Endoxifen, A new hope for Bipolar Disorder

Bipolar Disorder (BD), originally called manic depressive illness, is one of the most challenging and disabling psychiatric disorders to manage with an estimated life time prevalence of 1.02%. (1) One of the challenges is limitations in our understanding of the pathophysiology of the disorder which ultimately will lead to better treatment options. Despite available treatment options, literature reports breakthrough episodes in treated groups ranging from 40% to 60%. (2) This makes it even more crucial to gain more insight into the pathophysiology. Advances in molecular neuropsychiatry have reported that bipolar disorder is associated with overactive protein C kinase intracellular signaling. (3) Reportedly, lithium and valproate are protein C kinase inhibitors. Research has shown promise in effectiveness of Endoxifen. A multicenter, double-blind, active-controlled study was conducted using Endoxifen compared with Divalproex, the current standard treatment, in patients with BD. This new protein kinase C inhibitor has shown effectiveness in the treatment of acute mania and mixed mania. (4) One of the many advantages include similar efficacy as Divalproax without inducing thrombocytopenia and reportedly no need for drug monitoring due to wide therapeutic index is one of the reasons which results in decreased compliance. Additionally, it crosses the blood-brain barrier independent of CYP-2D6 metabolism. (4) With regards to disadvantages, cost effectiveness is a major hurdle. These new insights into pathophysiology and treatment options are crucial as till date BD remains one the most disabling mental health disorder affecting every aspect of life; individual, social, economic, global. BD is the fifth leading cause among psychiatric disorders of lost years of work. (5) It is therefore imperative that a new treatment is established and further research is warranted in regards to Endoxifen for better understanding to develop safe treatment, not only for management but possible cure. Continuous...

Understanding of “Feeling” and “Self-Consciousness” on the Border of the XIX–XX Centuries and M. Loewy’s Concept of Depersonalization

The aim was to review the understanding of the phenomena of “feeling” and “self-consciousness” in the concepts of the leading European scientists at the second half of XIX — beginning of the XX centuries.Method: H.R. Lotze, I.M. Sechenov, A. Bain, W. Wundt, G. Stoerring, Th. Lipps, K. Oesterreich, E. Kraepelin and some others are analyzed.Conclusion: while Th. Lipps, H.R. Lotze, W. Wundt and K. Oesterreich were striving for strict differentiation of the notions of “sensations” and “feelings”, A. Bain, I.M. Sechenov, G. Stoerring were not following an effi cient distinction of these phenomena. H.R. Lotze, I.M. Sechenov, A. Bain distinguished in the consciousness and self-consciousness the affective and intellectual components; Th. Lipps considered as the core of self-consciousness the feelings that were very manifold and accompanied different mental acts including the act of perception: “perceptions feeling”. G. Stoerring paid attention to the lack of the feeling of activity by depersonalization, and the Austrian psychiatrist and neurologist M. Loewy elaborated the concept of “ubiquitous” “action feelings” (Actionsgefuehle) that exist outside of “pleasure — displeasure” modality. According to M. Loewy’s concept every mental act is accompanied normally by two “feelings of act”: general and specifi c, in the abnormal case one or both of them may disappear. The clinical description of weakening or loss of the action feelings: impulse feeling, perception feeling of vital sensation, perception feelings of sensations from organs of sense, “feelings of the feeling process”, “thinking feeling”, M. Loewy accomplished by “personalizing” approach to the account of one of his patient, Russian female student. M. Loewy considered the depersonalization disorders in this case as a symbolic neurosis according to S. Freud and as a psychasthenia according to P. Janet. Although E. Kraepelin defi ned selfconsciousness as merely cognitive phenomenon he interpreted depersonalization as a kind of emotional disturbance including the disorders on the level of sensations in the frames of light depressive phase of the manic-depressive illness. The M. Loewy’s concept of the “action feelings” can be applied not only for the understanding of “neurotic” depersonalization but also for depersonalization cases on the ground of depressive and mixed phase affective states.

Art in suicide treatment and prevention

The theme ‘suicide’ in paintings mirror social, cultural, religious, and philosophical stances to suicide. However, behind these more public aspects of the artist’s work there is often a personal meaning. The motives and interests of the artists go beyond the theme of suicide. An important factor in suicidal behaviour is a depressive mood or disorder. However, the depressive mood as well as the underlying manic-depressive illness of some artists may be seen as an important prerequisite for their creativity. Despite the importance of suicidality in art and that art therapy is well-established for treating patients in psychiatry and psychotherapy, only a small body of empirical literature about the role of art therapy in depressed and suicidal patients exists. In paintings and sculptures of art therapy, done by patients primarily reflect the inner experiences of their illness and biography. Art therapy can help the patient to alleviate self-destructive ways of acting.

The characteristic signs and symptoms of mania and depression according to Kraepelin circa 1905: a comparison with DSM-III

Although the rise of operationalized diagnostic criteria and the creation of DSM-III were influenced in the USA by a neo-Kraepelinian ‘revival’ of interest in psychiatric nosology, Kraepelin was only a distal influence on the specific diagnostic criteria proposed. The historical origins of the DSM-III criteria for mania and major depression (MD) are traceable back to the 1950s and contain no direct link to Kraepelin's writings. George Dreyfus, a student and assistant to Kraepelin, authored in 1907 a monograph on Involutional Melancholia which reviewed cases seen by Kraepelin in Heidelberg. In this monograph, Dreyfus presents the ‘characteristic’ symptoms for mania and depression ‘as described by Kraepelin.’ This historical finding provides the unprecedented opportunity to examine the resemblance between the criteria proposed for mania and depression in DSM-III, inspired by Kraepelin's nosologic vision, and those specifically suggested by Kraepelin 73 years earlier. Kraepelin's symptoms and signs for mania paralleled seven of the eight DSM-III criteria (except the decreased need for sleep), with two not included in DSM-III (increased mental activity and short bursts of sadness). Kraepelin's signs and symptoms paralleled six of the nine DSM-III criteria for MD, lacking suicidal ideation and changes in appetite/weight and sleep but including obsessions, reduced expressive movements, and decreased mood responsiveness. Although Kraepelin's overall approach to mania and depression emphasized their close inter-relationship in the cyclic course of manic-depressive illness, it is noteworthy Kraepelin's ‘characteristic’ symptoms for mania and depression as described by Dreyfus, bear substantial but incomplete resemblance to the criteria proposed in DSM-III.

T93. RESHAPING THE DIAGNOSTIC BORDERS OF SCHIZOPHRENIA: THE LOOK OF HISTORY OF PSYCHIATRIC PRACTICES

Background The diagnostic concept of Schizophrenia as defined by DSM and ICD is increasingly being questioned. It is criticized above all for its lack of validity. It refers to very heterogeneous disorders in terms of signs and symptoms but also in terms of evolution and heritability. Clinicians and researchers are therefore considering how to rethink this concept, in the absence of known physiopathological mechanisms and etiology, by integrating various advances in fields such as genetics, molecular biology, brain imaging and cognitive sciences. However, the renewal of the concept of schizophrenia has yet to be explored in terms of its potential impact on psychiatric practice. It is an essential point because this diagnostic concept does not correspond to a theoretical entity that exists for itself but it is a tool of psychiatrists’ daily practice when they seek to name the disorders presented by a patient. Thus, a renewal of the concept of schizophrenia would necessarily have an impact on the diagnoses made by psychiatrists and we know how important the diagnosis in psychiatry is: for the medical care but also for the personal history of the patient. This impact that a renewal of the concept of schizophrenia could have on the diagnostic practices of psychiatrists can be better understood through the analysis of a historical example: the introduction of the concept of Schizophrenia at the Psychiatric Clinic of Strasbourg in France during the period 1920–1930. The concept of Schizophrenia was first discussed in 1908 by the swiss psychiatrist Eugen Bleuler at the Annual Meeting of the German Psychiatric Association in Berlin. At the Psychiatric Clinic of Strasbourg, it was first used by psychiatrists in 1922. How did this then new concept find its place among the other diagnostic concepts that had been used until then in this institution? Methods In an attempt to answer this question, we implemented a methodology that combined a quantitative and a qualitative approach. The first is a retrospective descriptive statistical study whose objective is to establish the evolution of the proportion of the different diagnoses made at the Psychiatric Clinic of Strasbourg during the period 1920–1930. This study includes all hospitalized patients and uses admission records for data collection. This quantitative approach was complemented by a qualitative approach that consists in reconstructing the diagnostic trajectory of some patients with a diagnosis of schizophrenia after the period of introduction of this concept. The diagnoses made during their previous hospitalizations were systematically collected and analyzed, this time using the medical records of these patients as sources. Results The diagnostic concept of Schizophrenia seems to have replaced the one of Dementia praecox within the diagnostic practices: the latter was given extensively in 1924, but hardly any longer in 1928. However, in the same period of time, other diagnostic concepts of the field of psychosis like Manic-depressive Illness were less commonly used while others like Catatonia were increasingly employed. The reconstruction of patients’ diagnostic trajectories tends to show that the diagnostic of schizophrenia would have taken over from the diagnostic of Dementia Praecox but also from some of the diagnoses of Manic-depressive Illness, Hebephrenia and Psychopathy. Discussion This historical perspective makes it possible to understand the impact on psychiatrist’s diagnostic practices of a “nosological innovation” that is theoretical, such as the renewal of the concept of schizophrenia could be. In the diagnostic practices, one diagnostic concept would not simply replace another, but it’s introduction could induce a broader reshaping of diagnostic mapping.

Diagnosis, classification, and differential diagnosis of mood disorders

This chapter discusses DSM and non-DSM definitions and approaches to mood illness. Before 1980, the concept of manic–depressive illness (MDI) meant both bipolar illness and recurrent unipolar depression. Evidence on diagnostic validators since 1980 has not strengthened that claim and may be interpreted to support the original MDI concept, that is, that bipolar illness and unipolar depression are part of the same overall disease (MDI). As a corollary, the concept of major depressive disorder (MDD) may represent a spectrum of different depressive subtypes: mixed (depression with manic symptoms), melancholic, pure, vascular, and neurotic depression. Each subtype differs from the other, based on diagnostic validators of course, genetics, and biological aspects and/or treatment effects. The scientific evidence for this heterogeneity of MDD appears to weaken the claim dating to DSM-III in 1980 that this condition is a different diagnosis/illness from bipolar disorder. The differential diagnosis of mood conditions is described.