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Abnormalities of neuroinflammatory process and serotonergic system have been reported in major depressive disorder (MDD). However, most previous studies were performed in recurrent MDD and only a few studies explored the interaction of the two systems. This study examined both systems concurrently and their clinical relevance in first-episode drug-naive MDD. Thirty-four MDD patients and 34 age and gender matched healthy controls (HC) were recruited. Plasma concentrations of the cytokines of interleukin-1 (IL-1) family, including IL-1α, IL-1β, IL-1 receptor antagonist (IL-1Ra) and IL-1 receptor type 2 (IL-1R2) were measured using enzyme-linked immune-sorbent assays. The serotonin transporter (SERT) availability in midbrain, thalamus, caudate, and putamen was examined by single-photon emission computed tomography with 123I-ADAM. There were significantly lower concentrations of pro-inflammatory IL-1β and its inhibitor, IL-1R2 in MDD than HC. The SERT availability was at the same level between groups. A negative association between IL-1Ra concentration and the SERT availability in midbrain was observed in MDD but not in HC. Both IL-1β concentration and the SERT availability in caudate negatively correlated with depression severity and the effect of IL-1β was not moderated or mediated by the SERT. In conclusion, this study demonstrated the involvement of IL-1 family in the early stage of MDD, especially for IL-1β. SERT was not the main central target of altered IL-1β and these two systems might contribute to MDD by different mechanisms. The pathophysiology might be varied between early and recurrent MDD and tuning treatment strategies at different clinical stages might be needed.

We compared serum levels of chemokines between male elders with major depressive disorder (MDD) and healthy controls, verifying whether any difference exists in the levels of these mediators between those with and without current suicidal ideation (SI).We enrolled 145 male elders aged 65 or older and analyzed 40 chemokines in patients with MDD with SI (The patients with MDD with SI presented higher levels of MCP-2/CCL8 (Current findings suggest a potential role of MCP-2/CCL8 in suicidality among elderly males with depression.

Aims Nonmotor symptoms (NMS) such as cognitive impairment and impulse‐control disorders in Parkinson's disease (PD) remain a therapeutic challenge. Transcranial direct current stimulation (tDCS) has emerged as a promising alternative, although its immediate effects on NMS have been less well defined. In this randomized, sham‐controlled, crossover study, we aimed to explore the single‐session tDCS effects on cognitive performance in PD. Methods Ten nondemented patients with PD completed two sessions in counterbalanced order, receiving 20 minutes of either 2 mA anodal or sham tDCS over the left dorsolateral prefrontal cortex (DLPFC). During stimulation, they performed the visual working memory and go/no‐go tasks. Performance of the tasks was compared between the two conditions. Results Single‐session anodal tDCS over the left DLPFC did not significantly improve cognitive tasks in PD compared with sham (P > .05). Conclusion Single‐session tDCS is ineffective in improving visual working memory and inhibitory control in PD. Further research may worth exploring alternative tDCS parameters, ideally with repeated sessions and concomitant training.

Major depressive disorder (MDD) is associated with the disharmonic functioning of the serotonin system. The serotonin system is mainly modulated by the serotonin transporter (SERT) which regulates serotonin uptake and the metabolism of its precursor, tryptophan and following kynurenine pathway. Currently, there is a lack of research examining both markers concurrently in MDD. This study evaluated the alterations and inter-relationships of both markers in first-episode drug-naive MDD patients. Thirty-three MDD patients and 33 age- and sex-matched healthy controls (HC) were recruited. The SERT availability were comparable between two groups in the midbrain, thalamus, caudate, and putamen. The kynurenine/tryptophan ratio which indicates tryptophan metabolism was lower in MDD than HC with no group difference in the tryptophan or kynurenine concentration. A negative correlation between the midbrain SERT availability and kynurenine concentration in HC was found. For the subgroup of HC with high kynurenine/tryptophan ratio, the SERT availability was positively associated with the kynurenine/tryptophan ratio and negatively correlated with tryptophan or kynurenine concentration. This study demonstrated the altered tryptophan metabolism and the relationship between tryptophan metabolism and the SERT availability in first-episode drug-naive MDD patients, which gave a new insight towards the future investigation of the pathophysiology of MDD.

Cognitive dysfunction has been reported in patients with carbon monoxide (CO) poisoning. However, the underpinning mechanism remained unclear. This study examined dopamine transporter (DAT) and metabolite ratios concurrently and their relationships with cognitive dysfunction in CO poisoning. Eighteen suicide attempters with charcoal burning which results in CO poisoning and 18 age- and gender- matched normal controls were recruited. A battery of cognitive assessments including attention, memory, and executive function was administered. Each participant received one single photon emission computed tomography with 99mTc-TRODAT for measuring striatal DAT availability and proton magnetic resonance spectroscopy to determine N-acetyl aspartate/creatine (NAA/Cr), choline-containing compounds/creatine (Cho/Cr) and myo-inositol/creatine (mI/Cr) in the left parietal white matter and mid-occipital gray matter (OGM). CO poisoning patients had significant impairments in memory and executive function. Compared to normal, CO poisoning patients had lower striatal DAT availability, lower NAA/Cr levels in both regions and higher Cho/Cr levels in both regions. In CO poisoning patients, the altered left striatal DAT availability and Cho/Cr level in OGM were significantly associated with executive dysfunction in the expected directions. Moreover, there was a significant interaction between these two imaging indices on their relationships with executive dysfunction and combination of them could adequately predict executive dysfunction in more CO poisoning cases than either alone. The current results suggested that both alterations in DAT availability and metabolite ratios might play crucial roles in executive dysfunction in CO poisoning. This research also highlights the importance of multimodal imaging approaches for studying neurotoxicity effects.

Objective: Late-life depression (LLD) is a severe public health problem. Given that pharmacological treatments for LLD are limited by their side effects, development of efficient and tolerable nonpharmacological treatment for LLD is urgently required. This study investigated whether high-frequency external muscle stimulation could reduce depressive symptoms in LLD. Methods: Twenty-two older male veterans with major depression were recruited and randomized into a treatment (n = 9) or sham control group (n = 13). The groups received high-frequency external muscle stimulation or sham intervention 3 times per week for 12 weeks. Clinical symptoms and muscle strength were evaluated at baseline and every 2 weeks. Results: The 2 groups were homogeneous in age, baseline clinical symptoms, and muscle strength. The treatment group showed significant improvement in depression and anxiety scores and muscle strength (all P < .01), whereas the control group showed no significant change after the 12-week follow-up. Compared to the control group, the treatment group showed significant improvements in depression (Geriatric Depression Scale, P = .009; Hamilton Depression Rating Scale, P = .007) and anxiety scores (HAMA, P = .008) and muscle strength (all P < .001). Changes in depression and anxiety levels were significantly correlated with changes in muscle strength after the study. In the treatment group, we observed a trend of correlation between the reduction in depression and muscle strength gains. Conclusion: High-frequency external muscle stimulation appears to be an effective treatment for older patients with LLD. Large studies with more tests and/or conducted in different populations are warranted to validate these preliminary findings.

Background Mental disorders are typically defined as distinct diagnostic entities, but similar patterns of clinical and cognitive impairments are frequently found across diagnostic groups. We investigated whether these transdiagnostic deficits result from common neural substrates across disorders or various illness-specific mechanisms, or a combination of both. Methods Functional magnetic resonance imaging data were collected from clinically stable patients with major depressive disorder (n = 53), bipolar disorder (n = 78), or schizophrenia (n = 100) and matched healthy control subjects (n = 109) using a single scanner. Group comparisons were conducted to identify transdiagnostic and illness-specific features, and possible confounding effects of medication were considered. A multivariate approach with cross-validation was used to associate dysconnectivity features with shared cognitive deficits. Results Transdiagnostic dysconnectivities were identified within somatomotor (Cohen’s d = 0.50–0.58) and salience (Cohen’s d = 0.52–0.58) networks and between subcortical-limbic (Cohen’s d = 0.55–0.69) and subcortical-dorsal attention (Cohen’s d = 0.56–0.61) networks. The executive control network was found to be illness-specifically disconnected from the prefrontal-limbic-pallidal circuit in major depressive disorder (Cohen’s d = 0.57–0.58), prefronto-striato-parietal circuit in bipolar disorder (Cohen’s d = 0.48–0.53), and default mode network in schizophrenia (Cohen’s d = 0.47–0.56). Working memory deficits were associated with a linear combination of 11 transdiagnostic and 5 illness-specific dysconnectivities (r = .322, p = 9.7 × 10−4, n = 340). The associations of the identified dysconnectivities with medication dosage were nonsignificant. Conclusions Disconnectivity in the somatomotor network was a common transdiagnostic profile, while there were illness-specific patterns in different parts of the prefrontal cortex for different disorders. These findings suggest that prominent psychiatric disorders share common impairments, possibly linked to perception and motor output, as well as unique dysconnectivity profiles that hypothetically mediate the more distinctive features of the disorder-specific psychopathology.

Medication overuse headache (MOH), previously known as analgesic abuse headache or medication misuse headaches, is a common form of chronic headache disorder that has a detrimental impact on health and society. Although it has been widely accepted that overusing abortive medications is paradoxically the cause of MOH and drug discontinuation is the treatment of choice, ongoing debates exist as to whether drug consumption per se is the cause or consequence of headache chronification. Certain features in MOH such as their compulsive drug-seeking behavior, withdrawal headaches and high relapse rates share similarities with drug dependence, suggesting that there might be common underlying biological and psychobehavioral mechanisms. In this regard, this article will discuss the updated evidence and current debates on the possible biobehavioral overlap between MOH and drug dependence. To begin with, we will discuss whether MOH has characteristics of substance dependence based on standard psychiatry diagnostic criteria and other widely used dependence scales. Recent epidemiological studies underscoring common psychiatric comorbidities between the two disorders will also be presented. Although both demonstrate seemingly distinct personality traits, recent studies revealed similar decision-making impairment from a cognitive perspective, indicating the presence of a maladaptive reward system in both disorders. In addition, emerging imaging studies also support this notion by showing reversible morphological and functional brain changes related to the mesocorticolimbic reward circuitry in MOH, with a strong resemblance to those in addiction. Finally, an increased familial risk for drug dependence and genetic association with dopaminergic and drug dependence molecular pathways in MOH also support a possible link between MOH and addiction. Understanding the role of dependence in MOH will have a great impact on disease management as this will provide the missing piece of the puzzle in current therapeutic strategies.

Frontotemporal dementia (FTD) is a common young-onset dementia presenting with heterogeneous and distinct syndromes. It is characterized by progressive deficits in behavior, language, and executive function. The disease may exhibit similar characteristics to many psychiatric disorders owing to its prominent behavioral features. The concept of precision medicine has recently emerged, and it involves neurodegenerative disease treatment that is personalized to match an individual's specific pattern of neuroimaging, neuropathology, and genetic variability. In this paper, the pathophysiology underlying FTD, which is characterized by the selective degeneration of the frontal and temporal cortices, is reviewed. We also discuss recent advancements in FTD research from the perspectives of clinical, imaging, molecular characterizations, and treatment. This review focuses on the approach of precision medicine to manage the clinical and biological complexities of FTD.

Transient global amnesia (TGA) has been proposed as a possible adverse effect of sildenafil. There are rare cases in the literature, but none had strong evidence to support. Our case is the first to demonstrate a focal punctate diffusion-weighted imaging lesion at the right hippocampus after the use of sildenafil. This finding, which is suggestive of cytotoxic edema and is typical for TGA, may provide us evidence for the implication of sildenafil in TGA. We speculate that sildenafil may precipitate TGA by altering blood flow, inducing venous congestion or cortical spreading depression at the hippocampus.