Can a single session of noninvasive brain stimulation applied over the prefrontal cortex prevent stress-induced cortisol release?

INTRODUCTION: A better understanding of how the hypothalamic-pituitary-adrenal (HPA) axis can be externally regulated is of major importance, especially because hyperreactivity to stress has been proposed as a key factor in the onset and maintenance of many psychiatric conditions. Over the past decades, numerous studies have investigated whether non-invasive brain stimulation (NIBS) can regulate HPA axis reactivity in acute stress situation. As the current results did not allow us to draw clear conclusions, we decided to conduct a systematic review of the literature investigating the effect of a single NIBS session on stress-induced cortisol release. METHODS: We searched MEDLINE and Web Of Science for articles indexed through December 2021. Among the 246 articles identified, 15 fulfilled our inclusion criteria with a quality estimated between 52 and 93%. RESULTS: Of the different NIBS used and targeted brain regions, stimulating the left dorsolateral prefrontal cortex, with either high frequency repetitive transcranial magnetic stimulation or anodal transcranial direct current stimulation, seems to be the most appropriate for reducing cortisol release in acute stress situations. CONCLUSIONS: Despite the heterogeneity of the stimulation parameters, the characteristics of participants, the modalities of cortisol collection, the timing of the NIBS session in relation to the stressor exposure, and methodological considerations, stimulating the left dorsolateral prefrontal cortex can be efficient to modulate stress-induced cortisol release.

Recent advances in noninvasive brain stimulation for schizophrenia.

PURPOSE OF REVIEW: Noninvasive brain stimulation has emerged in the last three decades as a promising treatment for patients with antipsychotic-resistant symptoms of schizophrenia. This review updates the latest progress in the use of noninvasive brain stimulation to treat schizophrenia symptoms. RECENT FINDINGS: Several recently published randomized-controlled trials support a long-lasting clinical effect of stimulation techniques on schizophrenia symptoms. In addition, efforts have been made in recent months to improve efficacy through several optimization strategies. Studies have tested new parameters of stimulation, such as theta burst stimulation, and alternative cortical or subcortical targets and have reported encouraging results. New forms of electrical stimulations such as alternating and random noise stimulation, have also been studied and have shown clinical and cognitive usefulness for patients. Accelerated stimulation protocols, and prospects could arise with deeper stimulation strategies. SUMMARY: Using brain stimulation to treat symptoms of schizophrenia seems promising and the great flexibility of the stimulation parameters leaves much room for developing optimization strategies and improving its effectiveness. Further studies need to identify the optimal parameters to maximize response rate.

Efficacy of Transcranial Direct Current Stimulation to Improve Insight in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND AND HYPOTHESIS: Impaired insight into the illness and its consequences is associated with poor outcomes in schizophrenia. While transcranial direct current stimulation (tDCS) may represent a potentially effective treatment strategy to relieve various symptoms of schizophrenia, its impact on insight remains unclear. To investigate whether tDCS would modulate insight in patients with schizophrenia, we undertook a meta-analysis based on results from previous RCTs that investigated the clinical efficacy of tDCS. We hypothesize that repeated sessions of tDCS will be associated with insight improvement among patients. STUDY DESIGN: PubMed and ScienceDirect databases were systematically searched to identify RCTs that delivered at least 10 tDCS sessions in patients with schizophrenia. The primary outcome was the change in insight score, assessed by the Positive and Negative Syndrome Scale (PANSS) item G12 following active tDCS sessions as opposed to sham stimulation. Effect sizes were calculated for all studies and pooled using a random-effects model. Meta-regression and subgroup analyses were conducted. STUDY RESULTS: Thirteen studies (587 patients with schizophrenia) were included. A significant pooled effect size (g) of -0.46 (95% CI [-0.78; -0.14]) in favor of active tDCS was observed. Age and G12 score at baseline were identified as significant moderators, while change in total PANSS score was not significant. CONCLUSIONS: Ten sessions of active tDCS with either frontotemporoparietal or bifrontal montage may improve insight into the illness in patients with schizophrenia. The effect of this treatment could contribute to the beneficial outcomes observed in patients following stimulation.

Frontotemporal Transcranial Direct Current Stimulation Decreases Serum Mature Brain-Derived Neurotrophic Factor in Schizophrenia.

Although transcranial direct current stimulation (tDCS) shows promise as a treatment for auditory verbal hallucinations in patients with schizophrenia, mechanisms through which tDCS may induce beneficial effects remain unclear. Evidence points to the involvement of neuronal plasticity mechanisms that are underpinned, amongst others, by brain-derived neurotrophic factor (BDNF) in its two main forms: pro and mature peptides. Here, we aimed to investigate whether tDCS modulates neural plasticity by measuring the acute effects of tDCS on peripheral mature BDNF levels in patients with schizophrenia. Blood samples were collected in 24 patients with schizophrenia before and after they received a single session of either active (20 min, 2 mA, n = 13) or sham (n = 11) frontotemporal tDCS with the anode over the left prefrontal cortex and the cathode over the left temporoparietal junction. We compared the tDCS-induced changes in serum mature BDNF (mBDNF) levels adjusted for baseline values between the two groups. The results showed that active tDCS was associated with a significantly larger decrease in mBDNF levels (mean -20% ± standard deviation 14) than sham tDCS (-8% ± 21) (F = 5.387; p = 0.030; η2 = 0.205). Thus, mature BDNF may be involved in the beneficial effects of frontotemporal tDCS observed in patients with schizophrenia.

Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review.

Patients with schizophrenia are often unaware of their condition and the consequences of their illness. This lack of insight results in impaired functioning, treatment non-adherence and poor prognosis. Here, we aimed to investigate the effects of non-invasive brain stimulation (NIBS) on two forms of insight, clinical and cognitive, in patients with schizophrenia. We conducted a systematic review of the literature registered in the PROSPERO database (CRD42020220323) according to PRISMA guidelines. The literature search was conducted in Medline and Web of Science databases based on studies published up until October 2020 that included pre-NIBS and post-NIBS measurements of clinical and/or cognitive insight in adults with schizophrenia. A total of 14 studies were finally included, and their methodological quality was assessed by using the QualSyst tool. Despite the lack of well-conducted large randomized-controlled studies using insight as the primary outcome, the available findings provide preliminary evidence that NIBS can improve clinical insight in patients with schizophrenia, with a majority of studies using transcranial direct current stimulation with a left frontotemporal montage. Further studies should investigate the effect of NIBS on insight as a primary outcome and how these effects on insight could translate into clinical and functional benefits in patients with schizophrenia.