Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD).

Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN.

Resting-state functional connectivity magnetic resonance imaging (rs–fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs–fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently.

Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1.

These findings may support the utility of the triple-network model in elucidating ketamine’s antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.

Cognitive impairment is common in late-life depression, which may increase Alzheimer disease (AD) risk. Therefore, we aimed to investigate whether late-life major depressive disorder (MDD) has worse cognition and increases the characteristic AD neuropathology. Furthermore, we carried out a comparison between treatment-resistant depression (TRD) and non-TRD. We hypothesized that patients with late-life depression and TRD may have increased β-amyloid (Aβ) deposits in brain regions responsible for global cognition.

We recruited 81 subjects, including 54 MDD patients (27 TRD and 27 non-TRD) and 27 matched healthy controls (HCs). Neurocognitive tasks were examined, including Mini-Mental State Examination and Montreal Cognitive Assessment to detect global cognitive functions. PET with Pittsburgh compound-B and fluorodeoxyglucose were used to capture brain Aβ pathology and glucose use, respectively, in some patients.

MDD patients performed worse in Montreal Cognitive Assessment (p = 0.003) and had more Aβ deposits than HCs across the brain (family-wise error-corrected p < 0.001), with the most significant finding in the left middle frontal gyrus. Significant negative correlations between global cognition and prefrontal Aβ deposits existed in MDD patients, whereas positive correlations were noted in HCs. TRD patients had significantly more deposits in the left-sided brain regions (corrected p < 0.001). The findings were not explained by APOE genotypes. No between-group fluorodeoxyglucose difference was detected.

Late-life depression, particularly TRD, had increased brain Aβ deposits and showed vulnerability to Aβ deposits. A detrimental role of Aβ deposits in global cognition in patients with late-onset or non-late-onset MDD supported the theory that late-life MDD could be a risk factor for AD.

Recent imaging studies of large datasets suggested that psychiatric disorders have common biological substrates. This study aimed to identify all the common neural substrates with connectomic abnormalities across four major psychiatric disorders by using the data-driven connectome-wide association method of multivariate distance matrix regression (MDMR).

This study analyzed a resting functional magnetic resonance imaging dataset of 100 patients with schizophrenia, 100 patients with bipolar I disorder, 100 patients with bipolar II disorder, 100 patients with major depressive disorder, and 100 healthy controls (HCs). We calculated a voxel-wise 4,330 × 4,330 matrix of whole-brain functional connectivity (FC) with 8-mm isotropic resolution for each participant and then performed MDMR to identify structures where the overall multivariate pattern of FC was significantly different between each patient group and the HC group. A conjunction analysis was performed to identify common neural regions with FC abnormalities across these four psychiatric disorders.

The conjunction of the MDMR maps revealed that the four groups of patients shared connectomic abnormalities in distributed cortical and subcortical structures, which included bilateral thalamus, cerebellum, frontal pole, supramarginal gyrus, postcentral gyrus, lingual gyrus, lateral occipital cortex, and parahippocampus. The follow-up analysis based on pair-wise FC of these regions demonstrated that these psychiatric disorders also shared similar patterns of FC abnormalities characterized by sensory/subcortical hyperconnectivity, association/subcortical hypoconnectivity, and sensory/association hyperconnectivity.

These findings suggest that major psychiatric disorders share common connectomic abnormalities in distributed cortical and subcortical regions and provide crucial support for the common network hypothesis of major psychiatric disorders.

Family coaggregation of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia have been presented in previous studies. The shared genetic and environmental factors among psychiatric disorders remain elusive.

This nationwide population-based study examined familial coaggregation of major psychiatric disorders in first-degree relatives (FDRs) of individuals with ASD. Taiwan's National Health Insurance Research Database was used to identify 26 667 individuals with ASD and 67 998 FDRs of individuals with ASD. The cohort was matched in 1:4 ratio to 271 992 controls. The relative risks (RRs) and 95% confidence intervals (CI) of ADHD, ASD, BD, MDD and schizophrenia were assessed among FDRs of individuals with ASD and ASD with intellectual disability (ASD-ID).

FDRs of individuals with ASD have higher RRs of major psychiatric disorders compared with controls: ASD 17.46 (CI 15.50–19.67), ADHD 3.94 (CI 3.72–4.17), schizophrenia 3.05 (CI 2.74–3.40), BD 2.22 (CI 1.98–2.48) and MDD 1.88 (CI 1.76–2.00). Higher RRs of schizophrenia (4.47, CI 3.95–5.06) and ASD (18.54, CI 16.18–21.23) were observed in FDRs of individuals with both ASD-ID, compared with ASD only.

The risk for major psychiatric disorders was consistently elevated across all types of FDRs of individuals with ASD. FDRs of individuals with ASD-ID are at further higher risk for ASD and schizophrenia. Our results provide leads for future investigation of shared etiologic pathways of ASD, ID and major psychiatric disorders and highlight the importance of mental health care delivered to at-risk families for early diagnoses and interventions.

Studies have suggested the detrimental effects of obesity and systemic inflammation on the cognitive function of patients with bipolar or major depressive disorder. However, the complex associations between affective disorder, obesity, systemic inflammation, and cognitive dysfunction remain unclear.

Overall, 110 patients with affective disorder (59 with bipolar I disorder and 51 with major depressive disorder) who scored ≥61 on the Global Assessment of Functioning and 51 age- and sex-matched controls were enrolled. Body mass index ≥25 kg/m2 was defined as obesity or overweight. Levels of proinflammatory cytokines—including interleukin-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP)—were measured, and cognitive function was assessed using various methods, including the Wisconsin Card Sorting Test (WCST) and go/no-go task.

Patients with bipolar I disorder or major depressive disorder were more likely to be obese or overweight, had higher CRP and TNF-α levels, and had greater executive dysfunction in the WCST than the controls. TNF-α level (P < .05) but not affective disorder diagnosis or obesity/overweight was significantly associated with cognitive function deficits, although obesity/overweight and diagnosis were significantly associated with increased TNF-α level.

Our findings may indicate that proinflammatory cytokines, but not obesity or overweight, have crucial effects on cognitive function in patients with bipolar I disorder or major depressive disorder, although proinflammatory cytokines and obesity or overweight were found to be strongly associated. The complex relationships between affective disorder diagnosis, proinflammatory cytokine levels, obesity or overweight, and cognitive function require further investigation.

The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown.

In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period.

Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo.

Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.

Whether the first-degree relatives (FDRs) of patients with obsessive-compulsive disorder (OCD) have an increased risk of the major psychiatric disorders, namely schizophrenia, bipolar disorder, OCD, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD), remains unclear.

Using the Taiwan National Health Insurance Research Database with the whole population sample size (n = 23 258 175), 89 500 FDRs, including parents, offspring, siblings, and twins, of patients with OCD were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with OCD.

FDRs of patients with OCD had higher RRs of major psychiatric disorders, namely OCD (RR 8.11, 95% confidence interval (CI) 7.68–8.57), bipolar disorder (RR 2.85, 95% CI 2.68–3.04), MDD (RR 2.67, 95% CI 2.58–2.76), ASD (RR 2.38, 95% CI 2.10–2.71), ADHD (RR 2.19, 95% CI 2.07–2.32), and schizophrenia (RR 1.97, 95% CI 1.86–2.09), compared with the total population. Different familial kinships of FDRs, such as parents, offspring, siblings, and twins consistently had increased risks for these disorders. In addition, a dose-dependent relationship was found between the numbers of OCD probands and the risk of each major psychiatric disorder.

The FDRs, including parents, offspring, siblings, and twins, of patients with OCD have a higher risk of OCD, schizophrenia, bipolar disorder, MDD, ADHD, and ASD. The familial co-aggregation of OCD with OCD and other major psychiatric disorders was existent in a dose-dependent manner. Given the increased risks of psychiatric disorders, medical practitioners should closely monitor the mental health of the FDRs of patients with OCD.

Research suggests an association between metabolic disorders, such as type 2 diabetes mellitus (T2DM), and schizophrenia. However, the risk of metabolic disorders in the unaffected siblings of patients with schizophrenia remains unclear.

Using the Taiwan National Health Insurance Research Database, 3135 unaffected siblings of schizophrenia probands and 12,540 age-/sex-matched control subjects were included and followed up to the end of 2011. Individuals who developed metabolic disorders during the follow-up period were identified.

The unaffected siblings of schizophrenia probands had a higher prevalence of T2DM (3.4% vs. 2.6%, p = 0.010) than the controls. Logistic regression analyses with the adjustment of demographic data revealed that the unaffected siblings of patients with schizophrenia were more likely to develop T2DM (odds ratio [OR]: 1.39, 95% confidence interval [CI]: 1.10–1.75) later in life compared with the control group. Moreover, only female siblings of schizophrenia probands had an increased risk of hypertension (OR: 1.47, 95% CI: 1.07–2.01) during the follow-up compared with the controls.

The unaffected siblings, especially sisters, of schizophrenia probands had a higher prevalence of T2DM and hypertension compared with the controls. Our study revealed a familial link between schizophrenia and T2DM in a large sample. Additional studies are required to investigate the shared pathophysiology of schizophrenia and T2DM.

Bipolar disorder is a highly heritable mental illness that transmits intergeneratively. Previous studies supported that first-degree relatives (FDRs), such as parents, offspring, and siblings, of patients with bipolar disorder, had a higher risk of bipolar disorder. However, whether FDRs of bipolar patients have an increased risk of schizophrenia, major depressive disorder (MDD), autism spectrum disorder (ASD), and attention deficit hyperactivity disorder (ADHD) remains unclear.

Among the entire population in Taiwan, 87 639 patients with bipolar disorder and 188 290 FDRs of patients with bipolar disorder were identified in our study. The relative risks (RRs) of major psychiatric disorders were assessed among FDRs of patients with bipolar disorder.

FDRs of patients with bipolar disorder were more likely to have a higher risk of major psychiatric disorders, including bipolar disorder (RR 6.12, 95% confidence interval (CI) 5.95–6.30), MDD (RR 2.89, 95% CI 2.82–2.96), schizophrenia (RR 2.64, 95% CI 2.55–2.73), ADHD (RR 2.21, 95% CI 2.13–2.30), and ASD (RR 2.10, 95% CI 1.92–2.29), than the total population did. These increased risks for major psychiatric disorders were consistent across different familial kinships, such as parents, offspring, siblings, and twins. A dose-dependent relationship was also found between risk of each major psychiatric disorder and numbers of bipolar patients.

Our study was the first study to support the familial coaggregation of bipolar disorder with other major psychiatric disorders, including schizophrenia, MDD, ADHD, and ASD, in a Taiwanese (non-Caucasian) population. Given the elevated risks of major psychiatric disorders, the public health government should pay more attention to the mental health of FDRs of patients with bipolar disorder.

Attention-deficit hyperactivity disorder (ADHD) increases the risk of suicidal behaviours through psychiatric comorbidities; however, a significant direct association has not been observed between ADHD and suicide attempts.

To evaluate the risk of suicide attempt in adolescents and young adults with ADHD.

Using a nationwide, population-based insurance claims database, this longitudinal cohort study enrolled 20 574 adolescents and young adults with ADHD and 61 722 age- and gender-matched controls between 2001 and 2009. Any suicide attempt was identified from enrolment to 31 December 2011. The association between ADHD medications and the likelihood of suicide attempt was assessed.

ADHD was an independent risk factor for any suicide attempt (hazard ratio = 3.84, 95% CI = 3.19–4.62) and repeated suicide attempts (hazard ratio = 6.52, 95% CI = 4.46–9.53). Subgroup analyses of men, women, adolescents and young adults demonstrated the same trend. Methylphenidate or atomoxetine treatment did not increase the risk of suicide attempt or repeated suicide attempts. Long-term methylphenidate treatment was associated with a significantly decreased risk of repeated suicide attempts in men (hazard ratio = 0.46, 95% CI = 0.22–0.97).

ADHD was a risk factor for suicide attempt and a stronger predictor of repeated suicide attempts, independent of comorbidities. Further investigation is warranted to explore the mechanism underlying the association between ADHD and suicidal behaviours.

None.

Previous evidence has shown positive associations between post-traumatic stress disorder (PTSD) and hypertension, dyslipidaemia and diabetes mellitus, which are all risk factors for stroke, but the role of PTSD in the subsequent development of stroke is still unknown.

To investigate the temporal association between PTSD and the development of stroke.

Identified from the Taiwan National Health Insurance Research Database, 5217 individuals aged 18 years, with PTSD but with no history of stroke, and 20 868 age- and gender-matched controls were enrolled between 2002 and 2009, and followed up until the end of 2011 to identify the development of stroke.

Individuals with PTSD had an increased risk of developing any stroke (hazard ratio (HR) 3.37, 95% CI 2.44–4.67) and ischaemic stroke (HR = 3.47, 95% CI 2.23–5.39) after adjusting for demographic data and medical comorbidities. Sensitivity tests showed consistent findings (any stroke HR = 3.02, 95% CI 2.13–4.28; ischaemic stroke HR = 2.89, 95% CI 1.79–4.66) after excluding the first year of observation.

Individuals with PTSD have an increased risk of developing any stroke and ischaemic stroke. Further studies are required to investigate the underlying mechanisms.

This study is aimed to explore the frequency characteristics of pain-evoked neuromagnetic responses in the secondary somatosensory (SII) cortices.

Thulium-laser nociceptive stimuli to the left hand dorsum of 10 right-handed healthy adults. The pain stimuli were rated as mild, moderate, and severe levels according to subjects' reports on a 10-point visual analog scale. We analyzed their cortical responses with wavelet-based frequency analyses and equivalent current dipole (ECD) modeling.

For each pain level, we found an increase of theta (4-8 Hz) and alpha (8-13 Hz) power in bilateral SII areas at 180-210 ms after stimulus onset. The power was larger for the moderate than for the mild pain level (p < 0.05), but there was no statistical power difference of these oscillations between moderate and severe pain stimulus conditions (p = 0.7). Within the SII area, we did not observe particular difference in theta and alpha ECD locations between varying pain level conditions.

The 4-13 Hz activities, peaking from 180 to 210 ms, are oscillatory correlates of SII activation in response to nociceptive stimulation, but their power may code the magnitude of pain stimuli only up to moderate level, as rated subjectively. This measure could be potentially used to evaluate SII activation in further pain studies.

To determine the impact of check size and interstimulus interval (ISI) on neuromagnetic visual cortical responses.

We recorded visual evoked fields to pattern-reversal stimulation with central occlusion in ten subjects. The ~100 ms magnetic activation (P100m) was analyzed by single dipole modeling.

With 1 s ISI, P100m strengths increased as check size increased from 15' up to 120' of visual arc, and larger checks elicited less P100m activation. With 120' checks, we found no P100m attenuation as ISI decreased from 4 s to 0.16 s. P100m sources around the calcarine sulcus did not vary with check size or ISI.

The magnitude of cortical activation during visual contrast processing is check size-dependent and the 120' checks are optimum for future studies on neuromagnetic visual cortical functions using central-occluded stimulation. The corresponding neuronal activation demonstrated a short refractory period less than 0.16 s. We also found significantly overlapping cortical representation areas for different check sizes or ISIs.

On April 27, 2011, a train derailed and crashed in Taiwan, causing a mass casualty incident (MCI) that was similar to a previous event and with similar consequences. In both disasters, the emergency operating centers (EOCs) could not effectively integrate associated agencies to deal with the incident. The coordination and utilization of resources were inefficient, which caused difficulty in command structure operation and casualty evacuation.

This study was designed to create a survey questionnaire with problem items using disaster management phases mandated by Taiwan’s Emergency Medical Care Law (EMCL), use statistical methods (t test) to analyze the results and issues the EOCs encountered during the operation, and propose solutions for those problems.

Findings showed that EOCs lacked authority to intervene or coordinate with associated agencies. Also, placing emphasis on the recovery phase should improve future prevention and response mechanisms.

To improve the response to MCIs, the EMCL needs to be amended to give EOCs the lead during disasters; use feedback from the recovery phase to improve future disaster management and operation coordination; and establish an information-sharing platform across agencies to address all aspects of relief work.(Disaster Med Public Health Preparedness. 2014;0:1-6)