Current Depressive Episode Research Articles

A Randomized Double-Blind Midazolam-Controlled Trial of Low-Dose Ketamine Infusion in Patients With Treatment-Resistant Depression and Prominent Suicidal Ideation.

The benefits of low-dose ketamine for patients with treatment-resistant depression (TRD) and prominent suicidal ideation require further investigation. The effects of treatment refractoriness, the duration of the current depressive episode, and the number of prior antidepressant failures on ketamine efficacy also require clarification. We recruited 84 outpatients with TRD and prominent suicidal ideation- defined as a score of ≥4 on Item 10 of the Montgomery-Asberg Depression Rating Scale (MADRS)-and randomized them into two groups to receive 0.5mg/kg ketamine or 0.045mg/kg midazolam. We assessed depressive and suicidal symptoms prior to infusion, 240min postinfusion, and 2, 3, 5, 7, and 14 days postinfusion. According to the MADRS scores, the antidepressant effect (p = .035) was noted significantly in the ketamine group up to 14 days than in the midazolam group. However, the antisuicidal effect of ketamine, as measured by the Columbia-Suicide Severity Rating Scale Ideation Severity Subscale (p = .040) and MADRS Item 10 (p = .023) persisted only 5 days postinfusion. Furthermore, the antidepressant and antisuicidal effects of ketamine infusion were noted particularly in patients whose current depressive episode lasted for <24 months or whose number of failed antidepressants was ≤4. Low-dose ketamine infusion is a safe, tolerable, and effective treatment for patients with TRD and prominent suicidal ideation. Our study highlights the importance of timing; specifically, ketamine is more likely to achieve therapeutic response when the current depressive episode lasted for <24 months and the number of failed antidepressants is ≤4.

Predictors of response and remission in patients with treatment-resistant depression: A post hoc pooled analysis of two acute trials of esketamine nasal spray

This exploratory post hoc analysis of two pooled 4-week, phase 3, double-blind, placebo- and active-controlled studies that compared esketamine nasal spray plus a newly initiated oral antidepressant (ESK+AD; n = 310) with a newly initiated oral AD plus placebo nasal spray (AD+PBO; n = 208) in patients with treatment-resistant depression (TRD) examined baseline patient demographic and psychiatric characteristics as potential predictors of response (≥50% reduction from baseline in Montgomery–Åsberg Depression Rating Scale [MADRS] total score) and remission (MADRS total score ≤12) at day 28. Overall, younger age, any employment, fewer failed ADs in the current depressive episode, and reduction in Clinical Global Impression-Severity (CGI-S) score at day 8 were significant positive predictors of response and remission at day 28. Treatment assignment was an important predictor of both response and remission. Patients treated with ESK+AD had 68% and 55% increased odds of achieving response and remission, respectively, versus those treated with AD+PBO. In the ESK+AD group, attainment of response and remission was more likely in patients who were employed, without significant anxiety at baseline, and who experienced a reduction in CGI-S score at day 8. Identification of predictors of response and remission may facilitate identification of those patients with TRD most likely to benefit from ESK+AD.Trial Registration: ClinicalTrials.gov: NCT02417064 (clinicaltrials.gov/ct2/show/NCT02417064) and NCT02418585 (clinicaltrials.gov/ct2/show/NCT02418585)

Thought Disorders in Depressive Adolescents with High-Risk for Schizophrenia

Background: the need to develop methods for early diagnostics and preventive interventions in individuals at clinical high-risk state for schizophrenia requires studying the characteristics of the specific symptoms of pre-onset stages. One of such symptoms may be thought disorder, which still have an ambiguous position in the psychopathological structure of schizophrenia.Aim: correlation analysis of thought disorders in patients with first depressive episode with attenuated symptoms of schizophrenia (ASS).Patients and methods: the study included 30 young men (mean age 19.2 ± 2.1 years) hospitalized with the first depressive episode (F32.1, F32.2, F32.28, F32.8 on ICD-10), in the structure of which ASS were noted. The severity of thought disorders was assessed using the Thought, Language and Communication scale (TLC) before discharge. Subsequently was performed the search for correlations of scores on the TLC and other characteristics as duration of the current depressive episode, severity of depressive symptoms according to the Hamilton Depression Rating Scale (HDRS), the severity of ASS according to Scale of Prodromal Symptoms (SOPS) and Scale for Assessment of Negative Symptoms (SANS), drug therapy doses.Results: the median value of the total score on the TLC was 20 [17.3;23.5]. The most important finding is the discovery of only weak correlations of thought disorders with depressive affect and ASS. Indeed, the total score on the TLC correlated only with the total score on the SOPS at admission (r = 0.370, p &lt; 0.05), which refiects the relationship between the thought disorders and the activity of endogenous process in the early stages, and with the SANS subscale “Attention” at discharge (r = 0.388, p &lt; 0.05), which also indirectly refiects the existing thought disorders. The greatest number of correlations was demonstrated by the TLC parameter “Illogicality”.Conclusion: the data obtained indicates the independent nature of thought disorders in youth patients with first-onset of depression, which indicates the need to determine its independent prognostic value for schizophrenia manifestation.

The influence of depression symptoms on postmorbid adaptation of patients after SARS-CoV-2 infection

IntroductionThe study discusses the possibility of assessing postmorbid adaptation in depressed patients who had SARS-CoV-2 infection, within the framework of a multimorbidity model. This model takes into account not only mental, but also somatic clusters and allows to identify non-randomly occurring, related conditions and their impact on the ability to recover.ObjectivesThe aim of the study is evaluation of the impact of psychosomatic and anxiety symptoms of depression on the formation of postmorbid adaptation in a group of patients who underwent outpatient SARS-CoV-2 infection.MethodsThe data of 54 patients aged 25-55 years with a current depressive episode who underwent outpatient SARS-CoV-2 infection were analyzed. We used the Hamilton depression rating scale (HDRS); the somatic condition was assessed using a general assessment of the patient’s function limitation at the stage of convalescence. A linear regression analysis was performed to assess the association of psychosomatic and anxiety symptoms with somatic condition in SARS-CoV-2 infection, regardless of other factors.ResultsAn association was established in patients with SARS-CoV-2 infection showing signs of psychosomatic and anxiety symptoms of depression. Patterns of somatic and anxiety symptoms were independently associated with impaired postmorbid adaptation, other manifestations of depression did not show such association. This fact raises the question of whether depression syndrome is really associated with an impaired postmorbid adaptation in the postcovid period, or only certain specific symptoms of somatic anxiety explain the low readaptation capacity in this group of patients.ConclusionsIdentification of clusters of symptoms associated with an impact on the full recovery possibilities in the SARS-CoV-2-postmorbid period can significantly help in providing high-quality and targeted psychopharmacological care.Disclosure of InterestNone Declared

Clinical characteristics of bipolar 1 disorder in relation to interleukin-6: a cross-sectional study among Egyptian patients

BackgroundStrong evidence in the literature points to the role of pro-inflammatory cytokines in bipolar disorder (BD) pathophysiology. Interleukin-6 (IL-6) is a pro and anti-inflammatory cytokine that was repeatedly found higher in bipolar patients than in healthy controls. However, studies on the phasic differences of IL-6 in bipolar type I (BP-I) were limited. This study aims to explore the phasic differences of serum IL-6 levels in BP-I during euthymia, depression, and mania and their association with the disease’s clinical characteristics in a sample of Egyptian BP-I patients. Thirty currently euthymic, 24 currently depressed, 29 currently manic BP-I patients, and 20 healthy subjects were recruited. Serum IL-6 levels were compared among BP-I groups and then between each group and a group of 20 healthy controls. Serum IL-6 levels (pg/ml) were measured with a sandwich enzyme-linked immunosorbent assay (ELISA). Depression and mania symptoms were assessed using the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS), respectively. Clinical characteristics were evaluated through a semi-structured clinical psychiatric interview, and cognitive status was tested using the Montreal Cognitive Assessment (MoCA).ResultsSerum IL-6 levels were significantly higher in each bipolar phase than in healthy subjects. In the BP-I patients, IL-6 levels were lower in patients with a current manic episode than in patients with a current depressive episode (P < 0.05) or who were currently euthymic (P < 0.001). Moreover, IL-6 levels correlated inversely with the YMRS score (rs = − 0.29; P < 0.05). Compared to patients without psychotic features, patients with psychotic features had decreased serum IL-6. Moreover, IL-6 levels were lower in inpatients compared to outpatients.ConclusionsBP-I disorder is associated with an inflammatory state. The decreased levels of IL-6 during manic episodes, affective episodes with psychotic features, and their inverse correlation with the severity of mania symptoms indicate a possible anti-inflammatory role of IL-6 in mania and psychotic symptoms pathogenesis.

A Case of Severe Somatized Depression in a Young Adult: Diagnostic Challenges

IntroductionDepressive disorders in adolescence and young adulthood have always been and remain an urgent problem due to their fairly high prevalence among the population, serious difficulties in diagnosis and untimely treatment. Timely diagnosis and adequate treatment can have a powerful impact on the future life of a person in a positive context. This process requires both standardized mechanisms, and an individual detailed study of each case, as the future of the individual depends on it.ObjectivesA young adult M., 20 years old, a university student, from a socially prosperous family, approached us.Main complaints: headaches that have been going on for almost 4 years. Pains did not depend on loads, both physical and mental, were of various characteristic and different localization. Non-steroidal anti-inflammatory drugs, as well as anti-migraine drugs, have little effect on the pathological experiences.MethodsOur main method of examination was clinical interview. In the complex assessment detailed neurological and ophtalmological examination included.ResultsThe parents referred patient for a medical examination about a year ago, because they noticed persistent mydriasis in him. During the year, the patient underwent a detailed examination (consultations of a therapist, endocrinologist, neurologist, ophthalmologist, MRI, EEG, dopplerography). Doctors expressed various assumptions about the diagnosis, because all the studies did not reveal any pathology that could explain the indicated complaints and mydriasis.During the initial interview, a high level of intelligence and knowledge was revealed, as well as a sufficient ability to learn. Examining the emotional-volitional sphere, a slight level of emotional instability, mild irritability, anhedonia and a slight degree of hypobulia (which can be explained by long-lasting and persistent pathological somatic experiences in the form of headaches) were found. Incomplete Protopopov’s triad was revealed.The patient was referred for repeated neurological and ophthalmological examination. Specialists with a high qualification level discovered the A. Athanassio symptom in him.He was diagnosed with recurrent depressive disorder, a current episode of severe depression with somatic symptoms, and appropriate treatment was prescribed.Conclusions1. Depressive disorders in adolescence and young adulthood require special attention from specialists of all medical specialties.2. The need for a detailed medical examination and modern neuroimaging methods is beyond doubt.3. Psychiatric examination cannot be limited to assessment of mental status only, and assessment of Protopopov’s triad should be part of psychiatric examination.4. Neurological and ophthalmological examination must necessarily include an assessment of neuro-ophthalmological symptoms.5. Individual selection of treatment should be carried out by a psychiatrist.Sorry to say, Professor Mykola Pityk died 27.12.2020Disclosure of InterestNone Declared

Effects of current and past depressive episodes on behavioral performance and subjective experience during an N-back task

Background and objectivesDepression impairs working memory (WM). And, while many studies have documented impairment in WM during depression remission, those using the N-back task did not find differences between individuals with remitted depression and healthy controls. One reason for these findings may be that certain depression phenotypes, such as the childhood-onset form, which is likely to be associated with persistent WM problems, are underrepresented or unevenly represented in the studies. Because childhood-onset depression (COD) affects individuals while cognitive development is still ongoing, it is more likely to have lasting detrimental effects, as evidenced in residual memory impairment, than depression that onsets later in life. Further, it is unclear if depression episodes have cumulative effects on WM when measured via the N-back. MethodsWe examined the effects of depression on WM performance (response time, accuracy, signal detection d’) and subjective experience (difficulty, mental effort required) during a four-level N-back task among 112 adults with COD (42 currently depressed; 70 remitted depressed) and 80 never-depressed controls. ResultsCompared to never-depressed controls, there was minimal evidence of impaired WM performance among participants with remitted or current depression; the groups also reported overall similar subjective experiences during the N-back. Notably, number of lifetime depressive episodes had a detrimental cumulative effect on response accuracy and d’. LimitationsWM was assessed only in regard to verbal memory. The sample size of currently depressed cases was smaller than that of the other groups. ConclusionsWM remains largely intact among adults with remitted COD, but increased number of depression episodes worsens WM performance.

Evaluating EEG complexity metrics as biomarkers for depression.

Nonlinear EEG analysis offers the potential for both increased diagnostic accuracy and deeper mechanistic understanding of psychopathology. EEG complexity measures have previously been shown to positively correlate with clinical depression. In this study, resting state EEG recordings were taken across multiple sessions and days with both eyes open and eyes closed conditions from a total of 306 subjects, 62 of which were in a current depressive episode, and 81 of which had a history of diagnosed depression but were not currently depressed. Three different EEG montages (mastoids, average, and Laplacian) were also computed. Higuchi fractal dimension (HFD) and sample entropy (SampEn) were calculated for each unique condition. The complexity metrics showed high internal consistency within session and high stability across days. Higher complexity was found in open-eye recordings compared to closed eyes. The predicted correlation between complexity and depression was not found. However, an unexpected sex effect was observed, in which males and females exhibited different topographic patterns of complexity.

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.

We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

AI-based dimensional neuroimaging system for characterizing heterogeneity in brain structure and function in major depressive disorder: COORDINATE-MDD consortium design and rationale

BackgroundEfforts to develop neuroimaging-based biomarkers in major depressive disorder (MDD), at the individual level, have been limited to date. As diagnostic criteria are currently symptom-based, MDD is conceptualized as a disorder rather than a disease with a known etiology; further, neural measures are often confounded by medication status and heterogeneous symptom states.MethodsWe describe a consortium to quantify neuroanatomical and neurofunctional heterogeneity via the dimensions of novel multivariate coordinate system (COORDINATE-MDD). Utilizing imaging harmonization and machine learning methods in a large cohort of medication-free, deeply phenotyped MDD participants, patterns of brain alteration are defined in replicable and neurobiologically-based dimensions and offer the potential to predict treatment response at the individual level.International datasets are being shared from multi-ethnic community populations, first episode and recurrent MDD, which are medication-free, in a current depressive episode with prospective longitudinal treatment outcomes and in remission. Neuroimaging data consist of de-identified, individual, structural MRI and resting-state functional MRI with additional positron emission tomography (PET) data at specific sites. State-of-the-art analytic methods include automated image processing for extraction of anatomical and functional imaging variables, statistical harmonization of imaging variables to account for site and scanner variations, and semi-supervised machine learning methods that identify dominant patterns associated with MDD from neural structure and function in healthy participants.ResultsWe are applying an iterative process by defining the neural dimensions that characterise deeply phenotyped samples and then testing the dimensions in novel samples to assess specificity and reliability. Crucially, we aim to use machine learning methods to identify novel predictors of treatment response based on prospective longitudinal treatment outcome data, and we can externally validate the dimensions in fully independent sites.ConclusionWe describe the consortium, imaging protocols and analytics using preliminary results. Our findings thus far demonstrate how datasets across many sites can be harmonized and constructively pooled to enable execution of this large-scale project.

Are serum levels of inflammatory markers associated with the severity of symptoms of bipolar disorder?

To explore the relationship between serum levels of inflammatory markers and symptomatic severity of bipolar disorder (BD). A cross-sectional study was conducted on 126 BD patients with current depressive episode (BDD), 102 BD patients with current mixed or (hypo)manic episode (BDM) and 94 healthy controls (HC). All participants were drug-naïve and had no current active physical illness associated with inflammatory response or history of substance abuse. Fasting serum levels of CRP, leptin (LEP), adiponectin (ADP), visfatin (VIS), TNF-α, IL-2, IL-6, IL-10, IL-17), and monocyte chemoattractant protein-1 (MCP-1) were measured with enzyme-linked immunosorbent assay (ELISA). Symptomatic severity of BD was assessed with HAMD-17 and YMRS. Generalized linear model was used to determine the association between the serum levels of inflammatory markers and symptomatic severity of BD. The serum levels of IL-6, IL-10 and IL-17, and the IL-6/IL-10 ratio were significantly lower in mild BDD than in HC. In moderate BDD, the serum levels of MCP, IL-6 and IL-17 were significantly lower than in HC. In severe BDD, the serum level of ADP, MCP-1, IL-10 and IL-17and the IL-17/IL-10 ratio were significantly lower than in HC. The serum levels of TNF-α and the IL-6/IL-10 ratio were significantly higher in mild BDM than in HC. In moderate BDM, the serum level of VIS, IL-2, and IL-17 were significantly higher than in HC, but the IL-6/IL-10 ratio was significantly lower than in control. In severe BDM, the serum levels of IL-6 and IL-17 and the ratios of IL-6/IL-10 and IL-17/IL-10 were significantly lower than in HC, but the neutrophil/lymphocyte ratio was significantly higher than in HC. In BDD, immune-inhibition is persistently predominant, while in mild-to-moderate BDM, immune system is activated but inhibited in severe BDM. The dynamic change of serum inflammatory markers suggests that alteration of peripheral inflammatory markers in BD is state-dependent instead of trait-marked.

Os transtornos mentais dos cuidadores podem estar associados a comportamentos alimentares obesogênicos na infância?

Abstract Objective: to assess the association between caregivers’ mental disorders and schoolchildren’s obesogenic eating behavior. Methods: cross-sectional study used a public school-based sample of children and their primary caregivers. Caregivers had to report depressive episodes or generalized anxiety disorder (GAD) during the Mini-International Neuropsychiatric Interview (MINI). Children’s obesogenic eating behavior were assessed using food responsiveness (FR) and emotional overeating (EOE) subscales of the Children’s Eating Behaviour Questionnaire (CEBQ). Bivariate analysis was conducted using the t-test, ANOVA, Pearson correlation, and adjusted linear regression model was used (including variables caregivers: sex, age, economic indicator, and schooling; schoolchildren: sex and nutritional status). Results: study includes 596 children-caregiver dyads (309 boys and 287 girls). Among caregivers, 24.7% had experienced current depressive episodes, 38.7% had past depressive episodes, and 17.2% had GAD. We observed, after adjusted analysis, that having a caregiver in a current depressive episode, increases schoolchildren’s obesogenic behavior of, for FR at 0.235 points (β=0.235; CI95%=0.022-0.449;) and EOE at 0.337 points (β=0.337; CI95%=0.162-0.512). Conclusion: caregivers’ current depressive episodes were associated with higher averages of obesogenic eating behavior (caregiver-reported), both in consuming palatable food without feeling hungry (FR) and in increasing food intake in response to negative emotions (EOE).

In vivo serotonin 1A receptor hippocampal binding potential in depression and reported childhood adversity.

Reported childhood adversity (CA) is associated with development of depression in adulthood and predicts a more severe course of illness. Although elevated serotonin 1A receptor (5-HT1AR) binding potential, especially in the raphe nuclei, has been shown to be a trait associated with major depression, we did not replicate this finding in an independent sample using the partial agonist positron emission tomography tracer [11C]CUMI-101. Evidence suggests that CA can induce long-lasting changes in expression of 5-HT1AR, and thus, a history of CA may explain the disparate findings. Following up on our initial report, 28 unmedicated participants in a current depressive episode (bipolar n=16, unipolar n=12) and 19 non-depressed healthy volunteers (HVs) underwent [11C]CUMI-101 imaging to quantify 5-HT1AR binding potential. Participants in a depressive episode were stratified into mild/moderate and severe CA groups via the Childhood Trauma Questionnaire. We hypothesized higher hippocampal and raphe nuclei 5-HT1AR with severe CA compared with mild/moderate CA and HVs. There was a group-by-region effect (p=0.011) when considering HV, depressive episode mild/moderate CA, and depressive episode severe CA groups, driven by significantly higher hippocampal 5-HT1AR binding potential in participants in a depressive episode with severe CA relative to HVs (p=0.019). Contrary to our hypothesis, no significant binding potential differences were detected in the raphe nuclei (p-values>0.05). With replication in larger samples, elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker through which to investigate the neurobiological link between CA and depression.

The impact of depression symptoms on postmorbid adaptation of patients who have undergone SARS-CoV-2 infection (assessment from the position of the multimorbidity model)

To evaluate the impact of psychosomatic and anxiety symptoms of depression on the formation of postmorbid adaptation in patients who have undergone SARS-CoV-2 infection. The data of 54 patients, aged 18-55 years, with a current depressive episode who had outpatient SARS-CoV-2 infection were analyzed. The Hamilton depression rating scale (HDRS) was used and somatic condition was assessed using a general assessment of the patient's function limitation at the stage of reconvalescence. A linear regression analysis was performed to assess the association of psychosomatic and anxiety symptoms with somatic condition in SARS-CoV-2 infection, regardless of other factors. The multimorbidity model took into account, in addition to SARS-CoV-2 caused by organic somatic disorders, psychosomatic manifestations (B=-1.9, p=0.004) and anxiety (B=-3.7, p=0.04) symptoms of depression. Somatic anxiety was significantly correlated with a pronounced impairment of postmorbid readaptation (p<0.05), while mental anxiety did not demonstrate such a relationship (p=0.46). The observed trend seems to be due to the overlap of manifestations of somatic anxiety with the construct of residual somatic symptoms, even though there is no multicollinearity between them. Identification of clusters of symptoms associated with reduced opportunities for full recovery in the SARS-CoV-2-postmorbid period can significantly help in providing a high-quality and targeted psychopharmacological care.

Brain stimulation for treatment-resistant depression.

Depression is one of the main public health problems in the world, having a high prevalence and being considered the main cause of disability. An important portion of patients does not respond to treatment with the initial trial of conventional antidepressants in the current depressive episode of moderate to severe intensity, which characterizes treatment-resistant depression. In this context, non-invasive neuromodulation procedures use an electric current or magnetic field to modulate the central nervous system, and they represent a new option for patients with treatment-resistant depression.

Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression

Introduction:Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.

Childhood trauma, inflammatory biomarkers and the presence of a current depressive episode: Is there a relationship in subjects from a population study?

This study aims to compare the serum cytokine levels between controls, individuals with a current depressive episode (CDE) with childhood trauma and individuals with CDE without childhood trauma. This is a cross-sectional with paired sample nested in a population-based study. For the purposes of the current study, subjects who had psychotic symptoms, generalized anxiety disorder, and who refused to perform blood collection were excluded. Subsequently, only individuals who had a current depressive episode were selected (n = 76). Another 76 subjects were randomly paired by sex and age, constituting a population control group. The measurements of serum cytokine levels were performed using the multiplex analysis method. In the group with a CDE, when compared to the population control group, the following cytokines were high: IL-1β, IL-2, IL-4, IL-6, IL-17A, IFN-γ and TNF-α (p < 0.05). On the other hand, there was a decrease in the levels of cytokines IL-10 (p = 0.027) and IL12p70 (p = 0.001). Bonferroni test demonstrates that there is no statistically significant difference in serum cytokine levels between subjects with a CDE, with and without trauma (p > 0.05). In a multivariable logistic regression, adjusting for socioeconomic status, tobacco, alcohol and illicit drugs abuse/dependence, and use of psychiatric medication, we found that cytokines serum levels remained associated with CDE even when adjusted for these potential confounders. Our findings demonstrate that monitoring cytokine levels and immune function may be beneficial in preventing the development of a CDE. However, future research is necessary to investigate the impact of trauma on the relationship between inflammation and CDE.

Influence of ADHD, especially attention-deficit characteristics, on the course of alcohol-dependent individuals

BackgroundWhile several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined.MethodsThis study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated.ResultsThe presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of “Recurrence” and lower rates of “Abstinence” and “Controlled drinking” (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003).ConclusionADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.

Factors associated with antidepressant responses to repetitive transcranial magnetic stimulation in antidepressant-resistant depression.

A significant proportion of patients with major depressive disorder (MDD) failed to respond to antidepressant medications. Repetitive transcranial magnetic stimulation (rTMS) is an effective option for treating such treatment-resistant patients with MDD (TRD). Reliable clinical predictors for antidepressant responses to rTMS remain elusive. In total, 212 patients with MDD who failed to respond to at least one adequate antidepressant trial and had a detailed evaluation before rTMS were recruited for chart review. Demographic data, clinical characteristics, psychiatric comorbidities, symptom ratings [e.g., objective and subjective depression, life stress, depression refractoriness by Maudsley Staging Method (MSM)], and antidepressant treatment responses were analyzed. MSM-subitem1 (duration of current depressive episode; Beta = 0.209, p = 0.004), MSM-subitem5 (a history of ECT treatment; Beta = -0.210, p = 0.004), and psychiatric admissions (Beta = 0.241, p = 0.001) predicted antidepressant response of rTMS treatment. ECT was underutilized (only 3.3%). Psychiatric admissions [Exp(B) = 1.382, p = 0.021], a comorbidity of OCD [0.047, 0.005], and life stress level [0.984, 0.029] predicted the history of ECT treatment. Several clinical variables (e.g., number of psychiatric admissions, OCD as a comorbidity, and life stress level) were reliable clinical factors associated with antidepressant responses of rTMS treatment and may be utilized in combination with MSM subitems to evaluate levels of TRD.

Reducing Anhedonia in Major Depressive Disorder with Future Event Specificity Training (FEST): A Randomized Controlled Trial

BackgroundImproving future thinking, such as characteristics of specificity, detail, and use of mental imagery, may be one means to reduce anhedonia, particularly in a Major Depressive Episode (MDE) in which future thinking is impaired. The current study aimed to test this using a validated program, Future Event Specificity Training (FEST).MethodsParticipants (N = 177; 80.8% women; M age = 43.7, SD = 11.8) with a current depressive episode with anhedonia and high symptom severity were randomized to FEST or no FEST. Future thinking, anhedonia-related variables, and other clinical outcomes were assessed at baseline, one- and three-month follow-up.ResultsRelative to the control group, FEST was associated with significantly improved future thinking characteristics, a reduced likelihood of anhedonia (35.1% vs. 61.1%, p = .015), improvements on other anhedonia-related variables such as anticipatory (d = 0.63, p = .004) and anticipated pleasure for future events (d = 0.77, p < .001), and desirable clinical outcomes such as less people meeting criteria for an MDE (37.8% vs. 64.8%, p = .011), higher behavioural activation (d = 0.71, p = .001) and improved global functioning (d = 0.52, p = .017). Changes in future thinking were found to mediate the effect of FEST on anhedonia.ConclusionThe quality of future thinking can be enhanced in Major Depression, and this leads to a substantially reduced likelihood of anhedonia, other significant clinical effects, and functional gains.