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AbstractBackgroundOcular abnormalities and visual dysfunction have been associated with autism spectrum disorder (ASD). Our study assessed the risks of developing retinal diseases in individuals with ASD.MethodsIn all, 18 874 patients with ASD and 188 740 controls were selected from the Taiwan National Health Insurance Research Database between 2001 and 2009. The control group was matched based on demographic characteristics and medical and ophthalmological comorbidities. The hazard ratios (HRs) with 95% confidence intervals were calculated with Cox-regression analyses adjusted for selected confounders.ResultsIndividuals with ASD had a higher incidence of developing retinal diseases (1.48‰ vs 0.73‰, P< .001), and the diagnosis of retinal diseases occurred earlier than the controls (3.73 vs 6.28 years, P< .001). When compared to the control group, the HR of developing retinal diseases in the ASD group was 1.75 (95%: 1.04-2.94) and 7.84 (95%: 3.51-17.47) for retinal detachment. There was no association between the cumulative daily dose of atypical antipsychotics and the incidence of retinal diseases in the ASD group.ConclusionIndividuals with ASD have a higher risk of developing retinal detachment and are diagnosed with retinal diseases earlier than controls. Future research is needed to elucidate the mechanisms mediating the progression of retinal diseases in the ASD population.

AbstractBackgroundEmotional dysregulation (ED) is a common characteristic of both attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MDD), especially in adolescents. However, whether ADHD and MDD may share the specific ED-related neural networks remains unknown.MethodsIn total, 43 adolescents with clinical ED (22 adolescents with ADHD and 21 with MDD) were recruited; in addition, 29 sex- and age-matched healthy controls (HCs) were included. Resting-state functional connectivity (RSFC) analysis, voxel-based morphometry, and diffusion tensor imaging analysis were performed for each patient. In addition, we determined the significant regions of interest in patients with ED due to ADHD and MDD as compared with HCs and tested their correlations with clinical rating scale scores.ResultsCompared with HCs, patients with ED had greater RSFC in the cerebellum and supramarginal gyrus (SMG), especially between vermis VI and the SMG in the attention networks, and lower RSFC between the right supplementary motor area and right lateral parietal area. Lower gray matter (GM) volume in the SMG was also found. RSFC was significantly correlated with clinical rating scale scores for all patients with ED due to ADHD or MDD. GM change was correlated with ED and MDD rating scale scores.DiscussionThe cerebellum and attention networks might play major roles in ED pathophysiology in adolescents with ADHD and MDD. Increased connectivity of the vermis to the SMG serves as a possible underlying neural network.

AbstractBackgroundEvidence has demonstrated associations of bipolar disorder (BD) with cognitive impairment, dysregulated proinflammatory cytokines, and appetite hormones.AimTo compare executive dysfunction, proinflammatory cytokines, and appetite hormones between patients with first-episode and multiple-episode BDs.MethodsThis cross-sectional study included young adults aged 18 to 39 years who were diagnosed as having type 1 BD in the first or recurrent episode and a group of age-/sex-matched healthy controls. Data regarding patient characteristics, clinical symptoms, cytokines (C-reactive protein [CRP], interleukin-6, and tumor necrosis factor [TNF]-α), appetite hormones (leptin, adiponectin, ghrelin, and insulin), and executive function evaluated using the Wisconsin Card Sorting Test (WCST) were collected.ResultsA total of 112 participants (38 patients in the multiple-episode BD group, 31 patients in the first-episode BD group, and 43 in the control group) were included. Multivariate analysis revealed that patients in the multiple-episode BD group performed significantly worse in the WCST (P< .05) and had higher levels of ghrelin (P= .002), and lower levels of CRP (P= .040) than those in the first-episode BD group. Patients with BD had significantly higher TNF-α and ghrelin levels compared with the healthy controls. No significant associations of CRP, TNF-α, and ghrelin levels with executive function were observed.ConclusionsProfiles in proinflammatory cytokines and appetite hormones as well as executive function significantly differed between patients with first-episode and multiple-episode BDs and controls, which may suggest their potential roles in the clinical stages and pathophysiology of type 1 BD.

AbstractBackgroundThe concurrent incidence of autoimmune comorbidities in obsessive–compulsive disorder (OCD) is known. However, the association between OCD and related autoimmune skin diseases (ASDs) has not been well studied.ObjectiveThis study aimed to investigate the association between OCD and the risk of ASDs.MethodsTo assess the risk of developing ASDs, we recruited 44 324 patients with OCD and 177 296 matched controls from the National Health Insurance Research Database in Taiwan. A Cox regression model was used for the analyses.ResultsAfter adjusting for confounders, an increased risk of ASDs among the patients with OCD (adjusted hazard ratio [aHR]: 6.36; 95% confidence interval [CI]: 5.43-7.45) was found when compared to the controls. Statistically significant associations were found between OCD and seven individual ASDs, including psoriasis (aHR: 12.52; 95% CI: 8.78-17.85), lichen planus (aHR: 27.22; 95% CI: 13.09-56.60), alopecia areata (aHR: 13.69; 95% CI: 9.38-19.98), autoimmune bullous diseases (aHR: 4.30; 95% CI: 2.03-9.11), hidradenitis suppurativa (aHR: 29.95; 95% CI: 3.35-267.62), vitiligo (aHR: 9.35; 95% CI: 5.35-16.32), and lupus erythematosus (aHR: 2.10; 95% CI: 1.52-2.91).ConclusionsPatients with OCD had an increased risk of developing ASDs compared to matched controls. Further studies are required to clarify the underlying mechanisms.

AbstractBackgroundFew studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.MethodsIn total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function.ResultsUsing generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP (P= .023), IL-6 (P= .022), and TNF-α (P= .011), and had the lowest IL-2 levels (P= .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels (P= .027) were negatively associated with WCST scores.DiscussionDysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.

AbstractBackgroundDysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear.MethodsA total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task.ResultsPatients with SI had higher levels of CRP than those without SI and controls (P= .007). CRP was positively associated with SI (β= 0.21, P= .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P< .05).ConclusionOur findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.

AbstractBackgroundAltered immunity and metabolic profiles have been compared between bipolar depression (BD) and major depressive disorder (MDD). This study aimed at developing a composite predictor of appetite hormones and proinflammatory cytokines to differentiate BD from MDD.MethodsThis cross-sectional study enrolled patients with BD and those with MDD aged 20 to 59 years and displaying depressive episodes. Clinical characteristics (age, sex, body mass index, and depression severity), cytokines (C-reactive protein, interleukin [IL]-2, IL-6, tumor necrosis factor [TNF]-α, P-selectin, and monocyte chemoattractant protein), and appetite hormones (leptin, adiponectin, ghrelin, and insulin) were assessed as potential predictors using a classification and regression tree (CRT) model for differentiating BD from MDD.ResultsThe predicted probability of a composite predictor of ghrelin and TNF-α was significantly greater (for BD: area under curve = 0.877; for MDD: area under curve = 0.914) than that of any one marker (all P> .05) to distinguish BD from MDD. The most powerful predictors for diagnosing BD were high ghrelin and TNF-α levels, whereas those for MDD were low ghrelin and TNF-α levels.ConclusionA composite predictor of ghrelin and TNF-α driven by CRT could assist in the differential diagnosis of BD from MDD with high specificity. Further clinical studies are warranted to validate our results and to explore underlying mechanisms.

AbstractBackgroundStudies 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.MethodsOverall, 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/m2was 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.ResultsPatients 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.ConclusionsOur 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.

AbstractBackgroundThe 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.MethodsIn 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.ResultsPatients 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.ConclusionsLow-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.

AbstractObjectiveSeveral studies suggested a potential role of viral infection in the pathophysiology of Parkinson’s disease (PD). However, the association between herpes zoster and PD was not investigated well till now.MethodsUsing the Taiwan National Health Insurance Research Database, 13 083 patients aged ≥45 years with herpes zoster and 52 332 (1:4) age-/sex-matched controls were enrolled between 1998 and 2008 and followed to the end of 2011. Those who developed PD during the follow-up period were identified.ResultsThe Cox regression analysis with adjustment of demographic characteristics, health system utilization, and comorbidities demonstrated that patients with herpes zoster had an increased risk (hazard ratio [HR]: 1.80, 95% confidence interval [CI]: 1.43-2.28) of developing PD in later life compared to the control group. Sensitivity tests after excluding the first year (HR: 1.50, 95% CI: 1.16-1.93) and first 2-year (HR: 1.44, 95% CI: 1.10-1.88) observation periods showed consistent results.ConclusionsPatients with herpes zoster were more likely to develop PD in later life compared to the controls. Additional studies are necessary for validating our results and to clarify the underlying pathophysiology between herpes zoster and PD.