A Narrative Review on REM Sleep Deprivation: A Promising Non-Pharmaceutical Alternative for Treating Endogenous Depression.

Endogenous depression represents a severe mental health condition projected to become one of the worldwide leading causes of years lived with disability. The currently available clinical and non-clinical interventions designed to alleviate endogenous depression-associated symptoms encounter a series of inconveniences, from the lack of intervention effectiveness and medication adherence to unpleasant side effects. In addition, depressive individuals tend to be more frequent users of primary care units, which markedly affects the overall treatment costs. In parallel with the growing incidence of endogenous depression, researchers in sleep science have discovered multiple links between rapid eye movement (REM) sleep patterns and endogenous depression. Recent findings suggest that prolonged periods of REM sleep are associated with different psychiatric disorders, including endogenous depression. In addition, a growing body of experimental work confidently describes REM sleep deprivation (REM-D) as the underlying mechanism of most pharmaceutical antidepressants, proving its utility as either an independent or adjuvant approach to alleviating the symptoms of endogenous depression. In this regard, REM-D is currently being explored for its potential value as a sleep intervention-based method for improving the clinical management of endogenous depression. Therefore, this narrative review represents a comprehensive inventory of the currently available evidence supporting the potential use of REM-D as a reliable, non-pharmaceutical approach for treating endogenous depression, or as an adjuvant practice that could improve the effectiveness of currently used medication.

[Hysteroform depressions in young female patients]. / Isteroformnye depressii u patsientok molodogo vozrasta.

OBJECTIVE: To study the features of the psychopathological structure of depression in young women with hysteroform symptoms, as well as the features of auto-aggressive non-suicidal and suicidal behavior in these conditions. MATERIAL AND METHODS: The results of a clinical/psychopathological examination of 50 female adolescent patients, aged 16 to 25 years, with endogenous depressions with one of the following ICD-10 diagnosis: (F31.3-4, F34.0, F21.3-4 + F31.3-4, F60.X + F31.3-4) and prevail of hysteroform symptoms in the form of conversion/dissociative disorders in their clinical picture were analyzed. RESULTS: Depression was characterized by an acute onset due to a traumatic situation represented by difficulties in personal or family relationships (36%, n=18), bereavement reactions (28%, n=14) and problems in school/work (22%, n=11). The depressive triad had an erased character, the thymic component was represented by a variable character of affect with a predominance of dysphoria (38%, n=19) and anxiety (32%, n=16). The ideational component of the triad was detected in 50% of cases (n=25), while in 38% (n=19) there was ideational acceleration. In 44% of cases (n=22), dissociative disorders were noted in the form of delusional fantasizing, represented by symptoms close to the «multiple personality¼ phenomenon. Often there were obsessional disorders (58%, n=29), anxiety-phobic symptoms in the form of panic attacks (46%, n=23), isolated phobias (28%, n=14), social phobias (30%, n=15). In 40% of cases (n=20) the formation of overvalued hypochondriacal ideas was noted. Non-suicidal self-harm occurred in 41 patients (82%), in 42% of cases (n=21) the patients made suicide attempts that were distinguished by a low danger to life. CONCLUSION: Hysteroform depressions in girls are characterized by polymorphism of the psychopathological structure, erosion of the depressive triad, originality of the clinical picture of dissociative disorders, presence of comorbid disorders, and frequent, but with a low danger to life suicidal attempts.

[The role of premorbid personality in the genesis of psychopathological symptomatology in patients with organic anxiety-depressive disorder, schizophrenia and endogenous depression]. / Rol' lichnosti premorbidnogo perioda v geneze psikhopatologicheskoi simptomatiki u bol'nykh organicheskim trevozhno-depressivnym rasstroistvom, shizofreniei i endogennoi depressiei.

OBJECTIVE: The current study has been performed in order to find the influence of premorbid personality traits on psychopathological symptomatology in patients with endogenous depression (ED), schizophrenia and organic anxiety-depressive disorder (OADD). MATERIAL AND METHODS: 191 patients (57 with OADD,93 with schizophrenia and 41 with ED) were included into study. The Munich personality test (MPT) and Toronto alexithymia scale (TAS) were used for the evaluation of premorbid personality; the SCL-90 - for the assessment of psychopathological structure. The multiple regression analysis has been used for the assessment of relationships between premorbid personality constructs and psychopathological status separately in each diagnostic group. RESULTS: The SCL-90 scores were maximal in ED and schizophrenia patients and minimal in OADD patients (p<0.047). Comparison of premorbid personality constructs revealed the maximal values of neuroticism and motivation in ED (p=0.005), rigidity, extraversion and esoteric tendencies in schizophrenia (p<0.007) and frustration tolerance, tendency to isolation and alexithymia in OADD (p<0.02). Regression analysis revealed the positive dependence of anxiety and depression on alexithymia score (TAS-26) (p<0.002) and negative dependence on frustration tolerance in ED and schizophrenia patients (p<0.016). The negative dependence of anxiety Zung scale score on frustration tolerance in OADD patients also has been observed (p=0.003). The rigidity construct has not stochastically significant relationships neither with anxiety, nor with depression in none diagnostic group. CONCLUSION: The analysis revealed the predominance of certain personality constructs in each of the diseases, with a universal negative effect of alexithymia and a positive effect of frustration tolerance in anxiety-depressive disorders of any etiology.

Serum NLRP3 Inflammasome and BDNF: Potential Biomarkers Differentiating Reactive and Endogenous Depression.

Background: The highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions. Methods: The clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay. Results: The NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression. Conclusion: Our findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.

[Comparison of premorbid personality and psychopathological structure of some anxiety-affective disorders]. / Sravnenie lichnosti premorbidnogo perioda i psikhopatologicheskoi struktury nekotorykh trevozhno-depressivnykh sostoyanii.

OBJECTIVE: To compare premorbid personality and structure of psychopathological status of organic anxiety-depressive disorder in comparison with endogenous depression and anxiety neurotic disorders. MATERIAL AND METHODS: One hundred and twelve patients, including 57 with organic anxiety-depressive disorder (OADD), 41 with endogenous depression (ED) and 14 with anxiety neurotic disorder (AND) were studied. have been included into the study. The Munich personality test (MPT) and Toronto alexithymia scale (TAS) were used for the evaluation of premorbid personality. Psychopathological structure was assessed with SCL-90. The correlation between premorbid personality and current structure of psychopathological states was studied. RESULTS: OADD patients were characterized by higher scores of frustration tolerance, rigidity and isolation tendency and less expression of neuroticism, esoteric tendencies and motivation compared with ED. In the AND patients, the values of neuroticism and motivation predominated compared with OADD, while the value of frustration tolerance was higher in OADD. A correlation analysis revealed the strong positive relationships of alexithymia, neuroticism and isolation tendency with depression, anxiety, somatization, obsessions and sensitivity in AND group. CONCLUSION: The comparison of correlations between OADD and ED revealed no significant differences. It implies the similarity in the pathogenesis of OADD and ED.

[Endogenous depressions with religious experience]. / Endogennye depressivnye sostoyaniya s religioznymi perezhivaniyami.

OBJECTIVE: To identify the specifics of psychopathology and phenomenology of religious experience in depressed patients, for early diagnosis of mental disorders masked by a «religious facade¼, and prevention of suicidal activity. MATERIAL AND METHODS: The study included 115 patients (41 men, 74 women) with depression contained religious distress in affective disorders (38 observations) and schizophrenia (77 observations), F31.3, F31.4, F32.1, F32.2, F33.1, F33.2 and F20.0, F20.4, F21 according to ICD-10. RESULTS: According the psychopathological structure of depressive states, five types of depression were identified. The predominant type was melancholic depression (61%). Based on characteristics of religious experience, types of depressions were distinguished as follows: with congruent religious ideas of guilt and sinfulness; with the loss of «living¼ faith, God-forsakenness; with overvalued doubts about the choice of faith; and with «spiritual hypochondria¼. CONCLUSION: Mental disorders, in particular depressive states, which have a religious «facade¼ often remain unrecognized due to the specific religious content, which often leads to severe and sometimes irreversible consequences as suicidal activity. Thus, these conditions require early diagnosis and specific approaches to the treatment.

[The status of leukocyte-inhibitory system of inflammation in different age groups of patients with endogenous depression]. / Status leikotsitarno-ingibitornoi sistemy vospaleniya pri endogennykh depressiyakh u patsientov raznykh vozrastnykh grupp.

OBJECTIVE: The comparison of inflammatory markers in different age groups of patients with endogenous depression and correlation of immunological parameters with the clinical features of depression. MATERIAL AND METHODS: The study included 140 patients with endogenous depression (ED) (F21, F31-F34, ICD-10) aged 15 to 82 years (39.8±23 years), including 55 patients of adolescent age (18.9±2.8 years), 30 middle-aged patients (38.7±10.3 years) and 55 elderly patients (69.1±7.1 years). The total duration of the disease differed from 5 months to 45 years. Psychometric assessment of patients was carried out using HDRS. The control groups consisted of 143 healthy people aged 16 to 75 years. The activity of inflammatory markers leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI), their ratio (leukocyte-inhibitory index, LII), the levels of antibodies to S100B and myelin basic protein (MBP) were determined in blood. RESULTS: Three immunological clusters were identified that correspond to different clinical variants of ED. A pro-inflammatory status with an activation of the leukocyte-inhibitory system is characteristic of 52.9% of patients (cluster 1). The clinical feature of this status is predominantly «classic¼ ED in the form of anxious, anxious-melancholic or anxious-apathetic depression without pronounced negative symptoms. Two other clusters are characterized by the imbalance of leukocyte-inhibitory system associated with insufficient a1-PI activity (cluster 2) and with insufficient LE activity (cluster 3). A common clinical feature of such ED is an atypical course with the predominance of apathetic-adynamic and dysphoric depression, the presence of negative disorders and a poor prognosis. The imbalance of leukocyte-inhibitory system associated with insufficient LE activity is typical mainly for elderly patients and is characterized by a longer duration of disease. CONCLUSIONS: The status of leukocyte-inhibitory system of inflammation is correlated with the clinical features of ED in different age groups of patients. LII can be considered as an additional paraclinical criterion for differential diagnosis and prognosis of ED.

Identifying Subjective Symptoms Associated with Psychomotor Disturbance in Melancholia: A Multiple Regression Analysis Study.

PURPOSE: Melancholia has recently been re-evaluated, because patients with major depressive disorder (MDD) were found to be heterogeneous. However, the DSM-5 criteria for melancholia (DSM-MEL) have been criticized, because of the difficulty in clearly distinguishing between melancholic and non-melancholic depression using DSM-MEL. Psychomotor disturbance (PMD) is one of the most important, as well as one of the only measurable symptoms of melancholia. Parker et al developed the CORE measure, which assesses PMD as a behavioral characteristic. The aim of our study was to objectively identify the subjective symptoms of melancholia by analyzing the symptoms associated with PMD. PATIENTS AND METHODS: A total of 106 participants with MDD were examined by psychiatrists. Multiple regression analysis was performed in which the total CORE score was the dependent variable, and items of the DSM-MEL and historically suggested melancholic features were independent variables. RESULTS: The following five independent variables were able to predict the total CORE score: 1) feelings of having lost feeling, 2) depressive delusions, 3) perplexity, 4) indecisiveness, and 5) no aggression against others. These five variables were more strongly associated with the total CORE score than the DSM-MEL. LIMITATION: The major limitation of this study was that when choosing non-DSM melancholic signs and symptoms, we did not comprehensively evaluate and select the symptoms but chose items that are clinically important. CONCLUSION: We identified five subjective symptoms that were associated with PMD. These five symptoms may be clinically useful as diagnostic criteria for melancholia.

Atypical depression and non-atypical depression: Is HPA axis function a biomarker? A systematic review.

BACKGROUND: The link between the abnormalities of the Hypothalamic-pituitary-adrenal (HPA) axis and depression has been one of the most consistently reported findings in psychiatry. At the same time, multiple studies have demonstrated a stronger association between the increased activation of HPA-axis and melancholic, or endogenous depression subtype. This association has not been confirmed for the atypical subtype, and some researchers have suggested that as an antinomic depressive subtype, it may be associated with the opposite type, i.e. hypo-function, of the HPA-axis, similarly to PTSD. The purpose of this systematic review is to summarise existing studies addressing the abnormalities of the HPA-axis in melancholic and/or atypical depression. METHOD: We conducted a systematic review in the literature by searching MEDLINE, PsycINFO, OvidSP and Embase databases until June 2017. The following search items were used: "hypothalamic-pituitary-adrenal" OR "HPA" OR "cortisol" OR "corticotropin releasing hormone" OR "corticotropin releasing factor" OR "glucocorticoid*" OR "adrenocorticotropic hormone" OR "ACTH" AND "atypical depression" OR "non-atypical depression" OR "melancholic depression" OR "non-melancholic depression" OR "endogenous depression" OR "endogenomorphic depression" OR "non-endogenous depression". Search limits were set to include papers in English or German language published in peer-reviewed journals at any period. All studies were scrutinized to determine the main methodological characteristics, and particularly possible sources of bias influencing the results reported. RESULTS: We selected 48 relevant studies. Detailed analysis of the methodologies used in the studies revealed significant variability especially regarding the samples' definition comparing the HPA axis activity of melancholic patients to atypical depression, including healthy controls. The results were subdivided into 4 sections: (1) 27 studies which compared melancholic OR endogenous depression vs. non-melancholic or non-endogenous depression or controls; (2) 9 studies which compared atypical depression or atypical traits vs. non-atypical depression or controls; (3) 7 studies which compared melancholic or endogenous and atypical depression subtypes and (4) 5 studies which used a longitudinal design, comparing the measures of HPA-axis across two or more time points. While the majority of studies did confirm the association between melancholic depression and increased post-challenge cortisol levels, the association with increases in basal cortisol and basal ACTH were less consistent. Some studies, particularly those focusing on reversed vegetative symptoms, demonstrated a decrease in the activity of the HPA axis in atypical depression compared to controls, but the majority did not distinguish it from healthy controls. CONCLUSIONS: In conclusion, our findings indicate that there is a difference in the activity of the HPA-axis between melancholic and atypical depressive subtypes. However, these are more likely explained by hypercortisolism in melancholia; and most often normal than decreased function in atypical depression. Further research should seek to distinguish a particular subtype of depression linked to HPA-axis abnormalities, based on symptom profile, with a focus on vegetative symptoms, neuroendocrine probes, and the history of adverse childhood events. New insights into the dichotomy addressed in this review might be obtained from genetic and epigenetic studies of HPA-axis related genes in both subtypes, with an emphasis on the presence of vegetative symptoms.

Diagnosing and treating depression in epilepsy.

At least one third of patients with active epilepsy suffer from significant impairment of their emotional well-being. A targeted examination for possible depression (irrespective of any social, financial or personal burdens) can identify patients who may benefit from medical attention and therapeutic support. Reliable screening instruments such as the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) are suitable for the timely identification of patients needing help. Neurologists should be capable of managing mild to moderate comorbid depression but referral to mental health specialists is mandatory in severe and difficult-to-treat depression, or if the patient is acutely suicidal. In terms of the therapeutic approach, it is essential first to optimize seizure control and minimize unwanted antiepileptic drug-related side effects. Psychotherapy for depression in epilepsy (including online self-treatment programs) is underutilized although it has proven effective in ten well-controlled trials. In contrast, the effectiveness of antidepressant drugs for depression in epilepsy is unknown. However, if modern antidepressants are used (e.g. SSRI, SNRI, NaSSA), concerns about an aggravation of seizures and or problematic interactions with antiepileptic drugs seem unwarranted. Epilepsy-related stress ("burden of epilepsy") explains depression in many patients but acute and temporary seizure-related states of depression or suicidality have also been reported. Limbic encephalitits may cause isolated mood alteration without any recognizable psychoetiological background indicating a possible role of neuroinflammation. This review will argue that, overall, a bio-psycho-social model best captures the currently available evidence relating to the etiology and treatment of depression as a comorbidity of epilepsy.

Enriched environment ameliorates depression-induced cognitive deficits and restores abnormal hippocampal synaptic plasticity.

Severe depression compromises structural and functional integrity of the brain and results in impaired learning and memory, maladaptive synaptic plasticity as well as degenerative changes in the hippocampus and amygdala. The precise mechanisms underlying cognitive dysfunctions in depression remain largely unknown. On the other hand, enriched environment (EE) offers beneficial effects on cognitive functions, synaptic plasticity in the hippocampus. However, the effect of EE on endogenous depression associated cognitive dysfunction has not been explored. Accordingly, we have attempted to address this issue by investigating behavioural, structural and synaptic plasticity mechanisms in an animal model of endogenous depression after exposure to enriched environment. Our results demonstrate that depression is associated with impaired spatial learning and enhanced anxiety-like behaviour which is correlated with hypotrophy of the dentate gyrus and amygdalar hypertrophy. We also observed a gross reduction in the hippocampal long-term potentiation (LTP). We report a complete behavioural recovery with reduced indices of anhedonia and behavioural despair, reduced anxiety-like behaviour and improved spatial learning along with a complete restoration of dentate gyrus and amygdalar volumes in depressive rats subjected to EE. Enrichment also facilitated CA3-Schaffer collateral LTP. Our study convincingly proves that depression-induces learning deficits and impairs hippocampal synaptic plasticity. It also highlights the role of environmental stimuli in restoring depression-induced cognitive deficits which might prove vital in outlining more effective strategies to treat major depressive disorders.

[A phenomenological approach of treatment-resistant depressions]. / Une approche clinico-phénoménologique des dépressions résistantes.

BACKGROUND: Hospital practitioners are regularly facing treatment-resistant depression, which may be defined according to the clinical picture or according to the therapeutic strategy. There are different levels of resistance and different levels of evidence for this resistance. Indeed, the notions of relative and absolute resistance describe the adequacy of assigned treatment. It thus seems necessary to specify the psychopathology of treatment-resistant depression and to highlight the endogeneity phenomenon in order to solve this problem. OBJECTIVE: Our work addresses the concept of endogeneity (previously clarified by Hubertus Tellenbach) and will consider its implications in the management of treatment-resistant depression. We attempt to demonstrate that the phenomenological approach is an interesting tool in clinical practice through the highlight of endogenous characteristics. METHOD: The first step consists in specifying the endogenous phenomena: abolition of rhythms, loss of the forward-looking deployment, overall impression, and reversibility, spatial and temporal characteristics from the phenotype. Our phenomenological approach continues by exploring the false resistances. Hence, we take into account anxious comorbidity, medical comorbidity, addictions, personality disorders and the hypothesis of a bipolar diathesis. First of all, it is difficult to show the patient in which way their behaviour results in stagnation. Indeed, it could strengthen the internal move that leads to an imperious necessity to cope with the surroundings. The psychotherapeutic help is elaborated by specifically highlighting the pathogenic situations whilst also taking into account the difficulties of an authentic therapeutic alliance. RESULTS: Our approach emphasizes the endogeneity phenomenon in depression, permitting the search for an optimal therapeutic strategy. It also provides assistance in resolving false resistance or what is apparent. In cases of endogenous depression, therapeutic orientation favours pharmacological and instrumental strategies (brain stimulation). If elements of self-understanding can be given to the patient, they must show that the rigid way in which the patient appropriates the daily reports is more stressful than the choice. Therefore, the psychotherapeutic help must take into account the situation and the individual vulnerability so as to develop a suitable care.

Psicopatología de la depresión: las contribuciones y cuestionamientos de Kurt Schneider / Psychopathology of depression: contributions and questionings of Kurt Schneider

The advance in the understanding of depressive disorders has been spectacular in all areas. However, the psychopathological analysis of his clinical features has remained stagnant since the advent of DSM-III. Kurt Schneider was concerned with particular care of their study and his contributions are still valid although much of his work remains unknown by the present world psychiatry. His main contributions concern the fields of methodology, conceptualization and description. He distinguishes different clinical entities: endogenous, basic, background, endoreactive, reactive, and existential depression and finally the depressive personality. Any progress on the psychopathology of depression requires a thoroughly deepening in his research.

El avance en el conocimiento de los trastornos depresivos ha sido espectacular en todaslas áreas. Sin embargo el análisis psicopatológico de sus cuadros ha permanecido estancado desde la aparición del DSM-III. Kurt Schneider se preocupó con especial cuidado de su estudio y sus contribuciones todavía están vigentes aunque en gran parte permanecen desconocidas. Sus principales aportes se dan en los campos de la metodología, conceptualización y descripción. Él distingue distintas entidades: depresión endógena, de base, de trasfondo, endorreactiva, reactiva, existencial y personalidad depresiva. Cualquier avance en la psicopatología de la depresión requiere por necesidad una profundización en sus investigaciones.

Effects of Prenatal Exposure to Nitric Oxide Synthase Inhibitor on Behavioral Changes in Forced Swimming Test in Postnatal Rats / 신경정신의학

OBJECTIVES: It has been demonstrated that nitric oxide (NO) serves as an inter- and intra-cellular messenger in the brain. NO has been implicated in the regulation of monoaminergic neurotransmission and the neuronal growth and synaptogenesis. Recently, NO has been suggested to be involved in the pathogenesis of depression. The aim of this study was to investigate the involvement of NO in the underlying mechanisms of biological vulnerability to depression. METHODS: The author measured locomotor activities and postnatal behavioral changes in the forced swimming test (FST) in rats that were exposed prenatally to N omega-nitro-L-arginine, a NO synthase (NOS) inhibitor. It was also investigated that paroxetine, a selective serotonin reuptake inhibitor, may affect the behavioral changes in the FST. RESULTS: Locomotor activities were significantly diminished, and the immobility times in the FST were significantly prolonged in the rats that were exposed prenatally to NOS inhibitor compared with controls. Pretreatment with paroxetine blocked the prolongation of the immobility times in the FST. CONCLUSION: The results indicate that postnatal behavioral changes due to prenatal exposure to NOS inhibitor in rats may suggest an animal model of endogenous depression, and that the glutamate-NMDA-NO pathway may be involved in the pathophysiology of depression. It is also indicated that the action of NO may, in part, be affected by serotonergic mechanism. This implicates that the glutamate-NMDA-NO pathway may lead to a novel approach to the treatment of depression.