Although there is growing evidence of alterations in the neurometabolite status associated with the pathophysiology of schizophrenia, how treatments influence these metabolite levels in patients with ...schizophrenia remains poorly studied.
We conducted a literature search using Embase, Medline, and PsycINFO to identify proton magnetic resonance spectroscopy studies that compared neurometabolite levels before and after treatment in patients with schizophrenia. Six neurometabolites (glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, myo-inositol) and six regions of interest (frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, hippocampus) were investigated.
Thirty-two studies (n = 773 at follow-up) were included in our meta-analysis. Our results demonstrated that the frontal glutamate + glutamine level was significantly decreased (14 groups; n = 292 at follow-up; effect size = −0.35, P = 0.0003; I2 = 22%) and the thalamic N-acetylaspartate level was significantly increased (7 groups; n = 184 at follow-up; effect size = 0.47, P < 0.00001; I2 = 0%) after treatment in schizophrenia patients. No significant associations were found between neurometabolite changes and age, gender, duration of illness, duration of treatment, or baseline symptom severity.
The current results suggest that glutamatergic neurometabolite levels in the frontal cortex and neuronal integrity in the thalamus in schizophrenia might be modified following treatment.
•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.
The limited efficacy of available antidepressant therapies may be due to how they affect the underlying brain network. The purpose of this study was to develop a melancholic MDD biomarker to identify ...critically important functional connections (FCs), and explore their association to treatments. Resting state fMRI data of 130 individuals (65 melancholic major depressive disorder (MDD) patients, 65 healthy controls) were included to build a melancholic MDD classifier, and 10 FCs were selected by our sparse machine learning algorithm. This biomarker generalized to a drug-free independent cohort of melancholic MDD, and did not generalize to other MDD subtypes or other psychiatric disorders. Moreover, we found that antidepressants had a heterogeneous effect on the identified FCs of 25 melancholic MDDs. In particular, it did impact the FC between left dorsolateral prefrontal cortex (DLPFC)/inferior frontal gyrus (IFG) and posterior cingulate cortex (PCC)/precuneus, ranked as the second 'most important' FC based on the biomarker weights, whilst other eight FCs were normalized. Given that left DLPFC has been proposed as an explicit target of depression treatments, this suggest that the limited efficacy of antidepressants might be compensated by combining therapies with targeted treatment as an optimized approach in the future.
Depression is one of the common psychiatric disorders in old age. Major depressive disorder (MDD) has been identified as a risk factor or prodrome for neurodegenerative dementias, suggesting ...neuropathological overlaps and a continuum between MDD and neurodegenerative disorders. In this study, we examined tau and amyloid-β (Aβ) accumulations in the brains of MDD and healthy controls using positron emission tomography (PET) to explore pathological substrates of this illness. Twenty MDD and twenty age-matched, healthy controls were examined by PET with a tau radioligand,
CPBB3, and an Aβ radioligand,
CPiB. Radioligand retentions were quantified as a standardized uptake value ratio (SUVR). We also assessed clinical manifestations of the patients using the 17-item Hamilton Depression Scale, the Geriatric Depression Scale, and psychotic symptoms. Mean cortical
CPBB3 SUVRs in MDD patients were significantly higher than those of healthy controls. These values were higher in MDD patients with psychotic symptoms than in those without any. The present findings indicate that tau depositions may underlie MDD, and especially in patients with psychotic symptoms. PET detection of tau accumulations may provide mechanistic insights into neuronal dysfunctions in these cases and could serve as predictions of their clinical consequences.
Tau deposits is a core feature of neurodegenerative disorder following traumatic brain injury (TBI). Despite ample evidence from post-mortem studies demonstrating exposure to both mild-repetitive and ...severe TBIs are linked to tau depositions, associations of topology of tau lesions with late-onset psychiatric symptoms due to TBI have not been explored. To address this issue, we assessed tau deposits in long-term survivors of TBI by PET with 11C-PBB3, and evaluated those associations with late-life neuropsychiatric outcomes. PET data were acquired from 27 subjects in the chronic stage following mild-repetitive or severe TBI and 15 healthy control subjects. Among the TBI patients, 14 were diagnosed as having late-onset symptoms based on the criteria of traumatic encephalopathy syndrome. For quantification of tau burden in TBI brains, we calculated 11C-PBB3 binding capacity (cm3), which is a summed voxel value of binding potentials (BP*ND) multiplied by voxel volume. Main outcomes of the present study were differences in 11C-PBB3 binding capacity between groups, and the association of regional 11C-PBB3 binding capacity with neuropsychiatric symptoms. To confirm 11C-PBB3 binding to tau deposits in TBI brains, we conducted in vitro PBB3 fluorescence and phospho-tau antibody immunofluorescence labelling of brain sections of chronic traumatic encephalopathy obtained from the Brain Bank. Our results showed that patients with TBI had higher 11C-PBB3 binding capacities in the neocortical grey and white matter segments than healthy control subjects. Furthermore, TBI patients with traumatic encephalopathy syndrome showed higher 11C-PBB3 binding capacity in the white matter segment than those without traumatic encephalopathy syndrome, and regional assessments revealed that subgroup difference was also significant in the frontal white matter. 11C-PBB3 binding capacity in the white matter segment correlated with the severity of psychosis. In vitro assays demonstrated PBB3-positive tau inclusions at the depth of neocortical sulci, confirming 11C-PBB3 binding to tau lesions. In conclusion, increased 11C-PBB3 binding capacity is associated with late-onset neuropsychiatric symptoms following TBI, and a close correlation was found between psychosis and 11C-PBB3 binding capacity in the white matter.
Background
Relatively low publication rates of s presented at scientific meetings (i.e. 37.3%, 95% CI: 35.3–39.3) have been reported across various fields worldwide. However, no study has ...investigated the publication rate of s presented at psychiatric meetings and factors associated with full publication in Japan. This study aimed to determine the proportion of conference s in the psychiatric field that reach full publication in English and its associated factors in Japan.
Methods
A retrospective study was conducted to determine the publication rate of s presented at the annual meetings of the Japanese Society of Psychiatry and Neurology (JSPN) in 2013 and 2014, the largest psychiatric meeting in Japan, by searching for full‐text publications in PubMed and Google Scholar. Furthermore, we examined factors associated with a successful full publication of the conference .
Results
Of the 737 s evaluated, 132 (17.9%) were published in peer‐reviewed journals; the publication rates for oral and poster presentations were 12.7% (46/363) and 23.0% (86/374), respectively. In multivariate logistic regression analyses, the following factors were significantly associated with successful publications: poster presentations (odds ratio OR: 1.67, 95% CI: 1.10–2.57), original studies (OR: 4.16, 95% CI: 2.44–7.47), and academic institutions (OR: 5.77, 95% CI: 3.44–10.19).
Conclusions
The publication rate in English of the conference s presented at the JSPN annual meetings was relatively lower than those in previous studies. Further encouragement of the publication of the s presented in psychiatric conferences in Japan would be helpful in disseminating scientific findings in the field of psychiatry.
The norepinephrine transporter has been suggested to play a crucial role in major depressive disorder. However, norepinephrine transporter availability in major depressive disorder and its role with ...clinical symptoms are not known. The authors tested norepinephrine transporter availability in patients with major depressive disorder with the aim to identify any associations between test results and clinical symptoms.
The present research was a cross-sectional study in which 19 patients with major depressive disorder and 19 age- and sex-matched healthy comparison subjects underwent positron emission tomography scanning to evaluate the norepinephrine transporter availability measured by the radioligand (S,S)-
FFMeNER-D
. Norepinephrine transporter availability in the thalamus and its subregions was quantified in terms of nondisplaceable binding potential (BP
). The authors also analyzed the association between norepinephrine transporter availability and clinical symptoms.
Compared with healthy subjects, patients with major depressive disorder showed 29.0% higher BP
values in the thalamus and, in particular, 28.2% higher values in the thalamic subregion anatomically connected to the prefrontal cortex. Elevated norepinephrine transporter availability in the thalamus in patients was positively correlated with attention, as measured by the Trail Making Test, part A.
These findings revealed altered norepinephrine transmission in patients with major depressive disorder, suggesting that this alteration could be related to attention in this patient population.
Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. ...Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.
Background
Alzheimer’s disease (AD) is the most common cause of dementia worldwide. In AD, abnormal tau accumulates within neurons of the brain, facilitated by extracellular β‐amyloid deposition, ...leading to neurodegeneration, and eventually, cognitive impairment. As this process is thought to be irreversible, early identification of abnormal tau in the brain is crucial for the development of new therapeutic interventions.
Aims
18F‐PI‐2620 is one of the second‐generation tau PET tracers with presumably less off‐target binding than its predecessors. Although a few clinical studies have recently reported the use of 18F‐PI‐2620 tau PET in patients with AD, its applicability to AD is yet to be thoroughly examined.
Methods
In the present pilot study, we performed 18F‐PI‐2620 tau PET in seven cases of probable AD (AD group) and seven healthy controls (HC group). Standardized uptake value ratios (SUVR) in regions of interest (ROIs) in the medial temporal region and neocortex were compared between the AD and HC groups. Furthermore, correlations between regional SUVR and plasma p‐tau181 as well as cognitive test scores were also analyzed.
Results
The uptake of 18F‐PI‐2620 was distinctly increased in the AD group across all the ROIs. SUVR in all the target ROIs were significantly correlated with plasma p‐tau181 levels, as well as with MMSE and ADAS‐cog scores.
Discussion & Conclusion
Our results add to accumulating evidence suggesting that 18F‐PI‐2620 is a promising tau PET tracer that allows patients with AD to be distinguished from healthy controls, although a study with a larger sample size is warranted.
The present pilot study examined the ability of 18F‐PI‐2620 tau PET tracer to distinguish between healthy control and Alzheimer's disease, as well as correlations with plasma p‐tau181 and cognitive test results. Though the sample size was small, seven for each group, its SUVR in the target brain regions showed distinct differences between them and high correlations with plasma p‐tau181 and cognitive test results.
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