Jen-Ping Hwang

The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.

Cortical and Subcortical Abnormalities in Late-Onset Depression With History of Suicide Attempts Investigated With MRI and Voxel-Based Morphometry

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.

Hoarding Behavior in Dementia: A Preliminary Report

Hoarding behavior has been reported in several mental disorders and is occasionally reported by the caregivers of dementia patients. Such behavior may have adverse effects on the patients and increase the burden of the caregivers. This study was conducted to investigate the prevalence of hoarding behavior in patients with dementia and identify the characteristics and psychiatric symptoms associated with it. The sample was 133 dementia patients admitted to a geropsychiatric ward. Of the 133 dementia patients, 30 (22.6%) showed hoarding. Hoarding was found in various types of dementia. Patients with hoarding had a higher prevalence of repetitive behaviors, hyperphagia, and pilfering. Results suggested that hoarding behavior is a common symptom in dementia patients and a complex phenomenon. Better understanding of the underlying pathogenesis may highlight specific pharmacological or behavioral methods for treatment of the behavior.

Cognitive and neuropsychiatric correlates of EEG dynamic complexity in patients with Alzheimer's disease.

This study assessed the utility of multiscale entropy (MSE), a complexity analysis of biological signals, to identify changes in dynamics of surface electroencephalogram (EEG) in patients with Alzheimers disease (AD) that was correlated to cognitive and behavioral dysfunction. A total of 108 AD patients were recruited and their digital EEG recordings were analyzed using MSE methods. We investigate the appropriate parameters and time scale factors for MSE calculation from EEG signals. We then assessed the within-subject consistency of MSE measures in different EEG epochs and correlations of MSE measures to cognitive and neuropsychiatric symptoms of AD patients. Increased severity of AD was associated with decreased MSE complexity as measured by short-time scales, and with increased MSE complexity as measured by long-time scales. MSE complexity in EEGs of the temporal and occipitoparietal electrodes correlated significantly with cognitive function. MSE complexity of EEGs in various brain areas was also correlated to subdomains of neuropsychiatric symptoms. MSE analysis revealed abnormal EEG complexity across short- and long-time scales that were correlated to cognitive and neuropsychiatric assessments. The MSE-based EEG complexity analysis may provide a simple and cost-effective method to quantify the severity of cognitive and neuropsychiatric symptoms in AD patients.

Gene-gene interactions of the brain-derived neurotrophic-factor and neurotrophic tyrosine kinase receptor 2 genes in geriatric depression.

Brain-derived neurotrophic-factor (BDNF) and its receptor neurotrophic tyrosine kinase receptor 2 (NTRK2) have been implicated in both major depression and cognitive function. This study examines the main effects of single loci and multilocus interactions to test the hypothesis that the BDNF and NTRK2 genes may contribute to the etiology of geriatric depression independently and/or through complex interactions. We genotyped the BDNF gene Val66Met (rs6265) polymorphism and four single-nucleotide polymorphisms (SNPs) (including rs1187323, rs1187329, rs1778929, and rs1545285) in the NTRK2 gene in 155 elderly inpatients diagnosed with major depression and 195 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. The genotype distributions of all five SNPs tested were significantly different between depressed patients and control subjects. BDNF rs6265, NTRK2 rs1187323, and NTRK2 rs1778929 (p = 0.0031, 0.002, and 0.0014, respectively) also displayed statistically significant differences in the genotypic tests after Bonferroni correction (p < 0.05/5 = 0.01). In addition, the 2-marker haplotype derived from the rs1187323 and rs1187329 polymorphisms demonstrated a significant difference between geriatric depression and control groups according to haplotype distribution (global p = 0.003). Furthermore, BDNF and NTRK2 interactions were found in the significant 2-locus, 3-locus, 4-locus, and 5-locus gene-gene interaction models (p = 0.014, <0.001, 0.007, and 0.032, respectively) using a generalized multifactor dimensionality reduction (GMDR) method. Analyses using logistic regression models confirmed the gene-gene interactions. The results suggest that the BDNF and NTRK2 genes may contribute to the risk of geriatric depression independently and in an interactive manner.

Behavioural disturbances in psychiatric inpatients with dementia of the Alzheimer's type in Taiwan

This report studied behavioural disturbances in psychiatric inpatients with dementia of the Alzheimers type (DAT) in Taiwan. The sample consisted of 75 inpatients with DAT who were consecutively admitted to the geropsychiatric ward. Their behavioural disturbances were obtained from semistructured interviews with families and ward observation. There were eight main behavioural disturbances: getting lost, repetitive phenomena, sleep disturbance, aggression, wandering, hyperphagia, hoarding behaviour, and inappropriate sexual behaviour. Number of behavioural disturbances, wandering, hyperphagia and sleep disturbance were significantly associated with the severity of cognitive impairment.

Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression.

Apolipoprotein E (APOE) has been associated with a variety of late-life neuropsychiatric disorders, including geriatric depression. This study determined whether APOE genotypes affect vulnerability to geriatric depression. We also tested the effect of the presence of the APOE Ε4 (APOE4) allele on age of onset, suicide attempt history and cognitive function in geriatric depressed patients. We genotyped APOE in 111 elderly inpatients diagnosed as having major depression and 144 normal controls. The depressed patients were evaluated at baseline using the Hamilton Rating Scale for Depression and the Mini-Mental State Examination (MMSE) after admission. Age of onset of depression and suicide attempt history in the depressed group were evaluated by interview and medical record. We found no association between APOE genotypes and geriatric depression (p = 0.342) or APOE4 status and age of onset of depression (p = 0.281). However, compared with depressed subjects lacking the APOE Ε4 allele, depressed subjects who were also APOE4 carriers showed significantly lower MMSE scores (p = 0.021) and an increased suicide attempt history (p = 0.012). The APOE genotype may contribute to cognitive performance and suicidality in geriatric depression, rather than being a specific risk factor for the disorder.

Association of CHRNA4 polymorphism with depression and loneliness in elderly males

The cholinergic receptor, nicotinic, alpha 4 (CHRNA4) gene encodes the neuronal nicotinic acetylcholine receptor alpha‐4 subunit. Recent research has shown that a variation in CHRNA4 (rs1044396) affects attention and negative emotionality in normal adults. To determine the link between CHRNA4 variation and cognitive function/depressed mood, this study conducted a genotype–phenotype correlation analysis between the common CHRNA4:rs1044396 variant and several baseline parameters of cognition and depressed mood in 192 elderly male subjects without major psychiatric disorders or dementia. Study findings identified a significant link between the CHRNA4:rs1044396 polymorphism and depression and loneliness in the aged. Compared to carriers of at least one T‐allele, carriers of the homozygous C/C genotype described themselves as more depressed and lonely. This is the first evidence which may implicate CHRNA4 in depressed emotions in the elderly.

Heterozygote advantage of the MTHFR C677T polymorphism on specific cognitive performance in elderly Chinese males without dementia.

Aims: Aging is associated with cognitive deterioration, and genetic factors are implicated in individual cognitive differences in the aged. The C677T mutation in the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) yields a common thermolabile variant (T) with reduced enzyme activity and consequent elevation of serum homocysteine concentrations. We designed the present study to investigate whether this functional polymorphism may affect global and specific cognitive functions in older Chinese males without dementia. Methods: The subjects included 356 elderly males without major psychiatric disorders or dementia, who were assessed by the Cognitive Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests. Results: A significant association was found between the MTHFR C677T polymorphism and total CASI scores (p = 0.012), particularly in short-term memory (p = 0.002) and concentration/mental manipulation (p = 0.007). Post hoc tests indicated that the C/T heterozygotes achieved better cognitive function test results than C/C or T/T carriers. No association was found between the MTHFR genotype and the Wechsler Digit Span Task tests. Conclusion: These results suggest that a heterozygote advantage exists for the MTHFR C677T polymorphism in specific cognitive functions in elderly Chinese males without dementia.

The efficacy and safety of quetiapine for treatment of geriatric psychosis

Quetiapine, an atypical antipsychotic, is effective for psychosis in younger patients, with limited adverse effects reported. This open-label naturalistic study was conducted to assess the 4-week efficacy and safety of quetiapine for treatment of geriatric psychosis. Clinical efficacy was evaluated using the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression Improvement (CGI-I) instruments before and after 4 weeks of quetiapine treatment. The sample population consisted of 100 geropsychiatric inpatients with psychosis, with the therapeutic evaluation completed by 91. Eighty-one of these 91 patients (89.0%) experienced mild-to-substantial improvement, as determined from the CGI-I. Further, a mean reduction in BPRS score of 39.5% (from baseline) was also determined. The mean daily dose of quetiapine for the fourth week was 276.1 177.2mg/day (range 50-800). Higher quetiapine dosages were administered for patients with functional psychoses compared to an analogous group with organic mental disorders. The most common adverse effects were somnolence (30.0%), lower-limb weakness (28.0%) and dizziness (27.0%). Body weight and fasting triglyceride were significantly elevated after quetiapine treatment (2.2% and 8.9% from baseline, respectively). Based on the results of this study, it appears that quetiapine is an efficacious and safe treatment for geriatric inpatients with psychosis, however, there is a wide dosing range and optimal dosage is diagnosis-dependent.