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ABSTRACT: The epsilon4 allele of the Apolipoprotein E (ApoE) gene has been linked to various neurological conditions and the aging process in the elderly. However, evidence has suggested that the influence of ApoE epsilon4 may commence in early life. This study examined the modulatory effects of ApoE epsilon4 on regional neural activity as well as inter-regional neural interactions in a young population aged 19-21. Blood samples and resting state eyes-closed EEG signals were collected from 265 healthy females, and stratified into two groups: epsilon4 carriers and non-carriers. The values of the log-transformed mean power of 18 electrodes and the mutual information of 20 channel pairs across delta, theta, alpha and beta frequencies were analyzed. Our connectivity analysis was based on information theory, which combined Morlet wavelet transform and mutual information calculation. Between-group statistics were performed by independent t-test. We notice a consistent trend across the brain, in which ApoE epsilon4 carriers possess lower regional power at the alpha band. The epsilon4 allele is also associated with lower regional power at the theta frequency in the left frontal and posterior brain regions. Functional connectivity analyses reveal a right-lateralized network that differentiates epsilon4 carriers and non-carriers, with lower connectivity strengths for the former. Our tonic EEG analyses complement those of previous reports in that the ApoE epsilon4 allele has a negative impact on regional neural synchronization and inter-regional neural interaction.
Brain Topography 05/2012; 25(4):431-42. · 3.45 Impact Factor
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ABSTRACT: The polymorphism of variable number of tandem repeat (VNTR) in dopamine receptor D4 (DRD4) gene exon III has been linked to various neuro-psychiatric conditions with disinhibition/impulsivity as one of the core features. This study examined the modulatory effects of long-allele variant of DRD4 VNTR on the regional neural activity as well as inter-regional neural interactions in a young female population. Blood sample and resting state eyes-closed EEG signals were collected in 233 healthy females, stratified into two groups by polymerase chain reaction: long-allele carriers (>4- repeat) and non-carriers (<=4-repeat/<=4-repeat). The values of mean power of 18 electrodes and mutual information of 38 channel pairs across theta, alpha, and beta frequencies were analyzed. Our connectivity analysis was based on information theory, which combined Morlet wavelet transform and mutual information calculation. Between-group differences of regional power and connectivity strength were quantified by independent t-test, while between-group differences in global trends were examined by non-parametric analyses. We noticed that DRD4 VNTR long-allele was associated with decreased global connectivity strength (from non-parametric analysis), especially over bi-frontal, biparietal and right fronto-parietal and right fronto-temporal connections (from independent t-tests). The between-group differences in regional power were not robust. Our findings fit with the networks of response inhibition, providing evidence bridging DRD4 long-allele and disinhibition/impulsivity in neuropsychiatric disorders. We suggest future DRD4 studies of imaging genetics incorporate connectivity analysis to unveil its impact on cerebral network.
The Open Neuroimaging Journal 01/2012; 6:19-25.
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ABSTRACT: Predicting treatment response in major depressive disorder (MDD) has been an important clinical issue given that the initial intent-to-treat response rate is only 50 to 60%. This study was designed to examine whether functional connectivity strengths of resting EEG could be potential biomarkers in predicting treatment response at 8 weeks of treatment. Resting state 3-min eyes-closed EEG activity was recorded at baseline and compared in 108 depressed patients. All patients were being treated with selective serotonin-reuptake inhibitors. Baseline coherence and power series correlation were compared between responders and non-responders evaluated at the 8th week by Hamilton Depression Rating Scale. Pearson correlation and receiver operating characteristic (ROC) analyses were applied to evaluate the performance of connectivity strengths in predicting/classifying treatment responses. The connectivity strengths of right fronto-temporal network at delta/theta frequencies differentiated responders and non-responders at the 8th week of treatment, such that the stronger the connectivity strengths, the poorer the treatment response. ROC analyses supported the value of these measures in classifying responders/non-responders. Our results suggest that fronto-temporal connectivity strengths could be potential biomarkers to differentiate responders and slow responders or non-responders in MDD.
Psychiatry Research 12/2011; 194(3):372-7. · 2.52 Impact Factor
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ABSTRACT: The oddball paradigm is widely applied to the investigation of cognitive function in neuroscience and in neuropsychiatry. Whether cortical oscillation in the resting state can predict the elicited oddball event-related potential (ERP) is still not clear. This study explored the relationship between resting electroencephalography (EEG) and oddball ERPs. The regional powers of 18 electrodes across delta, theta, alpha and beta frequencies were correlated with the amplitude and latency of N1, P2, N2 and P3 components of oddball ERPs. A multivariate analysis based on partial least squares (PLS) was applied to further examine the spatial pattern revealed by multiple correlations.
Higher synchronization in the resting state, especially at the alpha spectrum, is associated with higher neural responsiveness and faster neural propagation, as indicated by the higher amplitude change of N1/N2 and shorter latency of P2. None of the resting quantitative EEG indices predict P3 latency and amplitude. The PLS analysis confirms that the resting cortical dynamics which explains N1/N2 amplitude and P2 latency does not show regional specificity, indicating a global property of the brain.
This study differs from previous approaches by relating dynamics in the resting state to neural responsiveness in the activation state. Our analyses suggest that the neural characteristics carried by resting brain dynamics modulate the earlier/automatic stage of target detection.
BMC Neuroscience 11/2011; 12:121. · 3.04 Impact Factor
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ABSTRACT: The catechol-O-methyl-transferase (COMT) gene has been linked to a wide spectrum of human phenotypes, including cognition, affective response, pain sensitivity, anxiety and psychosis. This study examined the modulatory effects of COMT Val158Met on neural interactions, indicated by connectivity strengths. Blood samples and resting state eyes-closed EEG signals were collected in 254 healthy young females. The COMT Val158Met polymorphism was decoded into 3 groups: Val/Val, Val/Met and Met/Met. The values of mutual information of 20 frontal-related channel pairs across delta, theta, alpha and beta frequencies were analyzed based on the time-frequency mutual information method. Our one-way ANOVA analyses revealed that the significant connection-frequency pairs were relatively left lateralized (P<0.01) and included F7-T3 and F7-C3 at delta frequency, and F3-F4, F7-T3, F7-C3, F7-P3, F3-C3, F3-F7 and F4-F8 at theta frequency. The F-test at F7-T3 and F7-C3 theta surpassed the statistical threshold of P<0.003 (after Bonferroni correction). For all the above connection-frequency pairs, there was a dose-dependent trend in the connectivity strengths of the alleles as follows: Val/Val>Val/Met>Met/Met. Our analyses complemented previous literature regarding neural modulation by the COMT Val158Met polymorphism. The implication to the pathogenesis in schizophrenia was also discussed. Further studies are needed to clarify whether there is gender difference on this gene-brain interaction.
Brain research 03/2011; 1377:21-31. · 2.46 Impact Factor
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ABSTRACT: Diagnosis and treatment rely on symptom criteria in modern psychiatry. However, the cortical mechanisms of symptomatology in major depressive disorder (MDD) are still not clear. This study examined neural correlates of symptom clusters of MDD by electroencephalography (EEG).
Resting state eye-closed EEG signals were recorded in 196 depressive patients. Quantitative EEG (qEEG) of regional power, coherence and power series correlation across delta, theta, alpha and beta frequencies were used to correlate with overall depression severity evaluated by the Hamilton Depression Rating Scale (HDRS). Further, statistical comparisons between patients with high vs. low qEEG indices (median-split) were undertaken regarding symptom severity of core depression, sleep, activity, psychic anxiety, somatic anxiety, and delusion.
None of the qEEG indices significantly correlated with overall depression severity or differentiated symptom severity of core depression, sleep, activity and psychic anxiety. A higher symptom severity of somatic anxiety was associated with higher regional power over widespread cortical regions and lower strengths at bi-temporal, temporo-parietal and fronto-parietal connections. A higher symptom severity of delusion was associated with higher regional power in the frontal and temporal regions, and lower strengths at inter-hemispheric (frontal, temporal and parietal) and fronto-temporo-parietal connections.
Our EEG recording with sampling rate of 128Hz and 20 electrodes may provide restricted spatial and temporal precision.
Our results suggest that cortical mechanisms play important roles in the symptom manifestation of cognitive distortion (sub-score of delusion) and somatic anxiety in MDD. Our findings further imply that psychic anxiety and somatic anxiety are distinct entities.
Journal of affective disorders 01/2011; 131(1-3):243-50. · 3.76 Impact Factor
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ABSTRACT: The serotonin transporter gene (5-HTT) is a key regulator of serotonergic neurotransmission and has been linked to various psychiatric disorders. Among the genetic variants, polymorphisms in the 5-HTT gene-linked polymorphic region (5-HTTLPR) and variable-number-of-tandem-repeat in the second intron (5-HTTVNTR) have functional consequences. However, their genetic impact on cortical oscillation remains unclear. This study examined the modulatory effects of 5-HTTLPR (L-allele carriers vs. non-carriers) and 5-HTTVNTR (10-repeat allele carriers vs. non-carriers) polymorphism on regional neural activity in a young female population.
Blood samples and resting state eyes-closed electroencephalography (EEG) signals were collected from 195 healthy women and stratified into 2 sets of comparisons of 2 groups each: L-allele carriers (N=91) vs. non-carriers for 5-HTTLPR and 10-repeat allele carriers (N=25) vs. non-carriers for 5-HTTVNTR. The mean power of 18 electrodes across theta, alpha, beta, gamma, gamma1, and gamma2 frequencies was analyzed. Between-group statistics were performed by an independent t-test, and global trends of regional power were quantified by non-parametric analyses.
Among 5-HTTVNTR genotypes, 10-repeat allele carriers showed significantly low regional power at gamma frequencies across the brain. We noticed a consistent global trend that carriers with low transcription efficiency of 5-HTT possessed low regional powers, regardless of frequency bands. The non-parametric analyses confirmed this observation, with P values of 3.071×10-8 and 1.459×10-12 for 5-HTTLPR and 5-HTTVNTR, respectively. CONCLUSIONS AND LIMITATIONS: Our analyses showed that genotypes with low 5-HTT activity are associated with less local neural synchronization during relaxation. The implication with respect to genetic vulnerability of 5-HTT across a broad range of psychiatric disorders is discussed. Given the low frequency of 10-repeat allele of 5-HTTVNTR in our research sample, the possibility of false positive findings should also be considered.
BMC Neuroscience 01/2011; 12:33. · 3.04 Impact Factor
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ABSTRACT: Late-onset major depression is thought to have a biological (vascular) basis, which could be a result of brain structure change. Vascular lesions can affect both the gray matter (GM) and white matter (WM), while most previous studies addressed WM abnormality. This study explored the disease- and symptom (history of suicide attempt) -related GM morphometry in elderly male patients with late-onset depression. A total of 70 patients with depression admitted to our geriatric psychiatric ward were investigated, and 26 age-matched males were recruited as controls. We used T1-weighted magnetic resonance imaging (MRI) to obtain cerebral structural information and adopted voxel-based morphometry (VBM) to investigate brain volume change related to disease (depression vs control) and symptom (depression with history of suicide attempt vs depression without history of suicide attempt). Late-onset depression was associated with smaller volumes in several regions of GM (insula and the posterior cingulate region) and WM (subcallosal cingulate cortex, floor of lateral ventricles, parahippocampal region, insula, and the cerebellum). Compared with nonsuicidal counterpart, suicidal depression was associated with decreased GM and WM volume in the frontal, parietal, and temporal regions, and the insula, lentiform nucleus, midbrain, and the cerebellum. Marked regional volume reduction was noticed at dorsal medial prefrontal cortex. Our results demonstrate that the development of suicidal behaviors in major depression is related to widespread but discrete volume reduction in several cortical and subcortical structures, fitting with the hypothesis that decreased cerebral volume in certain regions renders biological susceptibility to attempt suicide during depressive states.
Journal of Geriatric Psychiatry and Neurology 09/2010; 23(3):171-84. · 3.07 Impact Factor
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ABSTRACT: Previous studies have delineated the neural processes of motor response inhibition during a stop signal task, with most reports focusing on the cortical mechanisms. A recent study highlighted the importance of subcortical processes during stop signal inhibition in 13 individuals and suggested that the subthalamic nucleus (STN) may play a role in blocking response execution (Aron and Poldrack, 2006. Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci 26, 2424-2433). Here in a functional magnetic resonance imaging (fMRI) study we replicated the finding of greater activation in the STN during stop (success or error) trials, compared to go trials, in a larger sample of subjects (n=30). However, since a contrast between stop and go trials involved processes that could be distinguished from response inhibition, the role of subthalamic activity during stop signal inhibition remained to be specified. To this end we followed an alternative strategy to isolate the neural correlates of response inhibition (Li et al., 2006a. Imaging response inhibition in a stop signal task--neural correlates independent of signal monitoring and post-response processing. J Neurosci 26, 186-192). We compared individuals with short and long stop signal reaction time (SSRT) as computed by the horse race model. The two groups of subjects did not differ in any other aspects of stop signal performance. We showed greater activity in the short than the long SSRT group in the caudate head during stop successes, as compared to stop errors. Caudate activity was positively correlated with medial prefrontal activity previously shown to mediate stop signal inhibition. Conversely, bilateral thalamic nuclei and other parts of the basal ganglia, including the STN, showed greater activation in subjects with long than short SSRT. Thus, fMRI delineated contrasting roles of the prefrontal-caudate and striato-thalamic activities in mediating motor response inhibition.
NeuroImage 08/2008; 41(4):1352-63. · 5.89 Impact Factor
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ABSTRACT: The stop signal task (SST) is widely used to explore neural processes involved in cognitive control. By randomly intermixing stop and go trials and imposing on participants to respond quickly to the go but not the stop signal, the SST also introduces an indirect element of risk, which participants may avert by slowing down or ignore by responding "as usual," during go trials. This "risk-taking" component of the SST has to our knowledge never been investigated. The current study took advantage of variability of go trial reaction time (RT) and compared the post-go go trials that showed a decrease in RT (risk-taking decision) and those post-go go trials that showed an increase in RT ("risk-aversive" decision) in 33 healthy individuals who underwent functional magnetic resonance imaging during the SST. This contrast revealed robust activation in bilateral visual cortices as well as left inferior parietal and posterior cingulate cortices, amygdala, and middle frontal gyrus (P < 0.05, family-wise error [FWE] corrected). Furthermore, we observed that the magnitude of amygdala activity is positively correlated with trait anxiety of the participants. These results thus delineated, for the first time, a neural analog of risk taking during stop signal performance, highlighting a novel aspect and broadening the utility of this behavioral paradigm.
Cerebral Cortex 08/2008; 19(4):839-48. · 6.54 Impact Factor
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ABSTRACT: Emotional facial expressions can engender similar expressions in others. However, adaptive social and motivational behavior can require individuals to suppress, conceal, or override prepotent imitative responses. We predicted, in line with a theory of "emotion contagion," that when viewing a facial expression, expressing a different emotion would manifest as behavioral conflict and interference. We employed facial electromyography (EMG) and functional magnetic resonance imaging (fMRI) to investigate brain activity related to this emotion expression interference (EEI) effect, where the expressed response was either concordant or discordant with the observed emotion. The Simon task was included as a nonemotional comparison for the fMRI study. Facilitation and interference effects were observed in the latency of facial EMG responses. Neuroimaging revealed activation of distributed brain regions including anterior right inferior frontal gyrus (brain area [BA] 47), supplementary motor area (facial area), posterior superior temporal sulcus (STS), and right anterior insula during emotion expression-associated interference. In contrast, nonemotional response conflict (Simon task) engaged a distinct frontostriatal network. Individual differences in empathy and emotion regulatory tendency predicted the magnitude of EEI-evoked regional activity with BA 47 and STS. Our findings point to these regions as providing a putative neural substrate underpinning a crucial adaptive aspect of social/emotional behavior.
Cerebral Cortex 02/2008; 18(1):104-13. · 6.54 Impact Factor
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Shin-Yuan Chen,
Chao-Chin Lee,
Sheng-Huang Lin,
Yue-Long Hsin, Tien-Wen Lee,
Pao-Sheng Yen,
Yu-Cheng Chou,
Chi-Wei Lee,
Wanhua Annie Hsieh,
Chain-Fa Su,
Shinn-Zong Lin
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ABSTRACT: The contribution of MER to improving bilateral STN-DBS is debatable. To resolve the controversy and elucidate the role of MER in DBS, we compared the outcome of bilateral STN-DBS surgery with and without MER in parkinsonian patients.
From February 2002 to November 2002, the first 7 of 13 consecutive parkinsonian patients received STN-DBS without MER (group A), and the last 6 received STN-DBS with MER (group B). Pre- and postoperative assessments included scoring of UPDRS with video taping, and MR images.
The mean Hoehn and Yahr stage was 3.6 in group A and 4.0 in group B. The mean follow-up was 7.4 months for group A and 5.3 months for group B. The mean coordinates of the tip of the permanent electrode relative to the mid-commissural point were x = 8.1 mm, y = 4.3 mm, and z = 5.9 mm for group A and x = 10.6 mm, y = 4.1 mm, and z = 6.9 mm for group B. When levodopa was withdrawn from group A for 12 hours at follow-up, the postoperative UPDRS total score improved by 27.6% (P = .01) and the motor score by 25.4% (P = .02); their LEDD decreased by 17.5% (P = .03). In group B, the postoperative UPDRS total score improved by 49.3% (P = .00002) and the motor score by 45.2% (P = .0004); LEDD decreased by 48.5% (P = .01).
Although STN-DBS is a promising surgical modality for advanced parkinsonian patients, there is an inevitable learning curve associated with adopting this new procedure. Intraoperative MER is an effective way to ensure correct electrode placement in the STN. With the assistance of intraoperative MER, the outcome of STN-DBS can be improved significantly.
Surgical Neurology 04/2006; 65(3):253-60; discussion 260-1. · 1.67 Impact Factor
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ABSTRACT: Intentionally adopting a discrete emotional facial expression can modulate the subjective feelings corresponding to that emotion; however, the underlying neural mechanism is poorly understood. We therefore used functional brain imaging (functional magnetic resonance imaging) to examine brain activity during intentional mimicry of emotional and non-emotional facial expressions and relate regional responses to the magnitude of expression-induced facial movement. Eighteen healthy subjects were scanned while imitating video clips depicting three emotional (sad, angry, happy), and two 'ingestive' (chewing and licking) facial expressions. Simultaneously, facial movement was monitored from displacement of fiducial markers (highly reflective dots) on each subject's face. Imitating emotional expressions enhanced activity within right inferior prefrontal cortex. This pattern was absent during passive viewing conditions. Moreover, the magnitude of facial movement during emotion-imitation predicted responses within right insula and motor/premotor cortices. Enhanced activity in ventromedial prefrontal cortex and frontal pole was observed during imitation of anger, in ventromedial prefrontal and rostral anterior cingulate during imitation of sadness and in striatal, amygdala and occipitotemporal during imitation of happiness. Our findings suggest a central role for right inferior frontal gyrus in the intentional imitation of emotional expressions. Further, by entering metrics for facial muscular change into analysis of brain imaging data, we highlight shared and discrete neural substrates supporting affective, action and social consequences of somatomotor emotional expression.
Social Cognitive and Affective Neuroscience 02/2006; 1(2):122-35. · 6.13 Impact Factor
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ABSTRACT: To investigate the loudness dependence of the auditory evoked potential (LDAEP) in predicting response to treatment for major depression.
One hundred patients of Chinese ethnicity with major depression were divided into 2 groups, having strong or weak pretreatment LDAEP; the cutoff was the median of the LDAEP slope (for amplitude as a function of intensity). There were no between-group differences before treatment in terms of score on the Hamilton Depression Rating Scale (HDRS), age or sex distribution. The LDAEP for 4 intensity levels (60, 70, 80 and 90 dB) was recorded before treatment. Each patient then received fluoxetine 20 mg per day for 4 weeks. The response to treatment was evaluated by means of the HDRS.
At week 4, the HDRS score had declined by 44.3; for the group with strong LDAEP and by 34.4% for the group with weak LDAEP (t for mean difference = 2.584, p = 0.011).
Strong pretreatment LDAEP predicted a favourable response to treatment with a selective serotonin reuptake inhibitor in patients with major depression.
Journal of psychiatry & neuroscience: JPN 06/2005; 30(3):202-5. · 5.34 Impact Factor
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ABSTRACT: The relationship between function level and P300 has long been ignored and awaits clarification. Further, previous Western studies have discussed the trait/state markers of schizophrenic P300; this has not been assessed for an analogous Chinese population. P300 was recorded and compared in 153 schizophrenic patients and 101 normal controls. Reduced and delayed P300 was demonstrated for the schizophrenic group. Regression analysis was performed to determine the factors contributing to P300 amplitude and latency variation. Global Assessment of Functioning score and age had a significant influence on P300 latency prolongation. Amplitude decrement was not affected by age, duration of illness, education, psychotic status, antipsychotic dosage, or function level. Our results were grossly concordant with analogous Western reports and provided evidence that function level is an important variable contributing to P300 latency change in Chinese schizophrenics. Besides, the effect of gender on P300 amplitude was noted in normal population.
Neuropsychobiology 02/2005; 51(1):45-52. · 2.67 Impact Factor
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ABSTRACT: Serotonergic dysfunction is believed to be involved in suicide attempts. The loudness-dependent auditory evoked potential (LDAEP) is one of the validated indicators of the activity of the central serotonin system in humans.
This study was designed to investigate possible differences in the LDAEP and P300 between those depressed patients who attempted suicide and those who did not.
The LDAEP and P300 levels were recorded for 66 depressive patients (among which 16 had attempted suicide).
Those who had attempted suicide showed a sharper slope of the LDAEP and increased frontal P300 amplitude. A high correlation between the LDAEP and P300, and a gender difference were also noted. Conclusions: Our results are concordant with previous assumptions about serotonin dysfunction in depressives who attempt suicide.
Neuropsychobiology 02/2005; 52(1):28-36. · 2.67 Impact Factor
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ABSTRACT: Distinct clinical entities, with and without delusions, have been reported for depressed patients. This study explores the clinical and phenomenological aspects of delusional and non-delusional major depression in elderly Chinese patients.
A total of 156 depressed patients (105 males and 51 females) admitted to our geriatric psychiatry ward were investigated. Sociodemographic and clinical characteristics were compared between patients divided into two groups-according to presence or absence of delusions.
On admission, higher risk of suicide attempt, higher chance of guilt feelings, and greater daily functional impairment were observed for the deluded group. Further, the score of Hamilton Depression Rating Scale was higher and the score of Mini-Mental State Examination was lower for delusional depressives.
Our findings were grossly concordant with previous Western reports, and highlight the importance of identifying the delusional subgroup of depressive patients because of the higher risk of suicide attempt.
International Journal of Geriatric Psychiatry 07/2003; 18(6):486-90. · 2.42 Impact Factor
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ABSTRACT: Elderly psychiatric patients often present with psychotic symptoms that need antipsychotic treatment. Olanzapine is one of the atypical antipsychotics with efficacy for psychotic symptoms and a safer side-effect profile than typical antipsychotics. This study was conducted to assess the efficacy and safety of olanzapine for treatment of geriatric psychosis. The sample population comprised 94 acute-ward patients who were 65 years of age or older. Clinical assessment was conducted at baseline and also at 4 weeks after commencement of olanzapine treatment, with use of the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments. A 4-week therapeutic evaluation was completed for 80 patients, 73 of whom (91.3%) experienced mild to substantial improvement as determined from the CGI-I. A mean 52.6% reduction from baseline was also determined from the BPRS. The mean daily dosage of olanzapine in the fourth week was 10.1 +/- 5.3 mg/d (range, 2.5-20.0). Higher olanzapine dosages were administered for patients with functional psychoses than for an analogous group with organic mental disorders. Adverse effects were monitored for all 94 patients, the most common of which were somnolence (18.1%), dizziness (18.1%), and weakness of legs or bradykinesia (16.0%). Body weight and fasting triglyceride and sugar levels were significantly elevated after olanzapine treatment (2.2, 39.9, and 8.9% from baseline, respectively). It seems reasonable to suggest that olanzapine is efficacious for geriatric patients with psychosis and that the dosage should be diagnosis-dependent.
Journal of Clinical Psychopharmacology 05/2003; 23(2):113-8. · 4.10 Impact Factor
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ABSTRACT: Olanzapine, an atypical antipsychotic, is often regarded as a safe choice for psychosis management. We hereby report an aged case that presented with conscious depression, bradycardia, hypotension, miosis and hypothermia. Olanzapine was thought to be the offending agent. His condition improved with supportive therapy.
The International Journal of Psychiatry in Medicine 02/2003; 33(4):399-401. · 1.03 Impact Factor
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Journal of Psychiatric Research 38(6):637-8. · 4.66 Impact Factor
