Nolan Williams, Postdoctoral Faculty Sponsor
Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial.
The American journal of psychiatry
OBJECTIVE: Depression is the leading cause of disability worldwide, and half of patients with depression have treatment-resistant depression. Intermittent theta-burst stimulation (iTBS) is approved by the U.S. Food and Drug Administration for the treatment of treatment-resistant depression but is limited by suboptimal efficacy and a 6-week duration. The authors addressed these limitations by developing a neuroscience-informed accelerated iTBS protocol, Stanford neuromodulation therapy (SNT; previously referred to as Stanford accelerated intelligent neuromodulation therapy, or SAINT). This protocol was associated with a remission rate of 90% after 5 days of open-label treatment. Here, the authors report the results of a sham-controlled double-blind trial of SNT for treatment-resistant depression.METHODS: Participants with treatment-resistant depression currently experiencing moderate to severe depressive episodes were randomly assigned to receive active or sham SNT. Resting-state functional MRI was used to individually target the region of the left dorsolateral prefrontal cortex most functionally anticorrelated with the subgenual anterior cingulate cortex. The primary outcome was score on the Montgomery-Asberg Depression Rating Scale (MADRS) 4 weeks after treatment.RESULTS: At the planned interim analysis, 32 participants with treatment-resistant depression had been enrolled, and 29 participants who continued to meet inclusion criteria received either active (N=14) or sham (N=15) SNT. The mean percent reduction from baseline in MADRS score 4 weeks after treatment was 52.5% in the active treatment group and 11.1% in the sham treatment group.CONCLUSIONS: SNT, a high-dose iTBS protocol with functional-connectivity-guided targeting, was more effective than sham stimulation for treatment-resistant depression. Further trials are needed to determine SNT's durability and to compare it with other treatments.
View details for DOI 10.1176/appi.ajp.2021.20101429
View details for PubMedID 34711062
Multiculturalism: A Challenge for Cognitive Screeners in Parkinson's Disease
MOVEMENT DISORDERS CLINICAL PRACTICE
2021; 8 (5): 733-742
The Montreal Cognitive Assessment (MoCA) and the Dementia Rating Scale-2 (DRS-2) are recommended screeners for Parkinson's disease mild cognitive impairment (PD-MCI). Cross-cultural studies examining their diagnostic precision have not addressed cultural bias in a multicultural setting.To compare DRS-2 and MoCA performance between patients born in Canada, the USA, and the UK (Anglosphere group) and immigrant patients born elsewhere (International group). To identify sources of cultural bias by comparing group characteristics, and by assessing the relationships between performance and immigration and socio-development variables. To examine the diagnostic precision of both tools in detecting PD-MCI in each group.We conducted a clinical chart review of advanced PD patients who completed cognitive screeners (MoCA: n = 288, 30% International group; DRS-2: n = 426, 31% International group). All completed a comprehensive neuropsychological assessment to apply Level II PD-MCI diagnostic criteria.The International group performed worse than the Anglosphere group on the MoCA and DRS-2, and the only variable that accounted for some of the group difference was the Historical Index of Human Development, a societal variable, which fully mediated the group effect on the DRS-2. Diagnostic precision of the MoCA was at chance level in the International group, and was poorer than that of the DRS-II in this group and that of the MoCA in the Anglosphere group, although these were considered poor.Our results support the recommendation to exert caution in using cognitive screeners to capture PD-MCI in all patients and particularly with first generation immigrants.
View details for DOI 10.1002/mdc3.13240
View details for Web of Science ID 000655135600001
View details for PubMedID 34307746
View details for PubMedCentralID PMC8287166
Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression.
The American journal of psychiatry
New antidepressant treatments are needed that are effective, rapid acting, safe, and tolerable. Intermittent theta-burst stimulation (iTBS) is a noninvasive brain stimulation treatment that has been approved by the U.S. Food and Drug Administration for treatment-resistant depression. Recent methodological advances suggest that the current iTBS protocol might be improved through 1) treating patients with multiple sessions per day at optimally spaced intervals, 2) applying a higher overall pulse dose of stimulation, and 3) precision targeting of the left dorsolateral prefrontal cortex (DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. The authors examined the feasibility, tolerability, and preliminary efficacy of Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT), an accelerated, high-dose resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for treatment-resistant depression.Twenty-two participants with treatment-resistant depression received open-label SAINT. fcMRI was used to individually target the region of the left DLPFC most anticorrelated with sgACC in each participant. Fifty iTBS sessions (1,800 pulses per session, 50-minute intersession interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.One participant withdrew, leaving a sample size of 21. Nineteen of 21 participants (90.5%) met remission criteria (defined as a score <11 on the Montgomery-Åsberg Depression Rating Scale). In the intent-to-treat analysis, 19 of 22 participants (86.4%) met remission criteria. Neuropsychological testing demonstrated no negative cognitive side effects.SAINT, an accelerated, high-dose, iTBS protocol with fcMRI-guided targeting, was well tolerated and safe. Double-blinded sham-controlled trials are needed to confirm the remission rate observed in this initial study.
View details for DOI 10.1176/appi.ajp.2019.19070720
View details for PubMedID 32252538
HPA axis in psychotic major depression and schizophrenia spectrum disorders: Cortisol, clinical symptomatology, and cognition.
The Hypothalamic Pituitary Adrenal (HPA) axis has been implicated in the pathophysiology of a variety of mood and cognitive disorders. Neuroendocrine studies have demonstrated HPA axis overactivity in major depression, a relationship of HPA axis activity to cognitive performance, and a potential role of HPA axis genetic variation in cognition. In schizophrenia differential HPA activity has been found, including higher rates of non-suppression to dexamethasone challenge and higher salivary cortisol levels, which have been a premonitory risk factor for conversion to psychosis in adolescents at risk for developing schizophrenia. The present study investigated the simultaneous roles HPA axis activity and clinical symptomatology play in poor cognitive performance. Patients with major depression with psychosis (PMD) or schizophrenia spectrum disorder (SCZ) and healthy controls (HC) were studied. All participants underwent a diagnostic interview and psychiatric ratings, a comprehensive neuropsychological battery, and overnight hourly blood sampling for cortisol. Cognitive performance did not differ between the clinical groups, though they both performed more poorly than the HC's across a variety of cognitive domains. Across all subjects, cognitive performance was negatively correlated with higher cortisol, and PMD patients had higher evening cortisol levels than did SCZ and HCs. Cortisol and clinical symptoms, as well as age, sex, and antipsychotic use predicted cognitive performance. Diathesis stress models and their links to symptomatology, cognition, and HPA function are discussed.
View details for DOI 10.1016/j.schres.2019.07.003
View details for PubMedID 31307859
High-Dose Spaced Theta-Burst Transcranial Magnetic Stimulation as a Rapid-Acting Anti- Depressant in Highly Refractory Depression
ELSEVIER SCIENCE INC. 2018: S191
View details for Web of Science ID 000432466300476
High-dose spaced theta-burst TMS as a rapid-acting antidepressant in highly refractory depression.
Brain : a journal of neurology
View details for PubMedID 29415152