutrophil count = 523/μl) developed 3 days after the coadministration of Paxlovid 2 doses per day, valproic acid 1,000 mg per day and clozapine 100 mg per day. The development of neutropenia may be attributed to the complicated interaction among Paxlovid, SARS-CoV-2 infection, valproic acid, fluvoxamine and clozapine.ConclusionsNeutropenia is a rare but life-threatening event if a concomitant infection occurs. The risk may increase during SARS-CoV-2 infection and the coadministration of clozapine and Paxlovid. Although the exact causes of neutropenia in this patient are not fully clear, the white blood cell count and absolute neutrophil count should be closely monitored during the administration of Paxlovid in clozapine-treated patients with SARS-CoV-2 infection.

Theta-burst stimulation is a non-invasive brain stimulation technique that was introduced as a potential augmentation treatment for patients with schizophrenia. The purpose of this meta-analysis was to investigate the therapeutic efficacy and safety of intermittent theta-burst stimulation in patients with schizophrenia. Following the PRISMA guidelines, the MEDLINE, Embase, Cochrane, Scopus, Web of Science, and CNKI databases were searched for relevant studies from database inception to 9 January 2022. Change in symptom severity among patients with schizophrenia was the primary outcome, and changes in cognitive function and safety profiles, including the discontinuation rate and adverse events, were secondary outcomes. In total, 13 double-blind randomized sham-controlled trials with 524 patients were included. Intermittent theta-burst stimulation adjunct to antipsychotics was associated with significantly improved psychopathology in patients with schizophrenia, particularly for negative symptoms and general psychopathology but not for positive symptoms or cognitive function. The stimulation parameters influenced the effectiveness of intermittent theta-burst stimulation. A more favorable effect was observed in patients who received theta-burst stimulation at the left dorsolateral prefrontal cortex, with ≥1800 pulses per day, for ≥20 sessions, and using an inactive sham coil as a placebo comparison in the study. The intermittent theta-burst stimulation is well tolerated and safe in patients with schizophrenia. Intermittent theta-burst stimulation adjunct to antipsychotics treatment is associated with significant improvement in negative symptoms and favorable tolerability in patients with schizophrenia. This meta-analysis may provide insights into the use of intermittent theta-burst stimulation as an additional treatment to alleviate the negative symptoms of schizophrenia.

The aim of the study was to assess the relationship between prolactin levels and sexual dysfunction in patients with schizophrenia who use olanzapine medication. The potential risk factors of hyperprolactinemia and sexual dysfunction were also investigated. Patients with schizophrenia undergoing olanzapine monotherapy were invited to participate in this cross-sectional study. The Arizona Sexual Experiences Scale (ASEX) and the Positive and Negative Syndrome Scale were used to evaluate subjective sexual dysfunction and psychopathology, respectively. Levels of prolactin and metabolic parameters were also measured. In total, 279 participants with schizophrenia were recruited. The overall incidences of hyperprolactinemia, sexual dysfunction, and metabolic syndrome were 51.6, 53.8, and 43.7%, respectively. Higher ASEX scores, higher insulin levels, female sex, and younger age were associated with hyperprolactinemia. Prolactin level was significantly correlated with ASEX score. Elevated prolactin levels, concomitant antidepressant, increased insulin resistance, longer illness duration, and female sex were associated with sexual dysfunction. Female participants recorded higher levels of sexual dysfunction than their male counterparts did, whereas male participants had comparatively lower prolactin levels and lower rates of spousal partnership. Hyperprolactinemia, metabolic syndrome, and sexual dysfunction are prevalent in patients with schizophrenia treated with olanzapine. Clinicians should maintain awareness of these problems and monitor them regularly with their patients.

Inadequate levels of 5-methyltetrahydrofolate (5-MTHF) and the T variant of MTHFR C677T have been suggested to be associated with an increased risk of developing mental illness, whereas the PON1 SNP variant provides a protective role. However, reports validating the methodology for plasma 5-MTHF levels in schizophrenia patients are limited. A sensitive LC–MS/MS system using an amide column and calibration curve was determined by dialyzed human plasma, and applied to schizophrenia patients and healthy controls in Taiwan, and the differences between the subgroups were discussed. This analysis system meets regulation criteria, and the lower limit of quantification for 5-MTHF levels was 4 nM from 200 μL plasma, within 7 min. The mean plasma 5-MTHF levels in schizophrenia patients (n = 34; 11.70 ± 10.37 nM) were lower than those in the healthy controls (n = 42; 22.67 ± 11.12 nM) significantly (p < 0.01). 5-MTHF concentrations were significantly lower in male carriers than in female carriers (18.30 ± 10.37 nM vs. 24.83 ± 11.01 nM, p < 0.05), especially in subjects who were MTHFR CT/PON1 Q allele carriers. In conclusion, this quantitative system, which employed sensitive and simple processing methods, was successfully applied, and identified that schizophrenic patients had significantly lower levels of 5-MTHF. Lower plasma 5-MTHF concentrations were observed in male subjects.

Objectives: Both superoxide dismutase 2 gene (SOD2), encoding a free radical scavenger, and dystrobrevin-binding protein 1 gene (DTNBP1), a candidate gene for schizophrenia, have been implicated in methamphetamine (METH) psychosis. In this study, we intended to compare the distribution of those two genes between METH users with and without psychosis and to evaluate whether the length of time of METH exposure influenced such relationship. Methods: The study sample consisted of 84 cases of patients with METH-induced psychosis and 187 controls (METH users without psychosis). Five single-nucleotide polymorphisms (SNPs) in SOD2 and three SNPs in DTNBP1 were genotyped. We did both single-locus and haplotype analyses, and adjusted for multiple comparisons with an effective number of markers, and multivariable logistic regression analyses for adjusting for age, sex, and duration of METH use. Results: None of the individual SNPs were associated with METH-induced psychosis after adjustment for multiple comparisons. In the subgroup analysis, both rs4880 and rs2855116 in SOD2 were significantly associated with prolonged METH-induced psychosis (p < 0.01 and p < 0.01, respectively). Under the assumption of a codominant model, the CC genotype of rs4880 was significantly associated with METH-induced psychosis after adjustments for age, sex, and the duration of METH use (p < 0.01). This association was not supported by the haplotype analyses or gene–gene interactions between SOD2 and DTNBP1. Conclusion: Functional C-allele of rs4880 in SOD2 was associated with the prolonged subtype of METH-induced psychosis in Taiwanese population. Oxidative stress mechanisms show a rôle in the development of METH-induced psychosis.

The high prevalence of metabolic syndrome in persons with schizophrenia has spurred investigational efforts to study the mechanism beneath its pathophysiology. Early psychosis dysfunction is present across multiple organ systems. On this account, schizophrenia may be a multisystem disorder in which one organ system is predominantly affected and where other organ systems are also concurrently involved. Growing evidence of the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, such as an association with cognitive dysfunction, altered autonomic nervous system regulation, desynchrony in the resting-state default mode network, and shared genetic liability, suggest that metabolic syndrome and schizophrenia are connected via common pathways that are central to schizophrenia pathogenesis, which may be underpinned by oxytocin system dysfunction. Oxytocin, a hormone that involves in the mechanisms of food intake and metabolic homeostasis, may partly explain this piece of the puzzle in the mechanism underlying this association. Given its prosocial and anorexigenic properties, oxytocin has been administered intranasally to investigate its therapeutic potential in schizophrenia and obesity. Although the pathophysiology and mechanisms of oxytocinergic dysfunction in metabolic syndrome and schizophrenia are both complex and it is still too early to draw a conclusion upon, oxytocinergic dysfunction may yield a new mechanistic insight into schizophrenia pathogenesis and treatment.

Antipsychotic-induced metabolic disturbance is a common adverse event occurring in patients treated with antipsychotic drugs. The mechanisms underlying metabolic dysregulation are complex, involving various neurochemical and hormonal systems, the interaction of genetic and lifestyle risk factors, and the antipsychotic drug prescribed. Recently, there has been increasing interest in the relationship between antipsychotic-induced metabolic disturbances and body weight regulatory hormones such as adiponectin. Adiponectin, an adipocyte-derived protein related to insulin sensitivity, weight gain, and anti-inflammation, has attracted great attention because of its potential role of being a biomarker to predict cardiovascular and metabolic diseases. Previous studies regarding the effects of antipsychotics on blood adiponectin levels have shown controversial results. Several factors might contribute to those inconsistent results, including different antipsychotic drugs, duration of antipsychotic exposure, age, sex, and ethnicity. Here we summarize the existing evidence on the link between blood adiponectin levels and metabolic disturbances related to antipsychotic drugs in patients with schizophrenia. We further discuss the effects of individual antipsychotics, patients' gender, ethnicity, age, and treatment duration on those relationships. We propose that olanzapine and clozapine might have a time-dependent biphasic effect on blood adiponectin levels in patients with schizophrenia.

BACKGROUND:The present study aimed to develop a new scale to evaluate the level of difficulty in treating major depressive disorder with antidepressants based on the lifetime treatment profile. METHODS:In addition to evaluating the difficulty of treatment with antidepressants (A subscale), the Treatment Resistance to Antidepressants Evaluation Scale (TRADES) is comprised of a subscale to account for the attributes that compromise the efficacy of treatment (B subscale). One hundred and six participants aged 18 to 65 years with remitted major depressive disorder were enrolled. Eligible cases were those with at least 2 years from disease onset until the scoring date of the TRADES (the index date), with a complete treatment record. Various psychosocial and clinical features, such as neuroticism, harm avoidance, and utilization of psychiatric services, were used to validate the TRADES. RESULTS:The mean duration of the course before and after the index date were 5.5 ± 3.5 and 3.1 ± 1.7 years, respectively. In a multiple regression analysis, the final total scores of the TRADES independently correlated with higher levels of neuroticism and harm avoidance. Total scores were also associated with a higher utilization of psychiatric outpatient and admission services before the index date. Furthermore, it is thought that total scores could predict a higher number of visits to psychiatric outpatient, emergency, and admission services following the index date. CONCLUSIONS:The TRADES has acceptable validity and could help to quantify the level of treatment difficulty with antidepressants in major depressive disorder.

Recent studies have suggested that gut–brain axis may be one of the mechanisms of major depression disorder (MDD). The current study aimed to investigate the effects of Lactobacillus plantarum PS128 (PS128) on psychophysiology in patients with MDD. We recruited 11 patients with MDD and gave them PS128 for 8 weeks. We compared depression symptoms, serum markers of inflammation and gut permeability, and gut microbiota before and after 8-week intervention and also explored the correlations among symptoms, biomarkers, and gut microbiota. After 8-week PS128 intervention, scores of Hamilton Depression Rating Scale-17 and Depression and Somatic symptoms Scale significantly decreased. Serum levels of high sensitivity c-reactive protein, interluekin-6, and tumor necrosis factor-α, zonulin and intestinal fatty acid binding protein, and the composition of gut microbiota did not significantly change after 8-week PS128 intervention. However, we found changes of some genera were correlated with changes of symptoms and biomarkers. In conclusion, this is an open trial with small sample size and has several limitations. The results need to be verified by randomized, double-blind, placebo-controlled trial with larger sample size.

Bipolar disorder (BD) is highly heritable and well known for its recurrent manic and depressive episodes. The present study focused on manic episode in BD patients and aimed to investigate state-specific transcriptome alterations between acute episode and remission, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and micro-RNAs (miRNAs), using microarray and RNA sequencing (RNA-Seq) platforms. BD patients were enrolled with clinical information, and peripheral blood samples collected at both acute and remission status spanning for at least 2 months were confirmed by follow-ups. Symptom severity was assessed by Young Mania Rating Scale. We enrolled six BD patients as the discovery samples and used the Affymetrix Human Transcriptome Array 2.0 to capture transcriptome data at the two time points. For replication, expression data from Gene Expression Omnibus that consisted of 11 BD patients were downloaded, and we performed a mega-analysis for microarray data of 17 patients. Moreover, we conducted RNA sequencing (RNA-Seq) in additional samples of 7 BD patients. To identify intraindividual differentially expressed genes (DEGs), we analyzed data using a linear model controlling for symptom severity. We found that noncoding genes were of majority among the top DEGs in microarray data. The expression fold change of coding genes among DEGs showed moderate to high correlations (∼0.5) across platforms. A number of lncRNAs and two miRNAs (MIR181B1 and MIR103A1) exhibited high levels of gene expression in the manic state. For coding genes, we reported that the taste function-related genes, including TAS2R5 and TAS2R3, may be mania state-specific markers. Additionally, four genes showed a nominal p-value of less than 0.05 in all our microarray data, mega-analysis, and RNA-Seq analysis. They were upregulated in the manic state and consisted of MS4A14, PYHIN1, UTRN, and DMXL2, and their gene expression patterns were further validated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We also performed weight gene coexpression network analysis to identify gene modules for manic episode. Genes in the mania-related modules were different from the susceptible loci of BD obtained from genome-wide association studies, and biological pathways in relation to these modules were mainly related to immune function, especially cytokine–cytokine receptor interaction. Results of the present study elucidated potential molecular targets and genomic networks that are involved in manic episode. Future studies are needed to further validate these biomarkers for their roles in the etiology of bipolar illness.

Background: High sedative use in a major depressive episode may imply specific clinical features. This study aims to examine the correlation between sedative use and clinical severity indicators in the initial treatment phase of first-onset major depressive disorder.Methods: A study cohort in the first episode of major depressive disorder was used to conduct pharmacological dissection. All participants had at least a 2-year follow-up period with a complete treatment record. The defined daily dose of antidepressants and augmentation agents were calculated as the antidepressant load and augmentation load, respectively. Sedative use, which was calculated as the equivalent dosage of lorazepam, were defined as the sedative load. These psychotropic loads were measured monthly and the averaged psychotropic loads for each day were obtained.Results: A total of 106 individuals (75.5% female) were included. The mean duration of disease course in participants was 5.5 ± 3.5 years. In the multiple regression analysis, after controlling for other classes of psychotropics and comorbid anxiety disorders, the sedative load independently correlated with higher number of antidepressants used, higher number of antidepressant used with an adequate dose and duration, more psychiatric emergency and outpatient visits within 2 years of disease onset.Conclusion: High loading of sedatives correlated with several indicators of clinical severity in major depressive disorder. The sedative load may be used as a specifier to identify subgroups in patients with major depressive disorder.

Schizophrenia is a form of mental disorder that is behaviorally characterized by abnormal behavior, such as social function deficits or other behaviors that are disconnected from reality. Dysregulation of oxytocin may play a role in regulating the expression of schizophrenia. Given oxytocin’s role in social cognition and behavior, a variety of studies have examined the potential clinical benefits of oxytocin in improving the psychopathology of patients with schizophrenia. In this review, we highlight the evidence for the role of endogenous oxytocin in schizophrenia, from animal models to human studies. We further discuss the potential of oxytocin as a therapeutic agent for schizophrenia and its implication in future treatment.

[This corrects the article DOI: 10.1371/journal.pone.0168347.].

Metformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. The lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. This study was designed to determine whether metformin at 500 mg/d and 1000 mg/d is effective in improving the metabolic profiles of clozapine-treated patients with pre-existing metabolic abnormalities, and whether its effectiveness depends on metformin dosage.In this 12-week, randomized, double-blind, placebo-controlled trial, metformin at 500 mg/d or 1000 mg/d was prescribed to clozapine-treated patients with schizophrenia who had pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at weeks 4, 8, and 12. The outcomes were any changes in metabolic traits.Among the 96 clozapine-treated patients with schizophrenia screened for the trial, 55 patients with pre-existing metabolic abnormalities were randomly assigned to placebo (n = 18), metformin dosage at 500 mg/d (n = 18), and metformin dosage at 1000 mg/d (n = 19) groups. The body weight (BW) of patients in the metformin 1000 mg/d group significantly decreased, by a mean of 0.97 kg over the 12 week trial period. Moreover, patients in the metformin at 500 mg/d and 1000 mg/d groups had a significant decrease in body mass index (BMI) after 12 weeks, with the mean decrease being 0.70 and 0.50 kg/m2, respectively. No significant changes were observed in the other metabolic parameters of patients in the three groups.Our results demonstrated that a low metformin dosage of either 500 mg/d or 1000 mg/d for 12 weeks slightly reduced the BW and BMI of clozapine-treated patients with pre-existing metabolic abnormalities. A longer period of treatment with a larger sample is warranted to determine the factors that influence the metformin treatment response.ClinicalTrials.gov NCT02751307.

BACKGROUND:This therapeutic drug monitoring (TDM) study aimed to determine the role of olanzapine (OLZ) and N-desmethyl-OLZ (DMO) levels in the therapeutic efficacy of OLZ in patients with schizophrenia. METHOD:Plasma concentrations of OLZ (COLZ) and DMO (CDMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of COLZ and CDMO with the various scores of the Positive and Negative Syndrome Scale (PANSS) were evaluated. A receiver operating characteristic curve (ROC) was utilized to identify the threshold COLZ and COLZ/CDMO ratio for maintenance of satisfactory efficacy. RESULTS:A total of 151 samples from patients with schizophrenia were analyzed for individual COLZ and CDMO levels. The mean COLZ and CDMO levels were 37.0 ± 25.6 and 6.9 ± 4.7 ng/mL, respectively, and COLZ was ~50% higher in female or nonsmokers (p

Alcohol-induced oxidative stress is the result of the combined production of reactive oxygen species [ROS; e.g. malondialdehyde (MDA), an index of lipid peroxidation] and impairment of antioxidant defenses [e.g. superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX), which are involved in the elimination of ROS]. Little is known about the oxidative stress markers among patients with alcohol dependence in Taiwan. This study aimed to investigate serial alterations of various oxidative stress markers during early detoxification in alcoholic patients. Methods: We enrolled 121 inpatients who fulfilled the DSM-IV-TR criteria for alcohol dependence, and 19 healthy controls. Fasting serum MDA level and antioxidant activity, including SOD, CAT and GPX, were measured at baseline in both groups, and after 1 and 2 weeks of detoxification in alcoholic patients. Results: MDA level in alcoholics was higher at baseline than in healthy controls. It decreased after 1 week of detoxification, and normalized at week 2. SOD and GPX activities remained significantly lower throughout the 2-week period. CAT activity in alcoholics was comparable to that in the controls at baseline, but decreased at week 1 of detoxification, and was significantly lower than that in the controls after 2 weeks. Moreover, baseline MDA level was correlated with baseline CAT activity in alcoholics; the magnitude of the decrease in MDA level was correlated with the decrease in CAT activity following the 1-week detoxification. Conclusion: The findings suggest severe oxidative stress and weakened antioxidant activity in alcoholic patients, and limited changes in oxidative stress in the early stages of alcohol withdrawal.