A qualitative investigation of the Montgomery-Åsberg depression rating scale: discrepancies in rater perceptions and data trends in remote assessments of rapid-acting antidepressants in treatment resistant depression.

Introduction: Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery-Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes. Methods: The aim of this study was to review item-level differences between rate of data change (MADRS score) and rater-weighted perception of the most useful items for assessing change in symptoms while remotely conducting the 10-item version of the MADRS in TRD in a clinical trial of rapid-acting antidepressants. Two studies of rapid-acting antidepressants in the treatment of TRD were used to identify item-scoring trends when MADRS is administered remotely and repeatedly (733 subjects across 10 visits). Scoring trends were evaluated in tandem to a rater survey completed by 75 raters. This was completed to gain insight on MADRS items' perceived level of helpfulness when assessing change of symptoms in rapid-acting antidepressant trials. Results: MADRS items 'Reduced sleep', 'Apparent sadness', and 'Pessimistic thoughts' were found to have the greatest average data change by visit, while raters ranked 'Reported sadness', 'Lassitude' and 'Apparent sadness' as the most helpful items when assessing symptom change. Discussion: The diversion between rate of data-change ranking and rater perception of helpfulness could be related to difficulty in assessing specific items, to the novel treatment itself, and/or to the sensitivity to symptom change to which raters are accustomed in traditional antidepressant treatments.

[Memories of the Future - A Narrative Literature Review of Episodic Future Thinking]. / A jövo emlékei ­ Az epizodikus jövogondolkodás narratív irodalmi áttekintése.

In recent years, the question of how we can grasp the ability to plan future events has come to the forefront in light of the retrieval of personal memories from the past. If episodic memory is responsible for envisioning future events, there appears to be an overlap between autobiographical memory and imagining the future. The aim of this current narrative literature review is to present existing theories and research findings, thereby facilitating the development of an organizational framework necessary for the unified investigation of future thinking. This article introduces the neural network processes underlying episodic future thinking, with particular emphasis on the significance of the hippocampus. It outlines the constructive episodic simulation hypothesis, suggesting that episodic memory and episodic future thinking largely rely on similar neural substrates and assumes that a primary function of the episodic memory system is to flexibly reorganize units of individual, contextual memories to simulate possible future events for the individual. The article presents research results related to memory deficits, as it can be presumed that impairment of autobiographical memory in psychiatric disorders also results in impaired episodic future thinking. Future-oriented thoughts serve various functions, such as decision-making, action planning, and emotional regulation. The article also delves into schema theories, as when generating episodic future thoughts, people often activate their general knowledge about their personal future before a specific event occurs. Future thinking is crucial for well-being, goal attainment, aging, optimism, and understanding clinical conditions. How people think about the future can influence their decisions. The elucidation of emotionally futureoriented thoughts, autobiographical knowledge structures, and life-history schemas plays a crucial role in the construction of episodic future thinking. Understanding the role of memory in simulating future events can be important in comprehending the constructive nature of memory and, in general, the functioning of memory systems in diseases, thereby contributing to the specific selection of treatments for these conditions.

Frontal two-electrode transcranial direct current stimulation protocols may not affect performance on a combined flanker Go/No-Go task.

Transcranial direct current stimulation (tDCS) has been tested to modulate cognitive control or response inhibition using various electrode montages. However, electrode montages and current polarities have not been systematically compared when examining tDCS effects on cognitive control and response inhibition. In this randomized, sham-controlled study, 38 healthy volunteers were randomly grouped into receiving one session of sham, anodal, and cathodal each in an electrode montage that targeted either the dorsolateral prefrontal cortex (DLPFC) or the fronto-medial (FM) region. Participants performed a combined flanker Go/No-Go task during stimulation. No effect of tDCS was found in the DLPFC and FM groups neither using anodal nor cathodal stimulation. No major adverse effects of tDCS were identified using either montage or stimulation type and the two groups did not differ in terms of the reported sensations. The present study suggests that single-session tDCS delivered in two two-electrode montages might not affect cognitive control or response inhibition, despite using widely popular stimulation parameters. This is in line with the heterogeneous findings in the field and calls for further systematic research to exclude less reliable methods from those with more pronounced effects, identify the determinants of responsiveness, and develop optimal ways to utilize this technique.

Voxel-based asymmetry of the regional gray matter over the inferior temporal gyrus correlates with depressive symptoms in medicated patients with major depressive disorder.

The number of patients suffering from major depressive disorder (MDD) is increasing worldwide. Imbalanced hemispherical brain activity may be an underlying factor of MDD; however, whether structural asymmetry also contributes to the symptoms experienced in MDD has been scarcely investigated. In this study, we aimed to examine cortical asymmetry in association with the severity of depressive and cognitive symptoms observed in MDD during stable medication. The association between the affective and cognitive symptoms and gray matter asymmetry was evaluated in 17 MDD patients using voxel-wise gray matter asymmetry analysis on high-resolution T1-weighted MR images. Asymmetry index values in the inferior temporal gyrus (ITG) correlated with the scores of the 17-item Hamilton Depression Rating Scale (HDRS), but no association was found with the Beck Hopelessness Scale, and performance on the 1-, 2- and 3-back task. Our results indicate that the asymmetry of gray matter content in the ITG might be associated with higher depression severity. Our findings might help to better understand how structural changes contribute to depression severity in patients with MDD.

The Effects of Bilateral Theta-burst Stimulation on Executive Functions and Affective Symptoms in Major Depressive Disorder.

Major depressive disorder (MDD) is characterized by severe affective as well as cognitive symptoms. Moreover, cognitive impairment in MDD can persist after the remission of affective symptoms. Theta-burst stimulation (TBS) is a promising tool to manage the affective symptoms of major depressive disorder (MDD); however, its cognition-enhancing effects are sparsely investigated. Here, we aimed to examine whether the administration of bilateral TBS has pro-cognitive effects in MDD. Ten daily sessions of neuronavigated active or sham TBS were delivered bilaterally over the dorsolateral prefrontal cortex to patients with MDD. The n-back task and the attention network task were administered to assess working memory and attention, respectively. Affective symptoms were measured using the 21-item Hamilton Depression Rating Scale. We observed moderate evidence that the depressive symptoms of patients receiving active TBS improved compared to participants in the sham stimulation. No effects of TBS on attention and working memory were detected, supported by a moderate-to-strong level of evidence. The effects of TBS on psychomotor processing speed should be further investigated. Bilateral TBS has a substantial antidepressive effect with no immediate adverse effects on executive functions.

Non-invasive Brain Stimulation in Alzheimer's Disease and Mild Cognitive Impairment-A State-of-the-Art Review on Methodological Characteristics and Stimulation Parameters.

Background: Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) have been proposed as a new therapeutic way to enhance the cognition of patients with dementia. However, serious methodological limitations appear to affect the estimates of their efficacy. We reviewed the stimulation parameters and methods of studies that used TMS or tDCS to alleviate the cognitive symptoms of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Moreover, we evaluated the risk of bias in these studies. Our aim was to highlight the current vulnerabilities of the field and to formulate recommendations on how to manage these issues when designing studies. Methods: Electronic databases and citation searching were used to identify studies administering TMS or tDCS on patients with AD or MCI to enhance cognitive function. Data were extracted by one review author into summary tables with the supervision of the authors. The risk of bias analysis of randomized-controlled trials was conducted by two independent assessors with version 2 of the Cochrane risk-of-bias tool for randomized trials. Results: Overall, 36 trials were identified of which 23 randomized-controlled trials underwent a risk of bias assessment. More than 75% of randomized-controlled trials involved some levels of bias in at least one domain. Stimulation parameters were highly variable with some ranges of effectiveness emerging. Studies with low risk of bias indicated TMS to be potentially effective for patients with AD or MCI while questioned the efficacy of tDCS. Conclusions: The presence and extent of methodical issues affecting TMS and tDCS research involving patients with AD and MCI were examined for the first time. The risk of bias frequently affected the domains of the randomization process and selection of the reported data while missing outcome was rare. Unclear reporting was present involving randomization, allocation concealment, and blinding. Methodological awareness can potentially reduce the high variability of the estimates regarding the effectiveness of TMS and tDCS. Studies with low risk of bias delineate a range within TMS parameters seem to be effective but question the efficacy of tDCS.

Speed or Accuracy Instructions During Skill Learning do not Affect the Acquired Knowledge.

A crucial question in skill learning research is how instruction affects the performance or the underlying representations. Little is known about the effects of instructions on one critical aspect of skill learning, namely, picking-up statistical regularities. More specifically, the present study tests how prelearning speed or accuracy instructions affect the acquisition of non-adjacent second-order dependencies. We trained 2 groups of participants on an implicit probabilistic sequence learning task: one group focused on being fast and the other on being accurate. As expected, we detected a strong instruction effect: accuracy instruction resulted in a nearly errorless performance, and speed instruction caused short reaction times (RTs). Despite the differences in the average RTs and accuracy scores, we found a similar level of statistical learning performance in the training phase. After the training phase, we tested the 2 groups under the same instruction (focusing on both speed and accuracy), and they showed comparable performance, suggesting a similar level of underlying statistical representations. Our findings support that skill learning can result in robust representations, and they highlight that this form of knowledge may appear with almost errorless performance. Moreover, multiple sessions with different instructions enabled the separation of competence from performance.

The effect of psychiatric comorbidities and stress-coping strategies on perceived quality of life in migraine.

BACKGROUND AND PURPOSE: Migraine is one of the most disabling primary headache conditions. We aimed to detect hidden symptoms of anxiety and depression and to survey stress-coping mechanisms and related quality of life in a large migraine population without any known psychiatric comorbidity. METHODS: 123 migraine patients (MG) and 66 healthy subjects (HC) completed the Beck Depression Inventory-II (BDI-II), the State and Trait Anxiety Inventory (S-STAI and T-STAI), the Stress and Coping Inventory (SCI) and the 36-Item Short Form Health Survey (SF-36). RESULTS: MG patients reached significantly higher scores on the BDI-II and the T-STAI yielding previously undetected anxiety and depression symptoms. Significant differences were present on the SCI: higher stress scores and lower coping levels suggested impaired stress-coping strategies in migraine. MG patients achieved significantly lower scores on most of SF-36 subscales indicating lower perceived quality of life. Significant correlations were found between BDI-II, T-STAI, SCI scores and subscales of the SF-36. CONCLUSION: Unrecognized symptoms of anxiety and depression, as well as less effective stress-coping strategies might be related to the lower perceived quality of life in migraine. The screening of these symptoms might lead to more focused and efficient therapeutic strategies. Addressing stress management techniques could improve quality of life on the long-term.

Continuous theta-burst stimulation over the dorsolateral prefrontal cortex inhibits improvement on a working memory task.

Theta-burst stimulation (TBS) over the dorsolateral prefrontal cortex (DLPFC) may be more effective for modulating cortical excitability compared to standard repetitive transcranial magnetic stimulation. However, the impact of intermittent (iTBS) and continuous TBS (cTBS) on working memory (WM) is poorly studied. The aim of our study was to compare the effects of iTBS and cTBS on WM over the left and right DLPFC. iTBS, cTBS or sham stimulation was administered over the right and left hemisphere of fifty-one healthy human subjects. WM was assessed before and after TBS using the 1-back, 2-back, and 3-back tasks. We found classical practice effects in the iTBS and the sham group: WM performance improved following stimulation as measured by the discriminability index. However, this effect could not be observed in the cTBS group. We did not find any hemisphere-dependent effects, suggesting that the practice effect is not lateralized, and TBS affects WM performance in a comparable manner if administered either over the left or the right hemisphere. We propose that our findings represent a useful addition to the literature of TBS-induced effects on WM. Moreover, these results indicate the possibility of clarifying processes underlying WM performance changes by using non-invasive brain stimulation.

[Schizotypal traits and verbal creativity]. / Szkizotip személyiségvonások és a nyelvi kreativitás összefüggéseinek vizsgálata.

BACKGROUND AND PURPOSE: The relationship of schizophrenia and its milder, subclinical forms, with creativity has been in the centre of theoretical interest for decades, however, the systematic research of the topic only prevailed more recently. Purpose - Here we aimed to examine the connection between different schizotypal and non-schizotypal personality traits and verbal creativity in a nonclinical sample. We also investigated the correspondence of two schizotypy inventories, the Oxford-Liverpool Inventory of Feelings and Experiences and a special character configuration of the Temperament and Character Inventory associated with schizotypy. METHODS: 57 healthy adults (14/43 m/f, mean age 21.51±1.43 years) - took part in the experiment. All participants received a detailed information sheet and gave informed consent prior to participation. Participants completed the Oxford-Liverpool Inventory and the Temperament and Character Inventory to measure both schizotypal and non-schizotypal personality traits. Torrance Test of Creative Thinking was used to measure verbal creativity. Associations between reported measures were examined with correlational and regression analyses. RESULTS: Out of the specific Temperament and Character configuration associated with schizotypy (low self-directedness, cooperativeness and high self- transcendence), we only found low self-directedness to be correlated significantly with Oxford-Liverpool schizotypy rates (Self-directedness-schizotypy: r=-.730, p<.01). There was no significant connection between schizotypal traits and verbal creativity. In our sample, the Self-directedness and Reward-dependence character and temperament subscales predicted significantly the verbal creativity level (Self-directedness: b=.330, p=.015; Reward - dependence: b=-.260; p=.049). CONCLUSION: Based on our results, besides schizotypal traits, other personality measures might be considered in relation to verbal creativity, providing further details to the empirical investigation of creativity. We found low self-directedness to be correlated with Oxford-Liverpool schizotypy rates, however, the sample size was not large enough to test the concurrent validity of the two inventories. Future studies might consider to extend the study sample, preferably to both clinical and non-clinical populations.

Gender-Specific Degeneration of Dementia-Related Subcortical Structures Throughout the Lifespan.

Age-related changes in brain structure are a question of interest to a broad field of research. Structural decline has been consistently, but not unambiguously, linked to functional consequences, including cognitive impairment and dementia. One of the areas considered of crucial importance throughout this process is the medial temporal lobe, and primarily the hippocampal region. Gender also has a considerable effect on volume deterioration of subcortical grey matter (GM) structures, such as the hippocampus. The influence of age×gender interaction on disproportionate GM volume changes might be mediated by hormonal effects on the brain. Hippocampal volume loss appears to become accelerated in the postmenopausal period. This decline might have significant influences on neuroplasticity in the CA1 region of the hippocampus highly vulnerable to pathological influences. Additionally, menopause has been associated with critical pathobiochemical changes involved in neurodegeneration. The micro- and macrostructural alterations and consequent functional deterioration of critical hippocampal regions might result in clinical cognitive impairment-especially if there already is a decline in the cognitive reserve capacity. Several lines of potential vulnerability factors appear to interact in the menopausal period eventually leading to cognitive decline, mild cognitive impairment, or Alzheimer's disease. This focused review aims to delineate the influence of unmodifiable risk factors of neurodegenerative processes, i.e., age and gender, on critical subcortical GM structures in the light of brain derived estrogen effects. The menopausal period appears to be of key importance for the risk of cognitive decline representing a time of special vulnerability for molecular, structural, and functional influences and offering only a narrow window for potential protective effects.

The Effect of Emotion and Reward Contingencies on Relational Memory in Major Depression: An Eye-Movement Study with Follow-Up.

Background: Episodic memory disturbances were found to constitute a potential trait marker for major depression (MD). The recall of positive or rewarding information in a relational context is specifically impaired. Eye-movement recording constitutes a novel, direct approach to examine implicit memory performance. Here we aimed to assess the effect of emotional context and implicit virtual monetary reward or loss on viewing patterns in association with relational memory in a 6-months follow-up study in MD. Materials and Methods: Twenty-eight patients with MD and 30 healthy participants were trained to associate a face (happy/sad/neutral) with a background scene. After each pair a virtual monetary reward or loss appeared briefly. During testing, scenes were presented as a cue and then overlaid with three previously studied faces. Participants were asked to recall the matching face if present (Match trials), with eye-movements and subsequent forced-choice recognition being recorded. Results: Explicit recognition of the matching face was impaired in the MD group as compared to controls. In correlation with this, viewing of the matching face was significantly reduced in the MD group. We found a significant interaction of group (MD vs HC) with the relational memory condition (Match and Non-match), facial emotion and monetary reward and loss. MD patients attended longer to previously rewarded stimuli, but significantly less to sad faces in the Match condition. The relational memory impairment persisted at follow-up and correlated with symptom severity both at baseline and follow-up. Viewing patterns associated with previous virtual reward were associated with clinical symptoms at follow-up. Conclusion: Our current results provide novel evidence for a specific relational memory impairment in MD as supported by abnormal eye-movement behavior and a deficit in explicit recognition. MD patients showed an attentional bias to rewarded stimuli and decreased viewing of sad faces when relational memory information was present.

[THE THERAPUETIC USE OF TRANSCRANIAL MAGNETIC STIMULATION IN MAJOR DEPRESSION]. / TRANSCRANIALIS MÁGNESES STIMULÁCIÓ TERÁPIÁS ALKALMAZÁSA MAJOR DEPRESSZIÓBAN.

The antidepressive effect of repetitive transcranial magnetic stimulation (rTMS) has been investigated for almost 20 years now. Several studies have been published aiming to identify the exact and reliable parameters leading to the desired therapeutic effect. However, the related literature shows great variability. The current overview aims to provide a comprehensive overview of factors associated with the therapeutic effect of rTMS in major depression. High frequency stimulation of the left dorsolateral prefrontal cortex (DLPFC) for 3-6 weeks leads to mood improvement comparable to the effect of antidepressive medications in 35-40% of patients. Pharmacotherapy resistant patients treated with rTMS reach remission for 3 months on average. Low frequency stimulation of the right DLPFC appears to be similarly effective, though much less investigated so far. In addition to the exact delineation of the stimulation area, treatment outcome is also related to stimulation intensity as well as the number of sessions and impulses. Considering the safety and tolerability aspects of rTMS, it might be a significant therapeutic support for therapy resistant patients. Above this, patients diagnosed with major depression might benefit from the additional positive influence of rTMS improving the effect of antidepressive medication. Based on converging research evidence, the Food and Drug Administration (FDA) agency approved the use of rTMS as a treatment option for therapy resistant major depression in 2008. So far, in Hungary rTMS is primarily considered as a promising tool in research settings only. Hopefully, patients suffering from major depression will increasingly benefit from the positive therapeutic effect of this intervention.

Male brain ages faster: the age and gender dependence of subcortical volumes.

Effects of gender on grey matter (GM) volume differences in subcortical structures of the human brain have consistently been reported. Recent research evidence suggests that both gender and brain size influences volume distribution in subcortical areas independently. The goal of this study was to determine the effects of the interplay between brain size, gender and age contributing to volume differences of subcortical GM in the human brain. High-resolution T1-weighted images were acquired from 53 healthy males and 50 age-matched healthy females. Total GM volume was determined using voxel-based morphometry. We used model-based subcortical segmentation analysis to measure the volume of subcortical nuclei. Main effects of gender, brain volume and aging on subcortical structures were examined using multivariate analysis of variance. No significant difference was found in total brain volume between the two genders after correcting for total intracranial volume. Our analysis revealed significantly larger hippocampus volume for females. Additionally, GM volumes of the caudate nucleus, putamen and thalamus displayed a significant age-related decrease in males as compared to females. In contrast to this only the thalamic volume loss proved significant for females. Strikingly, GM volume decreases faster in males than in females emphasizing the interplay between aging and gender on subcortical structures. These findings might have important implications for the interpretation of the effects of unalterable factors (i.e. gender and age) in cross-sectional structural MRI studies. Furthermore, the volume distribution and changes of subcortical structures have been consistently related to several neuropsychiatric disorders (e.g. Parkinson's disease, attention deficit hyperactivity disorder, etc.). Understanding these changes might yield further insight in the course and prognosis of these disorders.

The impact of intermediate-term alcohol abstinence on memory retrieval and suppression.

BACKGROUND: The nature of episodic memory deficit in intermediate-term abstinence from alcohol in alcohol dependence (AD) is not yet clarified. Deficits in inhibitory control are commonly reported in substance use disorders. However, much less is known about cognitive control suppressing interference from memory. The Think/No-think (TNT) paradigm is a well established method to investigate inhibition of associative memory retrieval. METHODS: Thirty-six unmedicated patients with AD and 36 healthy controls (HCs) performed the TNT task. Thirty image-word pairs were trained up to a predefined accuracy level. Cued recall was examined in three conditions: Think (T) for items instructed to-be-remembered, No-think (NT) assessing the ability to suppress retrieval and Baseline (B) for general relational memory. Premorbid IQ, clinical variables and impulsivity measures were quantified. RESULTS: AD patients had a significantly increased demand for training. Baseline memory abilities and effect of practice on retrieval were not markedly different between the groups. We found a significant main effect of group (HC vs. AD) × condition (B, T, and NT) and a significant difference in mean NT-B scores for the two groups. DISCUSSION: AD and HC groups did not differ essentially in their baseline memory abilities. Also, the instruction to focus on retrieval improved episodic memory performance in both groups. Crucially, control participants were able to suppress relational words in the NT condition supporting the critical effect of cognitive control processes over inhibition of retrieval. In contrast to this, the ability of AD patients to suppress retrieval was found to be impaired.

The Iowa Gambling Task in depression - what have we learned about sub-optimal decision-making strategies?

Our earlier study found patients with depression to show a preference for larger reward as measured by the Iowa Gambling Task (IGT). In this IGT version, larger rewards were associated with even larger consequent losses. In the light of the clinical markers defining depressive disorder, this finding might appear controversial at first. Performance of depressed patients on various decision-making (DM) tasks is typically found to be impaired. Evidence points toward reduced reward learning, as well as the difficulty to shift strategy and integrate environmental changes into DM contingencies. This results in an impaired ability to modulate behavior as a function of reward, or punishment, respectively. Clinical symptoms of the disorder, the genetic profile, as well as personality traits might also influence DM strategies. More severe depression increased sensitivity to immediate large punishment, thus predicting future decisions, and was also associated with higher harm avoidance. Anhedonic features diminished reward learning abilities to a greater extent, even predicting clinical outcome. Several questions about how these aspects relate remain to be clarified. Is there a genetic predisposition for the DM impairment preceding mood symptoms? Is it the consequence of clinical signs or even learned behavior serving as a coping strategy? Are patients prone to develop an aversion of loss or are they unable to sense or deal with reward or the preference of reward? Does the DM deficit normalize or is a persisting impairment predictor for clinical outcome or relapse risk? To what extent is it influenced by medication effects? How does a long-lasting DM deficit affect daily life and social interactions? Strikingly, research evidence indicates that depressed patients tend to behave less deceptive and more self-focused, resulting in impaired social DM. The difficulty in daily interpersonal interactions might contribute to social isolation, further intensifying depressive symptoms.

Personality traits and coping compensate for disadvantageous decision-making in long-term alcohol abstinence.

AIMS: High relapse rate and extreme difficulty to maintain abstinence are core characteristics of alcohol dependence (AD). Previous studies have demonstrated a persistent decision-making (DM) deficit in AD. We aimed to reveal specific personality features and stress-coping mechanisms presumed to compensate for ineffective DM skills. METHODS: Eighty-eight unmedicated patients with AD were enrolled. Intact general cognitive status was assured by IQ above 90. Forty-three patients had an average abstinence period of 12 weeks and were currently in an inpatient treatment program (short-term abstinence group, STA) and 45 patients were abstinent for at least 3 years (long-term abstinence group, LTA). The two groups were assessed using an integrative approach combining domains of DM, temperament and character dimensions and stress-coping measures. RESULTS: Both groups performed at chance level with no linear improvement tendency on the gambling task assessing DM adequacy. The LTA group scored significantly higher on scales of self-directedness and cooperativeness. In contrast, levels of harm avoidance, emotion-oriented coping and perceived stress were significantly higher in the STA group. CONCLUSION: Our findings provide new evidence for a persistent DM deficit with no learning effect in AD. Despite the deficit, alcohol-dependent patients can achieve LTA. STA patients perceive higher levels of stress and use non-adaptive coping strategies. We propose that the more adaptive personality profile of LTA patients contributes to the compensation of the trait-like DM deficit in alcoholism. These compensatory features represent promising new targets for preventive measures and therapeutic interventions in AD.

[Schizophrenia, environment and epigenetics]. / Szkizofrénia, környezet és epigenetika.

Psychotic, cognitive and affective symptoms defining schizophrenia may, though much less severe, manifest themselves in up to 10 to 20% of the general population. What explains the fact that in certain cases the symptoms require even constant medical supervision, while others are capable of living a normal life within social conventions? Which factors lead to the transition of mild, subclinical manifestations and vulnerability indicators towards the outburst of one of the most severe and depriving mental disorders? Genetic susceptibility is undoubtedly crucial. More recent research findings emphasize the modifying effect of specific environmental factors on gene expression. The gene-environment interplay may induce so-called epigenetic alterations which may manifest themselves over several generations. Future integrative, multi-dimensional and flexible schizophrenia research approaches focusing on the identification of neurobiological and cognitive outcomes are much needed to understand disease vulnerability, susceptibility mechanisms, periods and interactions. Research methods may differ, but our aim is common - establishing more effective diagnostic and therapeutic interventions.

Anesthesia for electroconvulsive therapy in early pregnancy.

Pharmacological treatment of major psychiatric conditions (eg, schizophrenia, bipolar disorder) is exceptionally difficult during pregnancy. Despite all efforts, medication-resistant life-threatening mental deterioration can emerge with the urgent need for rapid and effective intervention. In these cases, electroconvulsive therapy (ECT) may represent the only valid and safe therapeutic option. Here, we present the challenging medical case of a 31-year-old primigravida with a general medical history of obesity and hypertension, previously diagnosed with bipolar affective disorder, now presenting with severe, therapy-resistant manic agitation. Full symptomatic remission was achieved and preserved with ECT given between the 7th and 22nd gestational weeks, the pregnancy reached full term, and a healthy child was born by cesarean delivery performed because of preeclampsia. Although it is unusual to start ECT this early in pregnancy, with the thorough assessment of potential risk factors and preventive measures taken, it can be the most effective and presumably the least risky treatment approach. By delineating key aspects of both the psychiatric and anesthetic management of this case, we aim to highlight the importance of a close cooperation between all medical fields involved in clinical practice.