Comorbid Major Depressive Disorder Research Articles

Effects of intranasal (S)-ketamine on Veterans with co-morbid treatment-resistant depression and PTSD: A retrospective case series

SummaryBackground(S)-ketamine is a glutamatergic drug with potent and rapid acting effects for the treatment of depression. Little is known about the effectiveness of intranasal (S)-ketamine for treating patients with comorbid depression and post-traumatic stress disorder (PTSD).MethodsWe performed a retrospective case series analysis of clinical outcomes in 35 Veterans with co-morbid depression and PTSD who were treated with intranasal (S)-ketamine treatments at the VA San Diego Neuromodulation Clinic between Jan 2020 and March 2021. Veterans were not randomized or blinded to treatment. The primary outcome measured was a change in patient health questionnaire-9 (PHQ-9) and PTSD Checklist for DSM-5 (PCL-5) scores across the first 8 treatments (induction period) using a repeated measures analysis of variance (ANOVA). In a smaller sub-group (n = 19) of Veterans who received at least 8 additional treatments, we analyzed whether intranasal (S)-ketamine continued to show treatment effects. Finally, we performed a sub-group and correlation analyses to understand how changes in PHQ-9 and PCL-5 scores were related across treatments.FindingsDuring the induction phase of treatment there was an absolute reduction of 5.1 (SEM 0.7) on the patient health questionnaire-9 (PHQ-9) rating scale for depression, from 19.8 (SEM 0.7) at treatment 1 to 14.7 (SEM 0.8) at treatment 8 (week 4) (F(7238) = 8.3, p = 1e-6, partial η2 = 0.2). Five Veterans (14%) showed a clinically meaningful response (50% reduction in PHQ-9 score) at treatment 8. There was an absolute reduction of 15.5 +/- 2.4 on the patient checklist 5 (PCL-5) rating scale for PTSD, from 54.8 (SEM 2) at treatment 1 down to 39.3 (SEM 2.5) at treatment 8 (F(7238) = 15.5, p = 2e-7, partial η2 = 0.31). Sixteen Veterans (46%) showed a clinically meaningful response (reduction in PCL-5 of > 30%) in PTSD. Change in PHQ-9 correlated with change in PCL-5 at treatment 8 (r = 0.47, p = 0.005), but a decrease in PTSD symptoms were observable in some individuals with minimal anti-depressant response.InterpretationsWhile this is an open-label retrospective analysis, our results indicate that both depression and PTSD symptoms in Veterans with dual-diagnoses may improve with repeated intranasal (S)-ketamine treatment. The effects of (S)-ketamine on PTSD symptoms were temporally and individually distinct from those on depression, suggesting potentially different modes of action on the two disorders. This work may warrant formal randomized controlled studies on the effects of intranasal (S)-ketamine for individuals with co-morbid MDD and PTSD.FundingVA Center of Excellence in Stress and Mental Health, VA ORD (Career Development Award to DSR), Burroughs-Wellcome Fund Award (DSR), NIMH (EL)

P92. Comorbidities of PTSD With Major Depressive Disorder in Patients Undergoing ECT: A National Study Across the United States

To assess if there is a sizable number of patients who are treated with ECT for comorbid major depressive disorder (MDD) with PTSD.

School-Based Cognitive-Behavioral Therapy in an Inclusion Model for an Adolescent with Comorbid Major Depressive Disorder, Generalized Anxiety Disorder, and Attention Deficit Hyperactivity Disorder: A Case Study

The goal of the current case study was to illustrate evidence-based cognitive-behavioral treatment (CBT) for an adolescent female with comorbid major depressive disorder, generalized anxiety disorder, attention deficit hyperactivity disorder, suicidal ideations, and a history of multiple involuntary hospitalizations. Multimodal assessment of the child’s symptoms was conducted, including parent, teacher, and child self-report, academic data, and hospital records to inform case conceptualization. Treatment included a combination of psychoeducation, cognitive restructuring, positive self-talk, relaxation skills, and the support of a school-based personal aide. Significant improvements with inattentive, anxiety, and depressive symptoms were reported, with gains being maintained at 1 year follow-up. In addition to a reduction of reported psychosocial problems, treatment benefits also included a decrease in classroom disruptions, improvement in academic performance, and withdrawal of paraprofessional support at school. This study illustrates the use of school-based CBT strategies coupled with additional focused Tier 4 behavior supports as an efficacious treatment for youth with significant comorbidity.

Neurocognitive effects of repeated ketamine infusions in comorbid posttraumatic stress disorder and major depressive disorder

BackgroundThe glutamate N-methyl-d-aspartate (NMDA) receptor antagonist ketamine rapidly ameliorates posttraumatic stress disorder (PTSD) and depression symptoms in individuals with comorbid PTSD and major depressive disorder (MDD). However, concerns over ketamine's potential neurocognitive side effects have yet to be assessed in this population. The current study investigated 1) changes in neurocognitive performance after a repeated ketamine dosing regimen and 2) baseline neurocognitive performance as a predictor of ketamine treatment effect. MethodVeterans with comorbid PTSD and MDD (N = 15) received six infusions of 0.5 mg/kg ketamine over a 12-day period. Neurocognitive and clinical outcomes assessments occurred at baseline and within 7 days of infusion-series completion using the CogState battery. ResultsRepeated ketamine infusions did not significantly worsen any measures of cognition. Rather, significant improvement was observed in working memory following completion of the infusion series. In addition, greater improvements in PTSD and MDD symptoms were associated with lower working memory, slower processing speed and faster set shifting at baseline. Lower verbal learning was also predictive of improvement in depression. LimitationsThis study applied an open-label design without a placebo control. As such, it is not known to what extent the correlations or improvement in neurocognitive performance may have occurred under placebo conditions. ConclusionThis is the first study to examine the neurocognitive effects of repeated ketamine in participants with comorbid PTSD and MDD. Our findings suggest potential baseline neurocognitive predictors of ketamine response for comorbid PTSD and MDD symptoms.

Disorder- and cognitive demand-specific neurofunctional alterations during social emotional working memory in generalized anxiety disorder and major depressive disorder

BackgroundGeneralized Anxiety Disorder (GAD) and Major Depressive Disorder (MDD) are both characterized by cognitive and social impairments. Determining disorder-specific neurobiological alterations in GAD and MDD by means of functional magnetic resonance imaging (fMRI) may promote determination of precise diagnostic markers. MethodsThis study aimed to examine disorder-specific behavioral and neural alterations at the intersection of social and cognitive processing in treatment-naïve first-episode GAD (n = 35) and MDD (n = 37) patients compared to healthy controls (n = 35) by employing a social-emotional n-back fMRI paradigm. ResultsNo behavioral differences between patients and healthy controls were observed. However, GAD patients exhibited decreased bilateral dorsomedial prefrontal cortex (dmPFC) engagement during the 0-back condition yet increased dmPFC engagement during the 1-back condition compared to MDD and healthy participants. In contrast, MDD patients exhibited increased dmPFC-insula coupling during 0-back, yet decreased coupling during 1-back, compared to GAD and healthy participants. Dimensional symptom-load analysis confirmed that increased dmPFC-insula connectivity during 0-back was positively associated with depressive symptom load. LimitationsThe moderate sample size in the present study did not allow us to further explore gender differences. In addition, some patients exhibited GAD and MDD comorbidity according to the M.I.N.I. interview. Finally, the paradigm we used did not allow to further disentangle emotion-specific effects on working memory. ConclusionsThese findings suggest that the dmPFC engaged in integrating affective and cognitive components and self-other processing exhibits GAD-specific neurofunctional dysregulations whereas functional dmPFC communication with the insula, a region involved in salience processing, may represent an MDD-specific neurofunctional deficit.

Buprenorphine as a Treatment for Major Depression and Opioid Use Disorder.

Rates of major depressive disorder (MDD) are disproportionally high in subjects with opioid use disorder (OUD) relative to the general population. MDD is often more severe in OUD patients, leading to compliance issues with maintenance therapies and poor outcomes. A growing body of literature suggests that endogenous opioid system dysregulation may play a role in the emergence of MDD. Buprenorphine, a mixed opioid receptor agonist/antagonist approved for the treatment of OUD and chronic pain, may have potential as a novel therapeutic for MDD, especially for patients with a dual diagnosis of MDD and OUD. This paper presents a comprehensive review of papers relevant to the assessment of buprenorphine as a treatment for MDD, OUD, and/or suicide compiled using electronic databases per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The principal goal of this literature review was to compile the clinical studies that have interrogated the antidepressant activity of buprenorphine in opioid naïve MDD patients and OUD patients with comorbid MDD. Evidence supporting buprenorphine's superiority over methadone for treating comorbid OUD and MDD was also considered. Finally, recent evidence for the ability of buprenorphine to alleviate suicidal ideation in both opioid-naïve patients and opioid-experienced patients was evaluated. Synthesizing all of this information, buprenorphine emerges as a potentially effective therapeutic for the dual purposes of treating MDD and OUD.

Prolonged grief disorder and depression are distinguishable syndromes: A latent transition analysis for bereaved family caregivers of cancer patients.

To determine whether distinctive prolonged-grief-disorder- (PGD) and depressive-symptom states emerge among family caregivers of cancer patients over their first 2years of bereavement. This may extend cross-sectional evidence that PGD and major depressive disorder (MDD) symptoms can co-occur/occur independently and validate their construct distinctiveness. In this secondary-analysis study, PGD symptoms and depressive symptoms were measured over 666 caregivers using 11 grief symptom items of the Prolonged Grief-13 scale and 16 items of the Center for Epidemiologic Studies-Depression scale, respectively. Distinct PGD/depressive-symptom states were identified by latent transition analysis with dichotomous indicators (presence/absence) of PGD or depressive symptoms. Four distinct PGD/depressive-symptom states emerged. The resilient and subthreshold depression-dominant states showed low and moderate probabilities of the presence of majority of depressive symptoms, respectively, with no PGD symptoms having a greater than moderate probability of presence. The depression-dominant state was marked by a high probability of the presence for 9 of 16 depressive symptoms, with moderate probabilities for almost all PGD symptoms. The PGD-depression comorbid state was characterized by a high probability of presence of all PGD symptoms and depressive symptoms, except for moderate probabilities of presence of two depressive symptoms. Our longitudinal identification of a predominantly depressive state but absence of a PGD-dominant state provides further evidence that PGD and MDD are related but distinct constructs that can occur independently or concurrently as the PGD-depression comorbid state. When PGD is suspected, bereaved individuals should be assessed for the potential comorbidity of MDD.

Major depressive disorder comorbid with general anxiety disorder: Associations among neuroticism, adult stress, and the inflammatory index

Accumulating evidence shows that higher neuroticism and adult stress may be potential risk factors for major depressive disorder (MDD) comorbid with generalized anxiety disorder (GAD). Studies have shown that anxious and depressed patients have significantly more neurobiological abnormalities than non-anxious depressed patients. However, the biological mechanism of comorbidity remains unknown. A study of serum markers allows a better understanding of the mechanism. This was a multi-centre, cross-sectional study. A total of 169 MDD patients (42 MDD patients with comorbid GAD and 127 MDD patients without comorbid GAD) were studied to analyse the risk factors for MDD with comorbid GAD. Twenty-four peripheral serum markers were measured. Path analysis was applied to test the association among neuroticism, adult stress, inflammatory markers, and psychopathology. After Bonferroni correction, MDD patients with comorbid GAD had lower levels of CCL2 (P = 0.001) and higher levels of α2M (P < 0.001) and TLR-1 (P = 0.001) than MDD patients without comorbid GAD (adjusted P < 0.002). In the path analyses of the association among adult stress, the inflammatory index, and psychopathology, neuroticism had a direct effect (β = 0.238, P = 0.003) and an indirect effect (β = 0.068, P = 0.004) on MDD and GAD comorbidity through adult stress and the inflammatory index. Our results suggest that MDD with comorbid GAD is associated with higher levels of inflammatory markers, stress factors and personality traits, which may provide some cues for early identification or more tailored and comprehensive treatment for MDD with comorbid GAD.

Transdiagnostic Symptom Subtypes to Predict Response to Therapeutic Transcranial Magnetic Stimulation in Major Depressive Disorder and Posttraumatic Stress Disorder.

The diagnostic categories in psychiatry often encompass heterogeneous symptom profiles associated with differences in the underlying etiology, pathogenesis and prognosis. Prior work demonstrated that some of this heterogeneity can be quantified though dimensional analysis of the Depression Anxiety Stress Scale (DASS), yielding unique transdiagnostic symptom subtypes. This study investigated whether classifying patients according to these symptom profiles would have prognostic value for the treatment response to therapeutic transcranial magnetic stimulation (TMS) in comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD). A linear discriminant model was constructed using a simulation dataset to classify 35 participants into one of the following six pre-defined symptom profiles: Normative Mood, Tension, Anxious Arousal, Generalized Anxiety, Anhedonia and Melancholia. Clinical outcomes with TMS across MDD and PTSD were assessed. All six symptom profiles were present. After TMS, participants with anxious arousal were less likely to achieve MDD remission compared to other subtypes (FET, odds ratio 0.16, p = 0.034), exhibited poorer PTSD symptom reduction (21% vs. 46%; t (33) = 2.025, p = 0.051) and were less likely to complete TMS (FET, odds ratio 0.066, p = 0.011). These results offer preliminary evidence that classifying individuals according to these transdiagnostic symptom profiles may offer a simple method to inform TMS treatment decisions.

A Systematic Analysis on the Genes and Their Interaction Underlying the Comorbidity of Alzheimer's Disease and Major Depressive Disorder.

BackgroundDuring the past years, clinical and epidemiological studies have indicated a close relationship between Alzheimer's disease (AD) and other mental disorders like major depressive disorder (MDD). At the same time, a number of genes genetically associated with AD or MDD have been detected. However, our knowledge on the mechanisms that link the two disorders is still incomplete, and controversies exist. In such a situation, a systematic analysis on these genes could provide clues to understand the molecular features of two disorders and their comorbidity.MethodsIn this study, we compiled the genes reported to be associated with AD or MDD by a comprehensive search of human genetic studies and genes curated in disease-related database. Then, we investigated the features of the shared genes between AD and MDD using the functional enrichment analysis. Furthermore, the major biochemical pathways enriched in the AD- or MDD-associated genes were identified, and the cross talks between the pathways were analyzed. In addition, novel candidate genes related to AD and MDD were predicted in the context of human protein-protein interactome.ResultsWe obtained 650 AD-associated genes, 447 MDD-associated genes, and 77 shared genes between AD and MDD. The functional analysis revealed that biological processes involved in cognition, neural development, synaptic transmission, and immune-related processes were enriched in the common genes, indicating a complex mechanism underlying the comorbidity of the two diseases. In addition, we conducted the pathway enrichment analysis and found 102 shared pathways between AD and MDD, which involved in neuronal development, endocrine, cell growth, and immune response. By using the pathway cross-talk analysis, we found that these pathways could be roughly clustered into four modules, i.e., the immune response-related module, the neurodevelopmental module, the cancer or cell growth module, and the endocrine module. Furthermore, we obtained 37 novel candidate genes potentially related to AD and MDD with node degrees > 5.0 by mapping the shared genes to human protein-protein interaction network (PPIN). Finally, we found that 37 novel candidate genes are significantly expressed in the brain.ConclusionThese results indicated shared biological processes and pathways between AD and MDD and provided hints for the comorbidity of AD and MDD.

Social anxiety disorder with comorbid major depression – why fearful attachment style is relevant

Individuals with social anxiety disorder (SAD) often suffer from comorbid major depressive disorder (MDD), which goes along with increased clinical and functional impairment. There has been little research on underlying differences regarding childhood adversities and attachment styles between individuals with SAD with and without comorbid MDD. In the present study, the consecutive sample comprised 612 SCID-diagnosed participants. Of these, n = 472 (62.3% women, 40.7 ± 13.8 years) showed SAD and comorbid MDD (SAD-MDD group) and n = 140 (47.9% women, 43.7 ± 14.7 years) showed just SAD (SAD group). The two groups were compared regarding SAD symptom severity (Social Phobia Inventory; SPIN), childhood adversities (Adverse Childhood Experience Questionnaire; ACE) and attachment styles (Attachment Style Questionnaire, ASQ). The SAD-MDD group reported significantly more severe SAD symptoms (p = .002, d = 0.30), more childhood adversities (p < .001, d = 0.35) and a higher level of fearful attachment style (p < .001, d = 0.30). Group significantly moderated the association between fearful attachment style and SAD symptom severity (β = .292, p < .05) but not between preoccupied attachment style and SAD symptom severity (β = −.184, p = .124; R2adj = .168, p < .05). Fearful attachment style mediated the association between childhood adversities and SAD symptom severity in the SAD-MDD group. Our study could identify a specific significance of fearful attachment style for the association between negative childhood experiences and social anxiety symptoms in SAD-MDD. Findings have specific implications for the therapeutic relationship.

Mortality and Suicide Related to Major Depressive Disorder Before and After Type 2 Diabetes Mellitus.

Objective: This study investigated differences in suicide and all-cause mortality from ICD-9-CM comorbid major depressive disorder (MDD) and type 2 diabetes mellitus (T2DM) depending on which was diagnosed first.Methods: A longitudinal administrative claims database including 2 million samples and national death registry data from 2000 through 2015 in Taiwan were used. Patients with newly diagnosed T2DM were identified and further classified into 3 groups: (1) MDD before T2DM, (2) T2DM without any diagnosis of MDD (from which matched controls were selected), and (3) MDD after T2DM, based on the sequential occurrence dates between incident T2DM and MDD. Multivariable Cox proportional hazard models were analyzed.Results: Both the MDD before T2DM and MDD after T2DM groups had significantly higher risks of all-cause mortality (adjusted hazard ratio [AHR] = 1.21; 95% CI, 1.08-1.35 and AHR = 1.55; 95% CI, 1.45-1.66, respectively) and committed suicide (AHR = 5.05; 95% CI, 2.46-10.37and AHR = 14.32; 95% CI, 7.44-27.55, respectively) than their matched controls, while the MDD before T2DM and MDD after T2DM groups exhibited differences in mortality (significant; P < .0001) and death by suicide (nonsignificant).Conclusions: The study findings indicated suicide and mortality rates were higher in both the MDD before and MDD after T2DM groups when compared with matched controls. Public health initiatives are needed to survey and treat comorbid MDD with T2DM. Furthermore, additional studies are needed to clarify the underlying pathophysiology of the association between MDD and T2DM to find better suicide prevention strategies among those high-risk patients who have comorbid T2DM and MDD.

Relationship of the balloon analog risk task to neurocognitive impairment differs by HIV serostatus and history of major depressive disorder

HIV and major depressive disorder (MDD) commonly co-occur and are both linked to greater risk-taking behavior, possibly due to neurocognitive impairment (NCI). The present study examined the concordance of the Balloon Analog Risk Task (BART), a gold standard measure of risk-taking propensity, with NCI and real-world sexual risk behaviors in PWH with comorbid MDD. Participants included 259 adults, stratified by HIV serostatus (HIV + /HIV −) and lifetime MDD (MDD + /MDD −), who completed neuropsychological testing, the BART, and sexual risk behavior questionnaires. Logistic regression, stratified by HIV serostatus, examined joint effects of MDD and BART (linear and quadratic) on NCI. Follow-up linear regressions examined sexual risk behavior and neurocognitive domain T-scores as correlates of the BART. NCI prevalence was lowest in HIV − /MDD − , but BART scores did not differ by HIV/MDD status. In the HIV + group, BART performance predicted NCI such that high and low BART scores related to greater odds of NCI, but only in dual-risk HIV + /MDD + individuals. HIV + /MDD + individuals with both low and high BART scores exhibited poorer learning and recall, whereas processing speed and executive function were only poor in low BART risk-taking HIV + /MDD + . Higher BART scores linearly related to higher sexual risk behaviors only in MDD + individuals, independent of HIV serostatus. Low and high risk-taking on the BART may reflect discrete neurocognitive profiles in HIV + /MDD + individuals, with differential implications for real-world sexual risk behavior. HIV and comorbid MDD may disturb corticostriatal circuits responsible for integrating affective and neurocognitive components of decision-making, thereby contributing to risk-averse and risk-taking phenotypes.

Functional somatic symptoms and their predictors in patients with major depressive disorder and fibromyalgia syndrome

Despite being different medical conditions, functional somatic symptoms (FSSs) are common in patients with major depressive disorder (MDD) and fibromyalgia syndrome (FMS). Higher levels of depression, anxiety, somatosensory amplification, hypochondriacal worry and alexithymia may be related to the severity of somatization in patients with MDD and FMS. We aimed to investigate the typology and severity of FSSs and the association between FSSs and these psychiatric symptoms in patients with MDD and FMS. 56 MDD, 33 FMS, 21 CoMF (Comorbidity of MDD and FMS) patients, and 50 healthy participants were included in the study, respectively. Diagnosis of MDD and FMS was established according to DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, Revised Text), and ACR (American College of Rheumatology) 2010 diagnostic criteria. All participants were evaluated with self-report questionnaires including Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Somatosensory Amplification Scale (SSAS), Toronto Alexithymia Scale-20 (TAS-20), Whiteley Index-7 (WI-7), The Symptom Checklist-90-R (SCL-90-R) somatization subscale and Bradford Somatic Inventory-44 (BSI-44). The severity of somatization was statistically significantly highest in the CoMF group, and similar in the FMS and MDD groups, and lowest in the control group according to the BSI-44 and SCL-90-R results. The typology of FSSs was quite similar in patients with MDD and FMS, and weakness, tiredness and neck pain were the most common FSSs in both groups. Independent predictors of FSSs were age, the severity of anxiety and alexithymia in the MDD group, however, it was only the severity of anxiety in the FMS group. Our results show that the typology and severity of FSSs are similar in MDD and FMS patients. Moreover, somatization appears to be more associated with anxiety in patients with MDD and FMS.

Short term impact of antidepressants on the cardinal symptoms of depression in OSA patients with comorbid MDD who are APAP-adherent: A retrospective study in a veteran population.

• This study highlights the importance of continued assessment for depressive symptoms in veterans with OSA even after adequate treatment with automatic positive airway pressure (APAP). • Adding psychotropics to patients with depressive symptoms provides measurable benefit in reducing symptoms of depression, such as anhedonia, hopelessness and poor self-esteem, in patients with sleep apnea and comorbid major depressive disorder who are on APAP therapy. • If successful treatment of OSA does not alleviate the mood disturbance, the next step is to target the mood disorder. However, there are no supporting data for such an approach. Further studies are needed to analyze the connection between OSA and affective disorders, especially in the context of APAP treatment. Background: The purpose of the study is to determine whether the addition of antidepressants provides measurable benefit in diminishing symptoms of depression, such as anhedonia, hopelessness and poor self-esteem, in veterans with obstructive sleep apnea (OSA) and comorbid major depressive disorder (MDD) who are on automatic positive airway pressure (APAP) therapy. Methods: This is a retrospective study, involving veterans with MDD and treated OSA who were followed for 3 months. All veterans were compliant with APAP therapy for at least six months prior to their first mental health clinic appointment. The Clinically Useful Depression Outcome Scale (CUDOS) was administered during the first appointment and each subsequent visit with the respective psychiatrist to monitor mood symptoms. The CUDOS total scores were compared between the first visit, APAP pre- antidepressant period and after 3 months of treatment with an antidepressant. Results: The analysis was based on 47 participants, CUDOS scores decreased significantly from the initial score to month 3 with addition of antidepressants, as assessed using a Wilcoxon signed rank test for the paired observations within each participant ( p < 0.01), The median decrease was 21 points with an interquartile range of 14.5–26. Evaluation of the distribution of CUDOS cardinal symptoms of depression (anhedonia, poor self-esteem, and hopelessness) scores shows that scores for each item were reduced. Limitations: Our early work underscores the need for more definitive studies, these results are not ready for adoption to clinical care. Conclusion: Adding pharmacotherapy to patients with depressive symptoms on APAP has significant clinical benefits.

Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder Comorbid with Huntington’s Disease: A Case Report

Huntington’s disease (HD) is a rare genetic disorder resulting in progressive neurodegeneration leading to motor, cognitive and psychiatric symptoms. A high percentage of HD patients suffer from comorbid major depressive disorder (MDD). We are not aware of any literature on the use of repetitive transcranial magnetic stimulation (rTMS) for treating comorbid MDD in HD. We present the case of a 57-year-old man suffering from HD in which comorbid MDD was successfully treated with rTMS. Further work is required to better characterize the safety, tolerability and effectiveness of rTMS to treat comorbid MDD in HD.

Imaging of astrocytes in posttraumatic stress disorder: A PET study with the monoamine oxidase B radioligand [11C]SL25.1188

Posttraumatic stress disorder (PTSD) is a debilitating mental health condition that results from exposure to traumatic event(s). Decreased astrocyte-related proteins (e.g., glial fibrillary acidic protein, GFAP) and atrophic astrocytes in corticolimbic brain areas implicated in PTSD have been reported in experimental models suggesting that astrocyte pathology may be a feature of this disorder. We used positron emission tomography (PET) of the monoamine oxidase (MAO)-B probe [11C]SL25.1188 to test the hypothesis that levels of MAO-B, an index of astrocyte levels is decreased in PTSD. MAO-B availability ([11C]SL25.1188 distribution volume) was measured in 13 participants with PTSD (∼39 years, 6F) and 17 healthy controls (HC) (∼31 years, 9F). A magnetic resonance image was acquired to delineate 6 cortiolimbic brain regions. PTSD was associated with a trending reduction in [11C]SL25.1188 availability across regions (8-17%; p = 0.067) implicating the ventral striatum (p uncorrected = 0.015) and medial prefrontal cortex (p uncorrected = 0.060). [11C]SL25.1188 availability was ∼30% lower in corticolimbic regions in PTSD with co-morbid major depressive disorder (MDD) (n = 4) vs HC (p = 0.001) and vs PTSD without MDD (p = 0.005). Our preliminary results do not suggest astrogliosis (inferred from elevated availability) in PTSD, but rather point to a loss of astrocytes or an independent downregulation of MAO-B in PTSD with more severe negative affect. These exploratory findings, which are partly in line with preclinical literature and recent PET observations of decreased microglia marker, Translocator Protein, in PTSD, warrant replication in a larger PTSD cohort.

Transient neural oscillations reveal new biomarkers for therapeutic transcranial magnetic stimulation for comorbid MDD and PTSD

Abstract Repetitive transcranial magnetic stimulation (TMS) is a therapy for major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). TMS effectiveness varies across patients and optimal protocols are unknown. Electroencephalography (EEG) examines brain dynamics associated with TMS often in highly averaged data (Zandvakili et al, 2019). In non-averaged signals, EEG oscillations may emerge as high power transients, coined “events” (Jones, 2016; Shin et al, 2017). We applied methods to analyze event features to describe biomarkers of TMS and their relationship to clinical outcomes. We collected resting 8-channel EEG before and after therapeutic TMS for 23 patients with comorbid MDD and PTSD targeting the left dorsolateral prefrontal cortex. Using our open-source toolbox (https://github.com/jonescompneurolab/SpectralEvents), we tested if resting state oscillations can be quantified as events in non-averaged data using 2-second windows. We assessed if event characteristics – event rate, power, duration, frequency span – changed after TMS or correlated with symptom improvement. Averaged omnibus power spectral density revealed peaks in frequency bands including delta/theta (1-6 Hz), alpha (7-14 Hz), and beta (15-29 Hz). Transient high-power events emerged from non-averaged data. Overall, frontal delta/theta and alpha event number and medial delta/theta event duration decreased after TMS (all p < 0.05). Pretreatment event characteristics correlated with subsequent clinical response. Frontal delta/theta event frequency span negatively correlated with MDD & PTSD improvement; medial alpha event power and duration positively correlated with MDD improvement, whereas medial alpha event rate and duration positively correlated with PTSD improvement; and frontal beta duration negatively correlated with PTSD improvement (all r2 > 0.15). Novel methods to characterize spectral events in non-averaged signals identified periods of high power activity in resting EEG data and revealed changes in event features potentially predictive of TMS response. EEG-recorded events ultimately may provide new biomarkers of response and a better mechanistic understanding of TMS. Keywords: Transcranial magnetic stimulation, Resting state EEG, Major depressive disorder, Post-traumatic stress disorder

Circadian Functioning and Quality of Life in Substance Use Disorder Patients With and Without Comorbid Major Depressive Disorder.

Aim: Although a relationship between circadian disruption and development of several psychiatric disorders, such as major depressive disorder (MDD) and substance use disorder (SUD), has been observed, knowledge on this area is scarce yet. Therefore, this study aims to analyze the circadian functioning and quality of life (QOL) in SUD patients with and without comorbid MDD, two highly prevalent clinical entities with difficult therapeutic management.Methods: One hundred sixty-three male patients under treatment, 81 with SUD and 82 with SUD comorbid major depressive disorder (SUD + MDD), were evaluated. For the circadian functioning assessment, we calculated Social Jet Lag (SJL) and used the reduced Morningness–Eveningness Questionnaire (rMEQ) and the Pittsburgh Sleep Quality Index (PSQI). QOL was measured using the shortened version of the World Health Organization's Quality of Life Questionnaire (WHOQOL-BREF). We collected sociodemographic and clinical variables to evaluate their possible influence on the circadian functioning. Intergroup differences among the variables were examined by different analyses of covariance (ANCOVA and MANCOVA). The possible relationships of quantitative clinical variables with rMEQ, PSQI, and WHOQOL-BREF were explored using bivariate correlation analysis.Results: Lower SJL appears in the SUD + MDD group compared with SUD. The intermediate-type was more prevalent in the SUD group, while a higher percentage of morning-type patients was found in the SUD + MDD. Sleep quality (including latency and daytime dysfunction) was worse for SUD + MDD patients than for SUD even after controlling age and age of SUD onset variables. Last, QOL was poorer in patients with SUD + MDD and, for them, psychological health had a negative relationship with SJL and severity of depression.Conclusions: Our data support and extend previous findings indicating that SUD + MDD is associated with worse clinical characteristics, more sleep problems, and poorer QOL than SUD patients. These results underline the importance of a precise assessment of these measurements in future studies conducted in SUD patients with/without MDD comorbidity that could be considered from a therapeutic point of view.

Prefrontal cortex alterations in major depressive disorder, generalized anxiety disorder and their comorbidity during a verbal fluency task assessed by multi-channel near-infrared spectroscopy

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are frequently comorbid with each other, and both associated with substantial cognitive impairments; however, it is still unclear whether their impairments are neurobiologically similar or distinct. This study aims to investigate the cognitive functions of the prefrontal cortex (PFC) in patients with MDD and GAD during the verbal fluency task (VFT) using functional near-infrared spectroscopy (fNIRS). Fifty-two patients with MDD, fifty-one patients with GAD, fifty-two patients with the comorbidity of MDD and GAD (CMG), and forty-seven healthy controls (HC) participated in the study. Significant hypoactivation in the left ventrolateral and the left dorsolateral PFC was common in all patient groups when compared to HCs, suggesting a shared etiology. Furthermore, MDD patients showed significant hypoactivation at the right frontal pole cortex (FPoC) when compared to HCs and significant hypoactivation at the middle FPoC when compared to the CMG patients. Our work is the first fNIRS study to reveal the shared and unique neurobiological profiles of MDD, GAD and their comorbidity under the same standard experimentation condition, suggesting fNIRS holds promise as an adjutant to assist clinical diagnosis.