Marcelo Arancibia

Proteostasis and Mitochondrial Role on Psychiatric and Neurodegenerative Disorders: Current Perspectives

Proteostasis involves processes that are fundamental for neural viability. Thus, protein misfolding and the formation of toxic aggregates at neural level, secondary to dysregulation of the conservative mechanisms of proteostasis, are associated with several neuropsychiatric conditions. It has been observed that impaired mitochondrial function due to a dysregulated proteostasis control system, that is, ubiquitin-proteasome system and chaperones, could also have effects on neurodegenerative disorders. We aimed to critically analyze the available findings regarding the neurobiological implications of proteostasis on the development of neurodegenerative and psychiatric diseases, considering the mitochondrial role. Proteostasis alterations in the prefrontal cortex implicate proteome instability and accumulation of misfolded proteins. Altered mitochondrial dynamics, especially in proteostasis processes, could impede the normal compensatory mechanisms against cell damage. Thereby, altered mitochondrial functions on regulatory modulation of dendritic development, neuroinflammation, and respiratory function may underlie the development of some psychiatric conditions, such as schizophrenia, being influenced by a genetic background. It is expected that with the increasing evidence about proteostasis in neuropsychiatric disorders, new therapeutic alternatives will emerge.

Trastorno dismórfico corporal: aspectos clínicos, dimensiones nosológicas y controversias con la anorexia nerviosa

There is strong evidence about the co-existence of body dysmorphic disorder (BDD) and eating disorders (ED), particularly with anorexia nervosa (AN). An exhaustive review of the specialised literature regarding these disorders was carried out. The results show that their co-occurrence implies a more complex diagnosis and treatment, a more severe clinical symptomatology and a worse prognosis and outcome. Both disorders display common similarities, differences and comorbidities, which allow authors to classify them in different nosological spectra (somatomorphic, anxious, obsessive-compulsive, affective and psychotic). Their crossover involves higher levels of body dissatisfaction and body image distortion, depression, suicidal tendency, personality disorders, substance use/abuse, obsessive-compulsive disorder, social phobia, alexithymia and childhood abuse or neglect background. Treatment including cognitive-behavioral psychotherapy and selective reuptake serotonin inhibitors are effective for both, BDD and ED; nevertheless, plastic surgery could exacerbate BDD. Clinical traits of BDD must be systematically detected in patients suffering from ED and vice versa.

Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

Background The United States Food and Drug Administration (FDA) has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI) and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

Ascetismo y espiritualidad en la anorexia nerviosa: Un análisis psicosocial histórico

Background Asceticism is deeply related to spirituality and fasting practices that have been observed in anorexia nervosa (AN) through the history. Objective A psychosocial analysis of spirituality and asceticism within the historical context of the AN is made, from Middle Ages to XXI century, comparing the holy anorexia and the contemporary AN. Ad hoc illustrative cases are described. Method Medline/Pubmed, data bases and specialized textbooks were used to look for evidence on asceticism and spirituality in AN and its historical development. Results From a historical point of view, asceticism of medieval saints (holy anorexia) and that of modern anorectics, display common features; nevertheless, it is oriented to different goals: spirituality versus worldly appearance, respectively. Contemporary Puritanism and AN share distinctive characteristics of protestant ethics, mainly self-discipline, self-control, self-sacrifice, rationality, efficiency and goals achievement. Asceticism is significantly related to angry feelings, inmaturity features and purging. Discussion and conclusion Many medieval mystical women showed similar characteristics with present AN, nevertheless, while asceticism in saints were oriented to achieve the divine encounter, drive for thinness in contemporary young anorectics is rather related to sociocultural aesthetic ideals. The atemporal occurrence of the pathogenic essence of the anorectic syndrome suggests that factors like age, personality and/or psychosocial environment pathoplastically model it.

The delusional dimension of anorexia nervosa: phenomenological, neurobiological and clinical perspectives

Background Delusional characteristics have been largely ignored in patients suffering from anorexia nervosa (AN). Objectives To review the literature on delusional features in AN from phenomenological, neurobiological, and clinical viewpoints. Methods Data were obtained through searches of Medline, PubMed, SciELO and Cochrane Library. Results Distorted beliefs in AN may range from an overvalued idea to an overt delusion, involving affective, personality and/or psychotic disorders. Studies confirm alterations in monoaminergic systems. It has also been seen a decreased integration of visual/proprioceptive information, and alterations in neural networks involved in body processing. It is known that body image distortion may present “delusional proportions” as a consequence of great concern about body. Concomitantly, “embodied defence hypothesis” has been proposed. Restrictive AN exhibits higher levels of delusionality, and a particular delusional type of AN has been suggested, associated with a worse long-term outcome. Low doses of atypical antipsychotics are recommended combined with cognitive techniques. Discussion Delusional thinking in AN is likely a dynamic and dimensional phenomenon that can vary, both in nature and/or severity, whereas high insight levels, before and after refeeding, result in positive outcomes. Neurobiological research on this topic must be encouraged, since clinical and phenomenological approaches are comparatively more frequently reported.

Trypophobia: What Do We Know So Far? A Case Report and Comprehensive Review of the Literature

In this article, we describe the case of a girl who suffers from a phobia to repetitive patterns, known as trypophobia. This condition has not yet been recognised by diagnostic taxonomies such as the Diagnostic and Statistical Manual of Mental Disorders. Trypophobia usually involves an intense and disproportionate fear towards holes, repetitive patterns, protrusions, etc., and, in general, images that present high-contrast energy at low and midrange spatial frequencies. It is commonly accompanied by neurovegetative symptoms. In the case we present here, the patient also suffered from generalised anxiety disorder and was treated with sertraline. After she was diagnosed, she showed symptoms of both fear and disgust towards trypophobic images. After some time following treatment, she only showed disgust towards said images. We finish this case report presenting a comprehensive literature review of the peer reviewed articles we retrieved after an exhaustive search about trypophobia, we discuss how this case report contributes to the understanding of this anxiety disorder, and what questions future studies should address in order to achieve a better understanding of trypophobia.

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

Prenatal stress (PS) has been mainly investigated in animal models. It could trigger permanent neurobiological changes in the offpring through fetal programming, displayed as behavioral, cognitive, anxious, affective and psychotic disorders during infancy and adulthood. Main effects of PS have been related to the functioning of hypothalamic-pituitary-adrenal axis (HPA), serotonergic, glutamatergic and GABAergic systems, cortical (prefrontal, temporal and insular cortex) and subcortical structures (amygdala, hippocampus), cerebellum and placenta. Glucocorticoids are the most recognized transmission factors of maternal-fetal stress, with distinctive effects according to the moment of action, developmental stage and fetal gender. Alteration pattern of the HPA axis by PS would be similar to the one observed in some mental disorders. Other neuromodulators involved in the neurotoxicity of PS are nitric oxide and brain derived neurotrophic factor, associated to synaptic potentiation and depression. Also, serotonergic system has an important relationship with HPA axis, verifying a decreased number of serotonin transporters and an impaired placental synthesis of the neurotransmitter, essential for fetal neurodevelopment. Other epigenenomic mechanisms would be the modulation of synaptic plasticity by neurotrophins, adhesion and membrane molecules. Treatment with selective serotonin reuptake inhibitors has shown controversial outcomes. PS would affect fetal programming causing significant and permanent neurobiological alterations with clinical manifestations. This complex phenomenon must be further investigated, especially in human models.

Towards a neurobiological understanding of alexithymia

Although the specialized literature on the etiology of alexithymia is controversial, neurobiological research has shown relevant advances. The aim of this review is to analyze the available evidence regarding the neurophysiological bases of alexithymia. A comprehensive review of available articles from Medline/PubMed, EBSCO and SciELO was conducted. Previously, alexithymia was linked to a reduced interhemispheric brain connection. From a childhood traumatic perspective, the right prefrontal cortex and the default mode network would experience alterations, first hypermetabolic (dopaminergic and glutamatergic dysregulation) and then hypometabolic-dissociative (serotonergic and opioid dysregulation), resulting in a distorted interoceptive and emotional awareness. Mirror neurons are the essential neurobiological substrate of theory of mind and social cognition, intrinsically linked to alexithymia, involving parietal, temporal, premotor, and cingulate cortices, and inferior frontal gyrus. Other structures involved are the amygdala (facial expression and emotional reactivity), the insula (interoception, emotional integration and empathy) and the cerebellum (limbic cerebellum and somatosensory awareness). Molecular genetics has detected polymorphisms in genes of the serotonin transporter, in the enzyme genes of dopaminergic metabolism and brain-derived neurotrophic factor, while the role of oxytocin is controversial. To sum up, we found several studies demonstrating the overwhelming evidence of a neurobiological basis underlying alexithymia; nevertheless, research is still inconclusive and must include environmental, traumatic, social, and psychological factors that contribute to the origin of the alexithymia.

Psicofarmacología del suicidio II parte: Estabilizadores del ánimo y suicidio

Resumen El litio y los anticonvulsivantes han sido ampliamente empleados como estabilizadores del animo (EA) en el trastorno afectivo bipolar (TAB), demostrando ademas una reduccion del riesgo de suicidio. En el caso particular del litio, dicho efecto seria independiente de su accion estabilizadora. Si bien los mecanismos de accion de la droga no son completamente conocidos y la investigacion clinica se ve dificultada debido a la heterogeneidad de las muestras estudiadas, se han propuesto distintas vias que explicarian su efecto, relacionadas con el metabolismo de los neurotransmisores y con factores neurotroficos y neuroprotectores. Pese a la disminucion actual en el uso del litio como EA, continua siendo el farmaco antisuicida de eleccion en pacientes bipolares. Palabras clave: Estabilizador del animo, litio, anticonvulsivante, suicidio, trastorno afectivo bipolar. during lithium maintenance treatment. J Clin Psychiatry 2000; 61: 97-104.8. Lauterbach E, Felber W, Muller-Oerlinghausen B, Ahrens B, Bronisch T, Meyer T,

Funcionamiento psicosocial en pacientes agudos y crónicos no psiquiátricos en régimen hospitalario: depresión, alexitimia y falta de asertividad

Background: Depression, alexithymia, and lack of assertiveness interfere with individual psychosocial functioning and may result in longer hospitalization stay and poorer therapeutic results. Aim:To analyze the psychosocial functioning in acute and chronic patients and its association with psychological, clinical and sociodemographic variables.Material and methods: We performed a cross-sectional study that included 80 inpatients of both sexes with organic pathology, aged between 18 to 70 years old, without any current psychiatric disorder. Clinical and sociodemographic data were collected from a semi-structured interview and hospital records. Beck Depression Inventory-IA, Toronto Alexithymia Scale-20 and Rathus Assertiveness Scale were administered. Results: Fifty five percent of patients had some degree of depression, 33% alexithymia and 34% lack of assertiveness. The levels of depression, alexithymia and lack of assertiveness in chronic patients were significantly higher than those observed in acute patients. Women and participants older than 60 years exhibited the highest degrees of depression. Alexithymia and lack of assertiveness were associated with a lower educational level. A negative significant correlation between alexithymia and assertiveness scores was observed among acute patients. Conclusions: Participants with chronic diseases had a lower psychosocial functioning.Less educated patients showed more alexithymic and less assertive features. We emphasized the need of a better management of these aspects by the health team, since social functioning might interfere with the outcome of physical illnesses.