Accelerated rTMS : a potential treatment to alleviate refractory depression

Three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS) has yielded one clear treatment indication in psychiatry for major depression disorder (MDD). Although the clinical response equals the standard treatment algorithms, the effect sizes on the beneficial outcome remain rather modest. Over the last couple of years, to improve the efficacy in resistant depression, two new avenues have been developed: personalization and intensifying rTMS treatment. For the latter, we retrospectively compared accelerated high-frequency rTMS (arTMS) with accelerated intermittent theta burst stimulation (aiTBS) in the refractory depressed state. Although the clinical efficacy was not significantly different between both protocols, our observations substantiate the potential of the accelerated stimulation to shorten the treatment duration from the depressed state to the response state. Any time gain from the depressed state to the recovered state is in the patients' interest

Accelerated rTMS: A Potential Treatment to Alleviate Refractory Depression

Three decades of clinical research on repetitive transcranial magnetic stimulation (rTMS) has yielded one clear treatment indication in psychiatry for major depression disorder (MDD). Although the clinical response equals the standard treatment algorithms, the effect sizes on the beneficial outcome remain rather modest. Over the last couple of years, to improve the efficacy in resistant depression, two new avenues have been developed: personalization and intensifying rTMS treatment. For the latter, we retrospectively compared accelerated high-frequency rTMS (arTMS) with accelerated intermittent theta burst stimulation (aiTBS) in the refractory depressed state. Although the clinical efficacy was not significantly different between both protocols, our observations substantiate the potential of the accelerated stimulation to shorten the treatment duration from the depressed state to the response state. Any time gain from the depressed state to the recovered state is in the patients’ interest

Depressive symptoms in the elderly : an early symptom of dementia? A systematic review

Background Depression and dementia are common incapacitating diseases in old age. The exact nature of the relationship between these conditions remains unclear, and multiple explanations have been suggested: depressive symptoms may be a risk factor for, a prodromal symptom of, or a coincidental finding in dementia. They may even be unrelated or only connected through common risk factors. Multiple studies so far have provided conflicting results. Objectives To determine whether a systematic literature review can clarify the nature of the relation between depressive symptoms and dementia. Methods Using the Patient/Problem/Population, Intervention, Comparator, Outcome or PICO paradigm, a known framework for framing healthcare and evidence questions, we formulated the question "whether depressive symptoms in cognitively intact older adults are associated with a diagnosis of dementia later in life." We performed a systematic literature review of MEDLINE and PsycINFO in November 2018, looking for prospective cohort studies examining the aforementioned question. Results We critically analyzed and listed 31 relevant papers out of 1,656 and grouped them according to the main hypothesis they support: depressive symptoms as a risk factor, not a risk factor, a prodromal symptom, both, or some specific other hypothesis. All but three studies used clinical diagnostic criteria for dementia alone (i.e., no biomarkers or autopsy confirmation). Several studies contain solid arguments for the hypotheses they support, yet they do not formally contradict other findings or suggested explanations and are heterogeneous. Conclusions The exact nature of the relationship between depressive symptoms and dementia in the elderly remains inconclusive, with multiple studies supporting both the risk factor and prodromal hypotheses. Some provide arguments for common risk factors. It seems unlikely that there is no connection at all. We conclude that at least in a significant part of the patients, depressive symptoms and dementia are related. This may be due to common risk factors and/or depressive symptoms being a prodromal symptom of dementia and/or depression being a risk factor for dementia. These causal associations possibly overlap in some patients. Further research is warranted to develop predictive biomarkers and to develop interventions that may attenuate the risk of "conversion" from depressive symptoms to dementia in the elderly

Intermittent theta burst stimulation increases reward responsiveness in individuals with higher hedonic capacity

Background: Repetitive transcranial magnetic stimulation over the left dorsolateral prefrontal cortex (DLPFC) has been documented to influence striatal and orbitofrontal dopaminergic activity implicated in reward processing. However, the exact neuropsychological mechanisms of how DLPFC stimulation may affect the reward system and how trait hedonic capacity may interact with the effects remains to be elucidated. Objective: In this sham-controlled study in healthy individuals, we investigated the effects of a single session of neuronavigated intermittent theta burst stimulation (iTBS) on reward responsiveness, as well as the influence of trait hedonic capacity. Methods: We used a randomized crossover single session iTBS design with an interval of 1 week. We assessed reward responsiveness using a rewarded probabilistic learning task and measured individual trait hedonic capacity (the ability to experience pleasure) with the temporal experience of pleasure scale questionnaire. Results: As expected, the participants developed a response bias towards the most rewarded stimulus (rich stimulus). Reaction time and accuracy for the rich stimulus were respectively shorter and higher as compared to the less rewarded stimulus (lean stimulus). Active or sham stimulation did not seem to influence the outcome. However, when taking into account individual trait hedonic capacity, we found an early significant increase in the response bias only after active iTBS. The higher the individuals trait hedonic capacity, the more the response bias towards the rich stimulus increased after the active stimulation. Conclusion: When taking into account trait hedonic capacity, one active iTBS session over the left DLPFC improved reward responsiveness in healthy male participants with higher hedonic capacity. This suggests that individual differences in hedonic capacity may influence the effects of iTBS on the reward system

Brainstem glucose metabolism predicts reward dependence scores in treatment-resistant major depression

BACKGROUND: It has been suggested that individual differences in temperament could be involved in the (non-)response to antidepressant (AD) treatment. However, how neurobiological processes such as brain glucose metabolism may relate to personality features in the treatment-resistant depressed (TRD) state remains largely unclear. METHODS: To examine how brainstem metabolism in the TRD state may predict Cloninger's temperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), and Reward Dependence (RD), we collected (18)fluorodeoxyglucose positron emission tomography ((18)FDG PET) scans in 40 AD-free TRD patients. All participants were assessed with the Temperament and Character Inventory (TCI). We applied a multiple kernel learning (MKL) regression to predict the HA, NS, and RD from brainstem metabolic activity, the origin of respectively serotonergic, dopaminergic, and noradrenergic neurotransmitter (NT) systems. RESULTS: The MKL model was able to significantly predict RD but not HA and NS from the brainstem metabolic activity. The MKL pattern regression model identified increased metabolic activity in the pontine nuclei and locus coeruleus, the medial reticular formation, the dorsal/median raphe, and the ventral tegmental area that contributed to the predictions of RD. CONCLUSIONS: The MKL algorithm identified a likely metabolic marker in the brainstem for RD in major depression. Although (18)FDG PET does not investigate specific NT systems, the predictive value of brainstem glucose metabolism on RD scores however indicates that this temperament dimension in the TRD state could be mediated by different monoaminergic systems, all involved in higher order reward-related behavior

The effect of the interval-between-sessions on prefrontal transcranial direct current stimulation (tDCS) on cognitive outcomes: a systematic review and meta-analysis

Recently, there has been wide interest in the effects of transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (DLPFC) on cognitive functioning. However, many methodological questions remain unanswered. One of them is whether the time interval between active and sham-controlled stimulation sessions, i.e. the interval between sessions (IBS), influences DLPFC tDCS effects on cognitive functioning. Therefore, a systematic review and meta-analysis was performed of experimental studies published in PubMed, Science Direct, and other databases from the first data available to February 2016. Single session sham-controlled within-subject studies reporting the effects of tDCS of the DLPFC on cognitive functioning in healthy controls and neuropsychiatric patients were included. Cognitive tasks were categorized in tasks assessing memory, attention, and executive functioning. Evaluation of 188 trials showed that anodal vs. sham tDCS significantly decreased response times and increased accuracy, and specifically for the executive functioning tasks, in a sample of healthy participants and neuropsychiatric patients (although a slightly different pattern of improvement was found in analyses for both samples separately). The effects of cathodal vs. sham tDCS (45 trials), on the other hand, were not significant. IBS ranged from less than 1 h to up to 1 week (i.e. cathodal tDCS) or 2 weeks (i.e. anodal tDCS). This IBS length had no influence on the estimated effect size when performing a meta-regression of IBS on reaction time and accuracy outcomes in all three cognitive categories, both for anodal and cathodal stimulation. Practical recommendations and limitations of the study are further discussed