Electroconvulsive Therapy While Receiving OralAnticoagulation for Deep Venous Thrombosis:Report on Eight Cases and a Review of theLiterature.

BACKGROUND: Electroconvulsive therapy (ECT) is indicated for critical psychiatric conditions, which themselves constitute a risk for deep venous thrombosis (DVT) owing to prolonged immobility, dehydration, and venous stasis. OBJECTIVE: We describe challenging instances of ECT implementation while taking direct oral anticoagulants (DOACs). METHOD: We report on 8 patients receiving DOACs for DVT who were successfully treated with ECT at the University of Yamanashi Hospital. We also provide a literature review on this topic. RESULTS: There were 6 female patients (the average age was 60.9+/-13.4 y.o.) and diagnoses included major depression, bipolar depression and schizophrenia. DOACs were edoxaban for 4 patients, rivaroxaban for 2, and apixaban for 2. A total of 92 ECT sessions were cautiously and safely completed in collaboration with multidisciplinary medical professionals without problematic adverse events, such as bleeding. A literature search found one case series of warfarin but currently available evidence is confined to sporadic case reports regarding ECT and DOACs for DVT. These reports were represented by successful implementation of ECT to patients receiving treatment with anticoagulants for DVT or thromboembolism. Ours is the first of a successful treatment with ECT while taking apixaban or edoxaban. CONCLUSION: A clinical dilemma is that ECT is indicated for critical conditions that are likely to predispose patients to developing DVT. Paucity of data clearly highlights the need for more studies to support a contention that ECT, when carefully performed in consultation with other medical experts, is a viable treatment for those with DVT receiving oral anticoagulants.

Seizure threshold and the half-age method in bilateral electroconvulsive therapy in Japanese patients.

AIM: Seizure threshold (ST) in electroconvulsive therapy (ECT) has not been reported previously in Japanese patients. We investigated ST in bilateral ECT in Japanese patients using the dose-titration method. The associations between demographic and clinical characteristics and ST were analyzed to identify the predictors of ST. Finally, the validity of the half-age method for the stimulus dose was evaluated. METHODS: Fifty-four Japanese patients with mood disorder, schizophrenia, and other psychotic disorders received an acute course of bilateral ECT using a brief-pulse device. ST was determined at the first session using a fixed titration schedule. ST was correlated with age, sex, body mass index, history of previous ECT, and psychotropic drugs on multiple regression analysis. Furthermore, the rate of accomplished seizures was calculated using the half-age method. RESULTS: Mean ST was 136 mC. ST was influenced by age, sex, history of previous ECT, and medication with benzodiazepines. The accomplished seizure rate using the half-age method was 72%, which was significantly lower in men and subjects on benzodiazepines. CONCLUSION: ST in Japanese patients was equal to or slightly higher than that previously reported in other ethnic groups, which might be attributable, at least in part, to high prevalence of and large-dose benzodiazepine prescription. Higher age, male gender, no history of ECT, and benzodiazepines were related to higher ST. The half-age method was especially useful in female patients and subjects without benzodiazepine medication.

[Role of oxidative stress in the pathophysiology of neuropsychiatric disorders].

The brain is particularly vulnerable to oxidative damage because of its high rate of oxygen consumption, abundant lipid content, and relative paucity of antioxidant enzymes compared with other organs. It has been well established that oxidative stress (OS) is involved in the pathogenesis of age-associated neurodegenerative disorders such as Alzheimer's disease (AD). Indeed, a large number of genetic and environmental factors of neurodegenerative disorders are associated with OS. Of note, studies on the levels of oxidative damage in patients with the prodromal stage of AD, transgenic animal models of AD, and induced pluripotent stem (iPS) cells derived from AD patients support the early-stage involvement of OS in the pathological cascade of the disorder. Recently, a growing body of evidence suggests that a considerable number of genetic and environmental factors of psychiatric disorders such as schizophrenia (SZ), bipolar disorders, and depression are associated with OS. Not only genetic polymorphisms in genes encoding antioxidant enzymes but also several known susceptible genes for psychiatric disorders, i. e., Disrupted-in-Schizophrenia-1 (DISC1), Neuregulin 1 (NRG1), proline dehydrogenase (PRODH), and G72, are all associated with increased levels of OS or decreased antioxidant capacities. Moreover, environmental factors such as infection, hypoxia, malnutrition, illicit substance use, and psychosocial stress are possibly associated with OS. In fact, increased levels of oxidized nucleic acids, proteins, and lipids have been described in the postmortem brains of patients with SZ and bipolar disorders, and decreased antioxidant capacities have been described in blood samples obtained from patients with first-episode psychosis. In concordance, iPS cells from SZ patients show an increased level of OS. Of particular interest is a conditional gene knockout mouse model of SZ with the functional elimination of NMDA receptors specifically from cortical interneurons. The NMDA receptor knockout mouse shows behavioral phenotypes resembling symptoms of human SZ. Importantly, a marked increase of OS, particularly in the cortical parvalbumin-positive interneurons, is rapidly exacerbated by post-weaning social isolation, but treatment with antioxidants abolishes OS and partially alleviates the SZ-like behavioral phenotypes. Therefore, it is suggested that OS is a convergence point for genetic and environmental susceptibilities to not only neurodegenerative but also psychiatric disorders. In other words, OS potentially plays a central role in the pathomechanisms that integrate gene-environment interactions in neuropsychiatric disorders. Further investigations into the development of useful OS biomarkers and efficacious OS-targeting interventions may shed light on a promising approach for establishing preemptive strategies against neuropsychiatric disorders.

Catheter-related bloodstream infection in patients With severe anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) may be treated with intravenous hyperalimentation (IVH) that may be associated with catheter-related bloodstream infection (CRBSI). DESIGN AND METHODS: Retrospective chart review was conducted to compare those who developed CRBSI were compared with those who did not. FINDINGS: Of 34 patients, 17 episodes of AN treated with IVH were identified, of which five resulted in CRBSI. The average body mass index at admission was low at 12.2. Patients who needed physical restraint during IVH had a higher (albeit statistically nonsignificant) risk. Also, those with purging had numerically lower risk. PRACTICE IMPLICATIONS: CRBSI complicated IVH in 29.4% instances of severe life-threatening AN in our sample. Whether physical restraints and no purging constitute a risk factor of CRBSI needs to be further investigated.

Flumazenil for Successful Seizure Induction With Electroconvulsive Therapy: Case Report and Literature Review.

OBJECTIVE: Electroconvulsive therapy (ECT) is indicated for various psychiatric situations that are difficult to manage otherwise and may be regarded as a last resort but seizure induction is sometimes difficult, resulting in inadequate trials and futile outcomes. METHOD: We report on a 72-year-old female patient with bipolar depression whose seizure induction with ECT was challenging but the use of flumazenil was deemed effective to obtain remission in the end. We also provide a literature review on this topic. RESULTS: Seizure induction was managed with the use of flumazenil, a selective GABA-A receptor antagonist to neutralize the effects of benzodiazepine hypnotics, together with decreasing the amount of anesthesia, increasing the pulse width, and adding chlorpromazine. A PubMed search with keywords of flumazenil and ECT yielded only 14 hits (December 2020) and found some indication that flumazenil might be of use for this purpose even in the absence of benzodiazepines, although evidence base has remained very limited. CONCLUSIONS: Flumazenil, an antidote of benzodiazepines, may be effective regardless of whether benzodiazepines are in use. Because inefficient ECT is clinically problematic, more studies are necessary to investigate the effectiveness of flumazenil for successful seizure induction with ECT.

Intraneuronal amyloid beta accumulation and oxidative damage to nucleic acids in Alzheimer disease.

In an analysis of amyloid pathology in Alzheimer disease, we used an in situ approach to identify amyloid-beta (Abeta) accumulation and oxidative damage to nucleic acids in postmortem brain tissue of the hippocampal formation from subjects with Alzheimer disease. When carboxyl-terminal-specific antibodies directed against Abeta40 and Abeta42 were used for immunocytochemical analyses, Abeta42 was especially apparent within the neuronal cytoplasm, at sites not detected by the antibody specific to Abeta-oligomer. In comparison to the Abeta42-positive neurons, neurons bearing oxidative damage to nucleic acids were more widely distributed in the hippocampus. Comparative density measurements of the immunoreactivity revealed that levels of intraneuronal Abeta42 were inversely correlated with levels of intraneuronal 8-hydroxyguanosine, an oxidized nucleoside (r=- 0.61, p<0.02). Together with recent evidence that the Abeta peptide can act as an antioxidant, these results suggest that intraneuronal accumulation of non-oligomeric Abeta may be a compensatory response in neurons to oxidative stress in Alzheimer disease.

[Other treatments for depressive patients].

Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT.

Plasma Amyloid-ß and Alzheimer's Disease-Related Changes in Late-Life Depression.

To elucidate an involvement of amyloid dysmetabolism in the pathophysiology of depression, we investigated associations of plasma amyloid-ß (Aß) levels with Alzheimer's disease-related changes in neuroimaging and cognitive dysfunction in patients with late-life depression. Higher plasma Aß40, but not Aß42 nor Aß40/Aß42 ratio, was associated with higher degree of parahippocampal atrophy and lower verbal fluency performance. Indeed, high plasma Aß40 predicted poor cognitive prognosis of depressed patients with mild cognitive impairment. As an anti-depressive treatment, electroconvulsive therapy (ECT) resulted in a marginally significant reduction of plasma Aß40 compared to pharmacotherapy alone, suggesting protective effects of ECT against amyloid dysmetabolism.

The earliest stage of cognitive impairment in transition from normal aging to Alzheimer disease is marked by prominent RNA oxidation in vulnerable neurons.

Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approachto identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinicaldementia rating score and postmortem brain pathologic diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that, although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD.

Impairment of theory of mind in patients in remission following first episode of schizophrenia.

The aim of this study was to investigate theory of mind (ToM) ability in patients in remission after the first episode of schizophrenia. A ToM task which contained four pictures was given to 30 patients with schizophrenia in remission and 30 matched healthy controls. Patients with schizophrenia in remission showed statistically significant impairment in the ToM tasks. ToM impairment was not correlated with psychiatric symptoms. Thus, ToM deficit in schizophrenia may be a trait marker.