Parkinson's disease. Genetics and new possibilities for intervention.

 

Parkinson's disease is the most common movement disorder affecting people in their adult life between the ages of 40 and 70. It is a chronic neurodegenerative disease that occurs when the loss of neurons in the substantia nigra leads to a drop in dopamine production and the appearance of accumulations of the protein "alpha-synuclein" in various areas of the brain. The disease progressively causes more severe forms of akinesia, malfunctioning of various motor and vegetative functions, stiffening of the muscles, tremors and mental disorders (mainly of a depressive, anxious and cognitive nature) that limit and wear down the patient's quality of life. To date, there is no cure for Parkinson's disease and the main treatments are only capable of limiting the symptoms. For this reason, scientific research has launched a vast front of investigations aimed at identifying new therapeutic strategies, increasing expectations and quality of life as well as maintaining an adequate level of social inclusion of patients and their families.

In this regard, a study (Brown et al, 2021) conducted by researchers at the University of Sheffield and Luxembourg highlighted the role of the mutation of the Pink1 gene in the processes that determine the manifestation of Parkinson's disease. The deactivation of this gene would determine, in fact, an abrupt decline in the processes of neurogenesis of dopaminergic neurons and the consequent deficit of the networks that contribute to the regulation of postural reflexes, the inhibition of motor activity (dopaminergic nigrostriate system), the expression and emotional regulation (mesolimbic system) and cognitive functions (mesocortical system).

In addition, Italian researchers (Gialluisi et al. 2021) have succeeded in sequencing the genome of 500 patients affected by the disease and in identifying 26 genes involved in the pathogenesis of Parkinson's disease, 16 of which, expressed mainly in the midbrain, have been associated for the first time with the processes that determine its manifestation and progression.

Although the results of these investigations require further study and confirmation, the results obtained so far help to clarify the heterogeneous and complex genetics of this disease, the knowledge of which is crucial to achieve an early diagnosis (if not preventive) and more effective and decisive treatments. In this last area, it is worth mentioning that researchers at the University of Milan (Chiricozzi et al, 2021) have designed an oligosaccharide (called OligoGM1) which, when injected into mice, has proved capable of crossing the blood-brain barrier and ensuring a rapid recovery of motor and biological functions.

In such a complex scenario, the psychologist is crucial for the development of interventions aimed at the management of stress (which is known to worsen the symptoms of the disease such as tremors), anxiety, sleep disorders (whose implications on the management of emotions, mood, memory and in general on the functionality of the prefrontal cortex, the seat of all neurocognitive functions of higher order are known), the development of life skills and the strengthening of protective factors of individual and family resilience (D'Urso, 2020).

In conclusion, it has become imperative to address this disease with a biopsychosocial approach that allows the development of integrated strategies for the management of patients that are effective because they aim, even in crisis situations such as that resulting from the COVID-19 pandemic, at their complete physical, mental and social well-being.

Bibliography

Brown, S.J., Boussaad, I., Jarazo, J. et al. PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons. Sci Rep 11, 6617 (2021). https://doi.org/10.1038/s41598-021-84278-7

Chiricozzi, E., Di Biase, E., Lunghi, G. et al. Turning the spotlight on the oligosaccharide chain of GM1 ganglioside. Glycoconj J 38, 101–117 (2021).

D’Urso, G., Il Morbo di Parkinson, la Deep Brain Stimulation e lo sviluppo di strategie di intervento integrato nella gestione della malattia, ​State of Mind. Il giornale delle Scienze psicologiche. Id Articolo 179778 pubblicato il 25 novembre 2020

Gialluisi, A., Reccia, M.G., Modugno, N. et al. Identification of sixteen novel candidate genes for late onset Parkinson’s disease. Mol Neurodegeneration 16, 35 (2021). https://doi.org/10.1186/s13024-021-00455-2

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Enfermedad de Parkinson. La genética y las nuevas posibilidades de intervención.

La enfermedad de Parkinson es el más frecuente de los trastornos del movimiento que afectan a los individuos en la edad adulta, entre los cuarenta y los setenta años. Se trata de una enfermedad neurodegenerativa crónica que se produce cuando la pérdida de neuronas en la sustancia negra provoca una disminución de la producción de dopamina y la aparición de acumulaciones de la proteína "alfa-sinucleína" en diversas zonas del cerebro. La enfermedad provoca progresivamente formas más graves de acinesia, disfunciones de diversas funciones motoras y vegetativas, rigidez muscular, temblores y trastornos mentales (principalmente de carácter depresivo, ansioso y cognitivo) que limitan y desgastan la calidad de vida del paciente. Hasta la fecha, no hay cura para la enfermedad de Parkinson y los principales tratamientos sólo son capaces de limitar los síntomas. Por ello, la investigación científica ha puesto en marcha un amplio frente de investigaciones destinadas a identificar nuevas estrategias terapéuticas, aumentar las expectativas y la calidad de vida, así como mantener un nivel adecuado de inclusión social de los pacientes y sus familias.

En este sentido, un estudio (Brown et al, 2021) realizado por investigadores de la Universidad de Sheffield y Luxemburgo ha puesto de manifiesto el papel de la mutación del gen Pink1 en los procesos que determinan la manifestación de la enfermedad de Parkinson. La desactivación de este gen determinaría, de hecho, una disminución brusca de los procesos de neurogénesis de las neuronas dopaminérgicas y el consiguiente déficit de las redes que contribuyen a la regulación de los reflejos posturales, la inhibición de la actividad motora (sistema nigroestriado dopaminérgico), la expresión y regulación emocional (sistema mesolímbico) y las funciones cognitivas (sistema mesocortical).

Además, unos investigadores italianos (Gialluisi et al. 2021) lograron secuenciar el genoma de 500 pacientes afectados por la enfermedad e identificar 26 genes implicados en la patogénesis de la enfermedad de Parkinson, 16 de los cuales, expresados principalmente en el cerebro medio, han sido asociados por primera vez a los procesos que determinan la manifestación y la progresión.

Aunque los resultados de estas investigaciones requieren una mayor investigación y confirmación, los resultados alcanzados hasta ahora ayudan a clarificar la heterogénea y compleja genética de esta enfermedad, cuyo conocimiento es crucial para lograr un diagnóstico precoz (si no preventivo) y tratamientos más eficaces y resolutivos. En este último ámbito, cabe mencionar que algunos investigadores de la Universidad de Milán (Chiricozzi et al, 2021) han diseñado un oligosacárido (denominado OligoGM1) que, al ser inyectado en ratones, fue capaz de superar la barrera hematoencefálica y garantizar una rápida recuperación de las funciones motoras y biológicas.

En un escenario tan complejo, el psicólogo es crucial para el desarrollo de intervenciones dirigidas al manejo del estrés (que se sabe que provoca un empeoramiento de los síntomas de la enfermedad como los temblores), la ansiedad, los trastornos del sueño (cuyas implicaciones se conocen sobre el manejo de las emociones, el estado de ánimo, la memoria y en general sobre la funcionalidad de la corteza prefrontal, sede de todas las funciones neurocognitivas de orden superior), el desarrollo de habilidades para la vida y el fortalecimiento de los factores protectores de la resiliencia individual y familiar (D'Urso, 2020).

En conclusión, se ha hecho imprescindible abordar esta enfermedad con un enfoque biopsicosocial que permita desarrollar estrategias integradas para el manejo del paciente eficaces porque dirigidas, incluso en situaciones de crisis como la derivada de la pandemia de COVID-19, a su completo bienestar físico, mental y social.

Bibliografía

Brown, S.J., Boussaad, I., Jarazo, J. et al. PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons. Sci Rep 11, 6617 (2021). https://doi.org/10.1038/s41598-021-84278-7

Chiricozzi, E., Di Biase, E., Lunghi, G. et al. Turning the spotlight on the oligosaccharide chain of GM1 ganglioside. Glycoconj J 38, 101–117 (2021).

D’Urso, G., Il Morbo di Parkinson, la Deep Brain Stimulation e lo sviluppo di strategie di intervento integrato nella gestione della malattia, ​State of Mind. Il giornale delle Scienze psicologiche. Id Articolo 179778 pubblicato il 25 novembre 2020

Gialluisi, A., Reccia, M.G., Modugno, N. et al. Identification of sixteen novel candidate genes for late onset Parkinson’s disease. Mol Neurodegeneration 16, 35 (2021). https://doi.org/10.1186/s13024-021-00455-2

El autor de este artículo también ha editado el siguiente libro. Consúltelo haciendo clic en la siguiente imagen:

La curiosidad. Se ha identificado un origen neurobiológico

La curiosidad surge del deseo de conocer y se expresa en comportamientos o actitudes exploratorias en el entorno o en el propio mundo interior. La disposición a tener nuevas experiencias se considera, por tanto, un requisito necesario para aprender y para enriquecer el caudal de experiencias que en el curso de la evolución han permitido a los individuos sobrevivir en su hábitat, buscando lo que aporta placer (por ejemplo, comer) y huyendo de lo que provoca sufrimiento y dolor.

Explorar y sobrevivir en un entorno complejo no es fácil. La memoria y la capacidad del cerebro para adaptarse a las experiencias vividas a través de mecanismos de plasticidad cerebral son instrumentos preciosos que permiten al hombre evitar posibles peligros o afrontar, de forma eficaz, situaciones ya experimentadas.

En este contexto, algunos investigadores de la Universidad de Vanderbilt se han preguntado de dónde viene la curiosidad y si el impulso de investigar lo desconocido es innato o producto de procesos neurobiológicos similares a los que impulsan al individuo a dormir, comer o beber.

Los resultados de las investigaciones realizadas en ratones se han publicado recientemente en la revista Science y han puesto de manifiesto que la curiosidad es el producto de un proceso en el que intervienen el neurotransmisor Gaba (ácido γ-aminobutírico) y una población de neuronas del área incierta del cerebro (una agrupación nuclear cuyas funciones reales se desconocen. Constituye la prolongación de la formación reticular del cerebro medio y está conectada a través de redes nerviosas con el tálamo y parece estar implicada en procesos relacionados con el sueño, el hambre y el miedo).

Este descubrimiento, aunque requiere más confirmación e investigación, pone en tela de juicio la creencia de que la curiosidad se desencadena por la expectativa de una recompensa.

BIBLIOGRAFÍA

Farahbakhsh, Zahra Z., and Cody A. Siciliano. "Neurobiology of novelty seeking." Science 372.6543 (2021): 684-685.

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The Curiosity. Neurobiological origin identified

Curiosity stems from the desire to know and is expressed in exploratory behaviour or attitudes in the surrounding environment or in one's inner world. The willingness to experience new things is therefore considered a necessary prerequisite for learning and for enriching the wealth of experience that has enabled individuals to survive in their habitat over the course of evolution, seeking out what brings pleasure (e.g. eating) and fleeing from what causes suffering and pain.

Exploring and surviving in a complex environment is not easy. Memory and the brain's ability to adapt to experiences through brain plasticity mechanisms are invaluable tools that enable humans to avoid possible dangers or to deal effectively with situations they have already experienced.

In this context, researchers at Vanderbilt University have wondered where curiosity comes from and whether the urge to investigate the unknown is innate or the product of neurobiological processes similar to those that drive individuals to sleep, eat or drink.

The results of investigations in mice were recently published in the journal Science and revealed that curiosity is the product of a process involving the neurotransmitter Gaba (γ-aminobutyric acid) and a population of neurons in the uncertain zone of the brain (a nuclear grouping whose actual functions are unknown. It is an extension of the reticular formation of the midbrain and is connected through nerve networks to the thalamus and seems to be involved in processes related to sleep, hunger and fear).

This discovery, although requiring further confirmation and investigation, challenges the belief that curiosity is triggered by the expectation of reward.

Bibliography

Farahbakhsh, Zahra Z., and Cody A. Siciliano. "Neurobiology of novelty seeking." Science 372.6543 (2021): 684-685.

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¿Es importante la vuelta al trabajo para la salud mental? Una nueva posibilidad de intervención.

La depresión, los trastornos de ansiedad y el síndrome de Burnout se encuentran entre las causas más comunes de baja laboral y, en los casos más graves, de incapacidad laboral permanente. La pérdida de trabajo tiene un impacto negativo en el estado de salud mental, en la posibilidad de recuperación y en la percepción del propio bienestar psicofísico. Las intervenciones clínicas que incluyen el tratamiento farmacológico (cuando se considere necesario), la psicoterapia y el refuerzo de las habilidades del sujeto pueden reducir el impacto negativo del trastorno psicológico y mejorar gradualmente la capacidad de realizar un trabajo eficaz. Según los expertos, de hecho, la reinserción laboral permite, por ejemplo:

1. aumentar la sensación de eficacia y gratificación
2. disminuir los sentimientos de agotamiento y cinismo típicos de la depresión (Maslach et Leiter, 2016);
3. dan estabilidad y proporcionan un programa de actividades para hacer a diario (Lagerveld et al, 2012);
4. mantener la seguridad financiera y un buen nivel de integración social (Moore et al, 2017).

En los casos que la discapacidad se convierte en permanente, los esfuerzos de rehabilitación tienden a disminuir con un impacto negativo en la calidad de vida del individuo y en los costes sociales y sanitarios que soporta la comunidad. En este sentido, recientemente se ha presentado una intervención semi-estandarizada, orientada al paciente, de unas 80 horas (Behrens-Wittenberg et y Wedegaertner, 2021) y parece que prospectivamente puede ser muy eficaz. El procedimiento consta de 3 fases.

Fase 1: Estabilizar el estado de salud mental del paciente, garantizando la continuidad y la calidad del tratamiento y el apoyo necesario, incluido el apoyo burocrático. Una intervención de coaching puede ser útil para evaluar y reforzar las habilidades, capacidades y competencias necesarias para la recuperación. Estos pasos deben calibrarse según la estabilidad mental de los individuos y sus prioridades personales.

Fase 2a: Si el puesto de trabajo que ocupaba anteriormente el paciente está disponible, es preferible optar por la reintegración en el mismo lugar de servicio. La intervención requiere un reconocimiento del lugar de trabajo para verificar las posibles criticidades que deben examinarse junto con el empresario y el paciente, a fin de definir estrategias para limitar el impacto en el estado de salud.

Fase 2b: si no se dispone de un lugar de trabajo, mediante el uso del pensamiento lateral es necesario crear nuevas perspectivas de empleo, mejorando las habilidades y capacidades requeridas por los puestos de trabajo disponibles. En esta fase el individuo debe ser apoyado tanto en la fase de preparación/formación como en la preparación de los documentos de solicitud y la posterior fase de selección.

Fase 3: La fase de reempleo y/o inicio de una nueva actividad es apoyada por personal especializado hasta el final de la intervención. De hecho, es conveniente hacer sentir al individuo que es capaz de afrontar los nuevos retos sociales y laborales y que el psicólogo está siempre disponible para apoyarle y potenciar las habilidades que necesita para poder interactuar en el nuevo entorno.

Aunque la intervención tiene limitaciones y puede mejorarse, es una herramienta útil para mejorar la capacidad de trabajo y, en general, el bienestar biopsicosocial del individuo, que es el principal núcleo de negocio que se pretende conseguir.

Bibliografía

Behrens-Wittenberg E and Wedegaertner F (2021) A Return-to-Work Intervention for Prematurely Retired Depression or Anxiety Disorder Patients. Front. Psychiatry 12:662158. doi: 10.3389/fpsyt.2021.662158

Lagerveld SE, Blonk RW, Brenninkmeijer V, Wijngaards-de Meij L, Schaufeli WB. Work-focused treatment of common mental disorders and return to work: a comparative outcome study. J Occup Health Psychol. (2012) 17:220–34. doi: 10.1037/a0027049

Maslach C, Leiter MP. Understanding the burnout experience: recent research and its implications for psychiatry. World Psychiatry. (2016) 15:103–11. doi: 10.1002/wps.20311

Moore THM, Kapur N, Hawton K, Richards A, Metcalfe C, Gunnell D. Interventions to reduce the impact of unemployment and economic hardship on mental health in the general population: a systematic review. Psychol Med. (2017) 47:1062–84. doi: 10.1017/S0033291716002944

Is returning to work important for mental health? A new possibility for intervention.

Depression, anxiety disorders and burnout syndrome are among the most common causes of absence from the workplace and, in the most severe cases, permanent incapacity for work. The loss of work has a negative impact on one's mental health status, the possibility of recovery and the perception of one's psychophysical well-being. Clinical interventions including pharmacological treatment (where deemed necessary), psychotherapy and reinforcement of the individual's skills can reduce the negative impact of the psychological disorder and progressively improve the ability to carry out work effectively. According to experts, reintegration into work allows, for example, to

1. increase the sense of efficacy and gratification
2. decrease feelings of exhaustion and cynicism typical of depression (Maslach et Leiter, 2016);
3. provide stability and a programme of daily activities (Lagerveld et al, 2012);
4. maintain financial security and a good level of social integration (Moore et al, 2017).

In cases where disability becomes permanent, on the other hand, rehabilitation efforts tend to decline with a negative impact on the individual's quality of life and the social and health costs borne by the community. In this regard, a semi-standardised, patient-oriented intervention of about 80 hours has recently been presented (Behrens-Wittenberg et and Wedegaertner, 2021) and seems to be prospectively very effective. The procedure consists of 3 phases.

Phase 1: Stabilising the mental health status of the patient, ensuring continuity and quality of treatment and support, including bureaucratic support. Coaching can be helpful in assessing and reinforcing the skills, abilities and competences needed for recovery. These steps should be calibrated according to the mental stability of the individuals and their personal priorities.

Phase 2a: If the patient's previous job position is available, it is preferable to opt for reintegration in the same place of employment. The intervention requires a reconnaissance of the workplace to check for possible criticalities to be examined together with the employer and the patient, in order to define strategies to limit the impact on the state of health.

Phase 2b: If no place of employment is available, lateral thinking is used to create new job prospects by enhancing the skills and abilities required by the available jobs. In this phase the individual should be supported both in the preparation/training phase and in the drafting of application documents and the subsequent selection phase.

Phase 3: The phase of re-employment and/or starting a new activity is supported by specialised staff until the end of the intervention. It is important to make the individual feel that he/she is able to cope with the new social and work challenges and that the psychologist is always available to support him/her and to enhance the skills needed to interact in the new environment.

Although the intervention has limitations and can be further improved, it is a useful tool to improve work capacity and in general the biopsychosocial well-being of the individual, which is the main core business to be achieved.

Bibliography

Behrens-Wittenberg E and Wedegaertner F (2021) A Return-to-Work Intervention for Prematurely Retired Depression or Anxiety Disorder Patients. Front. Psychiatry 12:662158. doi: 10.3389/fpsyt.2021.662158

Lagerveld SE, Blonk RW, Brenninkmeijer V, Wijngaards-de Meij L, Schaufeli WB. Work-focused treatment of common mental disorders and return to work: a comparative outcome study. J Occup Health Psychol. (2012) 17:220–34. doi: 10.1037/a0027049

Maslach C, Leiter MP. Understanding the burnout experience: recent research and its implications for psychiatry. World Psychiatry. (2016) 15:103–11. doi: 10.1002/wps.20311

Moore THM, Kapur N, Hawton K, Richards A, Metcalfe C, Gunnell D. Interventions to reduce the impact of unemployment and economic hardship on mental health in the general population: a systematic review. Psychol Med. (2017) 47:1062–84. doi: 10.1017/S0033291716002944

the impact of COVID -19 on the psychological health of society and the role of the brain-derived neurotrophic factor and possible interventions.

 

Covid-19 has changed habits and lifestyles, contributing to behaviours that are potentially harmful to mental and physical health.

Recent studies on Covid-19 have shown that stress and lack of meaningful interpersonal relationships have made it increasingly common to diagnose sleep disorders, mood declines, apathy, anxiety, post-traumatic stress disorder, depression and personality disorders.

It is now known that COVID-19 has profoundly altered habits and lifestyles, contributing to behaviours that can be harmful to psychophysical health. In addition, the lockdown imposed a long experience of social isolation that left individuals defenceless in the face of intense media bombardment about the coronavirus' progress, the fear of losing one's job, of falling ill and not being able to receive adequate care or treatment, and the trauma of an unexpected diagnosis or bereavement.

 

In this regard, recent studies (Kwong & al, 2020 and Tacquet & al, 2020) have shown that exposure to high stress and a psychological condition characterised by a lack of meaningful interpersonal relationships have made it increasingly common to be diagnosed with sleep disorders, mood declines, apathy, anxiety, post-traumatic stress disorder, depression and personality disorders (Nenov-Matt & al, 2020). The elderly in particular represent the social group in which the virus has claimed the greatest number of victims and has abruptly interrupted active habits (sewing, embroidery, artistic activities, reading), social relationships and physical activity (Di Santo & al, 2020). This situational picture, combined with increased loneliness, can increase the risk of cognitive decline and over time dementia by 40% (Sutin & al., 2018). This may find a possible explanation (Buchman & al, 2016) in the reduction in the values of brain-derived neurotrophic factor (BDNF), a neurotrophin that contributes significantly to the survival and production of neurons as well as the activation of neuroplasticity processes. Indeed, it has been observed (Notaras & van den Buuse, 2020) that this neurotrophin is directly involved in physiological adaptation processes (resilience) to stressful events and that a reduction in BDNF levels, in addition to slowing synaptogenesis and neurogenesis, is the common denominator of many diseases and disorders (including anxiety, depression and cognitive decline) that are characterised by abnormalities in cognitive processes and emotion processing due to malfunctioning of the brain areas responsible for their regulation (Price & Duman, 2020). It is therefore very important to devise psycho-educational interventions to raise awareness of the need to maintain a healthy lifestyle (including motor activity and an adequate diet), to be curious, to cultivate interests, passions and hobbies that facilitate social inclusion. It is also useful to try to strengthen family resilience by promoting active listening and mutual support among family members as well as developing an adequate capacity to manage stress and emotions, including through the use of mindfulness and bioenergetic exercises.

It is also necessary to take note of the fact that the pandemic has strongly proposed the need to integrate psychological support into the citizen's basic care and at the same time to facilitate access to these services of public utility. Lastly, it is essential to develop a common conscience to break down prejudices and make recourse to a psychologist normal in times of difficulty.

The italian version is available at this link