Correlation between serum VEGF level and clinical symptoms in patients with first-episode drug-naive schizophrenia of different genders / 中华行为医学与脑科学杂志

Objective:To investigate the level of serum vascular endothelial growth factor (VEGF) and its correlation with clinical symptoms in patients with first-episode drug-naive schizophrenia patients of different genders.Methods:From January 2016 to October 2019, a total of 81 first-episode drug-naive schizophrenia patients(patient group, 41 male, 40 female) and 64 healthy controls (control group, 40 male, 24 female) were included in this study.The serum level of VEGF was detected with flow cytometric bear array (CBA). Positive and negative symptom scale (PANSS) was used to evaluate the relevant clinical symptoms of patients.SPSS 22.0 software was used for statistical analysis.Independent sample t-test and nonparametric test were used for comparison between groups.The relationship between VEGF and clinical variables was analyzed by Pearson correlation analysis and Spearman correlation analysis. Results:The level of serum VEGF in the patient group was significantly lower than that in the control group(148.08(75.89, 208.61)pg/mL, 179.94(99.14, 318.41)pg/mL, Z=-2.20, P=0.028). The total PANSS score((82.71±17.30), (73.45±16.36), t=2.473, P=0.016)and cognitive score((7.88±3.36), (6.23±2.81), t=2.402, P=0.019) in male patients were higher than those in female patients.There was a negative correlation between VEGF level and PANSS negative symptom score in the patient group( r=-0.228, P=0.041), as well as significant negtive correlation between VEGF level and cognitive score in male patients( r=-0.425, P=0.007). Conclusion:The level of serum VEGF is reduced in first-episode patients with schizophrenia, which influences their negative symptom. Moreover, the decline in serum VEGF level is implicated in cognitive impairments in male patients with first-episode schizophrenia.

Decreased White Matter Structural Connectivity in Psychotropic Drug-Naïve Adolescent Patients with First Onset Major Depressive Disorder / 정신신체의학

OBJECTIVES: Recent neuroimaging studies focus on dysfunctions in connectivity between cognitive circuits and emotional circuits: anterior cingulate cortex that connects dorsolateral orbitofrontal cortex and prefrontal cortex to limbic system. Previous studies on pediatric depression using DTI have reported decreased neural connectivity in several brain regions, including the amygdala, anterior cingulate cortex, superior longitudinal fasciculus. We compared the neural connectivity of psychotropic drug naïve adolescent patients with a first onset of major depressive episode with healthy controls using DTI. METHODS: Adolescent psychotropic drug naïve patients(n=26, 10 men, 16 women; age range, 13–18 years) who visited the Korea University Guro Hospital and were diagnosed with first onset major depressive disorder were registered. Healthy controls(n=27, 5 males, 22 females; age range, 12–17 years) were recruited. Psychiatric interviews, complete psychometrics including IQ and HAM-D, MRI including diffusion weighted image acquisition were conducted prior to antidepressant administration to the patients. Fractional anisotropy(FA), radial, mean, and axial diffusivity were estimated using DTI. FMRIB Software Library-Tract Based Spatial Statistics was used for statistical analysis. RESULTS: We did not observe any significant difference in whole brain analysis. However, ROI analysis on right superior longitudinal fasciculus resulted in 3 clusters with significant decrease of FA in patients group. CONCLUSIONS: The patients with adolescent major depressive disorder showed statistically significant FA decrease in the DTI-based structure compared with healthy control. Therefore we suppose DTI can be used as a biomarker in psychotropic drug-naïve adolescent patients with first onset major depressive disorder.

Alexithymia, suicidal ideation, and serum lipid levels among drug-naïve outpatients with obsessive-compulsive disorder

Objective: As obsessive-compulsive disorder (OCD) is a relatively common psychiatric disorder with a significant suicide risk, the individuation of potential biomarkers of suicidality, such as cholesterol levels, may enable recognition of at-risk subjects. Therefore, the aims of this study were to: 1) evaluate potential differences in clinical and laboratory parameters between patients with and without alexithymia and compare them with healthy controls; and 2) investigate which clinical and laboratory variables were associated with suicidal ideation. Methods: 79 drug-naïve adult outpatients with a DSM-IV diagnosis of OCD were recruited. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20), suicidal ideation was assessed with the Scale for Suicide Ideation, and depressive symptoms were evaluated with the Montgomery-Åsberg Depression Rating Scale (MADRS). Serum lipid levels of 40 healthy controls were also evaluated. Results: Alexithymic patients had altered serum lipid levels in comparison with non-alexithymics and healthy controls. Using a linear regression model, the presence of symmetry/ordering obsessions and compulsions, lower HDL-C levels, and difficulty in identifying feelings dimension of the TAS-20 were associated with higher suicidal ideation. Conclusions: Alexithymic individuals with OCD may exhibit dysregulation of the cholesterol balance, which in turn may be linked to suicidal ideation. Further prospective studies are required to elucidate this potential association. .

Metabolic syndrome in schizophrenia: how much is attributable to drug treatment.

Background: This study was planned to investigate new onset metabolic syndrome (MS) and its various components associated with two widely used second generation antipsychotics i.e. olanzapine and quetiapine in the management of schizophrenia using International Diabetic Federation (IDF) criteria. Methods: A total of 60 drug naïve patients with ICD-10 diagnosis of first episode schizophrenia, divided in two groups of 30 patients each, were randomly allocated to receive two different treatments i.e. olanzapine and quetiapine. Metabolic parameters were measured at day 0, then at 6 and 12 weeks. For categorical variables, ‘Chi-square test’ was used for comparison between the two groups. For continuous variables student’s t-test was used. Results: At 6 weeks none of the patient, treated with olanzapine, developed Metabolic Syndrome (MS), but among quetiapine group 3.33% (1 out of 30) developed MS. At the end of 12 weeks, 20% patients (i.e. 6 out of 30) had MS in olanzapine treatment group and 10% (3 out of 30) in quetiapine treatment group. Conclusion: Both olanzapine and quetiapine were found to cause comparable metabolic derangement and metabolic syndrome.

Neuropsychological Characteristics of Wandering in Patients with Drug-naive Alzheimer's Disease

BACKGROUND: Wandering represents one of a major problem occurring in patients with Alzheimer's disease (AD). To find the disproportionate neuropsychological deficit and behavioral psychological symptoms in dementia (BPSD) of AD patients with wandering compared to AD patients without wandering, this study examined the set of neuropsychological tests and caregiver-administered neuropsychiatric inventory (CGA-NPI). METHODS: Psychotropic-naive (drug-naive) probable AD patients with wandering (64) and without wondering (278) were assessed with the Seoul Neuropsychological Screening Battery, which included measures of memory, intelligence, and executive functioning. RESULTS: Patients with wandering had lower scores in the Rey-Osterrieth Complex Figure copy, Fist-edge-palm, Alternating hand movement tests compared to patients without wandering. The degree of wandering in AD patients was significantly related with CGA-NPI subdomains of aggression, disinhibition, depression, and delusions. CONCLUSION: This study showed that 1) AD patients with wandering have disproportionately cognitive deficit suggesting frontal and right parietal dysfunctions, 2) wanderings are related with specific BPSD. Considering these results, AD patients with wandering may have specific neuronal anatomic substrates related with pathology of Alzheimer.

Missing Data Analysis in Drug-Naive Alzheimer's Disease with Behavioral and Psychological Symptoms

PURPOSE: To clarify the effects of missing values due to behavioral and psychological symptoms in dementia (BPSD) in Alzheimer's disease (AD) patients on the neuropsychological tests, this study describes the pattern of missing values due to BPSD, and its influence on tests. MATERIALS AND METHODS: Drug-naive probable AD patients (n=127) with BPSD and without BPSD (n=32) were assessed with Seoul Neuropsychological Screening Battery including measures of memory, intelligence, and executive functioning. Moreover, patients were rated on Korean Neuropsychiatry Inventory (K-NPI). RESULTS: The more severe the K-NPI score, the less neuropsychological tests were assessable, leading to many missing values. Patients with BPSD were more severely demented than those without BPSD. K-NPI scores were significantly correlated with the number of missing values. The effect of BPSD was largest for tests measuring frontal functions. The replacement of the missing values due to BPSD by the lowest observed score also showed the largest effect on tests of frontal function. CONCLUSION: The global cognitive and behavior scales are related with missing values. Among K-NPI sub-domains, delusion, depressing, apathy, and aberrant motor behavior are significantly correlated for missing values. Data imputation of missing values due to BPSD provides a more differentiated picture of cognitive deficits in AD with BPSD.

Clinical Characteristics of Behavioral and Psychological Symptoms in Patients with Drug-naive Alzheimer's Disease

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are less well-defined aspects of Alzheimer's disease (AD). We designed this study to explore the followings: 1) the clinical profiles of BPSD 2) the clustered-groups domains of the Korean-Neuropsychiatric Inventory (K-NPI) assessment of BPSD 3) the clinical characteristics of the clustered-groups of BPSD in patients with drug-naive probable AD. METHODS: Descriptive and cluster analyses of the 12 K-NPI domains were done in 220 patients with drug-naive probable AD. After clustering these domains, characteristics of these positive symptoms clustered-group of patients were compared with the negative symptoms groups of patients. RESULTS: The mean Korean-Mini Mental Status Examination (K-MMSE), Clinical Dementia Rating (CDR) scale, and K-NPI scores were 15.0, 1.6, and 14.2, respectively. The CDR and K-MMSE scores correlated with total K-NPI scores, and depression was the most common symptom. According to cluster analysis, five major clusters were identified. Using the associated neuropsychological dysfunctions, characteristics of each group were defined. CONCLUSIONS: This study identified the clustered-domains for K-NPI, and suggested the possible anatomical substrates for these groups in drug-naive AD patients. These attempts may clarify the complex and bizarre behavioral and psychological symptoms as more neurologically relevant symptoms.

Prevalence of Antiretroviral Drug Resistance Mutations and HIV-1 Subtypes among Newly-diagnosed Drugnaïve Persons Visiting a Voluntary Testing and Counselling Centre in Northeastern South Africa.

Data on antiretroviral drug resistance among drug-naïve persons are important in developing sentinel surveillance policies. This study was conducted to determine the prevalence of antiretroviral drug resistance mutations among drug-naïve HIV-infected individuals attending a voluntary testing and counselling centre at the Mankweng Hospital in northeastern South Africa. In total, 79 drug-naïve HIV-positive individuals were sequentially recruited during February 2008–December 2008. Drug resistance mutations were determined using the calibrated population resistance tool available on the Stanford HIV drug resistance database. Viral DNA was obtained from 57 (72%) of the 79 individuals. Reliable nucleotide sequences were obtained for 54 reverse transcriptase (RT) and 54 protease (PR) gene regions from 54 individuals. Overall, five sequences (9.3%) harboured drug resistance mutations (95% confidence interval -1.53 to 16.99). Four (7.4%) of these were nucleoside RT inhibitor mutations (D67G, D67E, T69D, and T215Y), and one (1.9%) was a PR inhibitor mutation (M46I). No major non-nucleoside RT resistance mutation was detected. Several minor resistance mutations and polymorphisms common in subtype C viruses were observed in the PR and RT genes. Phylogenetic analysis of the partial pol sequences showed that 52 (96%) of the 54 isolates were HIV-1 subtype C. One isolate (08MB08ZA) was HIV-1 subtype B while another (08MB26ZA) was related to HIV-1 subtype J. HIV-1 subtype recombination analysis with REGA assigned the pol sequence to HIV subtype J (11_cpx) with a bootstrap value of 75%. The prevalence of drug resistance mutations observed in the population studied was relatively higher than previously reported from other parts of South Africa. In addition, this is apparently the first report of an HIV-1 subtype J-like virus from northeastern South Africa.

Correlation between Cognitive Functions and Psychotic Symptoms in Schizophrenic Patients

& executive function deficit could be reversible after treatment, and 3) medication might have a benefit in improving the cognitive functions in schizophrenia. Furthermore, the data supports that the better premorbid executive function was, the more favorable was the treatment response in schizophrenic patients. Finally, this study indicates that executive function might be an index of treatment improvement.

The Effect of Haloperidol on Regional Cerebral Blood Flow Assessed with 99m-Tc-ECD SPECT In Schizophrenic Patients / 신경정신의학

OBJECTIVES: Regional cerebral blood flow(rCBF)in schizophrenics is confounded by various factors including medication status. Previously, there have been numerous studies regarding the effects of antipsychotics on rCBF. However, these works have shown contradictory and inconsistent findings due to the different of type, dose and exposed duration of antipsychotics. The aim of this study was to observe the effect of antipsychotic medication on rCBF and exposed duration of antipsychotics under control. METHODS: Eighteen drug-naive schizophrenics and 19 schizophrenics medicated with haloperidol were included in the study. Regional cerebral blood flow was assessed with the singlephoton emission computed tomography(SPECT)under a resting state. Relative rCBF was compared between two groups. Haloperidol was selected as the antipsychotic drug as it has relatively selective action at the D2 receptor and less active metabolites. Exposed duration was limited from one to three weeks. RESULTS: Haloperidol-medicated schizophrenic patients had a significantly greater increase of relative cerebral perfusion in the right inferior temporal lobe, left inferior frontal lobe, both basal ganglia, left thalamus, both parieto-occipital lobes, and right parietal lobe than drug-naive schizophrenic patients. Haloperidol-medicated schizophrenic patients had a significant decrease of relative cerebral perfusion in left inferior temporal lobe. However, no significant differences in relative rCBF were found between drug-naive and haloperidol-medicated schizophrenic patients in right inferior frontal lobe, right thalamus, both superior temporal lobes, both superior frontal lobes, and left parietal lobe. CONCLUSION: These findings suggest that antipsychotics affect regional cerebral blood flow, and antipsychotic medication status must be considered in the relative rCBF studies of schizophrenic patients.

99m-Tc-ECD SPECT Study of Differences on Relative Cerebral Blood Flow between Drug-Naive and Drug-Free Schizophrenic Patients / 신경정신의학

OBJECTIVES: In schizophrenics, regional cerebral blood flow(rCBF) are affected by various confounding variables, i.e., age, sex, duration of illness, and clinical status. The pharmacological condition of patients is also a particular important variable to be taken into consideration. However, few data are available regarding the differences between the relative rCBF findings in drug-free and drug-naive schizophrenic patients. Currently, numerous studies have included drug-free and drug-naive schizophrenic patients in the same 'unmedicated' group under the assumption that the rCBF is identical between drug-free and drug-naive cases. Therefore, the aim of this study was to compare the rCBF between a group of drug-free schizophrenic patients and a group of drug-naive schizophrenic patients about the effects of age, sex, duration of illness, and clinical status(positive and negative symptoms) under control. METHODS: Eighteen drug-naive schizophrenics and fifteen drug-free schizophrenics were in-cluded in the study. Regional cerebral blood flow was studied with the single-photon emission computed tomography(SPECT) under resting state. Symptoms were assessed with Positive and Negative Syndrome Scale(PANSS). Regions of interest were both inferior temporal lobe, inferior frontal lobe, superior temporal lobe, thalamus, basal ganglia, parieto-occipital lobe, superior frontal lobe, and parietal lobe. RESULTS: No significant differences of relative rCBF were found between drug-free and drug-naive schizophrenic patients in left inferior temporal lobe, right inferior frontal lobe, both superior temporal lobe, both thalamus, both basal ganglia, right parieto-occipital lobe, and both superior frontal lobe. But, drug-free schizophrenic patients had a significant increase of perfusion in the right inferior temporal lobe and left inferior frontal lobe and a significant decrease of perfusion in both parietal lobes and left parieto-occipital lobe. CONCLUSIONS: Relative rCBF in drug-free schizophrenic patients is different from that in drug-naive schizophrenic patients. So, in the relative rCBF studies of schizophrenic patients, it must be considered whether the patients were previously medicated or not.

Comparison of Soft Neurologic Sings in Neuroleptic-naive, Treated, and Chronically Institutionalized Schizophrenics / 신경정신의학

OBJECTS: Many studies have demonstrated greater frequency of soft neurologic signs in patients with schizophrenia than in controls. However, factors associated with chronicity, institutionalization, individual differences and neuroleptic medication make it difficult to interpret these results. We report on our ongoing study of soft neurologic signs and their relationship to neuroleptics and institutionalization in schizophrenia. METHODS: Soft neurologic signs were examined with a standardized instrument, Neurological Evaluation Scale- Korean Version(NES-K) in 11 neuroleptic-naive patients with schizophrenia, 17 neuroleptic-treated patients and 14 chronically institutionalized patients. RESULTS: Scores of total items(p<0.005), sensory integration(p<0.05), sequencing of complex motor acts(p<0.05) and others(p<0.01) functional areas of NES-K were significantly different among three groups. There was no difference in the area of motor coordination. Posthoc analysis showed that scores of total items(p<0.005) and sensory integration areas(p<0.01) of NES-K were significantly higher in the institutionalized patients than those of neuroleptic-naive group. However scores of sequencing of complex motor act and others categories were not different in the institutionalized and neuroleptic-naive patients. CONCLUSION: These findings suggested that neuroleptic treatment or chronic institutionalization might partially affect soft neurologic signs, especially sensory integration area, in patients with schizophrenia. However, the soft neurologic signs of motor coordination area could be a biological trait marker of schizophrenia independent of confounding variables.