Variant GADL1 and response to lithium therapy in bipolar I disorder.

BACKGROUND: Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. METHODS: We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. RESULTS: Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. CONCLUSIONS: Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

Cultural adaptation and validation of the Chinese version of the Fatigue Severity Scale in patients with major depressive disorder and nondepressive people.

PURPOSE: The aims of the study were to adapt the Fatigue Severity Scale to Chinese conditions and assess the psychometric properties of the Chinese version in patients with major depressive disorder (MDD) and nondepressive people. METHODS: A total of 101 patients with MDD and 94 nondepressive persons were included in this study. A forward and backward translation procedure was performed for developing a culturally acceptable Chinese version of the Fatigue Severity Scale (CFSS). Validity was assessed according to construct validity, internal consistency, concurrent validity, divergent validity, and contrasted-group validity. RESULTS: The CFSS exhibited a one-factor structure in patients with MDD and the nondepressive participants. A 7-item version of CFSS and an 8-item version of the CFSS demonstrated better model fit than the original 9-item version in the patients with MDD and the nondepressive participants, respectively. In both participant groups, internal consistency values were within acceptable ranges. In addition, concurrent validity and divergent validity were confirmed in both groups. The average CFSS score of patients with MDD was significantly higher than that of the nondepressive participants. CONCLUSION: The 9-item CFSS is a valid instrument for assessing fatigue-related impairment in Chinese-speaking patients with MDD. However, the two reduced-item CFSS versions showed better psychometric properties than the original version in the patients with MDD and the nondepressive participants.

White matter abnormalities of fronto-striato-thalamic circuitry in obsessive-compulsive disorder: A study using diffusion spectrum imaging tractography.

Previous studies have reported white matter abnormalities in patients with obsessive-compulsive disorder (OCD). This study aimed to further explore white matter abnormalities in OCD patients through diffusion spectrum imaging (DSI) and tractography of the two white matter tracts which most probably play an important role in OCD neuropathology: the anterior segment of cingulum bundles (ACB) and the anterior thalamic radiations (ATR). Twelve right-handed, medicated adult patients with OCD and 12 matched controls underwent DSI on a 3 tesla magnetic resonance imaging (MRI) system. Tractography based on DSI data was reconstructed to define the ACB and ATR. Mean generalized fractional anisotropy (GFA) was calculated for each targeted tract and was used to analyze local changes in microstructural integrity along individual tracts. There was a significantly lower mean GFA in both the right ATR and left ACB in OCD subjects compared to controls. OCD subjects also demonstrated decreased left-lateralized asymmetry of the ACB when compared to controls. Furthermore, the mean GFA of the left ACB positively correlated with OCD subjects' obsessive subscores on the Yale-Brown Obsessive-Compulsive scale. This study supports the white matter abnormalities in the ACB and ATR of OCD subjects, which corroborates neurobiological models that posit a defect in fronto-striato-thalamic circuitry in OCD.

[The efficacy of multi-sensory environment therapy on psychological, behavioral symptoms among elderly patients with dementia].

BACKGROUND: The treatment and care of demented elderly represents a major medical and social issue in Taiwan. Many empirical studies have demonstrated the efficacy of applying multi-sensory environment therapy to improve mood symptoms and reduce disturbed behavior frequencies among this population. While the technique has been widely applied in various clinical settings in the West, a study focusing on the treatment efficacy of multi-sensory environment therapy has yet to be conducted in Taiwan. PURPOSE: The purpose of the current study was to investigate the treatment efficacy of multi-sensory environment therapy on psychological and behavioral symptomatology among elderly patients with dementia. METHODS: This quasi-experimental study recruited 20 study participants from a nursing home in northern Taiwan. Treatment and control groups were arranged to contain 10 cases each. Participants were stratified by Mini-Mental State Examination (MMSE) score before random assignment to one of the two groups. The treatment group received a total of 24 sessions of multi-sensory environment therapy for 12 weeks. The control group received routine nursing home care. Researchers assessed treatment outcomes by comparing Neuropsychiatry Inventory (NPI) scores at baseline, week 6, and week 12, respectively. RESULTS: The experimental group showed a significant improvement over the control group on the NPI item "Motor Disturbance" at week 6. The experimental group scored significantly better than the control group on overall NPI score and on NPI items "Irritability or Liability" and "Motor Disturbance" after completion of the 12-week treatment regimen. CONCLUSIONS: Multi-sensory environment therapy helps improve behavioral and emotional symptoms in elderly patients with dementia. This technique may offer the potential to both improve the life quality of this population and reduce caretaker burdens.

Clinical Decision Path for Identifying Recurrent Falls in Late Middle-Aged and Older Patients With Chronic Schizophrenia.

BACKGROUND: Falls are a major hazard for elderly patients with schizophrenia. As patients with schizophrenia may experience a more-accelerated rate of physical aging than the overall elderly population, the risk of falls may emerge during the late middle-age period in this population. Furthermore, the risk of falls is affected by multiple, interrelated risk factors. PURPOSE: This study was undertaken to capture the complexity of the risk of falls in patients with schizophrenia. A cross-sectional approach was used to apply classification and regression tree (CART) analysis to generate a clinical decision path to identify the risk factors of recurrent falls in late middle-aged and older patients with schizophrenia. METHODS: Two hundred ninety-one patients aged 55 years or older were recruited from psychiatric halfway houses for assessment. Frailty, physical functional performance, depressive severity, cognitive function, and level of fatigue were measured, respectively, using the Study of Osteoporotic Fractures Frailty Index, Short Physical Performance Battery (SPPB), Center for Epidemiological Studies Depression Scale, Short Portable Mental Status Questionnaire (SPMSQ), and Chinese version of the Fatigue Severity Scale. The variables revealed by descriptive statistics to be statistically significant were further analyzed using CART analysis. RESULTS: The overall proportion of recurrent fallers in this study was 19.2%. CART analysis revealed eight end groups and identified four predictors: frailty, physical functional performance, cognitive function, and sex. The most prominent condition for recurrent fallers was frailty, present in 57.1% of the frail participants. In the nonfrail group (both prefrail and robust), participants with an SPPB score of less than 10 had a 29.7% chance of being a recurrent faller versus 13.6% for those with an SPPB score of 10 or more. Furthermore, an SPMSQ score of 7 was the next-best split among participants without frailty, with an SPPB score of 10 or more. Finally, among participants without frailty and with an SPPB score of 10 or more and an SPMSQ score of more than 7, the proportion of recurrent fallers was higher in women than men. CONCLUSIONS: The results of this study indicate that assessing frailty status may be an effective, first-step approach to identifying schizophrenic patients at an increased risk of recurrent falls. Among patients with prefrailty or robust status, an SPPB score cutoff of 10, an SPMSQ score cutoff of 7, and being female may be used sequentially to identify individuals at a heightened risk of recurrent falls.

The microstructural integrity of the corpus callosum and associated impulsivity in alcohol dependence: a tractography-based segmentation study using diffusion spectrum imaging.

Previous post-mortem and structural magnetic resonance imaging (MRI) studies in patients with alcohol dependence have demonstrated abnormalities of brain white matter. The present study investigated the microstructural integrity in the corpus callosum and the associations of this integrity with neurobehavioral assessments. Twenty-five male cases fulfilling the DSM-IV diagnosis of alcohol dependence and 15 male control subjects were scanned using a 3T MRI system. Callosal fiber tracts were reconstructed by diffusion spectrum imaging tractography and were subdivided into seven functionally distinct segments. The microstructural integrity was quantified in terms of generalized fractional anisotropy (GFA). Compared with normal subjects, men with alcohol dependence showed lower GFA values on all segments of the corpus callosum. The segment interconnecting the bilateral orbitofrontal cortices was the most affected. The score on the Barratt Impulsivity Scale showed an inverse relationship with GFA on the callosal fiber tracts connecting the bilateral orbitofrontal cortices. Furthermore, the duration of regular use was negatively associated with GFA on the callosal fiber tracts connecting the bilateral temporal and parietal cortices. Our findings suggest that a high self-rated impulsivity level was associated with low anisotropy in white matter of corpus callosum sectors extending to the orbitofrontal cortex.

The effects of gender and a co-occurring depressive disorder on neurocognitive functioning in patients with alcohol dependence.

AIMS: The present study aims to examine neuropsychological impairments by comorbidity and gender among patients with alcohol dependence. METHODS: The study sample is comprised of 123 subjects who fulfilled a Diagnostic and Statistical Manual of Mental Disorders 4th Edition (DSM-IV) diagnosis of alcohol dependence from January 2006 to December 2007. Subjects were asked to complete the following psychological tests: the Barratt Impulsivity Scale (BIS), Wechsler Adult Intelligence Scale, Wechsler Memory Scale and Color Trails Test. We compared the results of neuropsychological assessments based on two types of classifications: people with comorbid depression and people without comorbidity; females and males. RESULTS: The immediate visual memory and the BIS scores in patients with comorbid depression were significantly different from the scores in patients without comorbidity. In addition, females performed significantly poorer on the Working Memory Index than males and had a later age of regular drinking. CONCLUSIONS: Further investigation of the mechanism associated with the gender difference on cognition and exploration of the temporal relationship between alcohol dependence and depressive disorder on the cognitive aspect is needed.

Anxiety, depressive symptom and suicidal ideation of outpatients with obsessive compulsive disorders in Taiwan.

AIMS AND OBJECTIVES: The major aims of this study were to explore the differences in anxiety, depressive symptoms and suicidal ideation between high and low obsessive compulsive symptom groups, as well as predictors for suicidal ideation among outpatients with obsessive compulsive disorder. BACKGROUND: Obsessive compulsive disorder is often accompanied by anxiety, depression and even suicidal ideation. However, there have been very few studies exploring the inter-relationships among anxiety, depressive symptoms and suicidal ideation for patients with obsessive compulsive disorder. DESIGN: This study employed a cross-sectional comparative research design. METHODS: A sample of 128 outpatients with obsessive compulsive disorder was recruited from a medical teaching hospital in Northern Taiwan. The major study instruments included the Beck Anxiety Inventory, Beck Depression Inventory II, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Beck Scale for Suicide Ideation. We divided outpatients into two groups: outpatients with Y-BOCS scores higher than 15 were placed in the high obsessive compulsive symptom group, while outpatients with Y-BOCS score lower than or equal to 15 were placed in the low obsessive compulsive symptom group. Statistical methods included Pearson's product-moment correlation, independent samples t-test, chi-square test and multiple regressions. RESULTS: Results revealed that obsessive compulsive disorder outpatients with high Y-BOCS scores also had higher rates of being single and having an earlier onset age, poorer disease control, higher levels of anxiety, depressive symptoms and suicidal ideation. The predictors for suicidal ideation were anxiety and depressive symptoms. CONCLUSIONS: Obsessive compulsive disorder patients with higher obsessive compulsive symptoms are at greater risk of higher levels of anxiety, depressive symptoms and suicidal ideation. In addition to depression, anxiety symptoms contribute significantly to suicidal ideation among patients with obsessive compulsive disorder. RELEVANCE TO CLINICAL PRACTICE: Standard nursing care of patients with obsessive compulsive disorder should incorporate assessing levels of obsessive compulsive symptoms to identify the severity of anxiety, depressive symptoms and suicidal ideation more accurately.

Continuous performance test in drug-naïve patients with obsessive-compulsive disorder: a case-controlled study.

Twenty drug-naïve patients with obsessive-compulsive disorder (OCD) were compared with matched controls on their performance of the Continuous Performance Test (CPT). There was no difference on any measure of the CPT in the two groups. Higher obsession scores, rather than compulsion scores, were associated with poorer sensitivity of the CPT in drug-naïve OCD patients.

Effect of valproic acid on dementia onset in patients with bipolar disorder.

BACKGROUND: Valproic acid (VPA) is widely used for treating patients with bipolar disorder; however, it has adverse effects on cognitive function. This study investigated the effect of VPA on the risk of dementia in patients with bipolar disorder. METHODS: We analyzed data from Taiwan's Longitudinal Health Insurance Database 2010. Patients with bipolar disorder who were prescribed VPA for 28 days or at least once per month for 3 consecutive months after the index date were classified as the VPA-treated group, whereas those who did not receive VPA were classified as the VPA-untreated group. Both groups were tracked until the end of 2013 or until loss to follow-up to identify new-onset dementia events. Multivariable Cox proportional hazards models were used to estimate the hazard ratio (HR) of subsequent dementia associated with VPA treatment after adjustment for confounding variables. RESULTS: The study comprised 5158 patients with bipolar disorder. The multivariable-adjusted HR for newly diagnosed dementia was 1.73 (95% confidence interval [CI], 1.24-2.41, P=0.001) for the VPA-treated group compared with the VPA-untreated group after adjustment for potential confounders. The VPA-treated group had a higher risk than did the VPA-untreated group after propensity score adjustment (HR=1.95, 95% CI=1.42-2.67, P<0.001). LIMITATION: Certain variables that may affect the incidence of dementia were unavailable in the claims database and thus could not be considered. CONCLUSION: Treating bipolar disorder with VPA increases the risk of dementia by 73-95%.

Cardiovascular Reactivity in Patients With Major Depressive Disorder With High- or Low-Level Depressive Symptoms: A Cross-Sectional Comparison of Cardiovascular Reactivity to Laboratory-Induced Mental Stress.

Depression increases the risk of adverse cardiac events. Cardiovascular reactivity is defined as the pattern of cardiovascular responses to mental stress. An altered pattern of cardiovascular reactivity is an indicator of subsequent cardiovascular disease. Because depression and adverse cardiac events may have a dose-dependent association, this study examined the differences in cardiovascular reactivity to mental stress between patients with major depressive disorder (MDD) with high depression levels and those with low depression levels. Moreover, autonomic nervous system regulation is a highly plausible biological mechanism for the pattern of cardiovascular reactivity to mental stress. The association between cardiovascular reactivity and parameters of heart rate variability (HRV), an index for quantifying autonomic nervous system activity modulation, was thus examined. This study included 88 patients with MDD. HRV was measured before stress induction. The Stroop Color and Word Test and mirror star-tracing task were used to induce mental stress. We observed no significant association between depressive symptom level and any of the cardiovascular reactivity parameters. Cardiovascular reactivity to mental stress was comparable between patients with MDD with high-level depressive symptoms and those with low-level depressive symptoms. After adjusting for confounding variables, the high-frequency domain of HRV was found to be an independent predictor of the magnitude of heart rate reactivity (ß = -.33, p = .002). In conclusion, the magnitude of cardiovascular reactivity may be independent of depression severity in patients with MDD. The autonomic regulation of cardiovascular responses to mental stress primarily influences heart rate reactivity in patients with MDD.

Case-control study of suicide attempts in the elderly.

BACKGROUND: Prior studies have inadequately explored the relationship between late-life suicidal behavior and subclinical/clinical symptoms. This study aimed to assess the risk associated with subclinical symptoms, mild cognitive impairment and clinical factors among late-life suicide attempters. METHOD: Forty-three elderly patients aged 60 years and older who sought emergency services in a university-affiliated general hospital for attempting suicide and 43 comparison subjects participated in this study between March 2005 and December 2006. The comparison group was recruited by advertising in the community around the hospital. DSM-IV based diagnostic interview and screening instruments including the GDS, MMSE, BSRS-5 and APGAR were applied. Adjusted odds ratios were measured in the final multiple logistic regression model. RESULTS: Suicide attempters were more likely to meet a diagnosis of depressive disorder, after adjustments for BSRS-5 score and drinking habit. The adjusted odds of suicide among people with a BSRS-5 score of more than 5 points was 17.8 times higher than those with the BSRS score less than or equal to 5 points. CONCLUSIONS: Our findings support the significant impact on late-life suicidal behavior from the assessment of subclinical symptoms, including anxiety, depression, hostility, sleep condition and interpersonal symptoms. The assessment of subclinical symptoms by the BSRS-5 may help in the future prevention of late-life suicidal behavior in primary care settings.

Suicide by charcoal burning in Taiwan: implications for means substitution by a case-linkage study.

OBJECTIVE: This study estimated the incidence of suicide mortality among suicide attempters in Taiwan and assessed the extent of means substitution among subjects with a non-fatal attempt and a subsequent fatal attempt during the study period. METHODS: A total of 5,261 suicide attempters registered in a surveillance system of a metropolitan catchment area from 2004 to 2005 were followed through 2005. Linkage to the death certification system revealed that 72 died by suicide. The association of completed suicide with the suicide method used at index attempt was examined using Cox proportional hazards regression. Incidence rate for the subsequent lethal suicide was estimated based on life tables. RESULTS: The 1-year incidence rate of suicide mortality was 0.017: 0.026 in males and 0.013 in females. There was a strong association between burning charcoal as the method used at the index attempt (relative hazard = 4.1, P < 0.001) and completed suicides. Those who used the method of burning charcoal at the index attempt frequently used the same means in a subsequent attempt leading to suicide mortality. However, a majority of suicide completers (59.1%) who died by burning charcoal had used a different method at their index attempt. CONCLUSIONS: Persons who attempt suicide by charcoal burning are a high-risk group for completed suicide. Those who burned charcoal in a suicide attempt were likely to use the same method in a later lethal attempt, and charcoal burning was a frequent cause of death among those who used different methods in earlier attempts. Charcoal burning should be a target for suicide prevention efforts.

A review of the legislative mechanisms available to protect the social participation rights of people with depression in the Asia Pacific region.

OBJECTIVE: To conduct a review of the legislative mechanisms potentially available to protect the social participation rights of people with depression in the Asia Pacific region. METHODS: Questions were sent to the SEBoD International Advisory Board and Internet and legal database searches were conducted to supplement responses from advisors. RESULTS: While it cannot be said that comprehensive antidiscrimination legislation in relation to disability exists in all countries in the Asia Pacific region, most countries have commenced the process. Many have implemented either human rights or antidiscrimination legislation and most have set up a Human Rights Commission to protect social participation rights and allow complaints to be lodged. CONCLUSIONS: This review highlighted the difference between legislation and practice. While many countries have enacted laws, insufficient resources have been committed to support the objectives to realise the protection of rights enshrined in legislation. Additionally, many people may not know that the laws exist or do not have the money or social supports to fight for their rights. Many countries, however, have commenced a concerted approach to tackling the larger issues and have developed comprehensive action plans to address the social participation rights of people with disability.