Concurrent conventional & high-definition transcranial direct current stimulation for treatment of schizophrenia with co-morbid obsessive-compulsive disorder: A case report

Non-invasive brain stimulation techniques such as conventional transcranial direct current stimulation (tDCS) and high definition tDCS (HD-tDCS) are increasingly being used as add-on treatment options in schizophrenia and obsessive-compulsive disorder (OCD). This is reporting of the use of a novel accelerated, symptom-specific, add-on tDCS (combining conventional and high definition) protocol in a patient with both schizophrenia and OCD. The intervention showed clinical utility by reducing both schizophrenia and OCD symptoms.     

Traumatisme et résilience associés à la pandémie de la COVID-19 dans les villes de Bafoussam et de Dschang au Cameroun

IntroductionThe emergence of the Covid-19 pandemic in Cameroon, as in Africa and around the world, was marked by a suddenness and unpredictability that fascinated the imagination. The considerable psychic and social repercussions of the pandemic mobilized a significant anguish of death. The sudden onset of the pandemic was followed by spectacular, high-profile deaths that fascinated the imagination, listing it in the order of traumatic events, provoking reactions of astonishment, flight and avoidance.GoalThe objective of this study is to determine the symptomatology of post-traumatic stress disorder, as well as the resilience, associated with the Covid-19 pandemic in the Western Region of Cameroon.MethodologyThe research was carried out following the model of general population mental health surveys. The availability of area frames (sampling) made it possible to opt for probabilistic calculations. First and second year master's students in clinical psychology from Dschang University were involved in data collection. They benefited from a two-day seminar on data collection techniques in the general population. The calculated sample size is 384 households. The anticipated response rate, set at 90%, made it possible to increase robustness and to anticipate a total sample of 424 households, spread over 3 districts of Bafoussam and Dschang, according to the choice previously made. The study followed the ethical provisions of the Helsinki Protocol. The data collection tools used are: the Impact of Event Scale-Revised and the Connor-Davidson Resilience Scale.Results409 subjects were recruited, representing a completion rate of 106.5%. 70.7% of subjects exhibited symptoms of PTSD. These symptoms are more often mild (40.9%) or moderate (25.6%). Women are more affected (73.7%) by PTSD than men (67.9%). In addition to sex and age, area of residence and marital status, appear to be significantly associated with symptoms of PTSD: subjects under 35 years of age have a significantly higher prevalence rate than those over 35; the rate of PTSD is significantly higher in subjects living in urban areas than in those living in rural areas; single subjects are more affected by PTSD (40.1%) than married subjects (26.7%). The average score recorded on the CD-RISC is 64.3, the standard deviation is 15.3 and the coefficient of variation is 24%. This average falls into the second quartile of the distribution, indicating average resilience. CD-RISC scores are not affected by gender, age, marital status, level of education, or occupational status. These characteristics are therefore not factors of resilience.ConclusionThe Covid-19 pandemic has had a psychological impact in Cameroon which has made it a major psychosocial stressor. More than 6 in 10 people have symptoms of PTSD. But this symptomatology is often weak or moderate, testifying to an effective resilience, to balance the traumatic effects of the pandemic.     

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

Deep brain stimulation (DBS) in psychiatric illnesses has been clinically tested over the past 20 years. The clinical application of DBS to the superolateral branch of the medial forebrain bundle in treatment‐resistant depressed patients—one of several targets under investigation—has shown to be promising in a number of uncontrolled open label trials. However, there are remain numerous questions that need to be investigated to understand and optimize the clinical use of DBS in depression, including, for example, the relationship between the symptoms, the biological substrates/projections and the stimulation itself. In the context of precision and customized medicine, the current paper focuses on clinical and experimental research of medial forebrain bundle DBS in depression or in animal models of depression, demonstrating how clinical and scientific progress can work in tandem to test the therapeutic value and investigate the mechanisms of this experimental treatment. As one of the hypotheses is that depression engenders changes in the reward and motivational networks, the review looks at how stimulation of the medial forebrain bundle impacts the dopaminergic system.     

Elevated peripheral inflammation is associated with attenuated striatal reward anticipation in major depressive disorder

BackgroundMajor depressive disorder (MDD) is the leading cause of years lived with disability worldwide, and up to 40% of individuals with MDD do not respond to current treatments. Studies suggest that peripheral inflammation plays an important role in the striatal mesolimbic dopamine pathway and corticostriatal reward circuitry in MDD. Although MDD patients show blunted striatal responses to reward, the link between degree of inflammation and attenuation of reward processing is unclear. We investigated whether MDD patients with elevated peripheral inflammation exhibit attenuated reward responses to enhance our understanding of MDD pathophysiology and develop more effective treatments for current non-responders.MethodsMDD subjects varying on serum C-reactive protein (CRP) concentrations (MDD-High CRP, >3 mg/L, n = 44; MDD-Low CRP, <3 mg/L, n = 44) and healthy comparisons (HC, n = 44) completed a monetary incentive delay (MID) task and provided blood samples to measure inflammation-related markers. MDD-High and MDD-Low were propensity score-matched on age, sex, body mass index (BMI), smoking status, exercise and MID task head motion. Percent change in blood oxygen level-dependent (BOLD) signal during anticipation of wins and losses was extracted from bilateral nucleus accumbens, dorsal caudate and dorsolateral putamen regions of interest (ROIs). A linear mixed-effects model was used to test group (MDD-High, MDD-Low and HC), condition (large-win, small-win and no win), and their interaction for these ROIs as well as whole-brain voxelwise data. Analyses also tested group differences in inflammatory mediators. Correlations were used to explore the relationship between inflammatory mediators and brain regions showing differences between MDD-High and MDD-Low.ResultsMDD-High exhibited: (a) lower BOLD signal change in dorsal caudate, thalamus, left insula and left precuneus during anticipation of small wins than MDD-Low; and (b) higher serum soluble intercellular adhesion molecule 1 (sICAM-1) and interleukin 6 (IL-6) concentrations than MDD-Low and HC. MDD as a whole, regardless of CRP-based inflammation, exhibited: (a) lower precuneus BOLD signal change to large wins than HC; and (b) higher Interleukin 1 receptor antagonist (IL-1ra), macrophage-derived chemokine (MDC) and macrophage inflammatory protein-1 alpha (MIP-1α) concentrations than HC. Higher serum sICAM-1 concentrations were associated with lower caudate BOLD signal change to small wins only within the MDD-High group.ConclusionWithin MDD patients, high inflammation (CRP, sICAM-1) was linked to reduced striatal activation recruited to discriminate intermediate reward magnitudes. These findings support an association between levels of peripheral inflammation and the degree of reward-related activation in individuals with MDD.Registration of clinical trialsThe ClinicalTrials.gov identifier for the clinical protocol associated with data published in this current paper is NCT02450240, “Latent Structure of Multi-level Assessments and Predictors of Outcomes in Psychiatric Disorders.”     

Internet-delivered exposure therapy versus internet-delivered cognitive behavioral therapy for panic disorder: A pilot randomized controlled trial

AimTo compare the efficacy and acceptability of internet-delivered exposure therapy for panic disorder, to multi-component internet-delivered cognitive behavioral therapy (iCBT) that included controlled breathing, cognitive restructuring and exposure.MethodsParticipants with panic disorder, with or without agoraphobia, were randomized to internet-delivered exposure therapy (n = 35) or iCBT (n = 34). Both programs were clinician guided, with six lessons delivered over eight weeks. Outcomes included panic disorder and agoraphobia symptom severity, as well as depression symptom severity, functional impairment and days out of role.ResultsParticipants in both conditions displayed a large reduction in panic disorder symptom severity (ds >1.30) from pre- to post-treatment. Participants in both conditions displayed medium to large reduction in agoraphobia and depression symptom severity, functional impairment and days out of role. Effects were maintained at three- and six-month follow-up. There was no significant difference between the interventions in clinical outcomes, adherence or treatment satisfaction.ConclusionsInternet-delivered exposure therapy appeared to be as acceptable and efficacious as more established iCBT, despite including less strategies. However, a fully powered replication is now needed to compare the two approaches.     

Early intervention in myelofibrosis and impact on outcomes: A pooled analysis of the COMFORT-I and COMFORT-II studies

Background

In a pooled analysis of the phase 3 Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment I (COMFORT-I) and COMFORT-II clinical trials, adult patients with intermediate-2 or high-risk myelofibrosis who received oral ruxolitinib at randomization or after crossover from placebo or best available therapy (BAT) had improved overall survival (OS).

Methods

This post hoc analysis of pooled COMFORT data examined relevant disease outcomes based on the disease duration (≤12 or >12 months from diagnosis) before ruxolitinib initiation.

Results

The analysis included 525 patients (ruxolitinib: ≤12 months, n = 84; >12 months, n = 216; placebo/BAT: ≤12 months, n = 66; >12 months, n = 159); the median age was 65.0–70.0 years. Fewer thrombocytopenia and anemia events were observed among patients who initiated ruxolitinib treatment earlier. At Weeks 24 and 48, the spleen volume response (SVR) was higher for patients who initiated ruxolitinib earlier (47.6% vs. 32.9% at Week 24, p = .0610; 44.0% vs. 26.9% at Week 48, p = .0149). In a multivariable analysis of factors associated with spleen volume reduction, a logistic regression model that controlled for confounding factors found that a significantly greater binary reduction was observed among patients with shorter versus longer disease duration (p = .022). At Week 240, OS was significantly improved among patients who initiated ruxolitinib earlier (63% [95% CI, 51%‒73%] vs. 57% [95% CI, 49%‒64%]; hazard ratio, 1.53; 95% CI, 1.01‒2.31; p = .0430). Regardless of disease duration, a longer OS was observed for patients who received ruxolitinib versus those who received placebo/BAT.

Conclusions

These findings suggest that earlier ruxolitinib initiation for adult patients with intermediate-2 and high-risk myelofibrosis may improve clinical outcomes, including fewer cytopenia events, durable SVR, and prolonged OS.

Plain Language Summary

• Patients with myelofibrosis, a bone marrow cancer, often do not live as long as the general population. These patients may also have an enlarged spleen and difficult symptoms such as fatigue.
• Two large clinical trials showed that patients treated with the drug ruxolitinib lived longer and had improved symptoms compared to those treated with placebo or other standard treatments.
• Here it was examined whether starting treatment with ruxolitinib earlier (i.e., within a year of diagnosis) provided benefits versus delaying treatment.
• Patients who received ruxolitinib within a year of diagnosis lived longer and experienced fewer disease symptoms than those whose treatment was delayed.