Cognitive Side Effects Research Articles

The number of anti-seizure medications mediates the relationship between cognitive performance and quality of life in temporal lobe epilepsy

ObjectivesTo assess whether cognitive performance predicts quality of life (QOL) in patients with drug-resistant temporal lobe epilepsy (TLE), using the Epitrack cognitive screening tool, while considering the mediating role of the number of anti-seizure medications (ASMs) and controlling for seizure-related, social, and emotional factors. MethodsSeventy-five adult patients with drug-resistant TLE (mean age = 39.76 years, SD = 11.66) underwent a presurgical neuropsychological assessment. Main Outcome Measures: Cognitive performance (Epitrack), depression (BDI-II), trait anxiety (STAI); and QOL (QOLIE-31) were assessed. ResultsAdjusting for seizure-related, social, and emotional factors, the Epitrack total score significantly contributed to QOL composite score, and energy and cognitive self-rating subscales. We found a significant indirect effect of the Epitrack total score on QOL composite score and seizure worry and social functioning subscales via the number of ASMs. ConclusionOur findings underline the relevance of cognitive functioning on QOL and the clinical utility of Epitrack to track cognitive side effects of ASMs and, consequently, to predict and manage QOL in this population.

Screening of the use of benzodiazepines during COVID-19 pandemic in the general population

Benzodiazepines have been commonly prescribed for the treatment of anxiety and insomnia in the last few decades. There has been a rising concern regarding safety of benzodiazepines due to overdose related deaths, addictions and cognitive side effects. COVID-19 pandemic is expected to cause a mental health crisis. Several studies have shown an increase in anxiety and insomnia. Тhe prescriptions of benzodiazepines could increase due to increase in anxiety and insomnia. The pandemic calls for a rapid adaptation of conventional medical practices to meet the evolving needs of such vulnerable patients. COVID-19 patients may frequently require treatment with psychotropic medications. This pandemic is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear, globally. The COVID-19 pandemic is a challenge to humanity. It is not only a health crisis but also a social crisis. The life is unlikely to be the same after we come out of the pandemic. There will be changes at the level of individuals, families, communities, states, nations, international relationships, and the way all of us will deal with a range of human and environmental situations. Disasters are always associated with increased rates of emotional health needs from distress to specific disorders, such as posttraumatic stress disorder. Past experiences have shown psychosocial interventions, ranging from self‑care, psychological first aid, counseling, social support and formal psychiatric care can minimize the emotional health impact of disasters. These activities can be initiated by individuals and professionals. Keywords: coronavirus, COVID-19, mental health, benzodiazepines

Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

Neurocognitive functioning after electroconvulsive therapy in late-life depression: A 4-year prospective study.

Despite the proven efficacy and safety of ECT, there is still concern about the possible cognitive side effects of ECT in older patients. In this study, we aimed to characterize the long-term cognitive effects of ECT in patients with late-life depression (LLD) from before the start until 4years after the index ECT course. Fourty one patients aged 55years and older with a unipolar depression, referred for ECT, were included. The neuropsychological test battery was assessed prior to ECT, 6months, 1year, 2years, 3years, and 4years after the last ECT session. We did not find any statistically significant cognitive changes from before the start to 4years after ending the ECT course. Although we could not detect cognitive changes at group level, we found clinically important differences on an individual level. Cognitive performance in patients with LLD runs a stable course from before the start of ECT until 4years after the index course. At an individual level, however, both cognitive decline and improvement can be witnessed. Older patients can tolerate ECT and most of them will not experience long-term cognitive side effects.

Is There Evidence That Stimulus Parameters and Electrode Placement Affect the Cognitive Side Effects of Electroconvulsive Therapy in Patients With Schizophrenia and Schizoaffective Disorder?: A Systematic Review.

Seventy percent of patients with treatment-resistant schizophrenia do not respond to clozapine. Electroconvulsive therapy (ECT) can potentially offer significant benefit in clozapine-resistant patients. However, cognitive side effects can occur with ECT and are a function of stimulus parameters and electrode placements. Thus, the objective of this article is to systematically review published clinical trials related to the effect of ECT stimulus parameters and electrode placements on cognitive side effects. We performed a systematic review of the literature up to July of 2020 for clinical studies published in English or German examining the effect of ECT stimulus parameters and/or electrode placement on cognitive side effects in patients with schizophrenia or schizoaffective disorder. The literature search generated 3 randomized, double-blind, clinical trials, 1 randomized, nonblinded trial, and 1 retrospective study. There are mixed findings regarding whether pulse width and stimulus dose impact on cognitive side effects. One study showed less cognitive side effect for right unilateral (RUL) than bitemporal (BT) electrode placement, and 2 studies showed a cognitive advantage for bifrontal (BF) compared with BT ECT. Only 1 retrospective study measured global cognition and showed post-ECT cognitive improvement with all treatment modalities using Montreal Cognitive Assessment in comparison to pre-ECT Montreal Cognitive Assessment scores. Current data are limited, but evolving. The evidence suggests that RUL or BF ECT have more favorable cognitive outcomes than BT ECT. Definitive larger clinical trials are needed to optimize parameter and electrode placement selection to minimize adverse cognitive effects.

Patients With Refractory Bipolar Depression May Benefit From ECT

Patients With Refractory Bipolar Depression May Benefit From ECT

Reliability of the Capacity to Consent to Treatment Instrument in Metastatic Cancer

Metastatic cancer patients undergo numerous treatment strategies with known cognitive side effects. It is unclear how medical decision-making capacity (MDC) is impacted by cognitive deficits in metastatic cancer. This study examines reliability of an objective measure of MDC compared with self-report. Participants with newly diagnosed metastasis to the brain and other sites were enrolled at the University of Alabama at Birmingham over seven years. At the study visit, participants completed a comprehensive neuropsychological battery including memory and executive functioning, and the Capacity to Consent to Treatment Instrument (CCTI) assessing medico-legal domains of MDC. The CCTI is a reliable and valid instrument containing two vignettes of hypothetical medical situations assessing four standards of consent. We examined reliability between the CCTI and self-reported MDC using Gwet’s AC1 statistic. Participants with brain metastasis with impairment on the CCTI demonstrated significantly lower executive functioning and memory skills than those without impairment (Trails B Raw: 158.20±86.82 vs. 118.90±77.98 p: 0.0248; Digit-Span Raw Forward: 9.13±2.30 vs. 10.12±2.03 p: 0.0254). There were no significant differences between intact and impaired participants with other metastases. Low reliability was observed between self-report and all medico-legal standards on the CCTI across both metastatic groups [Gwet’s AC1 Appreciation: 0.70 (0.58, 0.81); Reasoning: 0.34 (0.16, 0.52); Understanding: 0.44, (0.27, 0.60)]. Self-rating of MDC is unreliable in metastatic cancer patients. Patients with metastases (particularly brain metastases) may lack awareness of deficits in their MDC, so providers must affirm proper autonomy in their decisions.

Double-Blinded Randomized Pilot Clinical Trial Comparing Cognitive Side Effects of Standard Ultra-Brief Right Unilateral ECT to 0.5 A Low Amplitude Seizure Therapy (LAP-ST).

Background: Concerns over cognitive side effects (CSE) of electroconvulsive therapy (ECT) still limit its broader usage for treatment-resistant depression (TRD). The objectives of this study were to (1) examine the CSE of Low Amplitude Seizure Therapy (LAP-ST) at 0.5 A compared to Ultra-brief Right Unilateral (UB-RUL) ECT using Time to Reorientation (TRO) as the main acute primary outcome, and (2) to compare effects on depressive symptoms between the two treatment groups. Methods: Participants were referred for ECT, consented for the study, and were randomized to a course of LAP-ST or standard UB-RUL ECT. TRO and depression were measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). Results: Eleven patients consented. Of these, eight with a current major depressive episode (MDE) of unipolar or bipolar disorders were randomized. TRO was faster for the LAP-ST (mean = 6.8 min; SE = 4.9) than standard RUL ECT (mean = 15.5 min; SE = 6.5). Depression improved similarly in the two arms of the study from baseline (MADRS: LAP-ST = 41.0; SE = 2.0, RUL = 39.0; SE = 3.8) to endpoint (MADRS score: LAP-ST = 8.0; SE7.2, RUL = 9.5; SE = 3.8). Conclusions: This pilot, randomized and blinded clinical trial, suggests that the LAP-ST (at 0.5 A) has faster reorientation and possibly lower CSE compared to standard RUL-UB ECT. Caution is advised in interpreting these results due to the small sample size of this pilot study. Thus, future studies with similar design are warranted for replicating these findings.

L-Theanine Prevents Long-Term Affective and Cognitive Side Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry.

Chronic adolescent exposure to Δ-9-tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioral abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathologic alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations. l-Theanine is an amino acid analog of l-glutamate and l-glutamine derived from various plant sources, including green tea leaves. l-Theanine has previously been shown to modulate levels of GABA, DA, and glutamate in various neural regions and to possess neuroprotective properties. Using a preclinical model of adolescent THC exposure in male rats, we report that l-theanine pretreatment before adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect that persists into adulthood. In addition, pretreatment with l-theanine blocked THC-induced downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and subcortical DAergic dysregulation. Finally, l-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of l-theanine in the mesocorticolimbic system.SIGNIFICANCE STATEMENT With the increasing trend of cannabis legalization and consumption during adolescence, it is essential to expand knowledge on the potential effects of adolescent cannabis exposure on brain development and identify potential pharmacological strategies to minimize Δ-9-tetrahydrocannabinol (THC)-induced neuropathology. Previous evidence demonstrates that adolescent THC exposure induces long-lasting affective and cognitive abnormalities, mesocorticolimbic dysregulation, and schizophrenia-like molecular biomarkers that persist into adulthood. We demonstrate for the first time that l-theanine, an amino acid analog of l-glutamate and l-glutamine, is capable of preventing long-term THC side effects. l-Theanine prevented the development of THC-induced behavioral aberrations, blocked cortical downregulation of local GSK-3 (glycogen synthase kinase 3) and Akt signaling pathways, and normalized dysregulation of both PFC and VTA DAergic activity, demonstrating powerful and functional neuroprotective effects against THC-induced developmental neuropathology.

Cognitive impairment under treatment with second‐ and third‐generation antihistamines

AbstractBackgroundBrain histamine is involved in the regulation of arousal, cognition, and memory mainly through interactions with histamine H1 receptors. Histamine H1 antagonists often prescribed for treatment of allergic disorders, may induce sleepiness and cognitive deficits. Sedation as a consequence of treatment with 1st generation antihistamines has led to the development of 2nd and 3rd generation anthistamines, which are thought to be free of cognitive side effects. This proved to be true in studies on the cognitive effects of single doses in healthy volunteers. However, the relationship between treatment with 2nd or 3rd generation antihistamines and cognitive performance so fas has not been examined within a naturalistic study under everyday conditions. This may be relevant for Alzheimer’s disease treatment studies, because cognitive side effects as a consequence of treatment with 2nd or 3rd generation antihistamines may act as a confounding variable.Method380 patients with chronic spontaneous urticaria (CSU) were assessed in 30 dermatological practices and outpatient clinics in Germany. Severity of disease was assessed by means of the Urticaria Activity Score (UAS‐7) and the Urticaria Control Test (UCT), quality of life by the Dermatology Life Quality Index (DLQI) and the Chronic Urticaria Quality of Life Questionnaire (CU‐Q2oL). Cognitive performance was studied by means of the computer‐based Memory and Attention Test (MAT). Sociodemographic data, current medication in treatment categories, comorbidities, obesity, smoking and drinking habits are taken by a questionnaire.ResultThe assessments were carried out in 380 subjects at ages between 19 and 73 years (mean +/‐ SD: 49 +/‐ 15). In patients under treatment with 2nd or 3rd generation anthistamines compared to patients not under treatment with antihistamines, we found a significant impairment of episodic working memory, particularly in the elder subjects. The impairment was found independently whether antihistamines were applied at dosages licensed for treatment or at higher dosages. Episodic short‐term memory and selective attention were unimpaired.ConclusionTreatment with 2nd or 3rd generation antihistamines may be associated with cognitive impairment, particularly in elderly patients. This effect should be considered regarding the handling of concomitant medications in Alzheimer’s disease treatment trials.

Lamotrigine-Associated Progressive Dysphasia and Cognitive Dysfunction.

Lamotrigine is generally accepted as a well-tolerated medication with few cognitive side effects. Here, we report a case of a 62-year old female with a severe, rapidly progressive dementia-like process which was completely reversed after reduction of lamotrigine. Associated findings included hyperreflexia with clonus, ataxia, Wernicke-like dysphasia, global cognitive impairment, burst suppression on electroencephalogram (EEG), and bilateral parietal hypo-metabolism on fluorodeoxyglucose-Positron Emission Tomography (FDG-PET). To our knowledge, this is the first case of a severe neuropsychiatric syndrome attributed to lamotrigine at the Food and Drug administration (FDA) recommended dose and not associated with epileptic activity.

Corticosterone as a Potential Confounding Factor in Delineating Mechanisms Underlying Ketamine's Rapid Antidepressant Actions.

Recent research into the rapid antidepressant effect of subanesthetic doses of ketamine have identified a series of relevant protein cascades activated within hours of administration. Prior to, or concurrent with, these activation cascades, ketamine treatment generates dissociative and psychotomimetic side effects along with an increase in circulating glucocorticoids. In rats, we observed an over 3-fold increase in corticosterone levels in both serum and brain tissue, within an hour of administration of low dose ketamine (10 mg/kg), but not with (2R, 6R)-hydroxynorketamine (HNK) (10 mg/kg), a ketamine metabolite shown to produce antidepressant-like action in rodents without inducing immediate side-effects. Hippocampal tissue from ketamine, but not HNK, injected animals displayed a significant increase in the expression of sgk1, a downstream effector of glucocorticoid receptor signaling. To examine the role conscious sensation of ketamine’s side effects plays in the release of corticosterone, we assessed serum corticosterone levels after ketamine administration while under isoflurane anesthesia. Under anesthesia, ketamine failed to increase circulating corticosterone levels relative to saline controls. Concurrent with its antidepressant effects, ketamine generates a release of glucocorticoids potentially linked to disturbing cognitive side effects and the activation of distinct molecular pathways which should be considered when attempting to delineate the molecular mechanisms of its antidepressant function.

\u201cNo thanks, I don\u2019t want to see snakes again\u201d: a qualitative study of pain management versus preservation of cognition in palliative care patients

BackgroundTowards the end of life, use of opioid analgesics becomes more common in patients to control pain and improve quality of life. While pain medication may help manage pain, unwanted cognitive side effects are frequently noted. This balancing act presents a trade-off for patients between pain relief and adverse effects, where the desire to relieve pain must be evaluated against the desire to maintain cognitive clarity and may represent a difficult decision for patients receiving palliative care. Our goal was to understand how patients’ decision making about pain medications balances the pain relief from those medications against the cognitive decline often associated with them.MethodsWe conducted qualitative semi-structured interviews with patients receiving home-based palliative care from a program in Toronto, Canada. Interview recordings were transcribed and analyzed using thematic analysis.ResultsThirty-one interviews were conducted. Some patients preferred cognitive preservation over pain management because of a sense that cognition is central to their identity, the desire to maintain lucidity, a desire to continue participating in work or hobbies, and fear of addiction. Conversely, some patients preferred pain management over cognitive preservation because of a desire to avoid suffering, an inability to sleep without medications, or an acceptance of some cognitive compromise. A few patients attempted to find balance through tapering drugs, limiting their use of breakthrough analgesic doses, or using alternative strategies.ConclusionsDecision making around pain and pain management is a highly preference-sensitive process—with no clear right or wrong decisions, only the preferences of each patient. The findings from this study may influence the design of future patient-facing decision aids around pain management. Future studies should pilot interventions to better assist patients with this decision.

Cognitive and behavioral effects of cannabidiol in patients with treatment-resistant epilepsy

PurposeTherapeutic use of cannabidiol (CBD) in intractable epilepsies has increased considerably over the last ten years. As more evidence for the potentially beneficial effects of CBD on different epilepsy types is emerging, it is important to monitor potential cognitive and behavioral side effects. So far, studies including standardized neuropsychological data in the context of treatment with CBD in epilepsy patients are sparse. The present open-label study examines cognitive and behavioral effects of CBD in children and adults with treatment resistant epilepsy. MethodThirty-nine patients with treatment-resistant epilepsy completed the study protocol, i.e. they were tested at baseline (T0) and after three months of CBD treatment (T1). Patients completed standardized neuropsychological tests on memory, executive functions and attention if they were capable. For cognitively impaired patients who could not complete cognitive tests, caregiver interviews were conducted and caregiver questionnaires completed. ResultsSignificant cognitive decline from T0 to T1 was observed on none of the included measures. There was a significant improvement on a measure of selective attention and on a caregiver-rated behavioral measure. More than 89% of all individual test results remained stable or showed reliable improvement from T0 to T1. Cognitive and behavioral changes from T0 to T1 were not significantly correlated with CBD dose. Improvements in short-term/working memory were significantly related to better therapy response. ConclusionNo adverse group-level effects of CBD treatment were detected. On an individual level, most test results remained stable or were improved. Cognitive change was not related to CBD dose. The present results show that, from a cognitive and behavioral point of view, CBD seems to have an encouraging side-effect profile. The results need to be replicated with larger samples.

Association of Preoperative Visual Hallucinations With Cognitive Decline After Deep Brain Stimulation for Parkinson's Disease.

Deep brain stimulation (DBS) is effective for the motor symptoms of Parkinson's disease (PD). Although most patients benefit with minimal cognitive side effects, cognitive decline is a risk, and there is little available evidence to guide preoperative risk assessment. Visual illusions or visual hallucinations (VHs) and impulse-control behaviors (ICBs) are relatively common complications of PD and its treatment and may be a marker of more advanced disease, but their relationship with postoperative cognition has not been established. The authors aimed to determine whether any preoperative history of VHs or ICBs is associated with cognitive change after DBS. Retrospective chart review identified 54 patients with PD who received DBS of the subthalamic nucleus or globus pallidus internus and who completed both pre- and postoperative neuropsychological testing. Linear regression models were used to assess whether any preoperative history of VHs or ICBs was associated with changes in attention, executive function, language, memory, or visuospatial cognitive domains while controlling for surgical target and duration between evaluations. The investigators found that a history of VHs was associated with declines in attention (b=-4.04, p=0.041) and executive function (b=-4.24, p=0.021). A history of ICBs was not associated with any significant changes. These results suggest that a history of VHs may increase risk of cognitive decline after DBS; thus, specific preoperative counseling and targeted remediation strategies for these patients may be indicated. In contrast, a history of ICBs does not appear to be associated with increased cognitive risk.

A Computationally-Efficient, Online-Learning Algorithm for Detecting High-Voltage Spindles in the Parkinsonian Rats.

Abnormally-synchronized, high-voltage spindles (HVSs) are associated with motor deficits in 6-hydroxydopamine-lesioned parkinsonian rats. The non-stationary, spike-and-wave HVSs (5-13Hz) represent the cardinal parkinsonian state in the local field potentials (LFPs). Although deep brain stimulation (DBS) is an effective treatment for the Parkinson's disease, continuous stimulation results in cognitive and neuropsychiatric side effects. Therefore, an adaptive stimulator able to stimulate the brain only upon the occurrence of HVSs is demanded. This paper proposes an algorithm not only able to detect the HVSs with low latency but also friendly for hardware realization of an adaptive stimulator. The algorithm is based on autoregressive modeling at interval, whose parameters are learnt online by an adaptive Kalman filter. In the LFPs containing 1131 HVS episodes from different brain regions of four parkinsonian rats, the algorithm detects all HVSs with 100% sensitivity. The algorithm also achieves higher precision (96%) and lower latency (61ms), while requiring less computation time than the continuous wavelet transform method. As the latency is much shorter than the mean duration of an HVS episode (4.3s), the proposed algorithm is suitable for realization of a smart neuromodulator for mitigating HVSs effectively by closed-loop DBS.

Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center.

Right unilateral ultrabrief pulse (RUL-UBP) ECT has emerged as a promising technique for minimizing cognitive side effects of ECT while retaining clinical efficacy, but it is unknown how often patients will require alternative treatment parameters and at what point in the treatment course this occurs. To better define this problem, this study analyzes continuation in RUL-UBP ECT in a retrospective cohort of patients beginning acute course treatment. A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT from 2010 to 2017 starting with RUL-UBP treatment parameters. 1793 patients met study criteria. Patients received a mean of 10.0 ± 3.2 ECT treatments, of which a mean of 8.4 ± 3.4 were RUL-UBP treatments; proportion using RUL-UBP through 12 treatments was 57.8%. In total, 65.6% of patients were treated with RUL-UPB ECT exclusively. Mean dose increased from 7.6 × seizure threshold at the second RUL-UBP treatment to 14.3 × seizure threshold at the twelfth RUL-UBP treatment. Rates of continuation in RUL-UBP ECT did not differ based on age or on primary diagnosis of major depression vs. bipolar disorder. Among patients beginning acute-course treatment using RUL-UPB ECT, two thirds were treated with these parameters exclusively. Among patients who received twelve RUL-UBP treatments, mean final dose was 14.3 × seizure threshold. Further studies regarding optimal dosing of RUL-UBP ECT are indicated.

Examining cognitive change in magnetic resonance-guided focused ultrasound capsulotomy for psychiatric illness

Magnetic resonance-guided focused ultrasound (MRgFUS) anterior capsulotomy is a novel treatment option for patients with refractory obsessive compulsive disorder (OCD) or major depressive disorder (MDD). However, there is concern that lesional psychiatric surgery procedures may have adverse effects on cognition. In this study, we examined whether MRgFUS capsulotomy causes cognitive decline in patients with psychiatric illness. Ten patients with refractory OCD (n = 5) or MDD (n = 5) underwent MRgFUS capsulotomy. Cognitive functioning was measured at baseline as well as 6 months and 12 months postoperatively, with a battery of neuropsychological tests assessing domains of executive function, memory, and processing speed. Scores were analyzed at the individual-level, and changes ≥2 standard deviations were considered clinically significant. We also examined whether changes in clinical symptoms were associated with changes in cognitive performance. At baseline intellectual functioning was in the average to high-average range for the group. Following MRgFUS capsulotomy, there were no deteriorations in cognition that reached ≥2 standard deviations at 6 or 12 months. Eight out of ten patients demonstrated a ≥2 standard deviation improvement in at least one cognitive score at 6 or 12 months postoperatively. Improvements in clinical symptoms correlated significantly with self-reported improvements in frontal lobe function (p < 0.05), but not with objective measures of cognitive functioning. To summarize, MRgFUS capsulotomy did not result in cognitive decline in this cohort of patients with refractory OCD or MDD, suggesting that this procedure can be offered to patients with a very low risk of cognitive side effects.

Subgenual cingulate connectivity and hippocampal activation are related to MST therapeutic and adverse effects

Aberrant connectivity between the dorsolateral prefrontal cortex (DLPFC) and the subgenual cingulate cortex (SGC) has been linked to the pathophysiology of depression. Indirect evidence also links hippocampal activation to the cognitive side effects of seizure treatments. Magnetic seizure therapy (MST) is a novel treatment for patients with treatment resistant depression (TRD). Here we combine transcranial magnetic stimulation with electroencephalography (TMS-EEG) to evaluate the effects of MST on connectivity and activation between the DLPFC, the SGC and hippocampus (Hipp) in patients with TRD. The TMS-EEG was collected from 31 TRD patients prior to and after an MST treatment trial. Through TMS-EEG methodology we evaluated significant current scattering (SCS) as an index of effective connectivity between the SGC and left DLPFC. Significant current density (SCD) was used to assess activity at the level of the Hipp. The SCS between the SGC and DLPFC was reduced after the course of MST (p < 0.036). The DLPFC-SGC effective connectivity reduction correlated with the changes in Hamilton depression score pre-to-post treatment (R = 0.46; p < 0.031). The SCD localized to the Hipp was reduced after the course of MST (p < 0.015), and the SCD change was correlated with montreal cognitive assessment (MOCA) scores pre-post the course of MST (R = −0.59; p < 0.026). Our findings suggest that MST treatment is associated with SGC-DLPFC connectivity reduction and that changes to cognition are associated with Hipp activation reduction. These findings demonstrate two distinct processes which drive efficacy and side effects separately, and might eventually aid in delineating physiological TRD targets in clinical settings.

High-Dose Dependence and Cognitive Side Effects to Medical Prescription of Etizolam.

Introduction: The use of novel designer drugs has increased worldwide over the years. Etizolam is a designer benzodiazepine (BZD) that has raised concern because of its growing non-medical use, liability to tolerance and dependence, and related harms. Studies exploring the abuse liability and cognitive effects of etizolam outside the therapeutic doses are lacking.Aims: To explore the abuse liability of etizolam and the characteristics of patients affected by etizolam high-dose dependence in a nationwide tertiary referral addiction unit. To document the cognitive changes to etizolam high-dose use.Design and Methods: Sociodemographic and clinical data on subjects with etizolam high-dose use were retrospectively collected from a database of 1,293 patients consecutively admitted to the Addiction Medicine Unit, Verona University Hospital, Italy for detoxification from high-dose BZDs or Z-drugs dependence. Thorough neuropsychological testing explored the cognitive side effects of high-dose etizolam use.Results: We found eleven etizolam high-dose users, of which eight used etizolam only, and three used etizolam with other BZDs/zolpidem. All the patients were prescribed etizolam for medical reasons, i.e., anxiety and/or insomnia. Neuropsychological evaluation showed deficits of working memory, visuospatial memory and executive function in a 27-year-old woman who used etizolam 15 mg daily.Discussion: Our findings suggest that abuse and dependence liability of etizolam should be considered a public health and social problem. They offer preliminary evidence on the cognitive side effects of etizolam high-dose use.Conclusions: This report offers new information on the potential harms of etizolam in patients who are prescribed this drug for medical reasons.