Efficacy of transcranial direct current stimulation for treating anhedonia in patients with depression: A randomized, double-blind, sham-controlled clinical trial.

BACKGROUND: Anhedonia, the core symptom of major depressive disorder (MDD), is highly prevalent in patients with depression. Anhedonia is associated with low efficacy of drug treatment, high suicide rates, and poor social function. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technology that uses constant, low-intensity direct current to treat MDD by regulating cortical activity and neuronal excitability. However, little is known about the efficacy of tDCS for treating anhedonia in patients with depression, and even the existing results of clinical trials are conflicting. In addition, there is no consensus on what brain regions should be targeted by tDCS during the treatment of anhedonia in patients with depression. OBJECTIVE: This study aimed to evaluate the efficacy and safety of tDCS over the left dorsolateral prefrontal cortex (DLPFC) and right orbitofrontal cortex (OFC) in the improvement of anhedonia in patients with depression and finally identified suitable brain regions to be stimulated during treatment. METHODS: This randomized, double-blind, sham-controlled clinical trial recruited 70 patients with anhedonia and depressive episodes. Patients were randomly assigned to three groups according to the stimulation site: right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), and sham stimulation. Each group received twelve 20-min interventions (ten as primary treatment and two for consolidation). The primary outcome was a decrease in Snaith-Hamilton Pleasure Scale (SHAPS) scores after primary treatment. Evaluations were performed at baseline, post-treatment, and 8-week follow-up. RESULTS: The depression mood of the three groups of patients at each time point was better than the baseline, but there was no significant difference in the efficacy between the groups (p>0.05). On the basis of the improvement of depression, this study found that tDCS of the DLPFC significantly improved anhedonia (p = 0.028) after primary treatment (2 weeks), and tDCS of the DLPFC and OFC significantly improved social functioning (p = 0.005) at 8-week follow-up. LIMITATIONS: The sample size of this study was small, with only about 23/24 patients in each group completing the intervention assessments; due to the impact of the COVID-19 epidemic, data analysis was limited by the lack of patients during the follow-up period. CONCLUSIONS: tDCS of the DLPFC significantly improves anhedonia in depressed patients and is thus a potential adjuvant therapy for anhedonia in these patients.

Adjunctive duration-doubled transcranial direct current stimulation for the treatment of depressive patients with suicidal ideation: study protocol for a double-blind, randomized, sham-controlled trial.

BACKGROUND: The problem of suicide has become increasingly common in individuals with major depressive disorder (MDD). Transcranial direct current stimulation (tDCS) is an effective treatment for MDD with 2 milliamperes (mA) for at least 30 min per day for 2 weeks. This study aims to investigate the efficacy of daily duration-doubled tDCS as an adjunctive intervention for rapidly reducing suicidal ideation and improving depression in MDD patients. METHODS: In this double-blind, randomized, sham-controlled study, 76 MDD patients with suicidal ideation are randomly assigned to either active (n=38) or sham (n=38) tDCS group. The anode and cathode are placed over the scalp areas corresponding to left and right dorsolateral prefrontal cortex (DLPFC), respectively, and each stimulation lasts for 60 min. The primary outcome is defined as change of Beck Scale for Suicide Ideation (BSI) after 5 and 10 sessions. The change of other clinical assessments, blood biomarkers related to suicidal ideation and depressive sumptoms are defined as secondary outcomes. Blood biomarkers related to suicidal ideation are collected at baseline and after 10 sessions. DISCUSSION: This study suggests the adjunctive duration-doubled tDCS might be a novel method to rapidly reduce suicidal ideation and improve depressive symptom. The variation of biomarkers could be potential predictive models of suicide risk. TRIAL REGISTRATION: The trial protocol is registered with ClinicalTrials.gov under protocol registration number NCT05555927. Registered on September 25, 2022.

Comparison of 60-minute vs 30-minute transcranial direct current stimulation (tDCS) in major depressive disorder: Effects on depression suicidal ideation and anxiety.

We investigated whether changes through doubling the duration of each tDCS session would increase efficacy of tDCS for depression. tDCS was applied for 10 sessions, followed by two additional weekly sessions. 63 patients with MDD underwent randomization, with 22 being assigned to 60-min/d group, 25 to 30 min/d group, and 16 to sham group. HAMD-17 reductive ratios at week 2 and 4 were of no significant differences among treatment groups. 60 min group had a greater decrease in anxiety compared to 30 min group and sham group based on HAMA at 4 weeks but only in the completer analysis, not in ITT analysis.

Mechanism and Origins of Diastereo- and Regioselectivities of Palladium-Catalyzed Remote Diborylative Cyclization of Dienes via Chain-Walking Strategy.

Density functional theory calculations have been performed to investigate the palladium-catalyzed remote diborylative cyclization of dienes. The computations reveal that the reaction proceeds through a rarely explored Pd(II)/Pd(IV) catalytic cycle, and the formal σ-bond metathesis between the alkylpalladium intermediate and B2 pin2 occurs via the pathway of the B-B oxidative addition/C-B reductive elimination involving the high-valent Pd(IV) species. The diastereoselectivity is determined by the migratory insertion into the Pd-C bond, which is mainly due to the combination of the torsional strain effect, steric repulsion and C-H-O hydrogen-bonding interaction. The steric hindrance around the reacting carbon group in the C-B reductive elimination turns out to be a key factor to provide the driving force of the chain walking of the Pd center to the terminal primary carbon position, enabling the experimentally observed remote regioselectivity.

Efficacy of adjunctive intensive transcranial direct current stimulation of different cortices in treatment-resistant depression: a study protocol for a randomized double-blinded sham-controlled trial.

BACKGROUND: Treatment-resistant depression (TRD) carries a high economic burden worldwide. Transcranial direct current stimulation (tDCS) is advantageous for improving cognition and can be safely used in the treatment of depression. The effectiveness of tDCS of the left and right orbitofrontal cortex (OFC) as adjuvant treatment in patients with TRD has rarely been explored. Therefore, the objective of this trial is to evaluate the effectiveness there of when administering left dorsolateral prefrontal cortex (DLPFC) positive stimulation or OFC negative stimulation in patients with TRD. METHODS: Ninety eligible participants will be recruited to receive intervention at Shanghai Mental Health Center. Treatment will be randomly assigned in a double-blind fashion. Participants will receive either DLPFC (n = 30), OFC (n = 30), or sham (n = 30) tDCS, while continuing their usual pharmacotherapy at a stable dosage for at least 2 weeks before enrollment and throughout the stimulation period. All participants will receive 20 weekday stimulation sessions of 60 minutes duration each. Participants in the active group will be stimulated at 2 mA throughout the session, whereas the sham group will receive only a brief period of stimulation to mimic the sensation. After 20 stimulation sessions, no further treatment will be administered. Measurements will be conducted at regular points throughout and at 8 weeks after trial completion. The primary outcome is the change in the 17-item Hamilton Depression Rating Scale (HAMD-17) score after 20 sessions. Secondary outcomes were defined as changes in other measurement scales, cognitive function, resting-state functional magnetic resonance imaging (rs-fMRI), and serum biomarkers. DISCUSSION: We hypothesize that, in contrast to the sham group, both the active DLPFC and OFC tDCS groups will show superiority in HAMD-17 score reduction after 5, 10, and 20 sessions. Moreover, associations of the improvement of depressive symptoms with variations in rs-fMRI and TRD-related biomarkers will be evaluated. Our study may suggest that adjunctive intensive tDCS with left DLPFC positive stimulation or right OFC negative stimulation may be effective as a novel method to relieve depressive symptoms in patients with TRD. The variation of rs-fMRI, biomarkers could be used as a potential prediction model of treatment efficacy in TRD. TRIAL REGISTRATION: The trial protocol is registered with www.chictr.org.cn under protocol registration number ChiCTR2200058030. Date of registration: March 27, 2022. Recruitment started in September 2022 and is ongoing.

Short- and Long-Term Influences of Benzodiazepine and Z-Drug Use in Patients with Bipolar Disorder Combined Sleep Disturbance during Affective Period: A Nine-Month Follow-Up Analysis.

Background: Sleep disturbances and benzodiazepine (BZD)/Z-drug use are common in patients with bipolar disorder (BD). Objective: To investigate the short- and long-term effects of BZD/Z-drug use during acute affective episode. Methods: Participants diagnosed with BD as well as sleep disturbance chose BZDs/Z-drugs or not at will. Manic and depressive symptoms were assessed by Mental Disorders Questionnaire (MDQ) and Quick Inventory of Depressive Symptoms (QIDS) as self-reporting surveys. The participants were assessed by trained evaluators at baseline and months 1, 3, 6, and 9. Results: 61 patients with BD combined sleep disturbances were studied. At baseline, patients who used BZDs/Z-drugs had more amount of mood stabilizers (p = 0.038), other psychotropic medications (p = 0.040), and more risk of suicide attempt (p = 0.019). The BZD/Z-drug group had a significantly higher QIDS reductive ratio as compared with the no BZD/Z-drug group at month 1; no significant differences in the variability of MDQ, QIDS reductive ratio, or recurrence rate were found between these two groups at baseline, month 1, month 3, month 6, or month 9. Conclusions: During acute affective episode, patients with BD combined sleep disturbance who took BZDs/Z-drugs tended to use more amount of mood stabilizers. Polytherapy of BZDs/Z-drugs or other psychiatric drugs could increase suicide attempt during an acute affective episode. BZD/Z-drug use, however, had a significant effect on helping depressive symptoms alleviate during affective period.

Analysis of Seasonal Clinical Characteristics in Patients With Bipolar or Unipolar Depression.

This study was to investigate the characteristics of seasonal symptoms and non-enzymatic oxidative stress in the first hospitalized patients with bipolar and unipolar depression, aiming to differentiate bipolar depression from unipolar depression and reduce their misdiagnosis. A total of 450 patients with bipolar depression and 855 patients with depression were included in the present study. According to the season when the patients were admitted to the hospital due to the acute onset of depression, they were further divided into spring, summer, autumn and winter groups. According to the characteristics of symptoms of bipolar disorder in the DSM-5, the characteristic symptoms of bipolar disorder were collected from the medical record information, and clinical biochemical indicators that can reflect the oxidative stress were also recorded. The seasonal risk factors in patients with bipolar or unipolar depression were analyzed. The relationship of age and gender with the bipolar or unipolar depression which attacked in winter was explored. There were significant differences between groups in the melancholic features, atypical features and conjugated bilirubin in spring. In summer, there were significant differences between groups in the melancholic features, uric acid and conjugated bilirubin. In autumn, there were marked differences between groups in melancholic features, anxiety and pain, atypical features, uric acid, total bilirubin, conjugated bilirubin and albumin. In winter, the conjugated bilirubin and prealbumin were significantly different between two groups. The melancholic features and uric acid that in summer as well as melancholic features, uric acid and total bilirubin in autumn were the seasonal independent risk factors for the unipolar depression as compared to bipolar depression. In winter, significant difference was noted in the age between two groups. In conclusion, compared with patients with unipolar depression, patients with bipolar depression have seasonal characteristics. Clinical symptoms and indicators of oxidative stress may become factors for the differentiation of seasonal unipolar depression from bipolar depression. Young subjects aged 15-35 years are more likely to develop bipolar depression in winter.

Difference in the regulation of biological rhythm symptoms of Major depressive disorder between escitalopram and mirtazapine.

BACKGROUND: Biological rhythm plays an important role in major depressive disorder (MDD). The efficacy of antidepressant in biological rhythm remains unclear. This study is designed to explore the efficiency of escitalopram and mirtazapine in improving circadian rhythm, diurnal mood variation(DMV) and daily activity in MDD patients. METHODS: Four-hundred and fifty participants diagnosed with MDD were randomized to receive treatment with escitalopram (TWE), treatment with mirtazapine (TWM) or treatment as usual (TAU). Biological rhythm symptoms were assessed by relevant biological subscale in the Hamilton depression scale (HAMD) and the quick inventory of depressive symptomatology self-report (QIDS). The participants were assessed by trained evaluators at baseline and week 2, 4, 6 and 8. RESULTS: The differences of HAMD score among TWE(58%, 69%, 72%), TWM(56%, 64%, 76%) and TAU(49%, 57%, 68%) were significant(P<0.05). But the differences were significant only in patients without DMV; (2) Sleep rhythm items (difficulty falling asleep and early-wake) were significantly improved in TWM (P <0 .05) for both HAMD and QIDS. Decreased appetite and weight were significantly improved in TWM (P<0 .05) for both scales. (3) For daily activity-related items, feeling slowed down and concentration were significantly improved in TWE. And the retardation was significantly improved in TWE and in TWM. CONCLUSIONS: Both escitalopram and mirtazapine have superior anti-depressive effect, especially for MDD patients without DMV. Escitalopram was significantly more effective in daily activity, feeling slowed down and concentration difficulty, while mirtazapine was significantly more effective in improving sleep, appetite and weight of MDD.