Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD).

Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test.

euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068).

Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Interactions between the endocannabinoid system (ECS) and neurotransmitter systems might mediate the risk of developing a schizophrenia spectrum disorder (SSD). Consequently, we investigated in patients with SSD and healthy controls (HC) the relations between (1) plasma concentrations of two prototypical endocannabinoids (N-arachidonoylethanolamine [anandamide] and 2-arachidonoylglycerol [2-AG]) and (2) striatal dopamine synthesis capacity (DSC), and glutamate and y-aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC). As anandamide and 2-AG might reduce the activity of these neurotransmitters, we hypothesized negative correlations between their plasma levels and the abovementioned neurotransmitters in both groups.

Blood samples were obtained from 18 patients and 16 HC to measure anandamide and 2-AG plasma concentrations. For all subjects, we acquired proton magnetic resonance spectroscopy scans to assess Glx (i.e. glutamate plus glutamine) and GABA + (i.e. GABA plus macromolecules) concentrations in the ACC. Ten patients and 14 HC also underwent [18F]F-DOPA positron emission tomography for assessment of striatal DSC. Multiple linear regression analyses were used to investigate the relations between the outcome measures.

A negative association between 2-AG plasma concentration and ACC Glx concentration was found in patients (p = 0.008). We found no evidence of other significant relationships between 2-AG or anandamide plasma concentrations and dopaminergic, glutamatergic, or GABAergic measures in either group.

Our preliminary results suggest an association between peripheral 2-AG and ACC Glx levels in patients.

Despite frequent benzodiazepine use in anxiety disorders, the trajectory and magnitude of benzodiazepine response and the effects of benzodiazepine potency, lipophilicity, and dose on improvement are unknown.

We performed a meta-analysis using weekly symptom severity data from randomized, parallel group, placebo-controlled trials of benzodiazepines in adults with anxiety disorders. Response was modeled for the standardized change in continuous measures of anxiety using a Bayesian hierarchical model. Change in anxiety was evaluated as a function of medication, disorder, time, potency, lipophilicity, and standardized dose and compared among benzodiazepines.

Data from 65 trials (73 arms, 7 medications, 7110 patients) were included. In the logarithmic model of response, treatment effects emerged within 1 week of beginning treatment (standardized benzodiazepine-placebo difference = −0.235 ± 0.024, CrI: −0.283 to −0.186, P < .001) and placebo response plateaued at week 4. Doses <6 mg per day (lorazepam equivalents) produced faster and larger improvement than higher doses (P = .039 for low vs medium dose and P = .005 for high vs medium dose) and less lipophilic benzodiazepines (beta = 0.028 ± 0.013, P = .030) produced a greater response over time. Relative to the reference benzodiazepine (lorazepam), clonazepam (beta = −0.217 ± 0.95, P = .021) had a greater trajectory/magnitude of response (other specific benzodiazepines did not statistically differ from lorazepam).

In adults with anxiety disorders, benzodiazepine-related improvement emerges early, and the trajectory and magnitude of improvement is related to dose and lipophilicity. Lower doses and less lipophilic benzodiazepines produce greater improvement.

Studies examining gamma-aminobutyric acid (GABA) or glutamate in ultra-high risk for psychosis (UHR) have shown conflicting results, and a number of multimodal studies examining associations between metabolite and structural characteristics is very limited.

We aimed to investigate potential associations between GABA and glutamate levels and cortical thickness in the frontal lobe in UHR individuals and healthy controls (HC).

20 male UHR individuals and 19 healthy controls (HC) underwent structural MRI and MR spectroscopy at 3T Philips scanner. T1-weighted images were processed via FreeSurfer 6.0 to quantify cortical thickness for selected frontal regions labeled according to Desikan atlas. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GABA and glutamate were calculated as ratios to creatine + phosphocreatine.

The study revealed: 1) GABA/Cr ratios reduction in the left frontal lobe (p=0.001) which was not attributable to antipsychotic medication; 2) cortical thickness reductions in the left pars orbitalis (p=0.005) (the anterior part of the inferior frontal gyrus) in the UHR individuals compared to HC. No significant correlations between GABA/Cr ratios and cortical thickness were identified in both groups.

The findings indicate that the UHR state is associated with altered GABA levels and cortical thickness reductions in the prefrontal cortex. The results also show that GABA levels are not directly related to cortical abnormalities, suggesting that altered metabolite levels may be associated with a complex system of structural and functional impairments, rather than directly correlating with structural changes in separate cortical regions. The work was supported by RFBR grant 19-29-10040.

No significant relationships.

Anxiety disorders are a mental disorder that is widespread all over the world and are associated with a high burden of the disease. While poor dietary habits are common in depression, they can lead to worsening of the illness or prolong the treatment, which also leads to a higher risk of developing chronic diseases.

With the array of the treatment modalities including monoaminergic antidepressants, benzodiazepines, psychotherapy, there is the unmet need for the effective treatment of anxiety disorders resulting in full remission and relapse prevention. Benzodiazepines can quickly resolve anxiety due to their positive allosteric GABA modulation mechanism of action. Although, they are not recommended for chronic use.

Ketogenic diet(KD) may be hypothesized as the promising strategy impacting treatment strategies, in particularly facilitating full remission, recovery and preventing relapses. In this popular high-fat diet, where daily calories intake is consists in at least 70% from fat, up to 25 % from protein and as little sugar as possible is mainly known for its helpful role in drug resistant epilepsy treatment, glucose levels balance or fast way for weight-loss.

Could be effective in anxiety disorders treatment due to its possible role in GABA:glutamate balance change in favor of GABA levels, which may enhance the anxiolytic effect in sustaining remission and preventing relapse.

KD in some anxiety disorders may provide a rewarding outcome, but more research is needed. The evidence mentioned in this paper should encourage psychiatrists to recommend KD as advice somewhere between psychotherapy, pharmacology or as an add-on to those two.

Neurobehavioral research on the role of impulsivity in gambling disorder (GD) has produced heterogeneous findings. Impulsivity is multifaceted with different experimental tasks measuring different subprocesses, such as response inhibition and distractor interference. Little is known about the neurochemistry of inhibition and interference in GD.

We investigated inhibition with the stop signal task (SST) and interference with the Eriksen Flanker task, and related performance to metabolite levels in individuals with and without GD. We employed magnetic resonance spectroscopy (MRS) to record glutamate–glutamine (Glx/Cr) and inhibitory, γ-aminobutyric acid (GABA+/Cr) levels in the dorsal ACC (dACC), right dorsolateral prefrontal cortex (dlPFC), and an occipital control voxel.

We found slower processing of complex stimuli in the Flanker task in GD (P < .001, η2 p = 0.78), and no group differences in SST performance. Levels of dACC Glx/Cr and frequency of incongruent errors were correlated positively in GD only (r = 0.92, P = .001). Larger positive correlations were found for those with GD between dACC GABA+/Cr and SST Go error response times (z = 2.83, P = .004), as well as between dACC Glx/Cr and frequency of Go errors (z = 2.23, P = .03), indicating general Glx-related error processing deficits. Both groups expressed equivalent positive correlations between posterror slowing and Glx/Cr in the right dlPFC (GD: r = 0.74, P = .02; non-GD: r = .71, P = .01).

Inhibition and interference impairments are reflected in dACC baseline metabolite levels and error processing deficits in GD.

Cerebral glutamate and gamma-aminobutyric acid (GABA) levels might predict clinical outcome in individuals at ultrahigh risk (UHR) for psychosis but have previously primarily been investigated in smaller cohorts. We aimed to study whether baseline levels of glutamate and GABA in anterior cingulate cortex (ACC) and glutamate in thalamus could predict remission status and whether baseline metabolites differed in the remission versus the nonremission group. We also investigated the relationship between baseline metabolite levels and severity of clinical symptoms, functional outcome, and cognitive deficits at follow-up.

About 124 UHR individuals were recruited at baseline. In this, 74 UHR individuals were clinically and cognitively assessed after 12 months, while remission status was available for 81 (25 remission/56 nonremission). Glutamate and GABA levels were assessed at baseline using 3 T proton magnetic resonance spectroscopy. Psychopathology, symptom severity, and remission were assessed with the Comprehensive Assessment of At-Risk Mental States and Clinical Global Impression and functional outcome with the Social and Occupational Functioning Assessment Scale. Cognitive function was estimated with the Cambridge Neuropsychological Test Automated Battery.

There were no differences between baseline glutamate and GABA levels in subjects in the nonremission group compared with the remission group, and baseline metabolites could not predict remission status. However, higher baseline levels of GABA in ACC were associated with clinical global improvement (r = −0.34, N = 51, p = 0.01) in an explorative analysis.

The variety in findings across studies suggests a probable multifactorial influence on clinical outcome in UHR individuals. Future studies should combine multimodal approaches to attempt prediction of long-term outcome.

Les effets cliniques de l’intoxication alcoolique aiguë seraient liés à une modulation des systèmes de neurotransmission du GABA et du glutamate. Les caractéristiques longitudinales de cette modulation et l’impact de la dose d’éthanol absorbée restent mal connus. Nous avons voulu étudier in vivo les effets aigus de l’éthanol sur les niveaux de GABA et de glutamate du cortex préfrontal en spectroscopie par résonance magnétique (SRM).

Après une première acquisition de SRM (zone préfrontale), trois groupes de rats Wistar mâles (363 ± 27 g) ont reçu par voie intrapéritonéale (IP) :

– éthanol 1 g/kg (n = 6) ;

– éthanol 2 g/kg (n = 8) ;

– sérum physiologique (n = 5).

Des acquisitions répétées de SRM ont été réalisées jusque 300 minutes post-injection. Une cinétique de l’éthanolémie a également été réalisée dans des groupes similaires de rats Wistar. Après alcoolisation par voie IP, des prélèvements sanguins successifs ont été réalisés jusque 180 minutes pour le groupe 1 g/kg (n = 6) et 300 minutes pour le groupe 2 g/kg (n = 14). Pour la SRM, des analyses statistiques inter- et intragroupes ont été effectuées à l’aide d’un modèle linéaire mixte visant à étudier la variation des taux de GABA et glutamate.

La cinétique de l’éthanolémie était superposable à celle de la cinétique cérébrale. En SRM, une diminution significative du GABA, de 11,4 % ± 3,8 % (p < 0,0059) dans le groupe 1 g/kg et du glutamate de 13,8 % ± 2,6 % dans le groupe 2 g/kg (p < 0,0001) ont été observées, sans modification significative dans les autres groupes. La variation du ratio GABA/glutamate s’est montrée différente entre les deux groupes éthanol avec une augmentation dans le groupe 2 g/kg et une diminution dans le groupe 1 g/kg (p < 0,01).

La dose d’éthanol détermine les variations des niveaux de GABA et de glutamate du cortex préfrontal, pouvant expliquer les différents effets cliniques induits par l’alcool selon la dose.