Excess Mortality in Individuals with Autism Spectrum Disorder: A Population-Based Cohort Study.

Purpose: Autism spectrum disorder (ASD) may be associated with increased mortality, but relevant findings have been inconsistent. The modifying effects of gender and intellectual disability on excess mortality in individuals with ASD are underexplored. Patients and Methods: Using Taiwan's National Health Insurance Research Database and the National Death Registry, this population-based cohort study selected the data of 75,946 patients with ASD (ASD cohort) and 75,946 age group-, gender-, and income-matched (1:1) patients without ASD (non-ASD cohort). Cox proportional hazards models were used to compare mortality rates between the cohorts, and stratified analyses were used to evaluate the influence of gender and intellectual disability on mortality risk. Results: The ASD cohort had higher mortality rates for all causes of death than did the non-ASD cohort (adjusted hazard ratio 1.64, 95% confidence interval 1.54-1.75). Comorbid intellectual disability was associated with an increased risk of mortality, and this association was stronger in female patients than in male patients. Moreover, when focusing on deaths from natural causes, we found a significantly higher odds ratio for mortality in the ASD population with ID compared to those without ID. Conclusion: ASD is associated with increased mortality, especially among female individuals and those with intellectual disability.

Investigating the effect of hypertension on vascular cognitive impairment by using the resting-state functional connectome.

Hypertension (HTN) affects over 1.2 billion individuals worldwide and is defined as systolic blood pressure (BP) ≥ 140 mmHg and diastolic BP ≥ 90 mmHg. Hypertension is also considered a high risk factor for cerebrovascular diseases, which may lead to vascular cognitive impairment (VCI). VCI is associated with executive dysfunction and is also a transitional stage between hypertension and vascular dementia. Hence, it is essential to establish a reliable approach to diagnosing the severity of VCI. In 28 HTN (51-83 yrs; 18 males, 10 females) and 28 healthy controls (HC) (51-75 yrs; 7 males, 21 females), we investigated which regions demonstrate alterations in the resting-state functional connectome due to vascular cognitive impairment in HTN by using the amplitude of the low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and network-based statistic (NBS) methods. In the group comparison between ALFF/ReHo, HTN showed reduced spontaneous activity in the regions corresponding to vascular or metabolic dysfunction and enhanced brain activity, mainly in the primary somatosensory cortex and prefrontal areas. We also observed cognitive dysfunction in HTN, such as executive function, processing speed, and memory. Both the GTA and NBS analyses indicated that the HTN demonstrated complex local segregation, worse global integration, and weak functional connectivity. Our findings show that resting-state functional connectivity was altered, particularly in the frontal and parietal regions, by hypertensive individuals with potential vascular cognitive impairment.

Neuropsychiatric and cognitive symptoms in people with hypertension: An examination with the NINDS-CSN consensus protocol.

Hypertension has been associated with risk of cognitive impairments. The American Heart Association recommended the use of the harmonized neuropsychological protocol suggested by the National Institute of Neurologic Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN) for studying related cognitive impairments. Initially designed for vascular cognitive impairment, empirical data of results from NINDS-CSN protocol has not been well-established in hypertension. The present study recruited 58 adults diagnosed with hypertension and 44 normotensive controls. Tests from the NINDS-CSN protocol were given in three lengths, including neuropsychological tests and neuropsychiatric inventories. The results showed higher proportions of hypertensive adults with impairments on tests of memory and executive functions and that they performed worse as a group on several tests from the 30-minute protocol, but not on the other additional tests in the full-length version, nor on cognitive screening test in the 5-minute protocol such as the Mini-Mental State Examination or the Montreal Cognitive Assessment. There was no significant group difference on neuropsychiatric symptoms. These findings suggested that the 30-minute version of the NINDS-CSN protocol with the two supplemental tests was able to reveal selective cognitive deficits in hypertensive adults and provide a practical solution for related studies, balancing between the requirement of sensitivity, domain variety, and brevity.

Association Between Emotional Disorders and Speech and Language Impairments: A National Population-Based Study.

Anxiety and depression are common emotional problems in children and adolescents. This study used a long-term tracking large database to investigate whether the proportion of children who were diagnosed with speech and language impairments were later diagnosed with anxiety or depression were significantly greater than that of matched group of the same age and gender without speech and language impairments. More than 4300 eligible children with speech and language impairments and matched controls were identified and assessed for anxiety and depression. The risk of anxiety and depressive disorders in children with speech and language impairments were examined with Cox regression analyses and adjusting for covariables (gender, age, and comorbidities). The results showed that speech and language impairments were positively associated with anxiety disorders (adjusted hazard ratio [AHR] 2.87, 95% confidence interval [CI] 2.20-3.76) and depressive disorders (AHR 2.51, 95% CI 1.52-4.13). The number of boys with speech and language impairments was more than twofold that of girls, but boys did not different from girls in the risk of anxiety disorders (AHR 0.95, 95% CI 0.75-1.20) and depressive disorders (AHR 0.72, 95% CI 0.47-1.11). Infantile autism and intellectual disabilities were positively associated with anxiety (AHR 1.54, 95% CI 1.07-2.21; AHR 1.47, 95% CI 1.09-1.98), and the latter was positively associated with depression (AHR 1.83, 95% CI 1.06-3.17). In addition to speech and language impairments interventions, our findings supported the necessity of identification and interventions in anxiety and depressive disorders among children with speech and language impairments from elementary school until youth.

Association between enterovirus infection and speech and language impairments: A nationwide population-based study.

BACKGROUND AND AIMS: Delay and impairment in Speech and language are common developmental problems in younger populations. Hitherto, there has been minimal study of the association between common childhood infections (e.g. enterovirus [EV]) and speech and language. The impetus for evaluating this association is provided by evidence linking inflammation to neurodevelopmental disorders. Herein we sought to determine whether an association exists between EV infection and subsequent diagnoses of speech and language impairments in a nationwide population-based sample in Taiwan. METHODS: Our study acquired data from the Taiwan National Health Insurance Research Database. The sample was comprised of individuals under 18 years of age with newly diagnosed EV infection during the period from January 1998 to December 2011. 39669 eligible cases were compared to matched controls and assessed during the study period for incident cases of speech and language impairments. Cox regression analyses were applied, adjusting for sex, age and other physical and mental problems. RESULTS: In the fully adjusted Cox regression model for hazard ratios, EV infection as positively associated with speech and language impairments (HR = 1.14, 95% CI: 1.06-1.22) after adjusting for age, sex and other confounds. Compared to the control group, the hazard ratio for speech and language impairments was 1.12 (95% CI: 1.03-1.21) amongst the group of EV infection without hospitalization, and 1.26 (95% CI: 1.10-1.45) amongst the group of EV infection with hospitalization. CONCLUSIONS: EV infection is temporally associated with incident speech and language impairments. Our findings herein provide rationale for educating families that EV infection may be associated with subsequent speech and language problems in susceptible individuals and that monitoring for such a presentation would be warranted. WHAT THIS PAPER ADDS?: Speech and language impairments associated with central nervous system infections have been reported in the literature. EV are medically important human pathogens and associated with select neuropsychiatric diseases. Notwithstanding, relatively few reports have mentioned the effects of EV infection on speech and language problems. Our study used a nationwide longitudinal dataset and identified that children with EV infection have a greater risk for speech and language impairments as compared with control group. Infected children combined other comorbidities or risk factors might have greater possibility to develop speech problems. Clinicians should be vigilant for the onset of language developmental abnormalities of preschool children with EV infection.

The association between Mycoplasma pneumoniae infection and speech and language impairment: A nationwide population-based study in Taiwan.

Manifestations of Mycoplasma pneumoniae infection can range from self-limiting upper respiratory symptoms to various neurological complications, including speech and language impairment. But an association between Mycoplasma pneumoniae infection and speech and language impairment has not been sufficiently explored. In this study, we aim to investigate the association between Mycoplasma pneumoniae infection and subsequent speech and language impairment in a nationwide population-based sample using Taiwan's National Health Insurance Research Database. We identified 5,406 children with Mycoplasma pneumoniae infection (International Classification of Disease, Revision 9, Clinical Modification code 4830) and compared to 21,624 age-, sex-, urban- and income-matched controls on subsequent speech and language impairment. The mean follow-up interval for all subjects was 6.44 years (standard deviation = 2.42 years); the mean latency period between the initial Mycoplasma pneumoniae infection and presence of speech and language impairment was 1.96 years (standard deviation = 1.64 years). The results showed that Mycoplasma pneumoniae infection was significantly associated with greater incidence of speech and language impairment [hazard ratio (HR) = 1.49, 95% CI: 1.23-1.80]. In addition, significantly increased hazard ratio of subsequent speech and language impairment in the groups younger than 6 years old and no significant difference in the groups over the age of 6 years were found (HR = 1.43, 95% CI:1.09-1.88 for age 0-3 years group; HR = 1.67, 95% CI: 1.25-2.23 for age 4-5 years group; HR = 1.14, 95% CI: 0.54-2.39 for age 6-7 years group; and HR = 0.83, 95% CI:0.23-2.92 for age 8-18 years group). In conclusion, Mycoplasma pneumoniae infection is temporally associated with incident speech and language impairment.

Incidence and risk factors of poststroke depression in patients with acute ischemic stroke: A 1-year prospective study in Taiwan.

BACKGROUND: Poststroke depression (PSD) is one of the most frequent and devastating neuropsychiatric consequences of stroke. The purpose of this study was to investigate the incidence and risk factors for PSD in a general hospital in Taiwan. METHODS: One hundred and one patients with ischemic stroke were enrolled initially, and 91 (90.1%) completed the 1-year study. Assessments were performed at baseline, and at the 1st, 3rd, 6th, 9th, and 12th month after enrolment. The definition of PSD was in accordance with the diagnostic criteria of major depressive episode in the Diagnostic and Statistical Manual, fourth edition (DSM-IV). RESULTS: The accumulated incidence rates of PSD at the 1st, 3rd, 6th, and 9th, month were 4%, 8%, 9%, and 10%, respectively, and the overall incidence at 1 year was 11%. In multivariate regression analysis, female gender, higher depression score, and severity of stroke were significant risk factors. In subgroup analysis, a higher depression score was significantly associated with PSD, regardless of gender; however, stroke severity was a risk factor only in the female group. CONCLUSION: The 1-year incidence of PSD was 11%, based on the DSM-IV diagnostic criteria. More attention should be paid to patients with more risk factors to enable earlier detection and intervention.

Three-year mortality rate of suicide attempters in consultation-liaison service.

OBJECTIVE: Suicide attempters might be sent to the emergency room for urgent medical intervention. Some with more severe physical morbidity may be hospitalised, and psychiatrists might be consulted for suicide evaluation. The aim of our study was to investigate the three-year all-cause mortality rate of hospitalised suicide attempters with regard to the effect of consultation-liaison services, and to identify any risk factors associated with mortality. METHODS: Between 2002 and 2006, 196 inpatients from medical or surgical wards in a general hospital who had consulted psychiatrists because of suicide attempts were collected consecutively. We traced their mortality incidence during a three-year period, and calculated the mortality rate and time (days) to death. RESULTS: Three-year all-cause mortality was 20.4%, and there was a higher risk of mortality in the first two years after the index suicide attempt. In the adjusted Cox regression model, associated risks included male gender, older age, diagnosis of depressive disorders and lack of psychiatric follow-up. CONCLUSIONS: We found that hospitalised suicide attempters had higher all-cause mortality after discharge, and determined that psychiatric follow-up is helpful. More attention should be paid to those with potential risk factors, and timely intervention is suggested in order to reduce mortality.

The Role of Alexithymia in the Incidence of Poststroke Depression.

Poststroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke, and alexithymia is a construct characterized by the inability to identify and describe emotions. Our study aimed to determine whether alexithymia is a risk factor for the development of PSD. Patients with ischemic stroke admitted to a general teaching hospital were enrolled in this 6-month study. The patients were evaluated with the Toronto Alexithymia Scale-20 (TAS-20), Beck Anxiety Inventory (BAI), National Institute of Health Stroke Scale (NIHHS), and Mini-Mental Status Examination at baseline and then followed up each month for detection of PSD using the Center for Epidemiologic Studies of Depression scale. In all, 285 patients with ischemic stroke were enrolled, and 93.3% completed the 6-month study. The overall incidence of PSD within 6 months was 16.5%. In multivariate regression analyses, the incidence of PSD was significantly associated with higher BAI, higher NIHSS, and higher TAS-20 scores. In conclusion, our study highlights the importance of alexithymic symptoms as a risk factor for PSD.

Comparison of consecutive periods of 1-, 2-, and 3-year mortality of geriatric inpatients with delirium, dementia, and depression in a consultation-liaison service.

OBJECTIVES: Dementia, depression, and delirium are the most prevalent psychiatric disorders in elderly medical inpatients and are all associated with higher mortality. The purpose of this study was to assess and compare consecutive periods of 1-, 2-, and 3-year mortality among elderly patients with dementia, depression, and delirium seen by a psychiatry consultation-liaison service in a general hospital. METHODS: We consecutively enrolled inpatients 65 years of age and older that were referred for psychiatric consultation (N = 614) from 2002 to 2006: 172 were diagnosed with delirium, 92 with dementia, and 165 with depression. The 1-, 2-, and 3-year mortality rates for the three groups of patients were compared by log-rank test. The Cox proportional hazard regression model was used to identify any possible factors associated with mortality during the study period. RESULTS: Only 1-year mortality in the delirium group was significantly higher than that in the depression group (p < 0.05), but there was no significant difference among the three groups in 2- and 3-year mortality. In terms of gender, higher mortality was identified only in depressed male patients. Furthermore, male, older age, and longer length of hospital stay, but not multiple physical comorbidities, were associated with higher mortality. CONCLUSION: Clinical physicians should give special attention to delirious patients within the first year after referral. Patients at risk for mortality should be closely followed and early intervention provided in an effort to decrease or delay mortality.

One-year mortality of elderly inpatients with delirium, dementia, or depression seen by a consultation-liaison service.

BACKGROUND: Delirium, dementia and depression are the most prevalent mental disorders in elderly patients, and are associated with higher mortality. OBJECTIVE: The purpose of this study was to assess 1-year mortality among elderly patients with delirium, dementia, or depression seen by a psychiatry consultation-liaison service in a general hospital. METHODS: We consecutively enrolled inpatients 65 years of age and older who were referred for psychiatric consultation (n = 614) from 2002 to 2006: 172 were diagnosed with delirium, 92 with dementia, and 165 with depression. The 1-year mortality rates for the three groups of patients were compared by log-rank test. Logistic regression analysis was used to identify any possible factors associated with mortality. RESULTS: One-year mortality was significantly higher in the delirium group than in the depression group (p = 0.048), but not significantly different between the delirium and dementia groups (p = 0.206), or dementia and depression groups (p = 0.676). Male patients had a higher mortality rate than female patients in the depression group (p = 0.003), but there was no gender difference in the delirium and dementia groups. Furthermore, the 1-year mortality of all patients was significantly associated with older age (p < 0.001) and length of hospital stay (p < 0.001), but not with gender difference and multiple physical comorbidities. CONCLUSION: These results suggest that elderly inpatients with delirium seen by a psychiatric consultation service have significantly higher mortality than elderly inpatients with depression, and that mortality is significantly associated with older age and length of hospital stay.

Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis.

BACKGROUND: Abnormalities in brain monoamine transmission have been implicated in the pathogenesis of suicidal behavior. Studies examining the association between monoamine oxidase A (MAOA)-uVNTR polymorphism and suicide revealed inconsistent findings. This study aims to evaluate the possible association between the MAOA-uVNTR polymorphism and suicidal behaviors by examining our own subjects and conducting a meta-analytic review. METHODS: 373 unrelated psychiatric patients (including 160 suicide attempters and 213 non-suicide attempters) were genotyped for the MAOA-uVNTR polymorphism. A meta-analysis was then performed by pooling data from seven case-control association studies by random effects model. RESULTS: Our results indicate that there is no association between the MAOA-uVNTR polymorphism and suicide attempts in both genders. It also reveals that there is no association with violent suicide attempts. In the meta-analysis, there is no association between the polymorphism and suicidal behaviors. Also, there is no difference in the allelic distribution between psychiatric patients with and without suicidal behaviors. Limitations Our study was constrained by the insufficient information about environmental risk factors of suicide. CONCLUSIONS: Our study is the first one to use meta-analysis in exploring the role of the MAOA-uVNTR polymorphism in suicidal behavior in psychiatric patients. No significant association was found in our study, suggesting MAOA-uVNTR polymorphism is unlikely to contribute significantly to suicide behavior. Further studies investigating the gene-environment interaction or focusing on the genetic risk factors of endophenotypes of suicidal behaviors are warranted.

Three-year mortality of delirium among elderly inpatients in consultation-liaison service.

OBJECTIVE: The purpose of this study is to assess 3-year mortality in delirious patients receiving consultation-liaison service in a general hospital setting. METHODS: We consecutively enrolled inpatients 65 years of age and older that were referred for psychiatric consultation (N=614) from 2002 to 2006. One hundred and seventy-two patients were diagnosed with delirium. The exact date of death was based on the registration data from the Department of Health, Executive Yuan, in Taiwan and was used to calculate the mortality rate and time to death (days) after psychiatric consultation. Furthermore, the 1-year, 2-year and 3-year mortality rates of delirious patients were compared to mortality rates of nondelirious patients. Factors (e.g., age, length of hospital stay, gender, physical illness, use of antipsychotics) were analyzed by using the Cox proportional hazard model to identify possible associations with mortality. RESULTS: Delirious patients had a higher mortality rate each year than nondelirious patients. After analysis, 1-year mortality was significantly higher in the delirious group than in the nondelirious group (P=.043), but 2-year and 3-year mortality rates were not significantly different when comparing the delirious and nondelirious groups (P=.149; P=.439). In the Cox proportional hazard regression analysis, 1-year mortality in delirious patients was significantly associated with older age and length of hospital stay (P<.001), but not with gender, physical comorbidity or use of antipsychotics. CONCLUSION: These results suggest that elderly delirious inpatients in psychiatric consultation service had significantly higher mortality than nondelirious inpatients, especially in the first year after consultation. Clinical physicians should pay close attention to delirious patients, especially those with mortality-related risk factors, in order to reduce mortality in these patients.

Cytokine changes in the pathophysiology of poststroke depression.

OBJECTIVE: Poststroke depression (PSD) is a frequent psychiatric sequela after stroke, and its influence is detrimental. However, the etiology of PSD is still not clear. Although many studies have indicated that immune dysregulation plays an important role in the pathophysiology of depression, it is still unknown if PSD involves the same mechanism. Thus, the current study objectives were to evaluate whether there were cytokine changes when patients with ischemic stroke suffered from PSD. METHOD: We included ischemic stroke patients without depression when the stroke occurred and followed them for 1 year. The Hamilton Depression Rating Scale score and cytokines were assessed at baseline and at the 1st, 3rd, 6th, 9th and 12th months after stroke. RESULTS: One hundred four patients with ischemic stroke participated and completed the study, and 12 suffered from PSD during the 1-year study period. There were significant increases in the cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor α (TNF-α) and interferon-γ, and the ratios of IL-6/IL-10 and TNF-α/IL-10 were also elevated. Interleukin-1ß was too low to show any difference. CONCLUSION: Our study suggested that immune imbalance plays a possible role in the pathophysiology of PSD and that IL-6 and TNF-α are key cytokines.

Change in accuracy of recognizing psychiatric disorders by non-psychiatric physicians: five-year data from a psychiatric consultation-liaison service.

AIM: Psychiatric disorders are easily underestimated and under-recognized by physicians. The aim of the present study was to investigate the change in accuracy of recognizing psychiatric symptoms. METHODS: Consecutive 5-year consultation-liaison data were collected and patients with one of the five common psychiatric diagnoses, including depressive disorders, substance use disorders, delirium, anxiety disorders and psychotic disorders, were chosen for analysis. The primary care physician's initial impression of a psychiatric diagnosis was recorded based on their reason for referral on the referral sheets. Accurate recognition was defined as matching of the physician's initial impression with the psychiatrist's final diagnosis. Mentioning the core symptoms of psychiatric diagnostic criteria or common synonyms would be considered as correct recognition. RESULTS: The overall accuracy of recognition was 41.5% and there was no significant change during this 5-year period. Substance use disorders were the one diagnosis with the highest agreement, followed by delirium, depressive disorders, anxiety disorders, and psychotic disorders. As for the factors associated with accurate recognition, male patients or those with multiple physical illnesses were more likely to have their psychiatric symptoms recognized correctly. CONCLUSIONS: Without comprehensive postgraduate psychiatric education, the accuracy of recognizing psychiatric symptoms does not improve year by year. Education should focus on common psychiatric problems among medical inpatients, especially those easily misdiagnosed, such as depression and delirium.

Association between suicide attempt and a tri-allelic functional polymorphism in serotonin transporter gene promoter in Chinese patients with schizophrenia.

Mounting evidence supports the association between a polymorphism in the serotonin transporter gene promoter region (5-HTTLPR) and suicidal behaviour. Recently, a novel variant of the 5-HTTLPR L allele was identified. The previously unknown L(G) allele produced similar levels of gene expression to the S allele and might have been misclassified as a "high-expression" allele in previous association studies. In this study, we aimed to compare the genotype distribution of the tri-allelic 5-HTTLPR polymorphism in 168 Chinese patients with schizophrenia, including 60 suicide attempters and 108 non-suicide attempters. In our analysis, which used the L(A) dominant model, it was found that the L(A) allele carriers were significantly more likely to have attempted suicide (p=0.035). Further analysis showed this association existed only in male patients (p=0.012). A similar association between the L(A) allele and violent suicide attempt was also found (p=0.028). In addition, logistic regression confirmed our findings that male L(A) allele carriers were at a higher risk of suicide, although the lack of a significant association in females may reflect insufficient power due to small sample size. However, no association was found when we examined the traditional bi-allelic 5-HTTLPR. These findings differ from those reported in Caucasian subjects, where no associations have been reported. Different genetic backgrounds may give rise to different allelic distribution, causing differential effects on the expression of endophenotypes of suicide behaviours. Although the potential influence of multiple comparisons might weaken our findings, our study provides preliminary evidence for a potentially gender-specific role of a "high-expression" 5-HTTLPR polymorphism in susceptibility to suicide in Chinese patients with schizophrenia.

Prevention of poststroke depression with milnacipran in patients with acute ischemic stroke: a double-blind randomized placebo-controlled trial.

Poststroke depression (PSD) is one of the most frequent neuropsychiatric consequences of stroke. It has been shown to be associated with both impaired recovery and increased mortality. The purpose of this study is to investigate the prophylactic effect of milnacipran in PSD. Ninety-two patients were enrolled in the 12 months of this double-blind randomized placebo-controlled trial. The assessment was performed at baseline, and at the first, third, sixth, ninth and 12th month after enrollment. The definition of PSD was in accordance with the diagnostic criteria of major depressive episode based on the Diagnostic and Statistical Manual, fourth edition. Forty-six patients were randomized to the treatment group with milnacipran and another 46 patients to the placebo group. No significant differences were found between the two groups in terms of sex (P=0.83), age (P=0.08), marital status (P=0.66), occupation (P=0.22), educational level (P=0.29), and drug side-effects (P=0.73). The incidence of depression in the two groups was 2.22% and 15.22%, respectively. Milnacipran was proved to have a statistically significant advantage in preventing PSD (P<0.05). In conclusion, milnacipran could prevent the development of depression in the first year following a stroke and is safe to use without significant adverse effects in stroke patients.

Reversible Pisa syndrome induced by clozapine: a case report.

Pisa syndrome, manifested with persistent lateral flexion of the trunk, is most commonly associated with prolonged treatment with typical antipsychotics. However, it was also reported as occurring with atypical antipsychotics. To our knowledge, there have been very few reports of clozapine-associated Pisa syndrome. Here we report 1 case of Pisa syndrome in a 39-year-old woman with schizoaffective disorder who developed tonic flexion of trunk and head toward the left side after clozapine treatment (400 mg/d) for 5 months. Clozapine was reduced to 25 mg/d within 15 days; the dystonic reaction then completely resolved within the next 3 to 4 weeks. Caution should be taken while prolonged use of clozapine in patients with risk factors of Pisa syndrome.