Mood, psychomotor, and cognitive function in major depressive disorder: from biomarkers to rapid-acting antidepressants

Is ( S )-norketamine an alternative antidepressant for esketamine?

Antidepressants during pregnancy: a French drug utilisation study in EFEMERIS cohort Abstract Background Previous studies have suggested that exposure to some antidepressants (AD) during pregnancy could be associated with an increased risk of congenital malformations and neurodevelopment disorders for the child. We conducted a study to describe the use of AD during pregnancy in France. Methods We performed a drug utilisation study in EFEMERIS, a French cohort of pregnant women. At the time of the present study, 89,170 pregnant women, who were pregnant from 2005 to 2014 in Haute-Garonne were included. Prevalence and incidence of AD prescriptions during pregnancy, characteristics of AD users, and trends in AD use over the 10-year period were studied. Results During the 10-year study period, 1620 women registered in EFEMERIS (1.8%) received at least one prescription and dispensation for AD during pregnancy: 1363 during the first (1.5%), 591 during the second (0.7%), and 412 during the third (0.5%) trimester. A total of 2874 women (3.2%) got a prescription for an AD during the 3 months before and/or during pregnancy; 2187 of them (76.1%) stopped AD before pregnancy or during the first trimester. Selective serotonin reuptake inhibitors represented the most prescribed class during pregnancy (1.3%). A very slight decrease in the prevalence of AD prescriptions in pregnant women over time (1.7% in 2014 vs 2% in 2005) and some variations within classes were observed. Conclusions Nearly, 2% of women received antidepressant drugs during pregnancy. This assessment encourages following research on these drugs including the potential risk of neurodevelopmental disorders in children after an exposure to antidepressants during pregnancy.

Amygdala response and functional connectivity during cognitive emotion regulation of aversive image sequences Abstract Emotion regulation (ER) is crucial in terms of mental health and social functioning. Attention deployment (AD) and cognitive reappraisal (CR) are both efficient cognitive ER strategies, which are based on partially dissociated neural effects. Our understanding of the neural underpinnings of ER is based on laboratory paradigms that study changes of the brain activation related to isolated emotional stimuli. To track the neural response to ER in the changing and dynamic environment of daily life, we extended the common existing paradigms by applying a sequence of emotionally provocative stimuli involving three aversive images. Eighteen participants completed an ER paradigm, in which they had to either shift their attention away from the emotionally negative images by counting backwards (AD strategy) or reinterpret the meaning of stimuli (CR strategy) to attain a down-regulation of affective responses. An increased recruitment of left-sided lateral and medial PFC was shown upon regulation of negative emotions with CR as compared to AD. Remarkably, the amygdala activation showed an increasing pattern of activation during CR. The inverse relationship between PFC and amygdala was compromised during elongated blocks of reappraisal, reflecting a reduction in engagement of the top-down prefrontal regulatory circuitry upon repeated exposure to negative stimuli. These results highlight that temporal dynamic of amygdala response and its functional connectivity differentiates AD and CR strategies in regulating emotions. Findings of the current study underscore the importance of adopting temporally variant approaches for investigating the neural effects of ER. Identifying neural systems that subserve down-regulation of negative emotions is of importance in developing treatment strategies for various forms of psychopathology.

Combined cognitive, psychomotor and electrophysiological biomarkers in major depressive disorder Abstract The diagnosis of major depressive disorder (MDD) should be based on multimodal evidence, because MDD not only affects mood, but also psychomotor and cognitive functions. Clinical markers such as executive dysfunctions and a reduction in daily motor activity have been observed in MDD. Neurophysiological biomarkers have also been described. In this study, we investigate the utility of combining biomarkers related to executive dysfunctions, motor activity, neurophysiological patterns (i.e. alpha power asymmetry and EEG-vigilance as indicators of brain arousal), and the interaction of these parameters in the diagnosis of MDD. Twenty (female: 11) patients with MDD (age: 51.05 ± 10.50) and 20 (female: 13) healthy controls (HC; age: 47.15 ± 12.57) underwent a 10-min resting EEG. Executive dysfunctions were assessed using the Trail Making Test B (TMT B). Motor activity was analysed by actigraphy measurements. MDD patients displayed significant impairments in executive functions and reduced daily motor activity. In the EEG, MDD patients showed more right than left frontal activity and lower brain arousal relative to HC. TMT B and asymmetrical frontal alpha power alone discriminated between MDD patients and HC with an accuracy of 78%. The interaction of motor activity and the EEG-vigilance stage alongside TMT B increased the accuracy of the discrimination test to 81%. This improved accuracy suggests that the combination of these biomarkers in a discriminant analysis resulted in a more reliable identification of MDD patients.

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a voxel-based morphometry study Abstract Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = − 0.51, p = 0.04) and in male BD patients (r = − 0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Bipolar disorder in the balance Abstract Bipolar disorder (BD) is a severe mood disorder that lacks established electrophysiological, neuroimaging or biological markers to assist with both diagnosis and monitoring disease severity. This study’s aim is to describe the potential of new neurophysiological features assistive in BD diagnosis and severity measurement utilizing the recording of electrical activity from the outer ear canal called Electrovestibulography (EVestG). From EVestG data sensory vestibulo-acoustic features were extracted from a single supine-vertical translation stimulus to distinguish 50 depressed and partly remitted/remitted bipolar disorder patients [18 symptomatic (BD-S, MADRS > 19), 32 reduced symptomatic (BD-R, MADRS ≤ 19)] and 31 age and gender matched healthy individuals (controls). Six features were extracted from the measured firing pattern interval histogram and the extracted shape of the average field potential response. Five of the six features had low but significant correlations (p < 0.05) with the MADRS assessment. Using leave-one-out-cross-validation, unbiased parametric and non-parametric classification routines resulted in 75–79%, 84–86%, 76–85% and 79–82% accuracy for separation of control from BD, BD-S and BD-R as well as BD-S from BD-R groups, respectively. The main limitation of this study was the inability to fully disentangle the impact of prescribed medication from the responses recorded. A mix of stationary and movement evoked EVestG features produced good discrimination between control and BD patients whether BD-S or BD-R. Moreover, BD-S and BD-R appear to have measurably different pathophysiological manifestations. The firing pattern features used were dissimilar to those observed in a prior major depressive disorder study.

A novel seizure quality index based on ictal parameters for optimizing clinical decision-making in electroconvulsive therapy. Part 2: Validation Abstract Early identification of patients who are at a high risk for an unfavorable outcome to ECT during the treatment course might be beneficial because it provides an opportunity for timely intensification or optimization of stimulus conditions. We aimed to validate a previously developed seizure quality index (SQI) that delivers a clinically relevant outcome prediction early in the treatment course and can be used within common clinical setting. Therefore, a prospective study was conducted. Patients (n = 26) below the age of 65 years with a depressive episode and the clinical decision for ECT (right unilateral, brief pulse) were included and several ictal parameters, the SQI for non-response and non-remission, and the clinical outcome of the patients were documented. Logistic regression analysis revealed a statistically significant association between the SQI and non-response (p = 0.035). A significant association between the clinical outcome of non-response and the classified outcome of non-response was detected (p = 0.041). The overall classification accuracy regarding response/non-response was 71.3%, and the model revealed a sensitivity of 84.6% and a specificity of 61.5% for non-response. In this study, we could validate the SQI for the clinical outcome of non-response, but not for non-remission. Based on our data, the SQI might become an interesting clinical tool for early outcome prediction for ECT in patients with depression.

Prevalence of seasonal depression in a prospective cohort study Abstract The prevalence of autumn/winter seasonality in depression has been documented in the longitudinal Zurich cohort study by five comprehensive diagnostic interviews at intervals over more than 20 years (N = 499). Repeated winter major depressive episodes (MDE—unipolar + bipolar) showed a prevalence of 3.44% (5× more women than men), whereas MDE with a single winter episode was much higher (9.96%). A total of 7.52% suffered from autumn/winter seasonality in major and minor depressive mood states. The clinical interviews revealed novel findings: high comorbidity of Social Anxiety Disorder and Agoraphobia within the repeated seasonal MDE group, high incidence of classic diurnal variation of mood (with evening improvement), as well as a high rate of oversensitivity to light, noise, or smell. Nearly twice as many of these individuals as in the other MDE groups manifested the syndrome of atypical depression (DSM-V), which supports the prior description of seasonal affective disorder (SAD) as presenting primarily atypical symptoms (which include hypersomnia and increase in appetite and weight). This long-term database of regular structured interviews provides important confirmation of SAD as a valid diagnosis, predominantly found in women, and with atypical vegetative symptoms.

Relationship between VEGF-related gene polymorphisms and brain morphology in treatment-naïve patients with first-episode major depressive disorder Abstract Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype–diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype–diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The “hypochondriasis” scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.