Yang-Whan Jeon

Meta-analysis of P300 and schizophrenia: patients, paradigms, and practical implications.

The goal of the present meta-analysis was to identify factors that contribute to P300 event-related brain potential (ERP) differences in patients with schizophrenia compared to unaffected controls in an attempt to characterize the clinically relevant dimensions underlying P300 deficits in patients with schizophrenia. P300 effect size (d) was smaller in amplitude and longer in latency in schizophrenic patients compared to normal controls, with the strongest effects obtained from the auditory oddball. Paranoid subtype demonstrated larger P300 amplitude effect sizes than other disease subtypes, and P300 latency effect size decreased with disease duration. Psychopathology severity and antipsychotic medications were unrelated to P300 amplitude effect size. Gender proportion, educational level, and stimulus and task variables also affected P300 amplitude and latency effect sizes. The findings are used to formulate a theoretical account of the empirical data and provide suggestions for maximizing the utility of the P300 component in the assessment of schizophrenia.

P300 asymmetry in schizophrenia: a meta-analysis

P300 event-related brain potential (ERP) amplitude is smaller in patients with schizophrenia compared to unaffected controls, but whether left temporal component amplitude is also smaller is debated. The present study employed meta-analytical methods to quantitatively assess previous P300 schizophrenia asymmetry findings. All P300 articles on schizophrenia using an auditory oddball paradigm published before January 2000 were obtained by comprehensive literature searches and cross-referencing for related articles. A total of 19 original articles reporting complete midline electrode data and 11 articles reporting lateral asymmetry electrode data were reviewed, which included different independent conditions that yielded 50 independent data sets. P300 amplitude differences between patients with schizophrenia and control subjects from the midline electrodes yielded effect sizes that differed among recording sites, such that Fz was significantly smaller than Pz, with Cz effect sizes smaller than Pz but larger than Fz. Comparison of P300 amplitude from the lateral data for the T3 and T4 electrodes found no reliable effect size difference when these electrodes were analyzed separately. However, comparison of P300 amplitude effect sizes from the TCP1 was significantly larger than that from the TCP2 when these electrodes were analyzed separately. P300 amplitude is smaller overall in patients with schizophrenia compared to control subjects and differs in its effect size topography across the midline and temporal electrode sites, with the strongest effect sizes obtained for the Pz midline and TCP1 lateral electrodes.

P3a from a passive visual stimulus task.

OBJECTIVE Visual event-related brain potentials (ERPs) were elicited using a 3-stimulus oddball paradigm to assess the P3a with passive stimulus processing. METHODS Young adults (n=12) were presented with a series of visual stimuli consisting of a solid circle standard stimulus (P=0.76) that was difficult to discriminate from a larger target circle (P=0.12), with a large square distractor stimulus (P=0.12) presented randomly in the series. Subjects were instructed in the passive condition to simply look at the stimuli and in the active condition to press a mouse key only to the target stimulus. ERPs were recorded from 15 scalp electrodes, with the amplitude and latency of the P300 from the distractor and target stimuli assessed. RESULTS The P3a from the distractor stimulus was similar in amplitude, scalp topography, and peak latency across the passive and active task conditions. The P3b from the target stimulus demonstrated much smaller amplitude, highly altered scalp topography, and longer latency for the passive compared to active task conditions. CONCLUSIONS The P3a can be obtained with visual stimuli in the 3-stimulus paradigm under passive viewing conditions. Theoretical implications and clinical applications are discussed.

A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder.

The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigators Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56±1.29 (95% confidence interval: 3.39–3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigators Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.

Efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia.

To investigate the efficacy and safety of quetiapine for depressive symptoms in patients with schizophrenia.

Natural Killer T cells in patients with major depressive disorder

CD56 (Natural Killer T) cells showed a significant negative correlation with depressive symptom scale scores in acute and unmedicated patients with major depressive disorder. Decreased CD56 cells may reflect the severity of depressive symptoms but not the severity of anxiety symptoms in major depression.

Variation of the choline signal intensity in the dorsolateral prefrontal cortex of rats exposed to the forced swimming test as detected by in vivo 1H MR spectroscopy

BACKGROUND (1)H magnetic resonance spectroscopy (MRS) has documented an increased Cho/Cr ratio in the dorsolateral prefrontal cortex (DLPFC) in major depressive disorder (MDD). The aim of this study was to investigate neurochemical alterations in the left DLPFC, considered a main area of pathogenesis in depression, using rats exposed to the forced swimming test (FST). MATERIALS AND METHODS Twenty-four male rats were used for the MRI and in vivo(1)H MRS studies. Rats exposed to the FST to induce a depressed mental status. Using in vivo(1)H MRS, the metabolite ratios of the rats with a depressed mental status and the controls, were measured and the values of the two groups were compared. RESULTS The Cho/Cr and Cho/NAA ratios in the DLPFC of the rats with a depressed mental status were significantly higher than that in the controls. CONCLUSIONS The present study demonstrates a significantly increased Cho/Cr ratio in the DLPFC of rats with depression compared with controls. This result may suggest an accelerated turnover of membrane without neuronal loss is occurring in the DLPFC of the rats with depression.

Natural killer cell activity in patients with major depressive disorder treated with escitalopram.

BACKGROUND An association between depression and altered immunity has been suggested by many studies, although the findings are not fully consistent. The present investigation examined the effects of escitalopram on cellular immunity in patients with major depressive disorder (MDD). METHODS Fifty-one patients with MDD were evaluated with the Hamilton Rating Scale for Depression and Montgomery-Åsberg Depression Rating Scale. The patients were grouped into responders (n=32) and non-responders (n=19). Adrenocorticotropic hormone, cortisol, CD4, CD8, CD19, and natural killer cells were measured at baseline and after a 4 week treatment with escitalopram. Plasma hormones and immune parameters were compared between groups. RESULTS Responders showed increased activity, but not number, of natural killer cells after a 4 week treatment with escitalopram. There were no differences in plasma hormones and other immune parameters between groups, even though cortisol was decreased and CD19 was increased across both groups compared to baseline. CONCLUSIONS The results suggest that natural killer cells play an important role in improving the symptoms of depressive patients responding to selective serotonin inhibitors. To deepen our understanding of the pathogenesis of depression, interactions between serotonin and the immune system should be further explored.

Cholinesterase inhibitors for Alzheimer disease: do they provide more than symptomatic benefits?

OBJECTIVE This study aims to examine survival of patients with Alzheimer disease (AD) receiving clinical efficacy of cholinesterase inhibitors (ChEIs) and to compare their survival with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. DESIGN, SETTING, AND PARTICIPANTS The retrospective cohort study used national mortality data provided by the Korean National Statistics Office and electronic database of 15 general hospitals on older patients who began outpatient treatment with psychiatric medications including ChEIs (N = 3,813). The authors controlled for confounding by using multivariate models and propensity scoring methods. MEASUREMENTS Mortality rate of patients with AD receiving ChEIs was compared with those of patients with AD who never received ChEIs and cognitively intact old psychiatric outpatients. RESULTS Observed additional survival of patients with AD receiving ChEIs (mortality rate: 13.1%), when compared with patients with AD who never received ChEIs (15.4%) was not statistically significant (p = 0.74; hazard ratio [HR]: 1.03, 95% confidence interval [CI]: 0.67-1.59). Patients with AD receiving ChEIs showed higher mortality rate (13.1%) compared with that of cognitively intact old psychiatric outpatients (8.6%) (p <0.001; HR: 1.60, 95% CI: 0.96-2.68). CONCLUSION This study does not support that ChEIs increase survival of patients with AD, compared with patients with AD who have never treated with ChEIs. Therefore, all ChEIs should be considered for symptomatic use only and not to be capable of modifying mortality of patients with AD.

Severe urinary retention requiring urinary catheterization associated with combined treatment of depression with duloxetine and quetiapine.

PhD, Michele Fornaro, MD, PhD, Nicola Serroni, MD, Stefano Marini, MD, Francesco Saverio Moschetta, MD, Giovanni Martinotti, MD, PhD and Massimo Di Giannantonio, MD NHS, Department of Mental Health, Psychiatric Service of Diagnosis and Treatment, Hospital “G. Mazzini”, Teramo, Department of Neurosciences and Imaging, University “G. D’Annunzio”, Chieti, Villa S. Giuseppe Hospital, Hermanas Hospitalarias, Ascoli Piceno and Department of Formative Sciences, University of Catania, Catania, Italy E-mail: dodebera@aliceposta.it Received 12 January 2013; accepted 30 January 2013.