•We conducted the first meta-analysis on metabolite levels of kynurenine pathway in patients with depression.•Out of 899 initial records, 22 articles were identified.•Kynurenic acid and kynurenine ...levels are decreased in patients with depression.•Quinolinic acid levels are increased in unmedicated patients with depression.•Future research should examine relationships between treatment and kynurenine pathway.
Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively. KYNA and KYN levels were lower in patients with depression in comparison to controls, while QUIN levels did not differ between the two groups. Antidepressant-free patients showed decreased KYNA levels and increased QUIN levels compared with controls. Male ratios of the samples were negatively associated with study SMDs for KYNA. In conclusion, this meta-analysis revealed that patients with depression had decreased level of KYNA and KYN, whereas antidepressant-free patients showed increased level of QUIN. Nevertheless, given the heterogeneity among their sample characteristics, further research is clearly needed.
Alterations in glutamatergic neurotransmission are implicated in the pathophysiology of depression, and the glutamatergic system represents a treatment target for depression. To summarize the nature ...of glutamatergic alterations in patients with depression, we conducted a meta-analysis of proton magnetic resonance (
H-MRS) spectroscopy studies examining levels of glutamate. We used the search terms: depress* AND (MRS OR "magnetic resonance spectroscopy"). The search was performed with MEDLINE, Embase, and PsycINFO. The inclusion criteria were
H-MRS studies comparing levels of glutamate + glutamine (Glx), glutamate, or glutamine between patients with depression and healthy controls. Standardized mean differences (SMD) were calculated to assess group differences in the levels of glutamatergic neurometabolites. Forty-nine studies met the eligibility criteria, which included 1180 patients and 1066 healthy controls. There were significant decreases in Glx within the medial frontal cortex (SMD = -0.38; 95% CI, -0.69 to -0.07) in patients with depression compared with controls. Subanalyses revealed that there was a significant decrease in Glx in the medial frontal cortex in medicated patients with depression (SMD = -0.50; 95% CI, -0.80 to -0.20), but not in unmedicated patients (SMD = -0.27; 95% CI, -0.76 to 0.21) compared with controls. Overall, decreased levels of glutamatergic metabolites in the medial frontal cortex are linked with the pathophysiology of depression. These findings are in line with the hypothesis that depression may be associated with abnormal glutamatergic neurotransmission.
•Depressive patients less active with longer wake after sleep onset than healthy controls.•Total sleep time, sleep latency, and wake after sleep onset longer in euthymic/remitted patients than ...healthy controls.•Sleep latency, wake after sleep onset, and sleep efficiency significantly improved in pre- and post-treatment comparisons.
Actigraphy has enabled consecutive observation of individual health conditions such as sleep or daily activity. This study aimed to examine the usefulness of actigraphy in evaluating depressive and/or bipolar disorder symptoms.
A systematic review and meta-analysis was conducted. We selected studies that used actigraphy to compare either patients vs. healthy controls, or pre- vs. post-treatment data from the same patient group. Common actigraphy measurements, namely daily activity and sleep-related data, were extracted and synthesized.
Thirty-eight studies (n = 3,758) were included in the analysis. Compared with healthy controls, depressive patients were less active (standardized mean difference; SMD=1.27, 95%CI=0.97, 1.57, P<0.001) and had longer wake after sleep onset (SMD= − 0.729, 95%CI=− 1.20, − 0.25, p = 0.003). Total sleep time (SMD= − 0.33, 95%CI=− 0.55, − 0.11, P = 0.004), sleep latency (SMD= − 0.22, 95%CI=− 0.42, − 0.02, P = 0.032), and wake after sleep onset (SMD= − 0.22, 95%CI=− 0.39, − 0.04, P = 0.015) were longer in euthymic/remitted patients compared to healthy controls. In pre- and post-treatment comparisons, sleep latency (SMD=− 0.85, 95%CI=− 1.53, − 0.17, P = 0.015), wake after sleep onset (SMD= − 0.65, 95%CI=− 1.20, − 0.10, P = 0.022), and sleep efficiency (SMD=0.77, 95%CI=0.29, 1.24, P = 0.002) showed significant improvement.
The sample sizes for each outcome were small. The type of actigraphy devices and patients’ illness severity differed across studies. It is possible that hospitalizations and medication influenced the outcomes.
We found significant differences between healthy controls and mood disorders patients for some actigraphy-measured modalities. Specific measurement patterns characterizing each mood disorder/status were also found. Additional actigraphy data linked to severity and/or treatment could enhance the clinical utility of actigraphy.
•TMS combined with EMG permits the generation of key neurophysiological indices in the cortex.•AD patients had increased motor cortical excitability and decreased cholinergic and GABAergic functions ...compared with HC.•MCI patients had increased motor cortical excitability and decreased cholinergic function compared with HC.•TMS neurophysiology are useful measure to understand the pathophysiology of AD and MCI.
Transcranial magnetic stimulation (TMS) is a non-invasive neurophysiological tool that enables the investigation of cortical excitability in the human brain. Paired-pulse TMS paradigms include short- and long-interval intracortical inhibition (SICI/LICI), intracortical facilitation (ICF), and short-latency afferent inhibition (SAI), which can assess neurophysiological functions of GABAergic, glutamatergic, and cholinergic neural circuits, respectively. We conducted the first systematic review and meta-analysis to compare these TMS indices among patients with AD, mild cognitive impairment (MCI), and healthy controls (HC). Our meta-analyses indicated that RMT, SAI, SICI, and LICI were significantly lower in patients with AD, while ICF did not show a difference in patients with AD compared with HC. In patients with MCI, RMT and SAI were significantly lower than in HC. In conclusion, motor cortical excitability was increased, while cholinergic function was decreased in AD and MCI in comparison with HC and patients with AD had decreased GABAergic and glutamatergic functions compared with HC. Our results warrant further studies to differentiate AD, MCI, and HC, employing multimodal TMS neurophysiology.
Approximately 30% of patients with schizophrenia do not respond to antipsychotics and are thus considered to have treatment-resistant schizophrenia (TRS). To date, only four studies have examined ...glutamatergic neurometabolite levels using proton magnetic resonance spectroscopy (
H-MRS) in patients with TRS, collectively suggesting that glutamatergic dysfunction may be implicated in the pathophysiology of TRS. Notably, the TRS patient population in these studies had mild-to-moderate illness severity, which is not entirely reflective of what is observed in clinical practice. In this present work, we compared glutamate + glutamine (Glx) levels in the dorsal anterior cingulate cortex (dACC) and caudate among patients with TRS, patients with non-TRS, and healthy controls (HCs), using 3T
H-MRS (PRESS, TE = 35 ms). TRS criteria were defined by severe positive symptoms (i.e., ≥5 on 2 Positive and Negative Syndrome Scale (PANSS)-positive symptom items or ≥4 on 3 PANSS-positive symptom items), despite standard antipsychotic treatment. A total of 95 participants were included (29 TRS patients PANSS = 111.2 ± 20.4, 33 non-TRS patients PANSS = 49.8 ± 13.7, and 33 HCs). dACC Glx levels were higher in the TRS group vs. HCs (group effect: F2,75 = 4.74, p = 0.011; TRS vs. HCs: p = 0.012). No group differences were identified in the caudate. There were no associations between Glx levels and clinical severity in either patient group. Our results are suggestive of greater heterogeneity in TRS relative to non-TRS with respect to dACC Glx levels, necessitating further research to determine biological subtypes of TRS.
Repetitive transcranial magnetic stimulation (rTMS) is an effective clinical intervention for various neuropsychiatric diseases. However, it is still unclear whether rTMS has an effect on cognitive ...functioning. In this review, we aimed to systematically evaluate the cognitive effects of rTMS in depression, schizophrenia, and Alzheimer's disease. We searched PubMed (1996–2018) under the set terms to review randomized controlled trials (RCT) to examine the effectiveness of rTMS administered to the dorsolateral prefrontal cortex (DLPFC) and evaluated cognitive functions in patients with depression, schizophrenia, and Alzheimer's disease. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. The search identified 579 articles, 31 of which met inclusion and exclusion criteria. Among them, 15 were conducted in patients with depression, 11 in patients with schizophrenia, and 5 in patients with Alzheimer's disease. Specifically, 6 studies demonstrated a significant improvement of executive function across these diseases. Further, no evidence for cognitive adverse effects was found in these included rTMS studies. Although the heterogeneity between studies in terms of cognitive measures applied, stimulation parameters, and participants limits the ability to generalize conclusions, this review demonstrated that prefrontal rTMS could exert pro-cognitive effects on executive function and attention in some patients with depression but inconsistent cognitive impacts in any of the examined domains especially in patients with schizophrenia and Alzheimer's disease. The results warrant further rTMS studies that include systematic assessment of cognition across various neuropsychiatric diseases.
•Prefrontal rTMS could exert partial pro-cognitive effects in depression.•rTMS has inconsistent cognitive impacts in schizophrenia and Alzheimer's disease.•rTMS studies with comprehensive cognitive assessment in these diseases are needed.
Article Note: Present address: Koishikawa Tokyo Hospital, Tokyo, Japan (Seiwa Hospital has temporally moved due to reconstruction). CAPTION(S): Supplementary Information S1. Detailed methods, ...characteristics of our subjects, markers for the pathological sleepiness, REM abnormality in those with sleep prolongation, limitation and references. Figure S1. Representative 24-h polysomnography (PSG) hypnograms of patients in the three subtypes. Representative 24-h PSG hypnograms are shown with the time series variation of position sensors. L, S, R, and U in the position sensor indicated that the patients were in left lateral decubitus, supine, right lateral decubitus, and upright positions, respectively. The bottom line in the position sensor (U) indicates that the participant was in the upright position. Table S1. Clinical characteristics of patients. Demographic data, self-reported measures, HLA-DQB1 status, and frequency of clinical symptoms related to idiopathic hypersomnia are listed. A higher percentage of those with sleep prolongation experienced a symptom of 'always unrefreshed upon waking (unrefreshed nap),' and a higher percentage of those with high sleep propensity had experience of a symptom of 'sleep attack.' Table S2. Logistic regression models. Table S2A: Logistic regression model for sleep prolongation. Binary logistic regression using a backward elimination approach was performed to identify predictors of sleep prolongation. The initial model included age, sex, BMI, and candidate variables identified in the bivariate analyses. Those with 'always unrefreshed upon waking from naps' had a 44-fold higher risk for pathological sleep prolongation. This final model had good Nagelkerke's R square value. Table S2B: Logistic regression model for high sleep propensity. Similar logistic regression analysis was performed to identify predictors of high sleep propensity. The initial model included age, sex, BMI, and two symptoms: long nap >30min and the experience of sleep attack. Those with the experience of sleep attack had a 0.104-fold lower risk (that is, a 9.6-fold higher risk) for high sleep propensity. Only sleep attack remained in the final model with low Nagelkerke's R square value. Table S3. Sensitivity, specificity, and accuracy of Multiple Sleep Latency Test (MSLT) and 24-h polysomnography (PSG) for the diagnosis of idiopathic hypersomnia. The results of total sleep time (TST) on 24-h PSG and mean sleep latency (mSL) on MSLT, a marker for pathological sleepiness, were tabulated against the final diagnosis of idiopathic hypersomnia according to the International Classification of Sleep Disorders, 3rd edition (ICSD-3) criteria. Test sensitivity and accuracy were higher with 24-h PSG, indicating that 24-h PSG was a better diagnostic tool for our patients, who were suspected of idiopathic hypersomnia with long sleep time. Byline: Makoto Honda, Shinya Kimura, Kaori Sasaki, Masataka Wada, Wakako Ito
Mesoporous TiO2 nanocrystalline film was formed on fluorine‐doped tin oxide electrode (TiO2/FTO) and gold nanoparticles (NPs) of different sizes were loaded onto the surface with the loading amount ...kept constant (Au/TiO2/FTO). Visible‐light irradiation (λ>430 nm) of the Au/TiO2/FTO photoanode in a photoelectrochemical cell with the structure of photoanode|0.1 m NaClO4 aqueous solution|Ag/AgCl (reference electrode)|glassy carbon (cathode) leads to the oxidation of water to oxygen (O2). We show that the visible‐light activity of the Au/TiO2/FTO anode increases with a decrease in Au particle size (d) at 2.9≤d≤11.9 nm due to the enhancement of the charge separation and increasing photoelectrocatalytic activity.
Less is more: The visible‐light activity of a Au/TiO2/FTO (fluorine‐doped tin oxide) anode increases with a decrease in Au particle size due to the enhancement of the charge separation and increasing photoelectrocatalytic activity. These findings could aid the design of highly active plasmonic photocatalysts and photoelectrochemical cells for water splitting.
Background:
Glutathione is among the important antioxidants to prevent oxidative stress. However, the relationships between abnormality in the glutathione system and pathophysiology of schizophrenia ...remain uncertain due to inconsistent findings on glutathione levels and/or glutathione-related enzyme activities in patients with schizophrenia.
Methods:
A systematic literature search was conducted using Embase, Medline, PsycINFO, and PubMed. Original studies, in which three metabolite levels (glutathione, glutathione disulfide, and total glutathione (glutathione+glutathione disulfide)) and five enzyme activities (glutathione peroxidase, glutathione reductase, glutamate-cysteine ligase, glutathione synthetase, and glutathione S-transferase) were measured with any techniques in both patients with schizophrenia and healthy controls, were included. Standardized mean differences were calculated to determine the group differences in the glutathione levels with a random-effects model.
Results:
We identified 41, 9, 15, 38, and seven studies which examined glutathione, glutathione disulfide, total glutathione, glutathione peroxidase, and glutathione reductase, respectively. Patients with schizophrenia had lower levels of both glutathione and total glutathione and decreased activity of glutathione peroxidase compared to controls. Glutathione levels were lower in unmedicated patients with schizophrenia than those in controls while glutathione levels did not differ between patients with first-episode psychosis and controls.
Conclusions:
Our findings suggested that there may be glutathione deficits and abnormalities in the glutathione redox cycle in patients with schizophrenia. However, given the small number of studies examined the entire glutathione system, further studies are needed to elucidate a better understanding of disrupted glutathione function in schizophrenia, which may pave the way for the development of novel therapeutic strategies in this disorder.
•P300 reflected variety of cognitive dysfunction in patients with BD.•BD had reduced P3a/P3b amplitude and delayed P3b latency with any paradigm.•Phase, psychosis, and diagnostic subcategories did ...not affect P300 abnormalities.•P300 abnormalities may be a trait marker rather than a state marker of BD.
Neurophysiology including P300, that is a typical index of event-related potential, may be potential biomarkers for bipolar disorder (BD) and it can be useful towards elucidating the pathophysiology of BD. However, previous findings from P300 studies were inconsistent due to the heterogeneity of research methods, which make it difficult to understand the neurobiological significance of them. The aim of this study is to conduct a meta-analysis on P300 in patients with BD.
A literature search was conducted using PubMed to identify studies that compared P300 event-related potential between patients with BD and healthy controls (HCs). We analyzed P300 indices such as amplitude and latency of P3a and P3b in auditory or visual paradigms. Further, moderator analyses were conducted to investigate the influence of patient characteristics (i.e. history of psychosis, diagnostic subcategories BD-I/BD-II, and phase of illness euthymic, manic, or depressive) on P300 indices.
Out of 124 initial records, we included 30 articles (BD: N = 1331; HCs: N = 1818). Patients with BD showed reduced P3a and P3b amplitude in both paradigms and delayed P3b latency in auditory paradigms compared to HCs. There was no influence on the history of psychosis, diagnostic subcategories, or phase of illness on P300 indices.
The difference in medication use was difficult to control and it may affect the results.
This meta-analysis provides evidence for P300 abnormalities in patients with BD compared to HCs. Our results suggest that P300 may be trait markers rather than state markers in this illness.
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