Search

Ketamine treatment prompts a rapid antidepressant response in treatment-resistant depression (TRD). We performed an exploratory investigation of how ketamine treatment in TRD affects different cognitive domains and relates to antidepressant response. Patients with TRD (N = 66; 30 M/35F; age = 39.5 ± 11.1 years) received four ketamine infusions (0.5 mg/kg). Neurocognitive function and depressive symptoms were assessed at baseline, 24 h after the first and fourth ketamine infusion, and 5 weeks following end of treatment. Mixed effect models tested for changes in seven neurocognitive domains and antidepressant response, with post-hoc pairwise comparisons between timepoints, including follow-up. Relationships between change in neurocognitive function and antidepressant response over the course of treatment were tested with Pearson's correlation and mediation analyses. Associations between baseline neurocognitive performance and antidepressant response were tested with Pearson's correlation. Significant improvements in inhibition, working memory, processing speed, and overall fluid cognition were observed after the first and fourth ketamine infusion. Improvements in processing speed and overall fluid cognition persisted through follow-up. Significant improvements in depressive symptoms reverted towards baseline at follow-up. Baseline working memory and change in inhibition were moderately correlated with antidepressant response, however, improvements in neurocognitive performance were statistically independent from antidepressant response. Antidepressant ketamine leads to improved neurocognitive function, which persist for at least 5 weeks. Neurocognitive improvements observed appear independent of antidepressant response, suggesting ketamine may target overlapping but distinct functional brain systems. Limitations Research investigating repeated serial ketamine treatments is important to determine cognitive safety. This study is a naturalistic design and does not include placebo. • Improvements in neurocognitive function observed 24 h after first and fourth ketamine infusion • Improvements in processing speed and global fluid cognitive function through 5-week follow-up • Change in neurocognitive function independent from antidepressant response [ABSTRACT FROM AUTHOR]

Objective: Major Depressive Disorder (MDD) subtypes have been shown to differentially impact psychiatric symptom presentation, clinical features, and functional abilities. While there is extensive research regarding MDD subtypes and clinical characteristics, there has been limited information regarding the relationship between MDD subtypes and neurocognitive functioning. In particular, the neurocognitive impact of the subtype of treatment resistant depression (TRD), defined as MDD that is unresponsive to treatment, is unknown. The aim of this preliminary study was to address this gap by characterizing the neurocognitive profile of TRD. We characterized the performance of older adults with TRD on measures across multiple neurocognitive domains, and explored whether performance varied based on age and education. Participants and Methods: Data utilized were drawn from a broader NIMH-funded, randomized, controlled study conducted at the University of New Mexico that investigated the clinical and cognitive outcomes of varying pulse amplitudes during acute electroconvulsive therapy (ECT) in adults with MDD. Participants in the study were age 50+ with a diagnosis of MDD, and further delineated by subtype as TRD. For this analysis, we utilized demographic and baseline neurocognitive data collected prior to start of treatment for those diagnosed with MDD, recurrent, severe (TRD). Neurocognitive measures included the Delis Kaplan Executive Function System (D-KEFS) Verbal Fluency and Color-Word Interference Subtests, Hopkins Verbal Learning Test-Revised (HVLT-R), and the Wechsler Adult Intelligence Scale 4th Edition (WAIS-IV) Digit Spans. Demographic-adjusted scaled scores were computed, and descriptive statistics were used to characterize the demographic and neurocognitive features of the sample. Multiple Analysis of Variance (MANOVA) was used to investigate difference in performance across neurocognitive measures based on level of education, with age as a covariate. Results: The sample (n = 42) had a mean age of 65 (SD=8), education level between12 and 14 years, 66.6% were female and 93% were Caucasian. DKEFS Verbal Fluency Category Switching Total Switching Accuracy fell in the Average range (Mean SS=9.5, SD=3.1), and Color Word Inhibition Total Completion Time fell in the Average range (Mean SS=8.5, SD=3.3). HVLT-R Total Recall Correct fell in the Mildly Impaired range (Mean T=35.5, SD=9.9) and Delayed Recall Correct fell in the Mildly to Moderately Impaired range (Mean T=32.9, SD=11.0). WAIS-IV Digit Span fell in the Average range (Mean SS=9.5, SD=2.2). Results indicated that age did not adjust outcomes on the neurocognitive variables, Wilks's λ=0.63, F(6, 23)=2.13, p=0.08. We found no evidence for significant effect of level of education on neurocognitive functioning when controlling for the covariate of age, Wilks's λ=-0.16, F(36, 103.7)=1.47, p=0.07. Conclusions: To our knowledge, this is one of two studies to examine neurocognitive functioning in patients with TRD. The analysis indicated generally intact performance in the neurocognitive domains of executive function (inclusive of verbal fluency, cognitive flexibility, and inhibition), auditory attention and working memory, and Impaired performance on indices of verbal learning and memory. Age did not impact performance on neurocognitive measures, and there was no significant effect for level of education. Further research is warranted to confirm these findings and further explicate the neurocognitive profile of TRD. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is the most effective treatment for treatment-resistant depression (TRD), especially for acute suicidal ideation, but the associated cognitive adverse effects and negative stigma limit its use. Another seizure therapy under development is magnetic seizure therapy (MST), which could potentially overcome the restrictions associated with ECT with similar efficacy. The neurophysiological targets and mechanisms of seizure therapy, however, remain poorly understood.Methods/design: This neurophysiological study protocol is published as a companion to the overall Confirmatory Efficacy and Safety Trial of Magnetic Seizure Therapy for Depression (CREST-MST) protocol that describes our two-site, double-blind, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. Our aim for the neurophysiological component of the study is to evaluate two biomarkers, one to predict remission of suicidal ideation (primary outcome) and the other to predict cognitive impairment (secondary outcome). Suicidal ideation will be assessed through cortical inhibition, which according to our preliminary studies, correlates with remission of suicidal ideation. Cortical inhibition will be measured with simultaneous transcranial magnetic stimulation (TMS) and electroencephalography (EEG), TMS-EEG, which measures TMS-evoked EEG activity. Cognitive adverse effects associated with seizure therapy, on the contrary, will be evaluated via multiscale entropy analysis reflecting the complexity of ongoing resting-state EEG activity.Discussion: ECT and MST are known to influence cortical inhibition associated with depression, suicidal ideation severity, and clinical outcome. Therefore, evaluating cortical inhibition and brain temporal dynamics will help understand the pathophysiology of depression and suicidal ideation and define new biological targets that could aid clinicians in diagnosing and selecting treatments. Resting-state EEG complexity was previously associated with the degree of cognitive side effects after a seizure therapy. This neurophysiological metric may help clinicians assess the risk for adverse effects caused by these useful and effective treatments.Trial Registration: ClinicalTrials.gov NCT03191058 . Registered on June 19, 2017. [ABSTRACT FROM AUTHOR]

Depression has been shown to negatively impact neurocognitive functions, particularly those governed by fronto-subcortical networks, such as executive functions. Converging evidence suggests that depression-related executive dysfunction is greater at older ages, however, this has not been previously confirmed by meta-analysis. We performed a systematic review and meta-analysis, using three-level models, on peer-reviewed studies that examined depression-related differences in cognitive control in healthy community-dwelling individuals of any age. We focused on studies of cognitive control as defined by the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) framework, which centers on goal-directed behavior, such as goal selection (updating, representations, maintenance), response selection (inhibition or suppression), and performance monitoring. In 16,806 participants aged 7 to 97 across 76 studies, both clinical depression and subthreshold depressive symptoms were associated with cognitive control deficits (Hedges' g = -0.31). This relationship was stronger in study samples with an older mean age. Within studies with a mean age of 39 years or higher, which represents the median age in our analyses, the relationship was stronger in clinical compared to subthreshold depression and in individuals taking antidepressant medication. These findings highlight the importance of clinicians screening for cognitive control dysfunction in patients with depression, particularly in later stages of adulthood. [ABSTRACT FROM AUTHOR]

Objectives: To review brief cognitive screening instruments for routine clinical monitoring in electroconvulsive therapy. Methods: Brief cognitive screening instruments specifically developed for electroconvulsive therapy and commonly used brief generalised cognitive screening instruments were reviewed with relative advantages and disadvantages highlighted. Results: Several brief cognitive screening tests designed for use in electroconvulsive therapy have been found sensitive for monitoring electroconvulsive therapy–related cognitive side effects. The choice of a brief generalised cognitive screening instrument for use in an electroconvulsive therapy clinical context comes with several pertinent considerations. Conclusion: Electroconvulsive therapy is a highly effective treatment for pharmacoresistant and severe neuropsychiatric illness although cognitive side effects can be a barrier for treatment. Routine monitoring using brief cognitive screening instruments has advantages in busy clinical settings and can assist with optimising patient outcomes. More detailed neuropsychological assessment is recommended if the results from brief cognitive screening raise concerns. [ABSTRACT FROM AUTHOR]

Objective: Transcranial direct current stimulation (tDCS) has been found to have antidepressant effects and may have beneficial neurocognitive effects. However, prior research has produced an unclear understanding of the neurocognitive effects of repeated exposure to tDCS. The study's aim was to determine the neurocognitive effects following tDCS treatment in participants with unipolar or bipolar depression.Method: The study was a triple-masked, randomized, controlled clinical trial across six international academic medical centers. Participants were randomized to high dose (2.5 mA for 30 min) or low dose (0.034 mA, for 30 min) tDCS for 20 sessions over 4 weeks, followed by an optional 4 weeks of open-label high dose treatment. The tDCS anode was centered over the left dorsolateral prefrontal cortex at F3 (10/20 EEG system) and the cathode over F8. Participants completed clinical and neurocognitive assessments before and after tDCS. Genotype (BDNF Val66Met and catechol-o-methyltransferase [COMT] Val158Met polymorphisms) were explored as potential moderators of neurocognitive effects.Results: The study randomized 130 participants. Across the participants, tDCS treatment (high and low dose) resulted in improvements in verbal learning and recall, selective attention, information processing speed, and working memory, which were independent of mood effects. Similar improvements were observed in the subsample of participants with bipolar disorder. There was no observed significant effect of tDCS dose. However, BDNF Val66Met and COMT Val158Met polymorphisms interacted with tDCS dose and affected verbal memory and verbal fluency outcomes, respectively.Conclusions: These findings suggest that tDCS could have positive neurocognitive effects in unipolar and bipolar depression. Thus, tDCS stimulation parameters may interact with interindividual differences in BDNF and COMT polymorphisms to affect neurocognitive outcomes, which warrants further investigation. [ABSTRACT FROM AUTHOR]

A new era of scientific exploration has arrived in the neuropsychiatric arena, one in which the clinical neuropsychological community is well poised to ensure optimistic and promising outcomes (Parsons and Duffield, [5]). They examine a spectrum of cognitive outcomes, including a decline in cognitive test scores, diagnosis of mild cognitive impairment, and a diagnosis of AD or other type of dementia. [Extracted from the article]

Background: Repetitive transcranial magnetic stimulation (rTMS) is an approved therapeutic treatment of major depressive disorder and has increasing clinical use throughout the world. However, it remains unclear whether an rTMS course for depression may also produce cognitive enhancement. In a recent meta-analysis of sham-controlled randomized controlled studies (RCTs) conducted in patients with neuropsychiatric conditions, no evidence was found for generalized cognitive enhancing effects across cognitive domains with active compared to sham rTMS. Notwithstanding, there remains the possibility of cognitive effects following an rTMS course that are more highly specific, for example, in specific clinical conditions, or at the individual task level. This study aimed to determine whether a therapeutic rTMS course in patients with depression is associated with cognitive enhancing effects at the task level.Methods: A systematic review and meta-analysis of outcomes on individual neuropsychological tasks from sham-controlled RCTs where an rTMS course was administered to the dorsolateral prefrontal cortex (DLPFC) in patients with depression.Results: Eighteen studies met the inclusion criteria. Active rTMS treatment showed no specific enhancing effects on the majority of cognitive tasks. Modest effect size improvements with active compared to sham rTMS treatment were found for performance on the Trail Making Test Parts A (g = 0.28, 95% CI = 0.06-0.50) and B (g = 0.26, 95% CI = 0.06-0.47).Conclusion: A therapeutic rTMS course administered to the prefrontal cortex for depression may produce modest cognitive enhancing effects specific to psychomotor speed, visual scanning, and set-shifting ability. [ABSTRACT FROM AUTHOR]

Brain stimulation, in the form of electroconvulsive therapy (ECT), has long been a gold standard treatment for depression, but today, the field of neuromodulation is rapidly changing with the advent of newer and more precise tools to alter neuroplasticity and to treat brain-based disorders. Now there are new means to induce focal seizures, as with magnetic seizure therapy (MST), or modifications to ECT. There are also surgical approaches to target brain circuits via implanted stimulators placed in the brain or on cranial nerves. Finally, there are noninvasive subconvulsive approaches for the transcranial application of either electric or magnetic fields. Collectively, these tools have transformed the face of neurotherapeutics and informed our understanding of the brain basis of complex neurobehavioral conditions. [ABSTRACT FROM AUTHOR]

Background Treatment-resistant depression (TRD) is a pervasive and difficult to treat condition for which deep brain stimulation (DBS) of the subcallosal cingulate white matter (SCCwm) is an emerging therapeutic option. However, neuropsychological safety data for this novel treatment have only been published for a small number of subjects. Moreover, little is known regarding the neuropsychological profile present in TRD patients at baseline, prior to initiation of DBS therapy. This report describes the neuropsychological effects of TRD and acute and chronic DBS of the SCCwm in patients with unipolar and bipolar TRD. Methods Patients with TRD (N = 17) were compared to a healthy control group (N = 15) on subtests from the Cambridge Neuropsychological Test Automated Battery and the Stroop Task. Patients were then tested again at subsequent time points of 1 and 6 months following the initiation of chronic DBS of the SCCwm. Results Patients with TRD showed similar levels of performance to healthy controls on most neuropsychological measures, with the exception that the TRD group had slower processing speed. Patients with bipolar TRD, relative to those with unipolar TRD, obtained lower scores on measures of executive function and memory only at baseline. With acute and chronic SCCwm DBS, neuropsychological function improved in multiple domains including processing speed and executive function (planning, set shifting, response inhibition), and memory remained stable. Conclusions Patients with TRD show slowed processing speed but otherwise largely preserved neuropsychological functioning. DBS of the SCCwm does not result in worsening of any aspect of neuropsychological function and may improve certain domains. Future research is warranted to better understand the effects of TRD and DBS on neuropsychological function. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite the common occurrence and debilitating nature of treatment-resistant depression (TRD), currently there is no universally accepted definition for TRD. This review summarizes the different methods used to define TRD, and provides an overview of the TRD literature. METHODS: Psyclnfo, Medline, and Ovid were searched to identify relevant articles published in peer-reviewed journals. A combination and/or variation of the following keywords were searched: treatment resistant, treatment refractory, depression, defining, staging, and modeling. Identified articles provided a description of the methods utilized for defining and/or measuring TRD, prevalence and impact of TRD, risk factors for TRD, and/or factors that contribute to the misclassification of non-TRD patients. RESULTS: Multiple methods for defining/measuring TRD have been proposed; however, variability in these methods has limited the comparability between TRD studies. Although various risk factors for TRD have been suggested, few have been consistently supported. The misclassification of non-TRD patients as having TRD is related to various clinical and treatment-related factors. CONCLUSIONS : Adopting a universal standard definition for TRD is necessary to reduce the variability in how TRD is defined, and the misclassification of non-TRD patients. A universal definition would benefit clinical and research settings by allowing data to be easily compared across these settings. [ABSTRACT FROM AUTHOR]

Both the 17-item Hamilton Rating Scale for Depression (HRSD17) and 30-item Inventory of Depressive Symptomatology - Clinician-rated (IDS-C30) contain a subscale that assesses anxious symptoms. We used classical test theory and item response theory methods to assess and compare the psychometric properties of the two anxiety subscales (HRSDANX and IDS-CANX) in a large sample ( N = 3453) of outpatients with non-psychotic major depressive disorder in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Approximately 48% of evaluable participants had at least one concurrent anxiety disorder by the self-report Psychiatric Diagnostic Screening Questionnaire (PDSQ). The HRSDANX and IDS-CANX were highly correlated ( r = 0.75) and both had moderate internal consistency given their limited number of items (HRSDANX Cronbach's alpha = 0.48; IDS-CANX Cronbach's alpha = 0.58). The optimal threshold for ascribing the presence/absence of anxious features was found at a total score of eight or nine for the HRSDANX and seven or eight for the IDS-CANX. It would seem beneficial to delete item 17 (loss of insight) from the HRSDANX as it negatively correlated with the scale's total score. Both the HRSDANX and IDS-CANX subscales have acceptable psychometric properties and can be used to identify anxious features for clinical or research purposes. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Magnetic seizure therapy (MST) is a novel neurotherapeutic intervention in development for the treatment of major affective disorders. Like other neurotherapeutic strategies such as electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS), a primary interest will be to monitor the associated neurocognitive effects. Thus, the purpose of this systematic review was to synthesize the available data on the neurocognitive effects of MST. The authors performed two independent literature searches with the following terms terms: MST, magnetic, magnetic seizure therapy, depression, neurocognition, cognitive, preclinical. We included in this review a total of eleven articles that mentioned MST and neurocognition in the abstract. The articles were divided into three methodological domains that included virtual computer simulations, preclinical studies, and clinical investigations. Collectively, the available evidence suggests MST has little to no adverse cognitive effects. Specifically, virtual computer simulations found the magnetic field was localized to grey matter, and preclinical studies found no neurocortical or neurocognitive sequelae. Clinical investigations found MST to be associated with rapid reorientation and intact anterograde and retrograde memory. Future investigations using translational methods are warranted to confirm these findings and to further determine the effects of MST on neurocognitive functions. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Available evidence suggests benefits of TMS alone or in combination with neurophysiologic and neuroimaging methods, including positron emission tomography, single photon emission computed tomography, magnetic resonance imaging, functional magnetic resonance imaging, functional near infrared spectroscopy, magnetoencephalography, and electroencephalography, to explore neocortical function. With the multiple TMS techniques including single-pulse, paired-pulse, paired associative stimulation, and repetitive TMS and theta burst stimulation, combined with neurophysiologic and neuroimaging methods, there exists a plethora of TMS experimental paradigms to modulate neocortical physiologic processes. Specifically, TMS can measure cortical excitability, intracortical inhibitory and excitatory mechanisms, and local and network cortical plasticity. Coupled with functional and electrophysiologic modalities, TMS can provide insight into the mechanisms underlying healthy neurodevelopment and aging, as well as neuropsychiatric pathology. Thus, TMS could be a useful tool in the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia armamentarium of biomarker methods. Future investigations are warranted to optimize TMS methodologies for this purpose. [Copyright &y& Elsevier]

Abstract: Psychomotor retardation is a long established component of depression that can have significant clinical and therapeutic implications for treatment. Due to its negative impact on overall function in depressed patients, we review its biological correlates, optimal methods of measurement, and relevance in the context of therapeutic interventions. The aim of the paper is to provide a synthesis of the literature on psychomotor retardation in depression with the goal of enhanced awareness for clinicians and researchers. Increased knowledge and understanding of psychomotor retardation in major depressive disorder may lead to further research and better informed diagnosis in regards to psychomotor retardation. Manifestations of psychomotor retardation include slowed speech, decreased movement, and impaired cognitive function. It is common in patients with melancholic depression and those with psychotic features. Biological correlates may include abnormalities in the basal ganglia and dopaminergic pathways. Neurophysiologic tools such as neuroimaging and transcranial magnetic stimulation may play a role in the study of this symptom in the future. At present, there are three objective scales to evaluate psychomotor retardation severity. Studies examining the impact of psychomotor retardation on clinical outcome have found differential results. However, available evidence suggests that depressed patients with psychomotor retardation may respond well to electroconvulsive therapy (ECT). Current literature regarding antidepressants is inconclusive, though tricyclic antidepressants may be considered for treatment of patients with psychomotor retardation. Future work examining this objective aspect of major depressive disorder (MDD) is essential. This could further elucidate the biological underpinnings of depression and optimize its treatment. [Copyright &y& Elsevier]

Background: Magnetic seizure therapy (MST) is under investigation as an alternative form of convulsive therapy that induces more focal seizures and spares cortical regions involved in memory. With a newly expanded version of the Columbia University Primate Cognitive Profile, we compared the cognitive effects of high-dose MST delivered at 100 Hz (6 × seizure threshold) with electroconvulsive shock (ECS) delivered at 2.5 × seizure threshold. Methods: Daily high-dose MST, ECS, and sham (anesthesia-only) were administered for 4 weeks each in a within-subject crossover design. Rhesus macaques (n = 3) were trained on five cognitive tasks assessing automatic memory, anterograde learning and memory, combined anterograde and retrograde simultaneous chaining, and spatial and serial working memory. Acutely after each intervention, monkeys were tested on the cognitive battery twice daily, separated by a 3-hour retention interval. Results: Subjects were slower to complete criterion tasks (p values < .0001) after ECS, compared with sham and high-dose MST. Moreover, time to task-completion after high-dose MST did not differ from sham. Of six measures of accuracy, treatment effects were found in four; in all of these, ECS but not MST fared worse than sham. On all accuracy and time to completion measurements, subjects performed as well after high-dose MST as subjects from a previous study on moderate-dose MST. Conclusions: These findings provide evidence that high-dose MST results in benign acute cognitive side-effect profile relative to ECS and are in line with our previous studies. [Copyright &y& Elsevier]

Objective: To develop an individualized method for detecting cognitive adverse events (CAEs) in the context of an ongoing trial of electroconvulsive therapy for refractory agitation and aggression for advanced dementia (ECT-AD study). Methods: Literature search aimed at identifying (a) cognitive measures appropriate for patients with advanced dementia, (b) functional scales to use as a proxy for cognitive status in patients with floor effects on baseline cognitive testing, and (c) statistical approaches for defining a CAE, to develop CAEs monitoring plan specifically for the ECT-AD study. Results: Using the Severe Impairment Battery-8 (SIB-8), baseline floor effects are defined as a score of ≤5/16. For patients without floor effects, a decline of ≥6 points is considered a CAE. For patients with floor effects, a decline of ≥30 points from baseline on the Barthel Index is considered a CAE. These values were derived using the standard deviation index (SDI) approach to measuring reliable change. Conclusions: The proposed plan accounts for practical and statistical challenges in detecting CAEs in patients with advanced dementia. While this protocol was developed in the context of the ECT-AD study, the general approach can potentially be applied to other interventional neuropsychiatric studies that carry the risk of CAEs in patients with advanced dementia. [ABSTRACT FROM AUTHOR]

An introduction is presented in which the editor discusses various reports within the issue on topics including brain stimulation methods, brain stimulation in mood disorders and neuropsychiatric disorders.

An introduction is presented in which the editor discusses various reports within the issue on topics including multimorbidity, neurocognitive assessment in schizophrenia, and association of sleep onset delta activity and clinical pathology.

The article lists committee members of the Society for Clinical Neuropsychology including Jimmy Choi, Pamela Dean and Glen Getz.

Background: Although electroconvulsive therapy (ECT) is an effective treatment for depression, ECT cognitive impairment remains a major concern. The neurobiological underpinnings and mechanisms underlying ECT antidepressant and cognitive impairment effects remain unknown. This investigation aims to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks and assesses whether they are associated with the ECT-induced electric field (E-field) with an optimal pulse amplitude estimation. Methods: A single site clinical trial focused on amplitude (600, 700, and 800 mA) included longitudinal multimodal imaging and clinical and cognitive assessments completed before and immediately after the ECT series (n = 54) for late-life depression. Another two independent validation cohorts (n = 84, n = 260) were included. Symptom and cognition were used as references to supervise fMRI and sMRI fusion to identify ECT antidepressant-response and cognitive-impairment multimodal brain networks. Correlations between ECT-induced E-field within these two networks and clinical and cognitive outcomes were calculated. An optimal pulse amplitude was estimated based on E-field within antidepressant-response and cognitive-impairment networks. Results: Decreased function in the superior orbitofrontal cortex and caudate accompanied with increased volume in medial temporal cortex showed covarying functional and structural alterations in both antidepressant-response and cognitive-impairment networks. Volume increases in the hippocampal complex and thalamus were antidepressant-response specific, and functional decreases in the amygdala and hippocampal complex were cognitive-impairment specific, which were validated in two independent datasets. The E-field within these two networks showed an inverse relationship with HDRS reduction and cognitive impairment. The optimal E-filed range as [92.7–113.9] V/m was estimated to maximize antidepressant outcomes without compromising cognitive safety. Conclusions: The large degree of overlap between antidepressant-response and cognitive-impairment networks challenges parameter development focused on precise E-field dosing with new electrode placements. The determination of the optimal individualized ECT amplitude within the antidepressant and cognitive networks may improve the treatment benefit–risk ratio. Trial registration: ClinicalTrials.gov Identifier: NCT02999269. [ABSTRACT FROM AUTHOR]

Objective: To examine the sensitivity and specificity of the Montreal Cognitive Assessment (MoCA), a brief cognitive screening measure previously validated for use in Parkinson's disease (PD), and Alzheimer's Disease-8 (AD8), an eight-item informant report used to screen for dementia, but not yet validated for use in PD, to identify cognitive impairment in a sample of 111 patients with PD.Methods: Cognitive impairment was determined based on a battery of neuropsychological measures, excluding the MoCA and AD8. Classification rates of both the MoCA and AD8 in identifying cognitive impairment were examined using logistic regression and receiver operator characteristic (ROC) analysis. Optimal cutoff scores were determined to maximize sensitivity and specificity.Results: The MoCA correctly classified 78.4% of participants (p < 0.001), and ROC analysis yielded an area under the curve (AUC) of 0.82. A MoCA cutoff score of <25 yielded optimal sensitivity (0.77) and specificity (0.79) for identifying PD patients with cognitive impairment. Similar analyses for the AD8 were statistically nonsignificant, although the classification rate was 70.5%, with an AUC of 0.50.Conclusions: These results provide additional support for the MoCA, but not the AD8, in identifying cognitive impairment in patients with PD. [ABSTRACT FROM AUTHOR]

Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used to examine whether cognitive functioning was associated with appointment attendance, medication adherence, and return of medication bottles. This study found that higher baseline cognitive functioning measured by the Stroop Color–Word condition predicted better treatment adherence. However, this study also reports measurement sensitivity of cognition as it relates to treatment adherence when applied to this dual diagnosis population. Poorer performance in simple visual attention tasks as assessed by the Stroop Word condition was inversely associated with some measures of adherence. Future studies are warranted that include a comprehensive neuropsychological battery and advanced medication adherence measures to confirm these findings. [ABSTRACT FROM AUTHOR]

There is limited research regarding how executive processes contribute to key cognitive deficits in depression, particularly impoverished retrieval of autobiographical memory. This study tested a novel version of the Autobiographical Memory Test (AMT), the “Alternating Instructions” AMT (AMT-AI), to determine how participants could flexibly retrieve specific and categoric autobiographical memories. The AMT-AI consisted of a standard AMT (AMT-S), a categoric version of the AMT (AMT-R), and a section of alternating instructions (AI) in which the rules required the participant to alternate between retrieval of categoric and specific memories. A total of 49 university students completed the AMT-AI, and self-report measures of depressive symptomatology and ruminative thinking. Results showed that the mean proportion of specific memories recalled on the AMT-AI was significantly lower than on the AMT-S. Also, reduced memory specificity on the AMT-AI, but not the AMT-S, was significantly negatively correlated with increased scores on measures of depressive symptomatology and ruminative thinking. Collectively the data suggested that the AMT-AI, relative to the traditional AMT, may be more sensitive to memory specificity in non-clinical populations. Future research is warranted to further determine the psychometric properties and utility of the AMT-AI. [ABSTRACT FROM PUBLISHER]

• Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment for late-life depression (LLD), but treatment response varies. • Demographic, clinical, and cognitive predictors of remission after rTMS in LLD were evaluated. • Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. • A decision tree analyses established hierarchical order as well as cutoff values for the identified predictors. • No evidence that executive dysfunction worsened treatment outcomes was found, an important finding as executive dysfunction is consistently associated with worse outcomes with pharmacotherapy. Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment in patients with depression, yet treatment response remains variable. While previous work has identified predictors of remission in younger adults, relatively little data exists in late-life depression (LLD). To address this gap, data from 164 participants with LLD from a randomized non-inferiority treatment trial comparing standard bilateral rTMS to bilateral theta burst stimulation (TBS) (ClinicalTrials.gov identifier: NCT02998580) were analyzed using binary logistic regression and conditional inference tree (CIT) modeling. Lower baseline depression symptom severity, fewer prior antidepressant treatment failures, and higher global cognition predicted remission following rTMS treatment. The CIT predicted a higher likelihood of achieving remission for patients with a total score of 19 or lower on the Montgomery-Åsberg Depression Rating Scale, 1 or fewer prior antidepressant treatment failures, and a total score of 23 or higher on the Montreal Cognitive Assessment. Our results indicate that older adults with lower severity of depression, fewer antidepressant treatment failures, and higher global cognition benefit more from current forms of rTMS. The results suggest that there is potentially higher value in using rTMS earlier in the treatment pathway for depression in older adults. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure. Methods: In this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach. Discussion: Positive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy. Trial status: Enrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants. Trial registration: ClinicalTrials.gov NCT03191058, Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca, 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is well-established and effective for treatment-resistant depression (TRD), but in Canada and the USA, less than 1% of patients with TRD receive ECT mainly due to its cognitive adverse effects (i.e. amnesia). Thus, new treatment alternatives for TRD are urgently needed. One such treatment is magnetic seizure therapy (MST). ECT involves applying a train of high-frequency electrical stimuli to induce a seizure, whereas MST involves applying a train of high-frequency magnetic stimuli to induce a seizure.Methods: In this manuscript, we introduce our international, two-site, double-blinded, randomized, non-inferiority clinical trial to develop MST as an effective and safe treatment for TRD. This trial will compare the efficacy of MST to right unilateral ultra-brief pulse width electroconvulsive therapy (RUL-UB-ECT) with a combined primary endpoint of remission of depression and superior cognitive adverse effects in 260 patients with TRD. Amelioration of suicidal ideation will be assessed as a secondary endpoint. Inpatients or outpatients, over 18 years of age with a MINI International Neuropsychiatric Interview (MINI) diagnosis of non-psychotic major depressive disorder (MDD) can be enrolled in the study provided that they meet illness severity and full eligibility criteria. Participants are randomized to receive MST or RUL-UB ECT, 2-3 days per week over seven weeks, or a maximum of 21 treatments. The study will involve before-, during-, and after-treatment assessments of depression severity, suicidal ideation, subjective side-effects, and cognitive performance consistent with an intent-to-treat study design approach.Discussion: Positive results from this trial could have an immediate and tremendous impact for patients with TRD. If MST demonstrates comparable antidepressant treatment efficacy to ECT, but with greater cognitive safety, it could rapidly be adopted into clinical practice. Indeed, given that the administration of MST is nearly identical to ECT, the majority of ECT facilities in North America could readily adopt MST. Furthermore, the potential for cognitive safety could lead to improved treatment acceptability. Healthcare providers, patients and care partners, and policymakers would therefore demand this form of convulsive therapy.Trial Status: Enrollment for this study began on June 26, 2018, and is estimated to complete recruitment by July 2024. At the time of submission, we have enrolled and randomized 117 participants.Trial Registration: ClinicalTrials.gov NCT03191058 , Registered on June 19, 2017. Primary sponsor: Daniel Blumberger (DMB), Principal Investigator Daniel.Blumberger@camh.ca , 416-535-8501 x 33662 Contact for public queries: DMB, Daniel.Blumberger@camh.ca Contact for scientific queries: ZJD, Zdaskalakis@health.ucsd.edu. [ABSTRACT FROM AUTHOR]

Prospective memory (PM) is the ability to remember to perform a future action at a specified later time, which is investigated through the use of event-based and time-based tasks. Prior investigations have found that PM is impaired following traumatic brain injury (TBI). However, there is limited information regarding the cognitive functions that mediate TBI and PM performance. Thus, this study investigated time-based PM in TBI patients, and the relationship among time-based PM, time perception, and executive functions. To accomplish this objective, 18 severe TBI patients and 18 healthy matched controls performed a time-based PM task, a time reproduction task, and two executive functions (Stroop and n-back) tasks. While both groups increased their monitoring frequency close to the target time, TBI patients monitored more and were less accurate than healthy controls at the target time confirming the time-based PM dysfunction in these patients. Importantly, executive functions, particularly inhibition and updating abilities, were strongly related to time-based PM performance; both time perception and executive functions are involved in time-based prospective memory in controls, whereas, only executive functions appear to be involved in TBI time-based prospective memory performance. (JINS, 2012, 18, 1–9) [ABSTRACT FROM PUBLISHER]

Abstract: Electroconvulsive therapy (ECT) is an effective treatment for severe depression; however, the induced therapeutic seizure acts on the autonomic nervous system and results in significant cardiac effects. This is an important consideration particularly in the elderly. Magnetic seizure therapy (MST) is in development as a less invasive alternative, but its effects on cardiac function have not been studied. We sought to model those effects in nonhuman primates to inform the development of safer neurostimulation interventions. Twenty four rhesus monkeys were randomly assigned to receive 6 weeks of daily treatment with electroconvulsive stimulation (ECS), magnetic seizure therapy (MST) or anesthesia-alone sham. Digitally acquired ECG and an automated R-wave and inter-R interval (IRI) sampling were used to measure intervention effects on heart rate (HR). Significant differences between experimental conditions were found in the HR as evidenced by changes in the immediate post-stimulus, ictal and postictal epochs. Immediate post-stimulus bradycardia was seen with ECS but not with MST. ECS induced significantly more tachycardia than MST or sham in both the ictal and postictal periods. MST resulted in a small, but statistically significant increase in HR during the postictal period relative to baseline. HR was found to increase by 25% and 8% in the ECS and MST conditions, respectively. MST resulted in significantly less marked sympathetic and parasympathetic response than did ECS. This differential physiological response is consistent with MST having a more superficial cortical site of action with less impact on deeper brain structures implicated in cardiac control relative to ECT. The clinical relevance of the topographical seizure spread of MST and its associated effects on the autonomic nervous system remain to be determined in human clinical trials. [Copyright &y& Elsevier]

Background: There is growing interest in the potential of neuromodulation options in treatment‐resistant obsessive–compulsive disorder (OCD). Magnetic seizure therapy (MST), is a new treatment intervention in which generalized seizures are induced with transcranial magnetic stimulation. We conducted a pilot study to assess the efficacy and cognitive effects of MST in patients with treatment‐resistant OCD. Methods: In an open‐label pilot study, participants with treatment‐resistant OCD and a baseline Yale‐Brown Obsessive–Compulsive Scale (Y‐BOCS) scores of ≥16 were treated with up to 24 acute treatments. The primary clinical outcomes were clinical response (Y‐BOCS score reduction ≥30%) and remission (final Y‐BOCS score ≤8). A neurocognitive battery, the Quick Inventory for Depressive Symptoms–Self Report (QIDS‐SR), the Beck Scale for Suicidal Ideation (SSI), and the Quality of Life Enjoyment and Satisfaction Questionnaire‐Short Form (Q‐LES‐Q‐SF) were also completed as secondary measures. Results: Ten participants with OCD who had not responded to medications or psychotherapy enrolled in the study and seven completed an adequate trial (defined as ≥8 treatments). MST was associated with minimal cognitive effects except for some decrease in autobiographical memory and no serious adverse effects. Only one participant met the predefined criteria for response, and none for remission. The baseline and endpoint Y‐BOCS scores were not statistically different. Conclusion: Overall, MST was not beneficial in a small group of patients with treatment‐resistant OCD. At this time, other studies of MST for OCD are not warranted until different coil placements targeting other brain circuits can be proposed. [ABSTRACT FROM AUTHOR]

Objective: The anticonvulsant hypothesis posits that ECT's mechanism of action is related to enhancement of endogenous anticonvulsant brain mechanisms. Results of prior studies investigating the role of the inhibitory neurotransmitter gamma‐aminobutyric acid ("GABA+", GABA and coedited macromolecules) in the pathophysiology and treatment of depression remain inconclusive. The aim of our study was to investigate treatment‐responsive changes of GABA+ in subjects with a depressive episode receiving electroconvulsive therapy (ECT). Methods: In total, 41 depressed subjects (DEP) and 35 healthy controls (HC) were recruited at two independent sites in Norway and the USA. MEGA‐PRESS was used for investigation of GABA+ in the anterior cingulate cortex. We assessed longitudinal and cross‐sectional differences between DEP and HC, as well as the relationship between GABA+ change and change in depression severity and number of ECTs. We also assessed longitudinal differences in cognitive performance and GABA+ levels. Results: Depressive episode did not show a difference in GABA+ relative to HC (t71 = −0.36, p =.72) or in longitudinal analysis (t36 = 0.97, p =.34). Remitters and nonremitters did not show longitudinal (t36 = 1.12, p =.27) or cross‐sectional differences in GABA+. GABA+ levels were not related to changes in antidepressant response (t35 = 1.12, p =.27) or treatment number (t36 = 0.05, p =.96). An association between cognitive performance and GABA+ levels was found in DEP that completed cognitive effortful testing (t18 = 2.4, p =.03). Conclusion: Our results failed to support GABA as a marker for depression and abnormal mood state and provide no support for the anticonvulsant hypothesis of ECT. ECT‐induced change in GABA concentrations may be related to change in cognitive function. [ABSTRACT FROM AUTHOR]

Background: Treatment-resistant bipolar depression can be treated effectively using electroconvulsive therapy, but its use is limited because of stigma and cognitive adverse effects. Magnetic seizure therapy is a new convulsive therapy with promising early evidence of antidepressant effects and minimal cognitive adverse effects. However, there are no clinical trials of the efficacy and safety of magnetic seizure therapy for treatment-resistant bipolar depression. Methods: Participants with treatment-resistant bipolar depression were treated with magnetic seizure therapy for up to 24 sessions or until remission. Magnetic seizure therapy was applied over the prefrontal cortex at high (100 Hz; n = 8), medium (50 or 60 Hz; n = 9) or low (25 Hz; n = 3) frequency, or over the vertex at high frequency (n = 6). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression. Participants completed a comprehensive battery of neurocognitive tests. Results: Twenty-six participants completed a minimally adequate trial of magnetic seizure therapy (i.e., ≥ 8 sessions), and 20 completed full treatment per protocol. Participants showed a significant reduction in scores on the Hamilton Rating Scale for Depression. Adequate trial completers had a remission rate of 23.1% and a response rate of 38.5%. Per-protocol completers had a remission rate of 30% and a response rate of 50%. Almost all cognitive measures remained stable, except for significantly worsened recall consistency on the autobiographical memory inventory. Limitations: The open-label study design and modest sample size did not allow for comparisons between stimulation parameters. Conclusion: In treatment-resistant bipolar depression, magnetic seizure therapy produced significant improvements in depression symptoms with minimal effects on cognitive performance. These promising results warrant further investigation with larger randomized clinical trials comparing magnetic seizure therapy to electroconvulsive therapy. Clinical trial registration: NCT01596608; clinicaltrials.gov [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is usually reserved for treatment of severe major depressive disorder (MDD), but may be equally effective in the treatment of moderate-severity MDD. This possibility, however, has only been studied to a very limited extent. We therefore investigated the efficacy of ECT after stratifying patients into severe MDD and moderate-severity MDD.Methods: We used data from the Prolonging Remission in Depressed Elderly (PRIDE) study, in which 240 patients (≥60 years) with MDD were treated with right unilateral ultrabrief pulse ECT, combined with venlafaxine. We used the six-item core depression subscale (HAM-D6) of the Hamilton Depression Rating Scale to define depression severity. Participants with baseline total scores ≥12 on the HAM-D6 were considered to have severe MDD, while those with HAM-D6 total scores <12 were considered to have moderate-severity MDD.Results: Among the participants with severe MDD and moderate-severity MDD, the mean change in the HAM-D6 total score from baseline to endpoint was -8.2 (95% confidence interval (95%CI) = -7.5; -9.0, paired t-test: p < 0.001) and -5.9 (95%CI = -5.1; -6.6, paired t-test: p < 0.001), respectively. A total of 63% of those with severe MDD and 75% of those with moderate-severity MDD achieved remission (HAM-D6 total score ≤4) (Pearson's 2-sample chi-squared test of difference between groups: p = 0.27).Limitations: The PRIDE study was not designed to address this research question.Conclusions: ECT combined with venlafaxine appears to be an effective treatment for moderate-severity MDD. It may be appropriate to expand the indications for ECT to include patients with moderate-severity MDD. [ABSTRACT FROM AUTHOR]

Current first-line treatments for major depressive disorder (MDD) include pharmacotherapy and cognitive-behavioral therapy. However, one-third of depressed patients do not achieve remission after multiple medication trials, and psychotherapy can be costly and time-consuming. Although nonimplantable neuromodulation (NIN) techniques such as transcranial magnetic stimulation, transcranial direct current stimulation, electroconvulsive therapy, and magnetic seizure therapy are gaining momentum for treating MDD, the efficacy of non-convulsive techniques is still modest, whereas use of convulsive modalities is limited by their cognitive side effects. In this context, we propose that NIN techniques could benefit from a precision-oriented approach. In this review, we discuss the challenges and opportunities in implementing such a framework, focusing on enhancing NIN effects via a combination of individualized cognitive interventions, using closed-loop approaches, identifying multimodal biomarkers, using computer electric field modeling to guide targeting and quantify dosage, and using machine learning algorithms to integrate data collected at multiple biological levels and identify clinical responders. Though promising, this framework is currently limited, as previous studies have employed small samples and did not sufficiently explore pathophysiological mechanisms associated with NIN response and side effects. Moreover, cost-effectiveness analyses have not been performed. Nevertheless, further advancements in clinical trials of NIN could shift the field toward a more "precision-oriented" practice. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT) is a well-established treatment for severe depression but may result in adverse cognitive effects. Available cognitive screening instruments are nonspecific to the cognitive deficits associated with ECT. An ECT-cognitive assessment tool which can be easily administered was developed and validated in a clinical setting.Methods: One hundred and thirty-six participants were enrolled. The ElectroConvulsive therapy Cognitive Assessment (ECCA) and the Montreal Cognitive Assessment (MoCA) were administered prospectively to 55 participants with major depressive disorder (MDD) undergoing ECT at three time points: pre-treatment, before the sixth treatment and one-week post-treatment. The psychometric properties of the total and domain scores were evaluated at all three time points. Forty demographically comparable participants with MDD who did not receive ECT, and 41 healthy, age-matched controls were evaluated at a single time point.Results: ECCA and MoCA scores were not statistically different at baseline. Prior to the sixth and final ECT session, total ECCA scores were significantly lower than the MoCA total scores. The ECCA domains of subjective memory, informant-assessed memory, attention, autobiographical memory and delayed verbal recall were significantly lower post-ECT compared to pre-ECT.Limitations: The ECCA was compared only to the MoCA rather than to a more comprehensive neuropsychological testing. This limitation reflected the real-life clinical burden of performing full neuropsychological testing at three time points during the treatment course.Conclusions: The ECCA is a brief, reliable, bedside cognitive screening assessment tool that may be useful to monitor cognitive function in patients treated with ECT. The test can be downloaded from fuquacenter.org/ecca. [ABSTRACT FROM AUTHOR]

Electroconvulsive therapy is regarded as the most effective antidepressant treatment for severe and treatment‐resistant depressive episodes. Despite the efficacy of electroconvulsive therapy, the neurobiological underpinnings and mechanisms underlying electroconvulsive therapy induced antidepressant effects remain unclear. The objective of this investigation was to identify electroconvulsive therapy treatment responsive multimodal biomarkers with the 17‐item Hamilton Depression Rating Scale guided brain structure–function fusion in 118 patients with depressive episodes and 60 healthy controls. Results show that reduced fractional amplitude of low frequency fluctuations in the prefrontal cortex, insula and hippocampus, linked with increased gray matter volume in anterior cingulate, medial temporal cortex, insula, thalamus, caudate and hippocampus represent electroconvulsive therapy responsive covarying functional and structural brain networks. In addition, relative to nonresponders, responder‐specific electroconvulsive therapy related brain networks occur in frontal‐limbic network and are associated with successful therapeutic outcomes. Finally, electroconvulsive therapy responsive brain networks were unrelated to verbal declarative memory. Using a data‐driven, supervised‐learning method, we demonstrated that electroconvulsive therapy produces a remodeling of brain functional and structural covariance that was unique to antidepressant symptom response, but not linked to memory impairment. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmrl gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA maybe one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmrl KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmrl KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmrl KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ±0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has emerged as a promising new treatment for major depression. While recent randomised, sham-controlled studies found tDCS to have antidepressant effects, it remains to be determined whether a tDCS treatment course may also enhance cognitive function independent of mood effects in depressed patients. This systematic review and individual patient data (IPD) meta-analysis examined cognitive outcomes from randomised, sham-controlled trials of tDCS treatment for major depression. Seven randomised, sham-controlled trials (n = 478 participants, 260 in active and 218 in sham) of tDCS for major depression were included. Results showed no cognitive enhancement after active tDCS compared to sham for the 12 cognitive outcomes investigated. Active relative to sham tDCS treatment was associated with reduced performance gains on a measure of processing speed (β = −0.33, 95% CI −0.58; −0.08, p = 0.011). Active tDCS treatment for depression did not show cognitive benefits independent of mood effects. Rather, tDCS treatment relative to sham stimulation for major depression may instead be associated with a reduced practice effect for processing speed. [ABSTRACT FROM AUTHOR]

We examined whether electroconvulsive therapy (ECT) plus medications (“STABLE + PHARM” group) had superior HRQOL compared with medications alone (“PHARM” group) as continuation strategy after successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the “STABLE + PHARM” group versus the “PHARM” group. The overall study design was called “Prolonging Remission in Depressed Elderly” (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of “STABLE + PHARM” versus “PHARM”. Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks. Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The “PHARM” group received venlafaxine and lithium. The “STABLE + PHARM” received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. “STABLE + PHARM” patients received 4.5 ± 2.5 ECT sessions during Phase 2. “STABLE + PHARM” group had 7 point advantage (3.5–10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2–12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD. Clinical Trials.gov NCT01028508 [ABSTRACT FROM AUTHOR]

Reference 1 Qi S. Links between electroconvulsive therapy responsive and cognitive impairment multimodal brain networks in late-life major depressive disorder. B Correction: BMC Med 20, 477 (2022) b B https://doi.org/10.1186/s12916-022-02678-6 b The original article [[1]] mistakenly omitted panel (g) from Figure 1; the panel has since been re-inserted. [Extracted from the article]

Introduction: Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT.Methods: HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling.Results: At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores.Limitations: This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients.Discussion: ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT. [ABSTRACT FROM AUTHOR]

Objective: The Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy of right unilateral ultrabrief pulse electroconvulsive therapy (ECT) combined with venlafaxine for the treatment of geriatric depression.Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, combined with open-label venlafaxine at seven academic medical centers. In phase 2 (reported separately), patients who had remitted were randomly assigned to receive pharmacotherapy (venlafaxine plus lithium) or pharmacotherapy plus continuation ECT. In phase 1, depressed patients received high-dose ECT (at six times the seizure threshold) three times per week. Venlafaxine was started during the first week of treatment and continued throughout the study. The primary outcome measure was remission, assessed with the 24-item Hamilton Depression Rating Scale (HAM-D), which was administered three times per week. Secondary outcome measures were post-ECT reorientation and safety. Paired t tests were used to estimate and evaluate the significance of change from baseline in HAM-D scores.Results: Of 240 patients who entered phase 1 of the study, 172 completed it. Overall, 61.7% (148/240) of all patients met remission criteria, 10.0% (24/240) did not remit, and 28.3% (68/240) dropped out; 70% (169/240) met response criteria. Among those who remitted, the mean decrease in HAM-D score was 24.7 points (95% CI=23.4, 25.9), with a mean final score of 6.2 (SD=2.5) and an average change from baseline of 79%. The mean number of ECT treatments to remission was 7.3 (SD=3.1).Conclusions: Right unilateral ultrabrief pulse ECT, combined with venlafaxine, is a rapidly acting and highly effective treatment option for depressed geriatric patients, with excellent safety and tolerability. These data add to the evidence base supporting the efficacy of ECT to treat severe depression in elderly patients. [ABSTRACT FROM AUTHOR]

Objective: The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes.Results: At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score.Conclusions: Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients. [ABSTRACT FROM AUTHOR]

Transcranial Direct Current Stimulation (tDCS) is a new, non-invasive neuromodulation approach for treating depression that has shown promising efficacy. The aim of this trial was to conduct the first international, multicentre randomised controlled trial of tDCS as a treatment for unipolar and bipolar depression. The study recruited 120 participants across 6 sites in the USA and Australia. Participants received active or sham tDCS (2.5 mA, 20 sessions of 30 min duration over 4 weeks), followed by a 4-week open label active treatment phase and a 4-week taper phase. Mood and neuropsychological outcomes were assessed with the primary antidepressant outcome measure being the Montgomery-Asberg Depression Rating Scale (MADRS). A neuropsychological battery was administered to assess safety and examine cognitive effects. The study also investigated the possible influence of genetic polymorphisms on outcomes. The trial was triple-blinded. Participants, tDCS treaters and study raters were blinded to each participant's tDCS group allocation in the sham-controlled phase. Specific aspects of tDCS administration, device operation and group allocation were designed to optimise the integrity of blinding. Outcome measures will be tested using a mixed effects repeated measures analysis with the primary factors being Time as a repeated measure, tDCS condition (sham or active) and Diagnosis (unipolar or bipolar). A restricted number of random and fixed factors will be included as required to account for extraneous differences. As a promising treatment, tDCS has excellent potential for translation into widespread clinical use, being cost effective, portable, easy to operate and well tolerated. [ABSTRACT FROM AUTHOR]

We recently demonstrated that activation of tyrosine receptor kinase B (TrkB) by 7, 8-dihydroxyflavone (7, 8- DHF), the selective TrkB agonist, increased surface alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid ( AMPA) receptors ( AMPARs) AMPA receptor subunit GluR1 (GluA1) subunit expression at the synapses of Fragile X Syndrome mutant mice. This present study investigated the effects of 7, 8- DHF on both memory function and synapse structure in relation to the synapse protein level of AMPARs in the Tg2576 Alzheimer's disease ( AD) mouse model. The study found that chronic oral administration of 7, 8- DHF significantly improved spatial memory and minimized dendrite loss in the hippocampus of Tg2576 mice. A key feature of 7, 8- DHF action was the increased expression of both GluA1 and GluA2 at synapses. Interestingly, 7, 8- DHF had no effect on the attenuation of amyloid precursor protein or Aβ exhibiting in the Tg2576 AD brains, yet it activated the phosphorylation of TrkB receptors and its downstream signals including Ca MKII, Akt, Erk1/2, and cAMP-response element-binding protein. Importantly, cyclotraxin B (a TrkB inhibitor), U0126 (a Ras- ERK pathway inhibitor), Wortmannin (an Akt phosphorylation inhibitor), and KN-93 (a Ca MKII inhibitor) counteracted the enhanced expression and phosphorylation of AMPAR subunits induced by 7, 8- DHF. Collectively, our results demonstrated that 7, 8- DHF acted on TrkB and resolved learning and memory impairments in the absence of reduced amyloid in amyloid precursor protein transgenic mice partially through improved synaptic structure and enhanced synaptic AMPARs. The findings suggest that the application of 7, 8- DHF may be a promising new approach to improve cognitive abilities in AD. [ABSTRACT FROM AUTHOR]

Study Design: Cross-sequential study design that used data from Texas Scottish Rite Hospital for Children (TSRHC).Objective: Examine anxiety symptoms and family experiences subsequent to school scoliosis screening (SSS) referrals.Summary Of Background Data: Use of SSS remains controversial. Prior research suggested that SSS programs may result in anxiety for both children and parents. Unfortunately, no study has examined the SSS referral processes and anxiety in families.Methods: Study consisted of 2 groups-patients/parents from TSRHC evaluated for Adolescent Idiopathic Scoliosis (AIS) (n = 27) and control participants/parents (n = 27) between ages 9 and 17. All participants completed the primary outcome measure (State-Trait Anxiety Inventory) before and after the scoliosis evaluation or controlled wait time. Parents also rated experience and satisfaction with SSS.Results: Compared with the control group, children/parents in patient group experienced significantly elevated levels of state-anxiety at preappointment. Children/parents in the patient group not diagnosed with AIS experienced a significant decline in state-anxiety. Children/parents in the patient group diagnosed with AIS continued to report elevated levels of anxiety. The control group remained consistent, reporting of low levels of anxiety pre to post. More than half (55.5%) of families indicated they received no information from the school about scoliosis. A third of the families who received information indicated it did not adequately address their concerns. Nonetheless, most families reported overall satisfaction with SSS.Conclusion: This study suggested that children and parents referred through the SSS program experienced significantly elevated levels of state-anxiety. This supports the subjective concerns of anxiety experiences in families voiced by researchers previously. However, families deemed the costs of the SSS referral process as worth the benefits. Though challengers of SSS programs were accurate in observing anxiety in families, it may not constitute significant burden to eliminate SSS programs altogether. Improvements to the current system may be warranted.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

Objective Agitation and aggression are among the most frequent and disruptive behavioral complications of dementia that contribute to increased cost of care, hospitalization, caregiver burden, and risk of premature institutionalization. This current study examined the safety and efficacy of electroconvulsive therapy (ECT) as a treatment for behavioral disturbances in dementia. We hypothesized that ECT would result in reduced agitated and aggressive behaviors between baseline and discharge. Methods Twenty-three participants admitted to McLean Hospital (Belmont, MA, USA) and Pine Rest Christian Mental Health Services (Grand Rapids, MI, USA), with a diagnosis of dementia who were referred for ECT to treat agitation and/or aggression, were enrolled in the study. We administered the Cohen-Mansfield Agitation Inventory-Short Form, Neuropsychiatric Inventory-Nursing Home Version, Cornell Scale for Depression in Dementia, and the Clinical Global Impression Scale at baseline, during, and after the ECT course. Results Regression analyses revealed a significant decrease from baseline to discharge on the Cohen-Mansfield Agitation Inventory ( F(4,8) = 13.3; p = 0.006) and Neuropsychiatric Inventory ( F(4,31) = 14.6; p < 0.001). There was no statistically significant change in scores on the Cornell Scale for Depression in Dementia. The Clinical Global Impression scores on average changed from a rating of 'markedly agitated/aggressive' at baseline to 'borderline agitated/aggressive' at discharge. Treatment with ECT was well tolerated by most participants; discontinuation of ECT occurred for two participants because of recurrence of agitation and for three participants because of adverse events. Conclusions Electroconvulsive therapy may be a safe treatment option to reduce symptoms of agitation and aggression in patients with dementia whose behaviors are refractory to medication management. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fragile X syndrome (FXS) is characterized by immature dendritic spine architectures and cognitive impairment. 7, 8-Dihydroxyflavone (7, 8-DHF) has recently been identified as a high affinity tropomyosin receptor kinase B (TrkB) agonist. The purpose of this paper was to examine the utility of 7, 8-DHF as an effective pharmacotherapeutic agent that targets dendritic pathology and cognitive impairments in FXS mutant. We synthesized pharmacologic, behavioral, and biochemical approaches to examine the effects of 7, 8-DHF on spatial and fear memory functions, and morphological spine abnormalities in fragile X mental retardation 1 ( Fmr1 ) gene knock-out mice. The study found that 4 weeks of treatment with 7, 8-DHF improved spatial and fear memory, and ameliorated morphological spine abnormalities including the number and elongation of spines in the hippocampus and amygdala. Further mechanism analysis revealed that 7, 8-DHF enhanced the expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) GluA1 receptor, but reduced the normal levels of GluA2 at the synapses in Fmr1 . Potentially related to drug-induced changes in AMPA receptor subunits, 7, 8-DHF at the synapses led to phosphorylation of specific serine sites on subunits Ser818 and Ser813 of GluA1, and Ser880 of GluA2, as well as phosphorylation of TrkB, calcium/calmodulin-dependent protein kinase II, and protein kinase C. However, 7, 8-DHF neither affected behavioral performance nor increased TrkB phosphorylation in WT mice, which suggested that it had FXS-specific correcting effect. Altogether, these results demonstrated that 7, 8-DHF improved learning and memory, and reduced abnormalities in spine morphology, thus providing a potential pharmacotherapeutic strategy for FXS. [ABSTRACT FROM AUTHOR]