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.

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.

Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study.

OBJECTIVES: The serotonin hypothesis plays a critical role in the etiology of bipolar disorder (BD). Although many studies have demonstrated reciprocal relationships between serotonin metabolism and immune-inflammatory pathways that occur in depression, studies linking serotonergic function and cytokines are still limited concerning BD. The aim of this study was to investigate the interaction of brain serotonin transporter (SERT) and cytokines in BD. METHODS: Twenty patients with euthymic BD and 20 age- and sex-matched healthy controls (HC) were recruited. Single photon emission computed tomography with the radiotracer (123) I-ADAM was used for the SERT imaging. The specific uptake ratio, which represents SERT availability, was the primary measured outcome. Cytokines included the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine interleukin-10 (IL-10). Cytokine concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: SERT availability was significantly lower in the midbrain and caudate of patients with BD compared with HC, but not in the thalamus and putamen. IL-10 was significantly higher, whereas TNF-α was not different in euthymic patients with BD compared with HC. There was a significant association of SERT availability and IL-10 in the thalamus, but not in the midbrain, caudate, or putamen. CONCLUSIONS: Our results demonstrate the interaction of SERT availability and IL-10 in euthymic BD. This result may further explain the role of SERT and cytokines in the etiology of BD.

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.

Higher risk of developing mood disorders among adolescents with comorbidity of attention deficit hyperactivity disorder and disruptive behavior disorder: a nationwide prospective study.

Attention deficit hyperactivity disorder (ADHD), conduct disorder (CD), and oppositional defiant disorder (ODD) are frequently comorbid. Previous studies suggested that the comorbidity of CD and ODD in ADHD may increase the risk of a further development of mood disorder, but most studies had a small sample size. Using a population-based prospective study design, a large sample composed of 1277 adolescents with ADHD-alone, 46 with ADHD + ODD, 87 with ADHD + CD, and 5640 age/gender-matched controls were enrolled in 2003. These cases were followed to 2010 to identify the cases developing unipolar depressive disorder and bipolar disorder. ADHD + CD groups exhibited a higher prevalence of unipolar depressive disorder (23.0% vs. 13.0% vs. 8.7% vs. 0.7%, p < 0.001) and bipolar disorder (3.4% vs. 2.2% vs. 1.3% vs. 0.2%, p < 0.001) than ADHD + ODD group, ADHD-alone group, and control group. Adolescents with ADHD + CD, those with ADHD + ODD, and those with ADHD-alone had a higher likelihood of developing unipolar depressive disorder (hazard ratio [HR]: 44.34, 95% confidence interval [CI]: 23.95-71.36; HR: 18.76, 95%CI: 7.87-44.71; HR: 13.01, 95%CI: 8.99-18.82) and bipolar disorder (HR: 14.39, 95%CI: 4.00-51.80; HR: 8.32, 95%CI: 1.06-65.32; HR: 5.24, 95%CI: 2.44-11.24) than the controls. Adolescents with ADHD had elevated risks of unipolar depression and bipolar disorder in their later life, and especially, those with ADHD and comorbidity of CD or ODD exhibited the highest risk. Further study would be required to evaluate whether prompt intervention for ADHD and disruptive behavior problems would decrease the risk of developing mood disorder.

Attention deficit hyperactivity disorder, tic disorder, and allergy: is there a link? A nationwide population-based study.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) and tic disorder usually co-occur in the same individuals, but the underlying mechanisms remain unclear. Previous evidence has shown that a frequent coexistence of allergic diseases was noted in patients with ADHD or tic disorder. We attempted to investigate the possible link among ADHD, tic disorder, and various allergic diseases. METHODS: Utilizing the Taiwan National Health Insurance Research Database from 1996 to 2010, 5,811 patients with ADHD alone, 1,816 patients with tic disorder alone, and 349 patients with dual diagnoses of ADHD and tic disorder were identified and compared with age-/gender-matched controls (1:4) in an investigation of the association among ADHD, tic disorder, and allergic diseases. RESULTS: Patients with dual diagnoses of ADHD and tic disorder had a significantly higher prevalence of allergic diseases and psychiatric comorbidities, including allergic rhinitis (43% vs. 28.4% vs. 33.6% vs. 19.7%, p < 0.001), asthma (27.5% vs. 17.2% vs. 18.2% vs. 11.9%, p < 0.001), atopic dermatitis (10.6% vs. 8.4% vs. 7.0 vs. 5.9%, p < 0.001), allergic conjunctivitis (55.6% vs. 34.7% vs. 43.5% vs. 26.3%, p < 0.001), obsessive compulsive disorder (4.0% vs. 1.3% vs. 2.0% vs. 0.1%, p < 0.001), and anxiety disorder (22.1% vs. 18.0% vs. 6.0% vs. 0.5%, p < 0.001) than the ADHD alone group, the tic alone group, and the control group. Furthermore, ADHD patients with more allergic diseases (≥ 3 comorbidities: OR: 3.73, 95% CI: 2.65~5.25; 2 comorbidities: OR: 2.52, 95% CI: 1.82~3.47; 1 comorbidity: OR: 1.87, 95% CI: 1.41~2.49) exhibited an increased risk of tic disorder compared with ADHD patients without allergic disease. CONCLUSION: A significant association among ADHD, tic disorder, and allergic diseases was noted in our study. The results may inspire further studies to clarify the underlying mechanisms and help us understand more about the complex etiology of ADHD, tic disorder, and their co-occurrence.