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.

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

Abstract 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.

Caracterización fenomenológica de las conductas repetitivas impulsivas orientadas hacia el cuerpo y el trastorno por excoriación en estudiantes universitarios / Phenomenological characterization of body-focused repetitive impulsive behaviours and excoriation disorder in college students

Resumen Introducción: Las conductas repetitivas impulsivas orientadas hacia el cuerpo (CRIOC) se caracterizan por el rascado, mordido y/o remoción de uñas, pelos y piel, pudiendo llegar a constituir un desorden mental. El trastorno por excoriación (TE) o dermatilomanía ha sido recientemente incorporado como desorden específico al DSM-5 como parte del espectro obsesivo-compulsivo. Su fenomenología describe una conducta reactiva a la ansiedad, seguida de tensión psíquica progresiva y luego placentera al realizarla, finalizando muchas veces en culpa. Se ha reportado una mayor incidencia de TE en estudiantes universitarios, sin embargo, los estudios en Latinoamérica son escasos. Objetivos: Establecer la frecuencia y las características fenomenológicas de las CRIOC y del TE en población universitaria. Métodos: Se realizó un estudio transversal mediante la aplicación de un cuestionario de autorreporte sobre aspectos relacionados con el TE en estudiantes universitarios. Resultados: 440 estudiantes fueron incluidos. Un 22,2% sintió siempre o casi siempre el impulso de rascar su piel hasta lesionarse; 13,2% ejecutó estas acciones varias veces al día y 4,3% desplegó mucho esfuerzo en resistirlas. Los afectos más frecuentemente asociados fueron culpa, vergüenza, arrepentimiento y autorreproche. Un 24,1% creyó que estos comportamientos fueron anormales y 6,1% que constituyeron una patología. Según criterios DSM-5 y establecidos por los autores, se hallaron cuatro casos compatibles con TE (0,91%), al descartar patologías psiquiátricas y médicas comórbidas. Conclusión: Aunque las CRIOC fueron frecuentes en población universitaria, la frecuencia de TE fue similar a la de la población general, describiendo una fenomenología característica congruente con la reportada por la literatura.

Introduction: Body-focused repetitive impulsive behaviors (BFRIB) are characterized by skin, nail and hair removing, scratching and/or biting, that configurate a mental disorder in some cases. Excoriation disorder (ED) or dermatillomania has been recently added as a specific disorder in DSM-5 obsessive-compulsive spectrum. Its phenomenology describes a behavior that emerges from anxiety, followed by a progressive psychic tension and then a pleasurable sensation, concluding in many times in guilt. Evidence has reported a greater incidence of ED in college students; however, studies in Latin America are scarce. Objective: To establish frequence and phenomenological features of BFRIB and ED in college students. Methods: We performed a cross-sectional study through the application of a self-administered questionnaire about ED aspects in college students. Results: 440 students were included; 22.2% felt always or almost always the impulse to scratch their skin until they were injured; 13.2% made these actions many times a day and 4.3% deployed considerable efforts in resisting them. Most frequent reported affects were guilt, shame, repentance, and self-reproach; 24.1% thought these behaviors were abnormal and 6.1% considered they constitute a pathology. According to DSM-5 and authors' criteria, four cases of ED were found (0.91%), when psychiatric and medical comorbidities were discarded. Conclusion: Although BFRIB were frequent in college students, dermatillomania frequency was similar to general population. A characteristic phenomenology was described, similar to the evidence reported one.

Brief psychosis induced by methylphenidate in a child with attention deficit disorder: a case report and literature review. / Psicosis breve secundaria al uso de metilfenidato en un niño con trastorno por déficit de atención: reporte de caso y revisión de literatura.

Methylphenidate-induced psychosis has been scarcely studied due to bioethical and neurobiological issues regarding its research. Although some authors have hypothesized that there might be a vulnerability for the development of a major psychiatric disorder in the long term, there is no agreement about the predictive value of this type of psychosis in children and adolescents, and its origin is also uncertain. It has been suggested that higher dopamine levels in some cerebral regions and a family history of mental disorders might increase the risk of psychosis secondary to psychostimulants. We present the case of a nine-year-old child diagnosed with attention deficit disorder and oppositional defiant disorder, who exhibited visual and auditory hallucinations and delirious ideas about harm during methylphenidate treatment. The patient’s symptoms regressed after drug removal. We discuss the key issues related to the origin, causality, management, and prognosis of psychostimulant-induced psychosis.

La psicosis inducida por metilfenidato ha sido escasamente estudiada debido a los problemas bioéticos y neurobiológicos relacionados con su investigación. Si bien evidenciaría una vulnerabilidad a largo plazo para el desarrollo de un trastorno psiquiátrico mayor, no hay consenso sobre su valor predictivo en la población infanto-juvenil, mientras que su origen es incierto. Se ha sugerido que los mayores niveles de dopamina en ciertas zonas cerebrales y el antecedente familiar de algunos trastornos mentales, aumentaría el riesgo de presentar psicosis secundaria a psicoestimulantes. Presentamos el caso de un niño de nueve años de edad, con diagnóstico de trastorno por déficit de atención comórbido a una oposición desafiante, que durante el tratamiento con metilfenidato presentó alucinaciones visuales y auditivas e ideas deliriosas de daño que cedieron con la suspensión del fármaco. Se discuten los principales aspectos relacionados con el origen, la causalidad, el manejo y el pronóstico de la psicosis inducida por psicoestimulantes.

Towards a neurobiological understanding of alexithymia. / Hacia una comprensión neurobiológica de la alexitimia.

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.

Si bien la literatura especializada sobre la etiología de la alexitimia es controvertida, la investigación neurobiológica sobre el fenómeno ha demostrado importantes avances. El objetivo de esta revisión es analizar la evidencia disponible en relación a las bases neurofisiológicas de la alexitimia. Se realizó una revisión exhaustiva de artículos disponibles en MEDLINE/PubMed, EBSCO y SciELO. Inicialmente, se vinculó a la alexitimia con una conexión cerebral interhemisférica reducida. Desde la perspectiva traumática infantil, la corteza prefrontal derecha y la red neuronal por defecto experimentarían alteraciones, primero hipermetabólicas (desregulación dopaminérgica y glutamatérgica) y luego hipometabólicas-disociativas (desregulación serotoninérgica y opioide), resultando en una consciencia interoceptiva y emocional distorsionada. Las neuronas espejo son el sustrato neurobiológico fundamental de la teoría de la mente y la cognición social, intrínsecamente vinculadas con la alexitimia, involucrando cortezas como la parietal, la temporal, la premotora, la cingulada y el giro frontal inferior. Otras estructuras involucradas son amígdala (expresión facial y reactividad emocional), ínsula (interocepción, integración emocional y empatía) y cerebelo (cerebelo límbico y consciencia somatosensorial). La genética molecular ha detectado polimorfismos en el gen del transportador de serotonina, en los genes de las enzimas del metabolismo dopaminérgico y del factor neurotrófico derivado del cerebro, mientras que el rol de la oxitocina es controvertido. En conclusión, numerosos estudios demuestran contundentemente la existencia de una neurobiología subyacente a la alexitimia. Sin embargo, la investigación es aún poco concluyente y debe considerar los factores ambientales, traumáticos, sociales y psicológicos que contribuyen al origen del fenómeno.