Nuevos enfoques en el tratamiento de la depresión mayor resistente : propuesta de estudio piloto de tratamiento con Psilocibina

La depresión mayor es un trastorno que genera un gran sufrimiento y que actualmente se considera una pandemia. Conocemos poco del sustrato fisiopatológico, lo que hace muy complicado desarrollar terapias efectivas, además las terapias actuales presentan un alto índice de recidivas y efectos secundarios tras su administración. Todo ello pone de manifiesto la necesidad creciente de desarrollar nuevos procedimientos más efectivos. Recientemente, mediante el empleo de técnicas de resonancia magnética, se ha revelado una red neuronal conocida como Default Mode Network (DMN) que es crucial en funciones superiores, afectivas y cognitivas. Se ha comprobado que cuando los centros que integran esta red, funcionan de manera desorganizada, los sujetos experimentan síntomas que se engloban dentro de un gran espectro de patologías como la depresión. Nuevos estudios han demostrado que la administración de psilocibina, en las condiciones adecuadas de psicoterapia, tiene la capacidad de permitir la reconexión saludable entre dichos centros, lo que la convierte en una potencial terapia. Aceptando las hipótesis neuroquímicas actuales, en las que la depresión se explica por una disfunción de los sistemas de neurotransmisión noradrenérgico y serotoninérgico, el siguiente estudio se centra en la disfunción de dicha red, que complementa de una manera interesante las hipótesis biológicas actuales y permite introducir la psilocibina como un nuevo tratamiento. Se propone un ensayo piloto en base a la información recabada, que permita probar la eficacia de la psilocibina en depresión mayor resistente al tratamiento.Major depression is a disorder that generates great suffering and is currently considered a pandemic. We know little about the pathophysiological substrate, which makes it very complicated to develop effective therapies, a fact demonstrated by the high rate of recurrences after its administration. All this highlights are growing the need to develop new and more effective procedures. Recently, through the use of magnetic resonance techniques, a neural network known as the Default Mode Network (DMN), which is crucial in superior, affective and cognitive functions, has been revealed as an independent entity of external stimuli. It has been proven that when the hubs make up this network function in a disorganized manner, the subjects experience symptoms included within a wide spectrum of pathologies such as depression. New studies have been shown that psilocybin, under the right conditions of psychotherapy, has the ability to allow healthy reconnection between these hubs, which makes it a potential therapy. Accepting the current neurochemical hypotheses, in which depression is explained by a dysfunction of the noradrenergic and serotonergic neurotransmission systems, the following study focuses on the dysfunction of mentioned network, which complements in an interesting way the current biological hypotheses and allows to introduce Psilocybin as a new treatment. A pilot trial is proposed based on the information collected, which allows testing the efficacy of psilocybin in major depression resistant to treatment

Striatal adenosine A2A receptor neurons control active-period sleep via parvalbumin neurons in external globus pallidus

Dysfunction of the striatum is frequently associated with sleep disturbances. However, its role in sleep-wake regulation has been paid little attention even though the striatum densely expresses adenosine A2A receptors (A2ARs), which are essential for adenosine-induced sleep. Here we showed that chemogenetic activation of A2AR neurons in specific subregions of the striatum induced a remarkable increase in non-rapid eye movement (NREM) sleep. Anatomical mapping and immunoelectron microscopy revealed that striatal A2AR neurons innervated the external globus pallidus (GPe) in a topographically organized manner and preferentially formed inhibitory synapses with GPe parvalbumin (PV) neurons. Moreover, lesions of GPe PV neurons abolished the sleep-promoting effect of striatal A2AR neurons. In addition, chemogenetic inhibition of striatal A2AR neurons led to a significant decrease of NREM sleep at active period, but not inactive period of mice. These findings reveal a prominent contribution of striatal A2AR neuron/GPe PV neuron circuit in sleep control

Differential Resting-State Functional Connectivity of Striatal Subregions in Bipolar Depression and Hypomania

Bipolar disorder (BP) is characterized by periods of depression (BPD) and (hypo)mania (BPM), but the underlying state-related brain circuit abnormalities are not fully understood. Striatal functional activation and connectivity abnormalities have been noted in BP, but consistent findings have not been reported. To further elucidate striatal abnormalities in different BP states, this study investigated differences in resting-state functional connectivity of six striatal subregions in BPD, BPM, and healthy control (HC) subjects. Ninety medication-free subjects (30 BPD, 30 BPM, and 30 HC), closely matched for age and gender, were scanned using 3T functional magnetic resonance imaging (fMRI) acquired at resting state. Correlations of low-frequency blood oxygen level dependent signal fluctuations for six previously described striatal subregions were used to obtain connectivity maps of each subregion. Using a factorial design, main effects for differences between groups were obtained and post hoc pairwise group comparisons performed. BPD showed increased connectivity of the dorsal caudal putamen with somatosensory areas such as the insula and temporal gyrus. BPM group showed unique increased connectivity between left dorsal caudate and midbrain regions, as well as increased connectivity between ventral striatum inferior and thalamus. In addition, both BPD and BPM exhibited widespread functional connectivity abnormalities between striatal subregions and frontal cortices, limbic regions, and midbrain structures. In summary, BPD exhibited connectivity abnormalities of associative and somatosensory subregions of the putamen, while BPM exhibited connectivity abnormalities of associative and limbic caudate. Most other striatal subregion connectivity abnormalities were common to both groups and may be trait related

Neurocognitive Mechanisms Associated with Real-world Financial Savings among Individuals from Lower Income Households

Lower financial savings among individuals experiencing adverse social determinants of health (SDoH) such as low socioeconomic status (low-SES) increases health inequities during times of crisis. Despite evidence suggesting that economic stability established by better money-saving behavior may minimize socioeconomic disparities, neurocognitive mechanisms that regulate money-saving behavior remains to be understood. In the current studies, we utilized neuroimaging, behavioral, self-report, and real-world behavior data to examine neurocognitive mechanisms associated with money-saving behavior among low-SES population. In study 1, we utilized Balloon Analogue Risk task (BART) to probe decision-making (DM) related brain activity and further examined the relationship between brain activity, BART-performance, and real-world money-saving behavior. In study 2, we utilized n-back task to probe working memory (WM) mechanism and characterized the relationship between WM-related brain activity, WM-performance, and money-saving behavior. In study 3, we utilized resting-state fMRI data to characterize the resting-state functional connectivity (rsFC) of the brain regions associated with WM and their relationship with money-saving behavior. Regarding DM related brain-behavior relationship, elevated risk-related amygdala activity was associated with improved strategic-DM (i.e., BART task-performance measure) and improved strategic-DM, in turn, predicted better savings. Additionally, in an exploratory analysis, personality trait (i.e., alexithymia) moderated this mediation such that for individuals with low alexithymia (versus higher alexithymia), elevated risk-related amygdala activity was associated with better savings. Regarding WM related brain activity and associated behavior, laboratory WM performance (dprime) mediated the association between WM related DMN deactivation and real-world savings behavior such that increased DMN deactivation improves dprime which, in turn, results in better savings. Further, considering the rsFC of brain regions related to WM and associated behavior, dprime mediated the effect of fronto-limbic and fronto-frontal connectivity on real-world saving behavior such that higher frontal-limbic connectivity predicted worsened WM performance, which in turn, predicted reduced savings. Similarly, higher fronto-frontal connectivity predicted better WM performance, and, in turn, better WM performance predicted improved savings. This present study provides evidence that interventions targeting brain activity related to higher order executive function (DM and WM) and associated cognitive performance can augment success in terms of real-world money-saving behavior