Association between cortical thickness or surface area and divergent thinking in patients with bipolar disorder.

OBJECTIVE: Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry. METHODS: Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models. RESULTS: Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls. CONCLUSION: The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.

Obsessive-Compulsive Disorder and Dementia Risk: A Nationwide Longitudinal Study.

BACKGROUND: Several case reports have suggested an association between obsessive-compulsive disorder (OCD) and dementia. However, the exact relationship remains unclear. METHODS: Using the Taiwan National Health Insurance Research Database, 1,347 patients with OCD (ICD-9-CM code 300.3) aged ≥ 45 years and 13,470 controls matched for age, sex, residence, income, and dementia-related comorbidities were included between 1996 and 2013 for investigation of subsequent dementia from enrollment to the end of 2013. Stratified Cox regression analysis on each matched pair was applied to assess the dementia risk between the OCD and control groups. The analysis for the current study was performed in 2018. RESULTS: Patients with OCD had increased risk of developing any dementia (hazard ratio [HR] = 4.28; 95% confidence interval [CI], 2.96-6.21), Alzheimer's disease (HR = 4.04; 95% CI, 1.55-10.54), and vascular dementia (HR = 3.95; 95% CI, 1.70-9.18) compared with controls. DISCUSSION: Future research on the pathogenic mechanisms and molecular underpinnings of the relationship between OCD and dementia may lead to the development of novel therapeutics.

A pilot study on essential oil aroma stimulation for enhancing slow-wave EEG in sleeping brain.

Sleep quality is important to health and life quality. Lack of sleep can lead to a variety of health issues and reduce in daytime function. Recent study by Fultz et al. also indicated that sleep is crucial to brain metabolism. Delta power in sleep EEG often indicates good sleep quality while alpha power usually indicates sleep interruptions and poor sleep quality. Essential oil has been speculated to improve sleep quality. Previous studies also suggest essential oil aroma may affect human brain activity when applied awake. However, those studies were often not blinded, which makes the effectiveness and mechanism of aroma a heavily debated topic. In this study, we aim to explore the effect of essential oil aroma on human sleep quality and sleep EEG in a single-blinded setup. The aroma was released when the participants are asleep, which kept the influence of psychological expectation to the minimum. We recruited nine young, healthy participants with regular lifestyle and no sleep problem. All participants reported better sleep quality and more daytime vigorous after exposing to lavender aroma in sleep. We also observed that upon lavender aroma releases, alpha wave in wake stage was reduced while delta wave in slow-wave sleep (SWS) was increased. Lastly, we found that lavender oil promote occurrence of SWS. Overall, our study results show that essential oil aroma can be used to promote both subjective and objective sleep quality in healthy human subjects. This makes aroma intervention a potential solution for poor sleep quality and insomnia.

Cortico-thalamic dysconnection in early-stage schizophrenia: a functional connectivity magnetic resonance imaging study.

Studies have indicated thalamus-related network dysfunction in schizophrenia and psychotic disorders. However, whether thalamus-related functional connectivity (FC) contributes to the psychopathology and cognitive deficits of early-stage schizophrenia requires further investigation. A total of 34 patients with early-stage schizophrenia (illness duration = 1.62 ± 1.16 years; age = 26.00 ± 6.34 years) and 34 age- and sex-matched healthy controls were enrolled in our study and underwent comprehensive assessments of the clinical symptoms of schizophrenia, working memory tasks, and resting-state FC magnetic resonance imaging. The patients with early-stage schizophrenia had increased FC of the thalamus with the bilateral postcentral and temporal gyri, inferior occipital cortex, and temporal pole and decreased FC of the thalamus with the vestibulocerebellum and frontal pole compared with the controls. Furthermore, increased FC between the thalamus and temporal pole was positively correlated with positive scores of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and negatively correlated with performance on working memory tasks in early-stage schizophrenia. Increased FC of the thalamus with the inferior occipital cortex was positively associated with negative PANSS scores and negatively correlated with Personal and Social Performance Scale scores in early-stage schizophrenia. Our results supported the vital role of thalamus-related network dysfunction in the psychopathology and cognitive deficits of early-stage schizophrenia.

Critical role of glutamatergic and GABAergic neurotransmission in the central mechanisms of theta-burst stimulation.

Theta-burst stimulation (TBS) is a varied form of repetitive transcranial magnetic stimulation (rTMS) and has more rapid and powerful effects than rTMS. Experiments on the human motor cortex have demonstrated that intermittent TBS has facilitatory effects, whereas continuous TBS has inhibitory effects. Huang's simplified model provides a solid basis for elucidating such after-effects. However, evidence increasingly indicates that not all after-effects of TBS are as expected, and high variability among individuals has been observed. Studies have suggested that the GABAergic and glutamatergic neurotransmission play a vital role in the aforementioned after-effects, which might explain the interindividual differences in these after-effects. Herein, we reviewed the latest findings on TBS from animal and human experiments on glutamatergic and GABAergic neurotransmissions in response to TBS. Furthermore, an updated theoretical model integrating glutamatergic and GABAergic neurotransmissions is proposed.

Identification of Common Thalamocortical Dysconnectivity in Four Major Psychiatric Disorders.

BACKGROUND: Recent genetic and imaging analyses of large datasets suggested that common biological substrates exist across psychiatric diagnoses. Functional connectivity (FC) abnormalities of thalamocortical circuits were consistently found in patients with schizophrenia but have been less studied in other major psychiatric disorders. This study aimed to examine thalamocortical FC in 4 major psychiatric disorders to identify the common connectivity abnormalities across major psychiatric disorders. METHODS: This study recruited 100 patients with schizophrenia, 100 patients with bipolar I disorder, 88 patients with bipolar II disorder, 100 patients with major depressive disorder, and 160 healthy controls (HCs). Each participant underwent resting functional magnetic resonance imaging. The thalamus was used to derive FC maps, and group comparisons were made between each patient group and HCs using an independent-sample t test. Conjunction analysis was used to identify the common thalamocortical abnormalities among these 4 psychiatric disorders. RESULTS: The 4 groups of patients shared a similar pattern of thalamocortical dysconnectivity characterized by a decrease in thalamocortical FC with the dorsal anterior cingulate, anterior prefrontal cortex and inferior parietal cortex. The groups also showed an increase in FC with the postcentral gyrus, precentral gyrus, superior temporal cortex, and lateral occipital areas. Further network analysis demonstrated that the frontoparietal regions showing hypoconnectivity belonged to the salience network. CONCLUSION: Our findings provide FC evidence that supports the common network hypothesis by identifying common thalamocortical dysconnectivities across 4 major psychiatric disorders. The network analysis also supports the cardinal role of salience network abnormalities in major psychiatric disorders.

Risk of Type 2 Diabetes in Adolescents and Young Adults With Attention-Deficit/Hyperactivity Disorder: A Nationwide Longitudinal Study.

BACKGROUND: Studies have suggested there is an association between attention-deficit/hyperactivity disorder (ADHD) and type 2 diabetes mellitus (DM)-related risk factors, such as obesity, hypertension, and dyslipidemia. However, the association between ADHD and type 2 DM remains unknown. METHODS: Using the Taiwan National Health Insurance Research Database, we enrolled 35,949 adolescents and young adults with ADHD (ICD-9-CM code: 314) and 71,898 (1:2) age- and sex-matched controls from 2002 through 2009 and followed up with them until the end of 2011. Participants who developed type 2 DM during the follow-up period were identified. RESULTS: Adolescents (hazard ratio [HR] = 2.83; 95% CI, 1.96-4.09) and young adults (HR = 3.28; 95% CI, 1.41-7.63) with ADHD had a higher risk of developing type 2 DM than did the controls after adjustment for demographic characteristics, use of ADHD medications and atypical antipsychotics, and medical comorbidities. Individuals with ADHD had a shorter mean ± SD duration between enrollment and onset of type 2 DM (3.17 ± 2.33 vs 4.08 ± 2.11 years, P = .004) during the follow-up compared with the controls. Sensitivity analyses after excluding first-year (HR = 2.36; 95% CI, 1.65-3.38) and first-3-year (HR = 1.92; 95% CI, 1.19-3.09) observation periods were consistent. Long-term use of atypical antipsychotics was associated with a higher likelihood of subsequent type 2 DM (HR = 2.82, 95% CI, 1.74-4.58). DISCUSSION: Adolescents and young adults with ADHD were more likely than non-ADHD controls to develop type 2 DM in later life. In addition, those with ADHD taking atypical antipsychotics exhibited a higher risk. Although correlation does not equal causation, our findings merit further study about the relationship between ADHD and type 2 DM.

Post-traumatic stress disorder and risk of osteoporosis: A nationwide longitudinal study.

Several studies suggested a relationship between stress and related mental illnesses, such as depression and osteoporosis. However, it was unclear whether patients with post-traumatic stress disorder (PTSD) were at risk of developing osteoporosis in later life. In this study, 6,041 patients with PTSD and 24,164 age- or sex-matched controls were enrolled between 2002 and 2009 in our study and followed up to the end of 2011. Cases of osteoporosis were identified during the follow-up. Patients with PTSD had an elevated likelihood of developing osteoporosis (HR: 2.66, 95% CI [1.91, 3.71]) in later life compared with the controls. Sensitivity tests after excluding the first year observation (HR: 2.46, 95% CI [1.72, 3.53]) and the first 3-year observation (HR: 1.88, 95% CI [1.18, 3.01]) were consistent. Patients with PTSD had a higher risk of developing osteoporosis at an earlier age compared with those without PTSD. Further studies would be necessary to clarify the pathophysiology between PTSD and osteoporosis.

Risk of suicide attempts in adolescents and young adults with attention-deficit hyperactivity disorder: a nationwide longitudinal study.

BACKGROUND: 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. Aims To evaluate the risk of suicide attempt in adolescents and young adults with ADHD. METHOD: 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. RESULTS: 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). CONCLUSION: 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. Declaration of interest None.

Risk of stroke among patients with borderline personality disorder: A nationwide longitudinal study.

BACKGROUND: Previous studies suggested that patients with borderline personality disorder (BPD) had a higher prevalence of stroke-related risk factors, such as hypertension, dyslipidemia, and diabetes mellitus. But, the association between BPD and subsequent stroke has been rarely investigated. METHODS: Using the Taiwan National Health Insurance Research Database, 5969 borderline patients aged 18 years and older and 23,876 age-and sex-matched controls were enrolled between 2002 and 2009, and followed up to the end of 2011 to identify the development of stroke. RESULTS: The Cox regression model after adjusting for demographic data, psychiatric comorbidities, and medical comorbidities showed that BPD was associated with an increased risk of developing any stroke (HR: 4.82, 95% CI: 2.77-8.40) and ischemic stroke (HR: 5.67, 95% CI: 2.49-12.93). The findings of sensitivity analysis after excluding the first year of observation were consistent: any stroke (HR: 3.44, 95% CI: 1.83-6.47) and ischemic stroke (HR: 4.75, 95% CI: 1.91-11.77). DISCUSSION: Patients with BPD had an elevated vulnerability to subsequent stroke and ischemic stroke compared to those without BPD. Further studies would be required to investigate the underlying mechanisms.

Post-traumatic Stress Disorder and Risk of Parkinson Disease: A Nationwide Longitudinal Study.

OBJECTIVE: Increasing evidence has suggested a relationship between post-traumatic stress disorder (PTSD) and neurodegenerative disorder, such as Alzheimer disease. The association between PTSD and Parkinson disease (PD), however, remains unclear. METHOD: Using the Taiwan National Health Insurance Research Database, 7,280 subjects (1,456 patients aged ≥45 years with PTSD and 5,824 age-/sex-matched individuals without PTSD) were enrolled between 2002 and 2009 and followed to the end of 2011. Subjects who developed PD during the follow-up period were identified. RESULTS: An increased risk of developing PD was found in patients with PTSD (Wald χ2 = 12.061, hazard ratio [HR]: 3.46, 95% confidence interval [CI]: 1.72-6.96) compared with individuals without PTSD, after adjusting for demographic data and medical and psychiatric comorbidities. The sensitivity tests after excluding the first year observation (Wald χ2 = 7.948, HR: 3.01, 95% CI: 1.40-6.46) and the first 3-year observation (Wald χ2 = 5.099, HR: 3.07, 95% CI: 1.16-8.15) were consistent. CONCLUSIONS: Patients with PTSD had an elevated risk of developing PD in later life. Further studies would be required to clarify the exact pathophysiology between PTSD and PD and to investigate whether the prompt intervention for PTSD may reduce this risk.

Risk of developing major depression and bipolar disorder among adolescents with atopic diseases: A nationwide longitudinal study in Taiwan.

BACKGROUNDS: Previous studies have found an increased prevalence of atopic diseases among patients with major depression and bipolar disorder. But the temporal association between atopic diseases in adolescence and the subsequent risk of developing mood disorders has been rarely investigated. METHODS: Using the Taiwan National Health Insurance Research Databases, 5075 adolescents with atopic diseases (atopic cohort) and 44,729 without (non-atopic cohort) aged between 10 and 17 in 2000 were enrolled into our study and followed to the end of 2010. Subjects who developed major depression or bipolar disorder during the follow-up were identified. RESULTS: The atopic cohort had an increased risk of developing major depression (HR: 2.45, 95% CI: 1.93~3.11) and bipolar disorder (HR: 2.51, 95% CI: 1.71~3.67) compared to the non-atopic cohort, with a dose-dependent relationship between having a greater number of atopic comorbidities and a greater likelihood of major depression (1 atopic disease: HR: 1.80, 95% CI: 1.29~2.50; 2 atopic comorbidities: HR: 2.42, 95% CI: 1.93~3.04;≥3 atopic comorbidities: HR: 3.79, 95% CI: 3.05~4.72) and bipolar disorder (HR: 1.40, 95% CI: 0.57~3.44; HR: 2.81, 95% CI: 1.68~4.68; HR: 3.02, 95% CI: 1.69~5.38). DISCUSSION: Having atopic diseases in adolescence increased the risk of developing major depression and bipolar disorder in later life. Further studies may be required to clarify the underlying mechanism between atopy and mood disorders, and to investigate whether prompt intervention may decrease the risk of subsequent mood disorders.

Risk of developing major depression and anxiety disorders among women with endometriosis: A longitudinal follow-up study.

BACKGROUNDS: Several cross-sectional studies suggested a link between endometriosis and mood disorders. However, the temporal association between endometriosis and mood disorders (depression and anxiety disorders) is still unclear. METHODS: Using the Taiwan National Health Insurance Research Database, 10,439 women with endometriosis and 10,439 (1:1) age-/sex-matched controls between 1998 and 2009 were enrolled, and followed up to the end of 2011. Those who developed depression or anxiety disorders during the follow-up were identified. RESULTS: Women with endometriosis had an increased risk of developing major depression (hazard ratio [HR]: 1.56, 95% confidence interval [CI]:1.24-1.97), any depressive disorder (HR: 1.44, 95% CI: 1.25-1.65), and anxiety disorders (HR: 1.44, 95% CI: 1.22-1.70) in later life compared to those without endometriosis. Stratified by age group, women with endometriosis aged <40 years and those aged ≧40 years were both prone to developing major depression (HR: 1.52, 95% CI: 1.15-1.99; HR: 1.69, 95% CI: 1.09-2.62), any depressive disorder (HR: 1.43, 95% CI: 1.21-1.69; HR: 1.45, 95% CI: 1.13-1.56), and anxiety disorders (HR: 1.39, 95% CI: 1.14-1.71; HR: 1.53, 95% CI: 1.15-2.04). LIMITATION: the incidence of depression and anxiety disorders may be underestimated since only those who sought medical consultation and help would be enrolled in our study. CONCLUSION: Endometriosis was associated with an elevated likelihood of developing depression and anxiety disorders. Further studies may be required to investigate the underlying pathophysiology between endometriosis and both depression and anxiety disorders.

Bidirectional Association Between Depression and Fibromyalgia Syndrome: A Nationwide Longitudinal Study.

Several cross-sectional studies have reported a common comorbidity between depression and fibromyalgia syndrome (FMS). However, a bidirectional temporal association between these 2 distinct diseases has rarely been investigated. Using the Taiwan National Health Insurance Research Database, 25,969 patients with FMS and without any psychiatric disorder and 17,142 patients with depression and without FMS between 2000 and 2008 were enrolled and separately compared with age- and sex-matched (1:4) control groups. Patients with FMS who developed a new-onset depression and those with depression who developed new-onset FMS were identified during follow-up (to the end of 2011). The conditional Cox regression analyses, after adjustment for demographic data and medical comorbidities, showed that the patients with FMS were associated with an increased risk (hazard ratio [HR] 7.46, 95% confidence interval [CI] 6.77-8.22) of subsequent depression and that those with depression were associated with an increased risk (HR 6.28, 95% CI 5.67-6.96) of subsequent FMS. Our results supported a bidirectional temporal association between depression and FMS. Each disease occurring first may increase the risk of the other subsequently. Further study may be necessary to determine the underlying mechanism between depression and FMS and to clarify whether a prompt intervention for depression or FMS may decrease the risk of the other later in life. Perspective: Our study supported a bidirectional temporal association between depression and FMS such that each disease occurring first may increase the risk of the other subsequently. This result may imply a shared pathophysiology between FMS and depression, but further investigation is needed.

Network-specific cortico-thalamic dysconnection in schizophrenia revealed by intrinsic functional connectivity analyses.

BACKGROUND: Cortico-thalamic connections are thought to be abnormal in schizophrenia due to their important roles in sensory relay and higher cognitive control, both of which are affected by this devastating illness. This study tested the cortico-thalamic dysconnection hypothesis in schizophrenia and further explored cortico-thalamic network properties using functional connectivity MRI (fcMRI). METHODS: Forty-eight participants with schizophrenia and 48 healthy controls underwent resting fMRI scans and clinical evaluations. Six a priori cortical regions of interests (ROIs) were used to derive the six networks: dorsal default mode network (dDMN), fronto-parietal network (FPN), cingulo-opercular network (CON), primary sensorimotor network (SM1), primary auditory network (A1) and primary visual network (V1). The cortico-thalamic connectivity for each network was calculated for each participant and then compared between groups. RESULTS: A repeated measures analysis of variance (ANOVA) showed significant group×network interactions (F(5, 90)=9.5, P<0.001), which were driven by a significant increase in FC within the SM1 (t(94)=4.1, P<0.001) and A1 (t(94)=4.2, P<0.001) networks in schizophrenics, as well as a significant decrease within the CON (t(94)=-2.8, P=0.04). The cortico-thalamic dysconnection did not correlate with symptom severity, representing a state independent abnormality. CONCLUSION: The network analysis indicates that cortico-thalamic dysconnection in schizophrenia involves multiple networks and shows network specific changes. The findings provide support for dysfunctional thalamus-related networks in schizophrenia and further elaborate their network properties.

A predisposition for allergies predicts subsequent hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder: a nationwide longitudinal study.

BACKGROUND: Previous studies have shown that both severe mental disorders (schizophrenia and bipolar disorder) and atopic diseases were associated with an increased risk of metabolic syndrome. However, the role of atopy/the predisposition for allergies in the development of metabolic syndrome is still unknown among those with severe mental disorders. METHODS: Using the Taiwan National Health Insurance Research Database, 5826 patients with schizophrenia or bipolar disorder (1908 with a predisposition for allergies and 3918 without) were enrolled between 1998 and 2008. Those who developed hypertension, dyslipidemia, and/or diabetes mellitus were identified during the follow-up to the end of 2011. RESULTS: A predisposition for allergies increased the risk of developing hypertension (HR: 1.67), dyslipidemia (HR: 1.82), and diabetes mellitus (HR: 1.37) in later life among those with severe mental disorders. A dose-dependent relationship was noted between having more atopic comorbidities and a greater likelihood of hypertension (1 atopic disease: HR: 1.60; ≧ 2 atopic comorbidities: HR: 1.87), dyslipidemia (HR: 1.73; HR: 2.12), and diabetes mellitus (HR: 1.26; HR: 1.69). CONCLUSION: A predisposition for allergies was an independent risk factor for hypertension, dyslipidemia, and diabetes mellitus among patients with schizophrenia or bipolar disorder. Further studies would be required to elucidate the underlying pathophysiology among atopy, schizophrenia, bipolar disorder, and metabolic syndrome.

Altered resting-state functional connectivity of striatal-thalamic circuit in bipolar disorder.

Bipolar disorder is characterized by internally affective fluctuations. The abnormality of inherently mental state can be assessed using resting-state fMRI data without producing task-induced biases. In this study, we hypothesized that the resting-state connectivity related to the frontal, striatal, and thalamic regions, which were associated with mood regulations and cognitive functions, can be altered for bipolar disorder. We used the Pearson's correlation coefficients to estimate functional connectivity followed by the hierarchical modular analysis to categorize the resting-state functional regions of interest (ROIs). The selected functional connectivities associated with the striatal-thalamic circuit and default mode network (DMN) were compared between bipolar patients and healthy controls. Significantly decreased connectivity in the striatal-thalamic circuit and between the striatal regions and the middle and posterior cingulate cortex was observed in the bipolar patients. We also observed that the bipolar patients exhibited significantly increased connectivity between the thalamic regions and the parahippocampus. No significant changes of connectivity related to the frontal regions in the DMN were observed. The changed resting-state connectivity related to the striatal-thalamic circuit might be an inherent basis for the altered emotional and cognitive processing in the bipolar patients.

Disrupted thalamo-cortical connectivity in schizophrenia: a morphometric correlation analysis.

Increasing studies have implicated the thalamus in schizophrenia, supporting the view that this structure has an important role in this disorder. Given that extensive reciprocal connections exist between the thalamus and the cerebral cortex, it is believed that disruptions of the thalamo-cortical connections may underlie the multiplicity of schizophrenic symptoms. Therefore, assessing the relationship between the thalamus and the neocortex may provide new insights into the pathophysiology of schizophrenia. We analyzed magnetic resonance images from a sample of 101 schizophrenic patients and 101 healthy controls. By assessing the correlation between the thalamic volume and cortical thickness at each vertex on the cortical surface, a thalamo-cortical network was obtained for each group. We compared the patterns of thalamo-cortical connectivity between the two groups. Compared with healthy controls, less distributed cortical regions were identified in the thalamo-cortical network in patients with schizophrenia. Vertex-wise comparison revealed decreased thalamo-cortical connectivity in bilateral inferior frontal gyrus, the left superior temporal gyrus and the right parieto-occipital region in schizophrenia. The observed disruptions in thalamo-cortical connectivity might be the substrate underlying the wide range of schizophrenic symptoms and provide further evidence to support the notion of schizophrenia as a disorder of brain dysconnectivity.

Higher risk of developing major depression and bipolar disorder in later life among adolescents with asthma: a nationwide prospective study.

OBJECTIVE: Previous studies have suggested an immunological dysfunction in mood disorders, but rarely have investigated the temporal association between allergic diseases and mood disorders. Using the Taiwan National Health Insurance Research Database, we attempted to investigate the association between asthma in early adolescence and the risk of unipolar depression and bipolar disorder in later life. METHODS: In all, 1453 adolescents with asthma aged between 10 and 15 years and 5812 age-/gender-matched controls were selected in 1998-2000. Subjects with unipolar depression and bipolar disorder that occurred up to the end of follow-up (December 31 2010) were identified. RESULTS: Adolescents with asthma had a higher incidence of major depression (2.8% vs. 1.1%, p < 0.001), any depressive disorder (6.1% vs. 2.6%, p < 0.001), and bipolar disorder (1.0% vs. 0.3%, p < 0.001) than the control group. Cox regression analysis showed that asthma in early adolescence was associated with an increased risk of developing major depression (hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.14-2.89), any depressive disorder (HR: 1.74, 95% CI: 1.27-2.37), and bipolar disorder (HR: 2.27, 95% CI: 1.01-5.07), after adjusting for demographic data and comorbid allergic diseases. DISCUSSION: Adolescents with asthma had an elevated risk of developing mood disorders in later life. Further studies would be required to investigate the underlying mechanisms for this comorbid association and elucidate whether prompt intervention for asthma would decrease the risk of developing mood disorders.

Impaired prefronto-thalamic functional connectivity as a key feature of treatment-resistant depression: a combined MEG, PET and rTMS study.

Prefrontal left-right functional imbalance and disrupted prefronto-thalamic circuitry are plausible mechanisms for treatment-resistant depression (TRD). Add-on repetitive transcranial magnetic stimulation (rTMS), effective in treating antidepressant-refractory TRD, was administered to verify the core mechanisms underlying the refractoriness to antidepressants. Thirty TRD patients received a 2-week course of 10-Hz rTMS to the left dorsolateral prefrontal cortex (DLPFC). Depression scores were evaluated at baseline (W0), and the ends of weeks 1, 2, and 14 (W14). Responders were defined as those who showed an objective improvement in depression scores ≥50% after rTMS. Left-right frontal alpha asymmetry (FAA) was measured by magnetoencephalography at each time point as a proxy for left-right functional imbalance. Prefronto-thalamic connections at W0 and W14 were assessed by studying couplings between prefrontal alpha waves and thalamic glucose metabolism (PWTMC, reflecting intact thalamo-prefrontal connectivity). A group of healthy control subjects received magnetoencephalography at W0 (N = 50) to study whether FAA could have a diagnostic value for TRD, or received both magnetoencephalography and positron-emission-tomography at W0 (N = 10) to confirm the existence of PWTMC in the depression-free state. We found that FAA changes cannot differentiate between TRD and healthy subjects or between responders and non-responders. No PWTMC were found in the TRD group at W0, whereas restitution of the PWTMC was demonstrated only in the sustained responders at W14 and euthymic healthy controls. In conclusion, we affirmed impaired prefronto-thalamic functional connections, but not frontal functional imbalance, as a core deficit in TRD.