Serum neurofilament light chain (NFL) remains unchanged during electroconvulsive therapy.

Objectives: Although there is consistent evidence that electroconvulsive therapy (ECT) is safe and well tolerated by the majority of patients, some authors still accuse ECT to inevitably cause brain damage and permanent memory loss, assertions that may increase patients' worries about a useful treatment. Recently, the measurement of neurofilament light chain (NFL) in peripheral blood was technically implemented, permitting longitudinal analysis of this biomarker for axonal damage. NFL is part of the axonal cytoskeleton and is released into the CSF and peripheral blood in the context of neuronal damage.Methods: In our study, blood from 15 patients with major depressive disorder receiving ECT was collected before the first ECT as well as 24 h and seven days after the last ECT, respectively. NFL concentrations were analysed using the ultrasensitive single molecule array (Simoa) technology.Results: NFL concentrations did not differ between patients and healthy controls, and there was no significant change in NFL levels in the course of ECT. On the contrary, we even found a slight decrease in absolute NFL concentrations.Conclusions: Our study confirms the safety of ECT by using a most sensitive method for the detection of NFL in peripheral blood as a biomarker of neuronal damage.

Overlooking the obvious? Influence of electrolyte concentrations on seizure quality parameters in electroconvulsive therapy.

Clinical response to electroconvulsive therapy (ECT) depends on eliciting a generalized seizure. Though there are multiple ictal and other parameters to assess seizure quality, factors that influence these parameters have only been identified to a limited extend in antecedent studies (e.g., stimulus dosage, age). In the context of ECT, electrolyte concentrations have hardly been investigated so far-although hyponatremia is one well-known clinical factor to increase the risk of spontaneous seizures. In 31 patients with unipolar or bipolar depressive disorder, blood concentrations of sodium (Na), potassium (K), and calcium (Ca) were measured immediately prior to repeated sessions of maintenance ECT. Generalized linear mixed models were used to analyze the influence of Na, K, and Ca on seven seizure quality parameters: postictal suppression index (PSI), maximum sustained coherence (MSC), midictal amplitude, average seizure energy index, seizure duration (EEG/motor), and peak heart rate. Results show a statistically significant relationship between the serum sodium level and MSC: in the model, a reduction of 1 mmol/l led to an increase in interhemispheric coherence of 0.678%. The further markers remained unaffected by changes in electrolyte concentrations. This finding provides first evidence that a lower blood concentration of sodium could enhance the quality of ECT-induced seizures in terms of higher interhemispheric coherence.

Vagus Nerve Stimulation as a Treatment for Catatonia: A Hypothesis.

Background: Catatonia is a syndrome comprising psychomotor, behavioral, and autonomous symptoms which may occur in the context of severe schizophrenic, affective, and other mental disorders or medical conditions. Treatment options include high dose benzodiazepines (lorazepam) and electroconvulsive therapy (ECT) with some evidence for the effectiveness of glutamate antagonists. However, due to a lack of randomized controlled studies in this severely ill population, evidence base is weak. Methods: On occasion of the case of a patient with treatment resistant catatonia in schizoaffective disorder, we developed the hypothesis of vagus nerve stimulation (VNS) being a potential therapy for treatment resistant catatonia. Results: Based on a selective literature search, we found a remarkable overlap of the pathophysiology of catatonia on the one hand and the putative mechanisms of action of VNS on the other hand in several domains: functional brain imaging, involved neurotransmitter systems, clinical, and theoretical. We thus decided to use VNS as a single subject clinical trial. During the 1-year-follow-up, we observed a fluctuating, but ultimately marked improvement of both catatonic symptoms and general psychopathology. Conclusions: We assume there is a sufficient hypothetical corroboration for the potential effectiveness of VNS as a long-term treatment in predominantly catatonic syndromes. This hypothesis could be tested in proof-of-concept clinical trials.

Electroconvulsive Therapy in Incapable Patients Refusing Treatment: Prevalence, Effectiveness, and Associated Factors.

OBJECTIVES: Severe psychiatric disorders may be accompanied by life-threatening conditions, lack of insight, and treatment refusal. Involuntary treatment may be indicated in patients who lack capacity to consent and refuse treatment. In this context, there is a lack of systematic data regarding the use of electroconvulsive therapy (ECT) in Germany. METHODS: A questionnaire with 25 items comprising quantitative and qualitative data was sent to all psychiatric hospitals in Germany that perform ECT. Cases of ECT treatment in incapable patients refusing therapy were identified retrospectively in a 12-month period. RESULTS: Fifty-three hospitals completed the questionnaire, and 15 cases of ECT in incapable and refusing patients were reported. A marked clinical response was observed in 14 patients. Capacity to consent was restored in 11 patients. In contrast to this particularly good effectiveness, psychiatrists' attitudes revealed a widespread lack of experience as well as reservations and uncertainties regarding the use of ECT against the patient's wishes. CONCLUSIONS: In line with other recent publications, our data suggest a very good benefit-to-risk ratio for ECT in incapable patients refusing the treatment, while at the same time the provision of ECT in such patients is rare in Germany. In light of the scarcity of treatment alternatives and the possible consequences of a refusal to perform ECT in life-threatening conditions, a general rejection of involuntary ECT does not seem ethically appropriate.

Factors Influencing Staff's Attitude Toward Electroconvulsive Therapy: A Comparison of New Versus Experienced Electroconvulsive Therapy Clinics.

OBJECTIVES: Despite being a highly effective treatment, electroconvulsive therapy (ECT) is still stigmatized even among professionals. The aim of this study was to identify factors associated with a positive attitude toward ECT among health care workers. METHODS: We investigated staff's attitude and their self-assessment of knowledge while introducing ECT in 3 German psychiatric clinics. Furthermore, we compared this data to that of a clinic where ECT has been applied with a long tradition. An anonymous questionnaire was answered by n = 182 employees in the ECT-introducing clinics (novices) and n = 68 employees in the clinic with a long history of ECT (experts). RESULTS: Irrespective of the clinical history, the majority of participants approved the application of ECT in their clinic. Factors associated with a positive attitude were (a) profession (physicians presented a more positive mindset about ECT than nursing staff), (b) subjective feeling of being adequately informed, and (c) having had contact to patients undergoing ECT. Interestingly, the general attitude toward ECT did not differ between subjects who reported to have seen an ECT and those who had not. CONCLUSIONS: When introducing ECT as a new treatment into a clinic, formal information should be adapted to the needs of each profession with a special emphasis on nurses. To further increase acceptance, contact to ECT-experienced patients (professionals taught by patients) might result in a more positive attitude toward ECT than participation in an ECT treatment itself.

Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients.

BACKGROUND: Electroconvulsive therapy (ECT) and depression have been associated with brain volume changes, especially in the hippocampus and the amygdala. METHODS: In this retrospective study we collected data from individual pre-post ECT whole brain magnetic resonance imaging scans of depressed patients from six German university hospitals. Gray matter volume (GMV) changes were quantified via voxel-based morphometry in a total sample of 92 patients with major depressive episodes (MDE). Additionally, 43 healthy controls were scanned twice within a similar time interval. RESULTS: Most prominently longitudinal GMV increases occurred in temporal lobe regions. Within specific region of interests we detected significant increases of GMV in the hippocampus and the amygdala. These results were more pronounced in the right hemisphere. Decreases in GMV were not observed. GMV changes did not correlate with psychopathology, age, gender or number of ECT sessions. We ruled out white matter reductions as a possible indirect cause of the detected GMV increase. CONCLUSION: The present findings support the notion of hippocampus and amygdala modulation following an acute ECT series in patients with MDE. These results corroborate the hypothesis that ECT enables primarily unspecific and regionally dependent neuroplasticity effects to the brain.

Cortical Brain Abnormalities in 4474 Individuals With Schizophrenia and 5098 Control Subjects via the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) Consortium.

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia.

Influence of depressed patients' expectations prior to electroconvulsive therapy on its effectiveness and tolerability (Exp-ECT): a prospective study.

Electroconvulsive therapy (ECT) is the most effective therapy for severe depressive disorders. Though there are known clinical predictors of response (e.g., higher age, presence of psychotic symptoms), there is a lack of knowledge concerning the impact of patients' expectations on treatment outcome and tolerability in terms of possible placebo/nocebo effects. In 31 patients with unipolar or bipolar depressive disorder, we used a questionnaire to investigate the patients' expectations of ECT effectiveness and tolerability prior to and in the course of the treatment. Additionally, the questionnaire was used after the ECT course for a final assessment. Depressive symptoms and putative side-effects were measured at each time point. General linear models were used to analyze the course of depressive symptoms and patients' expectation of ECT effectiveness and tolerability. ECT significantly reduced depressive symptoms with large effect sizes. Patients' rating of ECT effectiveness decreased in parallel: While responders' rating of ECT effectiveness remained stable on a high level, non-responders' rating decreased significantly. Group difference was significant after, but not prior to and during the treatment. Regarding tolerability, there was a (temporary) significant increase in the severity of self-rated symptoms such as headache and memory impairment. In contrast, patients' expectation and assessment of ECT tolerability remained unchanged, and their expectations prior to ECT had no impact on the occurrence of side-effects. These findings contradict the presence of relevant placebo/nocebo effects in the context of ECT when investigating a population of mostly chronic or treatment resistant patients with moderate to severe depressive disorder.

Electroconvulsive therapy against the patients' will: A case series.

OBJECTIVES: Electroconvulsive therapy (ECT) is the most effective therapy for severe depressive and psychotic disorders. As patients may be subject to legal incapacity and lack of insight, treatment may be administered against the patient's will. There is only limited evidence on the use of ECT against the patient's non-autonomous will. METHODS: We report a series of eight patients who received ECT against their will in two German university medical hospitals between 2014 and 2016. The effectiveness, tolerability and patients' perspective are described. RESULTS: Seven of eight patients were much or very much improved according to the Clinical Global Impression Scale. Capacity to consent was restored in seven patients. Transient side effects occurred in four patients. Seven patients agreed to receive further ECT in the treatment course. CONCLUSIONS: This case series suggests that ECT may (and sometimes should) be administered to severely ill, non-consenting patients against their will with good effectiveness. Potential and mostly moderate and transient side effects have to be weighed up against the potentially life-saving character of ECT in patients with, e.g., suicidality and food refusal. Most importantly, the patients' retrospective appraisal also justifies the administration of ECT in situations of severe mental illness and legal incapacity.

Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks.

BACKGROUND: Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. METHODS: We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. RESULTS: We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. CONCLUSION: These findings provide evidence for a slightly lower capacity in both WM modalities in females.

Disturbed anterior prefrontal control of the mesolimbic reward system and increased impulsivity in bipolar disorder.

Bipolar disorder (BD) is characterized by recurrent mood episodes ranging from severe depression to acute full-blown mania. Both states of this severe psychiatric disorder have been associated with alterations of reward processing in the brain. Here, we present results of a functional magnetic resonance imaging (fMRI) study on the neural correlates and functional interactions underlying reward gain processing and reward dismissal in favor of a long-term goal in bipolar patients. Sixteen medicated patients diagnosed with bipolar I disorder, euthymic to mildly depressed, and sixteen matched healthy controls performed the 'desire-reason dilemma' (DRD) paradigm demanding rejection of priorly conditioned reward stimuli to successfully pursue a superordinate goal. Both groups exhibited significant activations in reward-related brain regions, particularly in the mesolimbic reward system. However, bipolar patients showed reduced neural responses of the ventral striatum (vStr) when exploiting a reward stimulus, and exhibited a decreased suppression of the reward-related activation of the mesolimbic reward system while having to reject immediate reward in favor of the long-term goal. Further, functional interaction between the anteroventral prefrontal cortex and the vStr in the 'DRD' was significantly impaired in the bipolar group. These findings provide evidence for a reduced responsivity of the vStr to reward stimuli in BD, possibly related to clinical features like anhedonia. The disturbed top-down control of mesolimbic reward signals by prefrontal brain regions in BD can be interpreted in terms of a disease-related enhanced impulsivity, a trait marker of BD.

Development of schizoaffective psychosis in the course of a long-term occupation as spiritual healer: coincidence or causality?

Psychotic reactions in the context of meditation and esoteric practices have been described in the psychiatric literature. In most cases, these psychotic conditions are transient and do not lead to functional impairment. The authors present the case of a 46-year-old woman who had worked as a spiritual healer for several years and, in the course of this occupation, increasingly developed a highly specific configuration of psychotic symptoms (all of which could be convincingly traced back to the formerly used spiritual techniques) along with depressive symptoms and severe functional impairment. The differential diagnosis was initially complicated by the relative conformity of the patient's psychotic symptoms with her occupational practices and the absence of other, more typical, symptoms of schizophrenia. Only a thorough anamnesis with another spiritual healer and precise identification of psychopathology helped to disentangle the merely uncommon from the pathologic features of this case. Possible mechanisms of psychotogenesis are discussed in light of the literature and the specific features of the presented case. Although a single case report cannot prove a causal link between spiritual healing and development of psychosis, the patient's specific psychopathology, with preeminently disturbed self-experience, and its consistency with the patient's spiritual practices suggest at least a contributory role in this case.

Differential working memory performance as support for the Kraepelinian dichotomy between schizophrenia and bipolar disorder? An experimental neuropsychological study using circuit-specific working memory tasks.

OBJECTIVES: The traditional clinical dichotomy of schizophrenia and bipolar disorder has been challenged by recent findings of an at least in part common genetic basis. The investigation of neurocognitive functions like working memory may thereby contribute to elucidate common versus distinct pathophysiological processes of the major psychoses. To date direct comparisons of working memory functioning in schizophrenia and bipolar disorder have been rare and moreover have revealed inconsistent findings. In this study we aimed to further clarify the diagnostic specificity of working memory deficits in schizophrenia and bipolar disorder. METHODS: Fifty patients with schizophrenia, 23 patients with bipolar disorder and 53 healthy controls were tested with regard to specific dysfunctions of verbal and visuospatial working memory components using a set of well-characterized, brain circuit-specific paradigms with established brain-behaviour relationships. RESULTS: Patients with schizophrenia showed marked deficits across different working memory domains while bipolar patients performed intermediate with no significant differences compared to the control group. Working memory performance of patients with schizophrenia and bipolar disorder significantly differed in only one particular task requiring articulatory rehearsal of verbal information. CONCLUSIONS: While these results do not provide unequivocal support for the Kraepelinian dichotomy, they are consistent with recent findings suggesting the existence of a specific subgroup of schizophrenia patients phenotypically characterized by selective deficits of the articulatory rehearsal mechanism of verbal working memory.

Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning.

Working memory deficits are found in different psychiatric populations and are most pronounced in schizophrenia. There is preliminary evidence from pharmacological studies that the verbal and visuospatial subcomponents of working memory are subject to differential neurotransmitter modulation. Here, we investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals. Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit-specific working memory tasks. DAT genotype revealed a significant and selective effect on visuospatial working memory, while there was no effect on verbal working memory functioning. 5-HTT genotype, by contrast, exerted a significant and selective effect on verbal working memory task performance. COMT genotype did not show any influence on either working memory domain. The results of the present study provide evidence for a differential impact of genetic polymorphisms of the dopaminergic and serotonergic systems on verbal and visuospatial working memory functioning. Together with prior evidence suggesting the existence of subgroups of schizophrenia patients exhibiting isolated deficits in only one working memory domain, this finding further supports the idea of endophenotypically and pathophysiologically distinct subgroups of schizophrenia with implications for personalized therapeutic approaches.

A systematic experimental neuropsychological investigation of the functional integrity of working memory circuits in major depression.

Verbal and visuospatial working memory (WM) impairment is a well-documented finding in psychiatric patients suffering from major psychoses such as schizophrenia or bipolar affective disorder. However, in major depression (MDD) the literature on the presence and the extent of WM deficits is inconsistent. The use of a multitude of different WM tasks most of which lack process-specificity may have contributed to these inconsistencies. Eighteen MDD patients and 18 healthy controls matched with regard to age, gender and education were tested using process- and circuit-specific WM tasks for which clear brain-behaviour relationships had been established in prior functional neuroimaging studies. Patients suffering from acute MDD showed a selective impairment in articulatory rehearsal of verbal information in working memory. By contrast, visuospatial WM was unimpaired in this sample. There were no significant correlations between symptom severity and WM performance. These data indicate a dysfunction of a specific verbal WM system in acutely ill patients with MDD. As the observed functional deficit did not correlate with different symptom scores, further, longitudinal studies are required to clarify whether and how this deficit is related to illness acuity and clinical state of MDD patients.