Treatment Of Affective Disorders Research Articles

Touch medicine: bridging the gap between recent insights from touch research and clinical medicine and its special significance for the treatment of affective disorders.

Interpersonal touch represents the primal sensory experience between humans, fostering social bonding from the cradle to the death bed. In recent decades "affective touch" has been intensely studied, stimulated by the discovery of a population of mechanosensitive unmyelinated C-tactile afferents in mammalian skin. A lack of touch in childhood is associated with negative consequences for psychosocial and physical health and the benefits of professional touch techniques in the prevention and treatment of various diseases have been shown over and over again in clinical studies. However, its application in mainstream clinical applications remains limited. To bridge the gap between recent discoveries in touch research and clinical medicine, we propose the establishment of a new discipline: 'Touch Medicine'. Here, we unfold the potential of Touch Medicine by focusing on the treatment of depression, which in our view is primarily a disorder of the lived body. Controlled studies and systematic reviews have demonstrated the antidepressant, anxiolytic and analgesic effects of specific massage techniques. Underlying mechanisms of action are currently under investigation, ranging from interoceptive, endocrinological, to stress-related or psychological underpinnings. Touch Medicine represents a novel interdisciplinary field connected to various medical specialities such as neonatology, pediatrics, pain medicine, neurology, psychiatry, and geriatrics - but also clinical psychology and psychosomatic medicine might benefit from the integration of these findings into their daily practice.

SIRT1 Coordinates Transcriptional Regulation of Neural Activity and Modulates Depression-Like Behaviors in the Nucleus Accumbens

BackgroundMajor depression and anxiety disorders are significant causes of disability and socioeconomic burden. Despite the prevalence and considerable impact of these affective disorders, their pathophysiology remains elusive. Thus, there is an urgent need to develop novel therapeutics for these conditions. We evaluated the role of SIRT1 in regulating dysfunctional processes of reward by using chronic social defeat stress to induce depression- and anxiety-like behaviors. Chronic social defeat stress induces physiological and behavioral changes that recapitulate depression-like symptomatology and alters gene expression programs in the nucleus accumbens, but cell type–specific changes in this critical structure remain largely unknown. MethodsWe examined transcriptional profiles of D1-expressing medium spiny neurons (MSNs) lacking deacetylase activity of SIRT1 by RNA sequencing in a cell type–specific manner using the RiboTag line of mice. We analyzed differentially expressed genes using gene ontology tools including SynGO and EnrichR and further demonstrated functional changes in D1-MSN–specific SIRT1 knockout (KO) mice using electrophysiological and behavioral measurements. ResultsRNA sequencing revealed altered transcriptional profiles of D1-MSNs lacking functional SIRT1 and showed specific changes in synaptic genes including glutamatergic and GABAergic (gamma-aminobutyric acidergic) receptors in D1-MSNs. These molecular changes may be associated with decreased excitatory and increased inhibitory neural activity in Sirt1 KO D1-MSNs, accompanied by morphological changes. Moreover, the D1-MSN–specific Sirt1 KO mice exhibited proresilient changes in anxiety- and depression-like behaviors. ConclusionsSIRT1 coordinates excitatory and inhibitory synaptic genes to regulate the GABAergic output tone of D1-MSNs. These findings reveal a novel signaling pathway that has potential for the development of innovative treatments for affective disorders.

Workshop report: Workshop on psychiatric prescribing and psychology testing and intervention in children and adults with Duchenne muscular dystrophy

This workshop aimed at summarising knowledge and key issues in psychiatric prescribing and psychological testing in children and adults with Duchenne muscular dystrophy (DMD). It comprised clinicians and patient representatives from the UK and the Netherlands. The following topics were discussed: a model for capturing the range of non-motor problems in the domains of cognition, learning, emotion and behaviour; psychosocial screening tools for use with children and adults; assessing neurocognitive functioning in children and adults; parent and teacher perspectives on psychosocial needs; and psychopharmacological treatment for affective disorders, anxiety disorders, obsessive compulsive disorder, attention deficit hyperactivity disorder (ADHD) and insomnia. Some key considerations included: the need for tools used to assess behavioural and psychosocial functioning to consider motor aspects in DMD; to understand more about working memory performance; the need for early interventions for automatisation problems, which affect reading and arithmetic; appropriate selection of tests for neuropsychology assessments; in schools, acknowledging the range of psychosocial risks and gathering evidence of psychosocial needs; the suitability of selective serotonin reuptake inhibitors for mood and anxiety disorders; the use of stimulant medications for ADHD; melatonin use for insomnia; the cautious use of benzodiazepines; and the need for improving pathways for psychosocial care.

Long-Term Impact of Early Life Stress on Serotonin Connectivity

BackgroundChronic childhood stress is a prominent risk factor for developing affective disorders, yet mechanisms underlying this association remain unclear. Maintenance of optimal serotonin (5-HT) levels during early postnatal development is critical for the maturation of brain circuits. Understanding the long-lasting effects of early life stress (ELS) on serotonin-modulated brain connectivity is crucial to develop treatments for affective disorders arising from childhood stress. MethodsUsing a mouse model of chronic developmental stress, we determined the long-lasting consequences of ELS on 5-HT circuits and behavior in females and males. Using FosTRAP mice, we cross-correlated regional c-Fos density to determine brain-wide functional connectivity of the raphe nucleus. We next performed in vivo fiber photometry to establish ELS-induced deficits in 5-HT dynamics and optogenetics to stimulate 5-HT release to improve behavior. ResultsAdult female and male mice exposed to ELS showed heightened anxiety-like behavior. ELS further enhanced susceptibility to acute stress by disrupting the brain-wide functional connectivity of the raphe nucleus and the activity of 5-HT neuron population, in conjunction with increased orbitofrontal cortex (OFC) activity and disrupted 5-HT release in medial OFC. Optogenetic stimulation of 5-HT terminals in the medial OFC elicited an anxiolytic effect in ELS mice in a sex-dependent manner. ConclusionsThese findings suggest a significant disruption in 5-HT–modulated brain connectivity in response to ELS, with implications for sex-dependent vulnerability. The anxiolytic effect of the raphe–medial OFC circuit stimulation has potential implications for developing targeted stimulation-based treatments for affective disorders that arise from early life adversities.

Lithium treatment for affective disorders: Exploring the potential of salivary therapeutic monitoring

Lithium is one of the most effective medications for treatment-resistant depression and bipolar disorder. However, lithium has a narrow therapeutic window: overdosing can lead to life-threatening lithium intoxication while underdosing results in a lack of desired therapeutic effects. Therefore, lithium treatment requires close monitoring with regular laboratory assessments of blood serum concentrations. An alternative method for monitoring lithium at home would increase the safety and empowerment of patients. In our project, we are investigating the potential of saliva as a readily accessible medium. We are exploring a) the best method for collecting and processing saliva, b) methods to measure salivary lithium levels, and c) the correlation between blood serum and saliva concentrations of lithium, and influencing factors; with the aim to develop a Point-of-care home testing device.

Lithium treatment for affective disorders in old age

Lithium is considered the gold standard for the treatment of bipolar affective disorder for the prevention of recurrence of manic and depressive episodes and for augmentation treatment in unipolar severe depressive episodes. The indications for treatment with lithium do not differ for older or younger patients. Nevertheless, there are anumber of aspects to be considered with respect to drug safety in the group of old patients. The aim was to give an overview of the current literature on lithium treatment in old age and from this to derive recommendations for action. Aselective literature review on lithium treatment in old age was conducted to answer questions on drug safety, monitoring (particularly with respect to comorbidities) and potential alternatives to lithium. Lithium is an effective and, if used correctly, safe drug also in old people; however, with respect to somatic comorbidities that increase with age, special caution is required when using lithium in order to prevent nephropathy and intoxication.

If it Ain't Broke, Don't Fix it: Positive Versus Negative Emotion Regulation in Daily Life and Depressive Symptoms

BackgroundDespite the importance of positive emotions for affective psychopathology, prior research primarily focused on negative emotion regulation. To address this gap, this ecological momentary assessment study compared a broad set of emotion regulation strategies in the context of positive versus negative emotions regarding their effectiveness and associations with depressive symptoms. MethodsWe analyzed data from 1066 participants who were notified five times daily for seven consecutive days to complete a smartphone survey assessing their predominant emotions, strategies to regulate them, and subsequent emotional outcomes. ResultsFindings show that the effectiveness of most regulation strategies depended on whether the emotional context was positive or negative. While acceptance and savoring predicted improved emotional outcomes across emotional contexts, reappraisal and problem-solving were associated with deteriorated emotional outcomes and increased depressive symptoms when regulating positive but not negative emotions. LimitationsFuture studies should replicate our findings in demographically and culturally diverse clinical samples to improve generalizability. ConclusionThese results emphasize that strategies effective for regulating negative emotions may be less helpful in the context of positive emotions. Thus, context-specific interventions may be a promising approach to improve the treatment of affective disorders.

Use of lithium in psychiatric, viral and neurological disorders - a review

Introduction: Lithium is one of the longest used drugs in psychiatry and is currently a mainstay in the long-term prophylaxis of bipolar disorder, preventing recurrent manic and depressive episodes. It also remains an important drug in the treatment of acute episodes of mania and depression. Out of the normothymic drugs, lithium has the greatest effect in preventing suicidal behavior. It also exhibits antiviral activity and in recent years evidence has also accumulated of the drug's neuroprotective properties. 
 Aim of the study: The aim was to collect and analyze publications on the use of lithium in affective disorders, dementia and viral diseases, as well as its effect on reducing suicidal tendencies.
 Materials and Methods: The literature available in the PubMed database was reviewed, using the key words: "lithium"; "bipolar disorder"; "mania", "depression"; "suicidal risk", "side effects".
 Results: Chronic use of lithium in patients with bipolar disorder has an effect on preventing recurrence of manic and depressive episodes and can successfully last for 40 years or longer. Studies support the theory that long-term lithium pharmacotherapy has a significant impact on preventing suicidal tendencies among patients with affective disorders. In recent years, the antiviral and neuroprotective properties of the drug have also become known. Despite the rather high risk of overdose, as well as the occurrence of numerous side effects, lithium is still very often used in the treatment of affective disorders due to its high efficacy.
 Conclusions: Lithium has been one of the mainstays of psychopharmacology for several decades and is a precursor to mood-stabilizing drugs. In recent years evidence has also been collected for its potential use in non-psychiatric conditions. Conducting further research on lithium will certainly allow for wider use of the drug and a more thorough understanding of its mechanism of action.

Mizán of Affect in Material v. Metaphysical Models of Human Consciousness

From the viewpoint of the description of the human reality in the Bahá’í authoritative texts, the essence of a human being is the soul, a metaphysical reality from which emanate all our distinctively human capacities. Unlike materialist views of the human reality, the Bahá’í teachings assert that our essence—the spiritual “self”—takes its beginning during the process of conception, whereupon it associates with the body so long as the physical temple remains capable of manifesting the reality and powers of the soul. Once the body/brain deceases, the soul dissociates from this relationship and exists and functions and progresses eternally. This hypothesis in no way diminishes the importance of a healthy brain as essential to our physical, intellectual, and spiritual development; indeed, it posits the brain as a transceiver by means of which the self manifests the soul’s condition and development in action, speech, and comportment. Therefore, when the brain becomes dysfunctional, whether through trauma or mental illness, the transparency of the soul’s relation to reality ceases. This paper explores the implications of this relationship for our understanding of emotion and presents a model for understanding the function of emotion as providing us essential feedback on, and guidance for, our lives, feedback whose ultimate purpose is to help us better calibrate our approach to spiritual growth. Given the brain-as-transceiver model, this emotional feedback is reliable only so long as the brain remains transparent in this systematic relationship. The paper suggests ways in which the model could inform approaches to treatment for affective disorders.

Polydatin Alleviates Chronic Stress-Induced Depressive and Anxiety-like Behaviors in a Mouse Model.

We aimed to investigate whether polydatin could suppress stress-induced depression- and anxiety-like behaviors in a mouse model. Mice were divided into the control group, chronic unpredictable mild stress (CUMS) exposure group, and CUMS mice treated with polydatin group. Following CUMS exposure and polydatin treatment, mice were subjected to behavioral assays to assess depressive-like and anxiety-like behaviors. Synaptic function was determined by the levels of brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD95), and synaptophysin (SYN) in the hippocampus and cultured hippocampal neurons. The number and length of dendrites were assessed in cultured hippocampal neurons. Finally, we investigated the effect of polydatin on CUMS-induced inflammation and oxidative stress in the hippocampus by measuring inflammatory cytokine levels, oxidative stress markers such as reactive oxygen species, glutathione peroxidase, catalase, and superoxide dismutase, as well as components of the Nrf2 signaling pathway. Polydatin alleviated CUMS-induced depressive-like behaviors in forced swimming, tail suspension and sucrose preference tests, and anxiety-like behaviors in marble-burying and elevated plus maze tests. Polydatin increased the number and length of dendrites of cultured hippocampal neurons from mice exposed to CUMS and alleviated CUMS-induced synaptic deficits by restoring BDNF, PSD95, and SYN levels in vivo and in vitro. Importantly, polydatin inhibited CUMS-induced hippocampal inflammation and oxidative stress and suppressed the activation of NFκB and Nrf2 pathways. Our study suggests that polydatin may be an effective drug for the treatment of affective disorders through inhibiting neuroinflammation and oxidative stress. Our current findings warrant further study to investigate the potential clinical application of polydatin.

Sigma Receptors – Literature Review

The paper reviewed data confirming that sigma1 receptors modulate NMDA neurotransmission. It has been established that they can enhance the spontaneous release of glutamate in the hippocampus, potentiate the release of a neurotrophic factor induced by glutamate, and also participate in the processes of synaptic restructuring (facilitation of long-term potentiation) in the mammalian hippocampus. But the use of high doses of agonists or antagonists of sigma1 receptors in animal models does not have any effect on memory modulation or learning processes in control animals. These findings indicate that sigma1 receptors do not affect the physiological (normal) processes of memory consolidation. The effects of sigma1 receptors considered in the work speak of effects on cognitive processes only in conditions of neurotransmitter imbalance. In a number of works, with the participation of various experimental models, the possible involvement of sigma1 receptors in the processes of memory recovery was revealed. A real breakthrough in the treatment of affective disorders is being made in our time due to an increasingly detailed study of the mechanisms of intracellular receptor structures and chaperone proteins, in particular, sigma receptors. By acting on these mechanisms, side effects in the treatment of depression, inevitable with the use of traditional antidepressants, can be avoided. Also, thanks to modern drugs based on interaction with sigma receptors, it is possible to influence neurogenesis, learning and memory processes. Thus, the sigma-1 receptor is an extremely promising object that can be considered as a potential therapeutic target for the treatment of neuropathological diseases

Mental ecology in the structure of the COVID-19 pandemic (review)

Currently, sufficient data are available on the negative impact of the COVID-19 pandemic and its socio-economic consequences on human mental health and the mental ecology in general. The success of public health strategies to cope with pandemics is largely determined by psychological factors and the mental values prevailing in the community at large.
 The present review systematized the psychological response features of various social, professional, and national representatives during the COVID-19 period within the framework of the main mental ecology provisions.
 The review methodology was based on the World Health Organization documents and open sources of the Scopus and Web of Science databases on the population's mental health under COVID-19 pandemic conditions.
 A significant increase in adaptive and anxiety-depressive disorders was noted during the COVID-19 pandemic. Among the specific mental phenomena associated with the pandemic, coronaphobia, COVID-19-stress syndrome, covid-dissidence manifestations with the involvement of conspiracy theories, and mythological thinking were identified. The negative infodemia impact on the mental ecology, as well as the adherence to anti-epidemic measures and readiness for vaccination, were also established. Negative trends were demonstrated in communities where the maximum infection and death risk were associated with low adherence to the epidemiological measures and refusal to vaccination.
 It was revealed that belonging to certain social or professional groups largely determines a person's behavior in relation to a new coronavirus infection within the framework of accepted social norms. Based on the analysis of a large domestic and international data number on the impact of the COVID-19 pandemic emergency on the human psyche, its significant adverse contribution to the overall mental ecology was noted. The necessity of developing special therapeutic and psycho-prophylactic programs aimed at coping with the stress pandemic impact and treatment of affective disorders, countering infodemia, and strengthening behavioral patterns to maintain mental health and personal well-being is substantiated.

State-Trait Anxiety Condition and Its Affecting Factors in Pregnant Women Linked to the COVID-19 Pandemic.

This study intends to address the COVID-19 pandemic process with specific regard to pregnant women, aiming to determine their state-trait anxiety levels. The study has a quantitative design. Ethical permissions were obtained, data were collected digitally, and power analysis was performed for sample size. The sample size was calculated as 656 pregnant women. In the collection of the data, the Personal Information Form, and the State-Trait Anxiety Inventory (STAI) were used. In our study, the majority of pregnant women (86.3%) were concerned about the pandemic process, with more than half thinking that their pregnancy (62.9%) and delivery processes would be affected (66.2%). In the meantime, 60.2% of the pregnant women postponed their health checks and they indicated being most concerned about their babies (57.1%). In 51.2% of the pregnant women, the state anxiety levels were low, and 89.8% of the trait anxiety levels were moderate. In crisis periods like the pandemic, pregnant women are among the priority groups. Screening, prevention, early diagnosis, and treatment of affective disorders in the prenatal period are important for maternal and fetal health.

An Exploratory Feasibility Study of Incorporating Volunteering Into Treatment for Adolescent Depression and Anxiety.

Community volunteering is an under-utilized, at least under-researched, strategy to supplement existing treatment for affective disorders. We present findings from a feasibility study incorporating community volunteering into clinical treatment for depression and anxiety among adolescents and young adults. This exploratory pilot study had four aims: to investigate recruitment feasibility; to describe participants’ experiences with volunteering; to explore psychosocial assets by which volunteering might decrease depressive and anxiety symptoms; and to document preliminary changes in mental health outcomes before and after the volunteering intervention. Interviews and surveys were employed with participants (N = 9; ages 14–20, Mage = 16 years old; eight women and one man) newly diagnosed with: mild to moderate depression (single episode), mild to moderate anxiety, or adjustment disorder. Recruitment was feasible overall, successes and challenges are discussed. Experiences with volunteering were very positive. Qualitative findings revealed perceived positive effects of volunteering on mood and well-being such as helping with social anxiety and being a positive distraction. Qualitative findings revealed several psychosocial assets that improved related to volunteering (e.g., sense of purpose/meaning and sense of community). On average, participants reported a 19% decrease in depressive symptoms from the pre-survey (before volunteering) to the post-survey (after volunteering). Although more research is warranted, the implication of this study for practicing psychologists treating adolescents and young adults for mild to moderate depression and/or anxiety is that they may wish to consider incorporating community volunteer activities into treatment. Volunteering was a desirable activity for interested participants in treatment for affective disorders.

Functional ultrasound imaging of recent and remote memory recall in the associative fear neural network in mice

Emotional learning and memory are affected in numerous psychiatric disorders. At a systems level, however, the underlying neural circuitry is not well defined. Rodent fear conditioning (FC) provides a translational model to study the networks underlying associative memory retrieval. In the current study, functional connectivity among regions related to the cue associative fear network were investigated using functional ultrasound (fUS), a novel imaging technique with great potential for detecting neural activity through cerebral blood flow. Behavioral fear expression and fUS imaging were performed one and thirty-one days after FC to assess recent and remote memory recall. Cue-evoked increases in functional connectivity were detected throughout the amygdala, with the lateral (LA) and central (CeA) amygdalar nuclei emerging as major hubs of connectivity, although CeA connectivity was reduced during remote recall. Hippocampal and sensory cortical regions displayed heightened connectivity with the LA during remote recall, whereas interconnectivity between the primary auditory cortex and temporal association areas was reduced. Subregions of the prefrontal cortex exhibited variable changes, where prelimbic connectivity with the amygdala was refined while specific connections between the infralimbic cortex and amygdalar subregions emerged during remote memory retrieval, a signature of extinction memory. Moreover, freezing behavior positively correlated with functional connectivity between hubs of the associative fear network, suggesting that emotional response intensity reflected the strength of the cue-evoked functional network. Overall, our data provide evidence of the functionality of fUS imaging to investigate the neural dynamics of memory retrieval, applicable in the development of innovative treatments for affective disorders.

КЛИНИКА И ЛЕЧЕНИЕ АЛКОГОЛЬНОЙ ЗАВИСИМОСТИ У ПАЦИЕНТОВ С АГРЕССИВНЫМ И АУТОАГРЕССИВНЫМ ПОВЕДЕНИЕМ (ОБЗОР ЛИТЕРАТУРЫ)

This review article is an attempt to generalize and systematize the knowledge on the issues of affective disorders accompanied by the acts of aggression in the context of alcohol addiction. Achieving this goal required the consistent implementation of a number of tasks, and namely, a theoretical review of the material accumulated in recent years within the framework of the topic under study, its subsequent analysis and meaningful generalization. The methods of theoretical analysis and synthesis of the obtained material were used in the given work. The indicated topic of the review seems to be relevant due to the fact that, in modern psychiatry, narcology and related specialties, much attention is currently paid to aggressiveness as a stable personality trait to show aggression in all its forms. The reason for such close attention to aggressiveness is high probability of lethality in people of working age due to aggressive or autoaggressive actions. As living standards, well-being, and, subsequently, health care system improve, people are less likely to die of urgent pathology, most diseases respond to treatment and do not lead to sudden death of a patient. The situation is different with external causes of death, the lion’s share of them being caused precisely by aggressive actions in their various forms. The latter in one way or another are often interconnected with alcoholization of an individual: acts of aggression are either provoked by alcohol intoxication, or may result from an already formed dependence syndrome. The special features of the development, clinical pattern and treatment of affective disorders in alcohol dependence syndrome, accompanied by aggression and autoaggression have been considered in the present paper. As a result of the review, the main concepts of the development of affective disorders accompanied by the acts of aggressive behavior in the alcohol dependence syndrome have been identified; the main mechanisms of the occurrence of aggression in alcohol-dependent patients have been indicated; the key points of pharmacotherapy influence have been determined, and namely, the use of normotimic drugs, the most rational of which, in terms of the effectiveness-adverse reactions ratio, are oxcarbazepine and topiramate, as well as the use of drugs of the selective serotonin reuptake inhibitors (SSRIs) group, as the most relevant when choosing antidepressant therapy for alcohol-dependent patients. The effectiveness of the long-term therapy with disulfiram has been determined in cases of ensuring compliance control. The relevance of the proper use of lithium salts in the treatment of this group of patients has been designated.

What do experimental animal models of mood disorders tell clinicians about influence of probiotics on the gut-brain axis?

Abstract It is commonly pointed out that enteric microbiota have a significant impact on the behavioral and neurophysiological parameters relevant to brain-gut axis disorders. Accordingly, many data have demonstrated that probiotics can alter the central nervous system function via this gut-brain axis and commensal bacteria consumption can ameliorate stress-related neuropsychiatric disorders. Thus, modulating the enteric microbiota is increasingly considered a new therapeutic approach for these disorders, although so far there is a lack of reliable pre-clinical and clinical data confirming the usefulness of probiotics in the treatment of affective disorders. In this review, we discuss various mechanisms linking specific probiotic bacteria with behaviors related to anhedonia and the exact mechanisms of their action, including data provided by using animal models and tests. Finally, we point to potential clinical impact resulting from future studies investigating the gut-brain axis activity with respect to the efficacy of probiotic treatment of mental disorders.

Emotional Reactivity, Emotion Regulation, and Social Emotions in Affective Disorders

Abstract. Affective disorders, specifically Major Depressive Disorder and Bipolar Disorders, show high prevalence, relapse rates, and a high likelihood to develop a chronic course. For the past two decades, research has investigated the neural correlates of emotion processing and emotion regulation in patients with affective disorders. Putative underlying causal mechanisms of dysregulated affect have been informed by knowledge from the intersection of neuroimaging and clinical psychology. More recent investigations also consider processing the role of mostly negative, self-blaming social emotions, which have been linked to treatment resistance and, hence, provide a prolific target for intervention. Several psychotherapeutic treatment approaches already focus on emotion, and here specific knowledge about the mechanisms underlying persistent changes in affect bears the potential to improve the treatment of affective disorders. In this narrative review, we delineate why and how our insights into the neural correlates of emotion processing and regulation can be applied to the treatment of patients with affective disorders.

Transcranial Direct Current Stimulation Reduces Anxiety, Depression and Plasmatic Corticosterone in a Rat Model of Atypical Generalized Epilepsy

Affective disorders (i.e. anxiety and depression) are commonly observed in patients with epilepsy and induce seizure aggravation. Animal models of epilepsy that exhibit affective disorder features are essential in developing new neuromodulatory treatments. GEAS-W rats (Generalized Epilepsy with Absence Seizures, Wistar background) are an inbred model of generalized epilepsy showing spontaneous spike-wave discharges concomitant with immobility. Transcranial Direct Current Stimulation (tDCS) is a safe non-invasive neuromodulatory therapy used to modulate dysfunctional circuitries frequently and successfully applied in affective disorders for symptom alleviation. Here we investigated anxiolytic and antidepressant effects of tDCS in GEAS-W rats and the role of corticosterone as a possible mechanism of action. GEAS-W and Wistar rats were randomly divided into control, sham-tDCS and active-tDCS groups. Both tDCS groups received 15 sessions of sham or active-tDCS (1 mA, cathode). Behavioural tests included the Open Field and Forced Swimming tests followed by corticosterone analysis. We observed a main effect of treatment and a significant treatment by strain interaction on anxiety-like and depressive-like behaviours, with active-tDCS GEAS-W rats entering the center of the open field more often and showing less immobility in the forced swimming test. Furthermore, there was a main effect of treatment on corticosterone with active-tDCS animals showing marked reduction in plasmatic levels. This study described preclinical evidence to support tDCS treatment of affective disorders in epilepsy and highlights corticosterone as a possible mechanism of action.

Ketamine and other N-methyl-D-aspartate receptor modulators in treatment of depression

Since the first successful ketamine application in treatment-resistant depressive patients, the newly developed pharmaceutical class of rapid-acting antidepressants has been intensively investigated. The underlying mechanism of action by influencing the glutamatergic neurotransmission via amodulation of N‑methyl-D-aspartate (NMDA) receptors, represents acompletely new and promising interventional strategy in the treatment of affective disorders. In this very dynamic field, Spravato® (esketamine) is so far the only approved drug; however, many other substances are currently in the development and evaluation processes. This narrative review provides acritical overview of the most important substances, target structures and developmental stages of NMDAR modulators.