Dopamine Imbalance Research Articles

Serotonin syndrome caused by escitalopram in Parkinson’s disease psychosis: a case report

BackgroundSerotonin syndrome and Parkinson’s disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning.Case presentationA 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition.ConclusionsThis case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome.

Development of Trp-AuNPs-rGO based electrochemical active biosensing interface for dopamine detection

Neurotransmitters are essential for learning, mental alertness, blood flow, and emotions. An imbalance of neurotransmitters in the human system causes neurological disorders. An imbalance of dopamine, a neurotransmitter, can cause severe diseases such as Parkinson's disease, restless legs syndrome, depression, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Dopamine detection is essential but requires high sensitivity, temporal resolution, and favorable electrochemical techniques for the sensing mechanism. The ultrasensitive and selective real-time diagnosis of dopamine depends on the fabrication of a brain-on-a-chip model. Prior to fabrication of this device, it is very essential to develop a novel metal nanomaterial that exhibits biocompatibility and fast detection and is capable of improving the quality of the device. In this respect, we prepared amino acid-reduced gold nanoparticles that were supported by reduced graphene oxide. The prepared composite has been characterized by various techniques for internal and external morphology. The electrochemical behavior was examined on a glassy carbon electrode via various electrochemical techniques by a potentiostat instrument towards the diagnosis of dopamine at a micromolar level in the presence of its interference. Finally, as expected, we found 43.59 μAμM−1cm-2 sensitivity toward DA in the linear range of 1-11 μM. Trp-AuNPS-rGO shows promising results toward the diagnosis of dopamine in the presence of its interference and proves that this nanomaterial will be very promising toward the fabrication of a brain-on chip.

Angiotensin II involvement in the development and persistence of amphetamine-induced sensitization: Striatal dopamine reuptake implications.

Amphetamine (AMPH) exposure induces behavioural and neurochemical sensitization observed in rodents as hyperlocomotion and increased dopamine release in response to a subsequent dose. Brain Angiotensin II modulates dopaminergic neurotransmission through its AT1 receptors (AT1-R), positively regulating striatal dopamine synthesis and release. This work aims to evaluate the AT1-R role in the development and maintenance of AMPH-induced sensitization. Also, the AT1-R involvement in striatal dopamine reuptake was analysed. The sensitization protocol consisted of daily AMPH administration for 5days and tested 21 days after withdrawal. An AT1-R antagonist, candesartan, was administered before or after AMPH exposure to evaluate the participation of AT1-R in the development and maintenance of sensitization, respectively. Sensitization was evaluated by locomotor activity and c-Fos immunostaining. Changes in dopamine reuptake kinetics were evaluated 1day after AT1-R blockade withdrawal treatment, with or without the addition of AMPH in vitro. The social interaction test was performed as another behavioural output. Repeated AMPH exposure induced behavioural and neurochemical sensitization, which was prevented and reversed by candesartan. The AT1-R blockade increased the dopamine reuptake kinetics. Neither the AMPH administration nor the AT1-R blockade altered the performance of social interaction. Our results highlight the AT1-R's crucial role in AMPH sensitization. The enhancement of dopamine reuptake kinetics induced by the AT1-R blockade might attenuate the neuroadaptive changes that lead to AMPH sensitization and its self-perpetuation. Therefore, AT1-R is a prominent candidate as a target for pharmacological treatment of pathologies related to dopamine imbalance, including drug addiction and schizophrenia.

Lasting mesothalamic dopamine imbalance and altered exploratory behavior in rats after a mild neonatal hypoxic event.

Adversities during the perinatal period can decrease oxygen supply to the fetal brain, leading to various hypoxic brain injuries, which can compromise the regularity of brain development in different aspects. To examine the catecholaminergic contribution to the link between an early-life hypoxic insult and adolescent behavioral aberrations, we used a previously established rat model of perinatal hypoxia but altered the hypobaric to normobaric conditions. Exploratory and social behavior and learning abilities were tested in 70 rats of both sexes at adolescent age. Inherent vertical locomotion, sensory-motor functions and spatial learning abilities were explored in a subset of animals to clarify the background of altered exploratory behavior. Finally, the concentrations of dopamine (DA) and noradrenaline in midbrain and pons, and the relative expression of genes for DA receptors D1 and D2, and their down-stream targets (DA- and cAMP-regulated phosphoprotein, Mr 32 kDa, the regulatory subunit of protein kinase A, and inhibitor-5 of protein phosphatase 1) in the hippocampus and thalamus were investigated in 31 rats. A lesser extent of alterations in exploratory and cognitive aspects of behavior in the present study suggests that normobaric conditions mitigate the hypoxic injury compared to the one obtained under hypobaric conditions. Increased exploratory rearing was the most prominent consequence, with impaired spatial learning in the background. In affected rats, increased midbrain/pons DA content, as well as mRNA levels for DA receptors and their down-stream elements in the thalamus, but not the hippocampus, were found. We can conclude that a mild hypoxic event induced long-lasting disbalances in mesothalamic DA signaling, contributing to the observed behavioral alterations. The thalamus was thereby indicated as another structure, besides the well-established striatum, involved in mediating hypoxic effects on behavior through DA signaling.

Multilevel evidence of MECP2-associated mitochondrial dysfunction and its therapeutic implications.

We present a male patient carrying a pathogenic MECP2 p. Arg179Trp variant with predominant negative psychiatric features and multilevel evidence of mitochondrial dysfunction who responded to the cariprazine treatment. He had delayed speech development and later experienced severe social anxiety, learning disabilities, cognitive slowing, and predominant negative psychiatric symptoms associated with rigidity. Clinical examinations showed multisystemic involvement. Together with elevated ergometric lactate levels, the clinical picture suggested mitochondrial disease, which was also supported by muscle histopathology. Exploratory transcriptome analysis also revealed the involvement of metabolic and oxidative phosphorylation pathways. Whole-exome sequencing identified a pathogenic MECP2 variant, which can explain both the dopamine imbalance and mitochondrial dysfunction in this patient. Mitochondrial dysfunction was previously suggested in classical Rett syndrome, and we detected related phenotype evidence on multiple consistent levels for the first time in a MECP2 variant carrier male. This study further supports the importance of the MECP2 gene in the mitochondrial pathways, which can open the gate for more personalized therapeutic interventions. Good cariprazine response highlights the role of dopamine dysfunction in the complex psychiatric symptoms of Rett syndrome. This can help identify the optimal treatment strategy from a transdiagnostic perspective instead of a classical diagnostic category.

Establishment of a 6-OHDA InducedUnilaterally Lesioned Male Wistar Rat Model of Parkinson's Disease.

Robust preclinical models of Parkinson's disease (PD) are valuable tools for understanding the biology and treatment of this complex disease. 6-Hydroxydopamine (6-OHDA) is a selective catecholaminergic drug injected into the substantia nigra pars compacta (SNc), medial forebrain bundle (MFB), or striatum, which is then metabolized to induce parkinsonism. Unilateral injectionof 6-OHDA produces loss of dopaminergic (DAergic) neurons on the injected side with a marked motor asymmetry known as hemiparkinsonism, typically characterized by a rotational behavior to the impaired side. The present work describes a stable unilateral 6-OHDA-lesioned rat model of PD. 6-OHDA was administered into the MFB, leading to the consistent loss of striatal dopamine (DA) and behavioral imbalance in unilateral 6-OHDA-lesioned rats to establish the model of PD. This model of PD is a valuable tool for understanding the mechanisms underlying the generation of parkinsonian symptoms.

АНТИСПЕРМАЛЬНЫЕ АНТИТЕЛА И ПЕРИФЕРИЧЕСКИЙ ДОФАМИН У МУЖЧИН С УЧЕТОМ КОНТРАСТНОЙ ФОТОПЕРИОДИКИ ЕВРОПЕЙСКОГО СЕВЕРА

The physiological role of reference levels of antispermal antibodies (ASABs) in fertile men and mechanisms controlling their concentration are still not fully understood. It is hypothesized that they may contribute to the immunological tolerance of testicles in healthy organism. We investigated the relation between ASABs and dopamine in blood of different groups of males living in the European North with consideration of contrast photoperiodism. Participants were 20 Caucasian males in Arkhangelsk observed over 4 seasonal photoperiods and 108 male dwellers of local settlements (Caucasians, Nenets, komi and metis aborigines), and aborigines migrating nearby who were observed in the periods of minimal light days (December) and then in March. IFA was used to determine concentrations of ASABs in serum and dopamine in blood. Minimal ASABs and increasing dopamine were determined in Archangelsk in the period of maximal daylight hours and in the Caucasian males in settlements in the period of light time which can serve as an argument for specifying periods most favorable for conception. Males in settlements and migrants were distinguished by a higher ASABs level in comparison to the male population in Archangelsk in December against dopamine imbalance due to, probably, oxidative stress and increased permeability of the blood-testis barrier. This finding calls for a close attention to the reproductive system condition. Elevated ASABs levels were observed on the backgrounds of undetectable (0 nmol/l) and abnormal (>0.653 nmol/l) dopamine values, whereas decreased ASABs concentrations were found with dopamine at reference levels. Based on these results of the investigation we assume a dose-dependent dopamine effect on ASABs and propose a hypothesis that control of dopamine in blood could prevent autoimmune sterility.

Under the umbrella of depression and Alzheimer's disease physiopathology: Can cannabinoids be a dual-pleiotropic therapy?

Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60-80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises. Herein, we discuss the current state-of-art regarding the contribution of the endocannabinoid system (ECS) in synaptic transmission processes, synapses plasticity and neurogenesis and consequently the use of exogenous cannabinoids in the treatment of depression and on delaying the progression of AD. Besides the well-known imbalance of neurotransmitter levels, including serotonin, noradrenaline, dopamine and glutamate, recent scientific evidence highlights aberrant spine density, neuroinflammation, dysregulation of neurotrophic factor levels and formation of amyloid beta (Aβ) peptides, as the main physiopathological mechanisms compromised in depression and AD. The contribution of the ECS in these mechanisms is herein specified as well as the pleiotropic effects of phytocannabinoids. At the end, it became evident that Cannabinol, Cannabidiol, Cannabigerol, Cannabidivarin and Cannabichromene may act in novel therapeutic targets, presenting high potential in the pharmacotherapy of both diseases.

In-silico Validation of Pyrazolone Derivatives as the Potent Scaff old for Modulating Protein Abnormalities Associated with Parkinson’s Disease

Aim: We explored pyrazolone derivatives for anti-Parkinson’s activity using in-silico tools to identify novel lead hits against Parkinson’s disease. Background: Parkinson’s disease is the most predominant neuronal degenerative disorder, caused by protein aggregation and dopamine imbalance. The available therapeutic agents on prolonged exposure lead to severe adverse eff ects and provide only symptomatic relief. Therefore, it is a need for novel drug molecules that would modulate the disease condition. Objectives: To identify novel hit molecule for a sequence of molecules designed using pyrazolone as a parent moiety by computer-aided drug design techniques. Materials and Methods: Derivatives are generated by various substituted functional groups and further, pharmacokinetic profi le, the biological spectrum, adverse drug eff ect, molecular docking, molecular dynamic, and MMPBSA evaluation was performed. Results: Thirty-four compounds follow a pharmacokinetic profi le. 15 compounds were predicted to possess a positive central nervous system activity score. The compounds C13, C12, C14, A1, C9, and C7 possessed the highest binding affi nity of -7.81, -3.15, -8.49, -3.43, -6.09, and -2.77 kcal/mol with various targets involved in Parkinson’s disease. Compound C13 exhibit ed highest binding score of -9.78 kcal/mol formono amino oxidase-B. Conclusion: From our investigations, we hope that novel substituted pyrazolone derivatives can act as an assuring virtual hit molecule for developing anti-Parkinson’s agents. These predictions obtained via in-silico techniques could aid the development of pharmacological inhibitors for Parkinson’s disease.

Bridging the gaps towards precision psychiatry: Mechanistic biomarkers for early detection and intervention

Early detection and intervention in schizophrenia, improving prognosis, requires mechanism-based biomarkers that capture circuitry dysfunction, allowing optimized patient stratification, disease monitoring and treatment.Dr. Do's translational research, bridging basic neuroscience and clinical psychiatry, tackles an urgent need to develop effective treatments that target mechanisms underlying cognitive deficits, a critical dimension of schizophrenia, currently not well treated. By adopting a reverse translation of validated circuitry relevant human endpoints, her research brought new insights in mechanism-based biomarker guided treatment of patients in early stages of psychosis. She showed that oxidative stress/redox dysregulation, in reciprocal interaction with dopamine imbalance, NMDAR hypofunction, neuroinflammation and mitochondrial bioenergetic dysfunction, may represent a "hub" on which both genetic and environmental risk factors converge during neurodevelopment. This leads to impairments of structural and functional connectivity in microcircuits, involving impaired parvalbumin fast-spiking GABA neurons, and macrocircuits, impacting myelination of fiber tracts, at the basis of neural synchronization abnormalities, as well as sensory and cognitive deficits. These unique insights led to successful proof-of-concept clinical trials, targeting oxidative stress through antioxidant-based strategies in patients at various disease stages, paving the way for precision medicine in psychiatry.

Dorsal striatial hypoconnectivity predicts antipsychotic medication treatment response in first-episode psychosis and unmedicated patients with schizophrenia.

The dorsal striatum, comprised of the caudate and putamen, is implicated in the pathophysiology of psychosis spectrum disorders. Given the high concentration of dopamine receptors in the striatum, striatal dopamine imbalance is a likely cause in cortico-striatal dysconnectivity. There is great interest in understanding the relationship between striatal abnormalities in psychosis and antipsychotic treatment response, but few studies have considered differential involvement of the caudate and putamen. This study's goals were twofold. First, identify patterns of dorsal striatal dysconnectivity for the caudate and putamen separately in patients with a psychosis spectrum disorder; second, determine if these dysconnectivity patterns were predictive of treatment response. Using resting state functional connectivity, we evaluated dorsal striatal connectivity using separate bilateral caudate and putamen seed regions in two cohorts of subjects: a cohort of 71 medication-naïve first episode psychosis patients and a cohort of 42 unmedicated patients with schizophrenia (along with matched controls). Patient and control connectivity maps were contrasted for each cohort. After receiving 6 weeks of risperidone treatment, patients' clinical response was calculated. We used regression analyses to determine the relationship between baseline dysconnectivity and treatment response. This dysconnectivity was also predictive of treatment response in both cohorts. These findings suggest that the caudate may be more of a driving factor than the putamen in early cortico-striatal dysconnectivity.

Influence of the Co-Adsorbed Ions on the Surface-Enhanced Raman Scattering Spectra of Dopamine Adsorbed on Nanostructured Silver.

The abnormal metabolism or imbalance of dopamine may lead to some neurological disorders. Therefore, the facile and fast detection of this neurotransmitter is essential in the early diagnosis of some diseases. One of the methods that can be used for the detection and determination of dopamine is the surface-enhanced Raman scattering (SERS). In this contribution, we report a very strong influence of some salts (we used salts containing Na+ cations and the following anions: SO42−, F−, Cl−, Br−, and I−) on the spectral patterns and intensity of the SERS spectra of dopamine adsorbed on a nanostructured macroscopic silver substrate. The analysis of the recorded SERS spectra based on the assignments of Raman bands from the density-functional theory (DFT) calculations and based on the SERS surface selection rules reveals that when molecules of dopamine are adsorbed from an aqueous solution to which no electrolytes have been added, they adopt a flat orientation versus the silver surface; whereas, the molecules of dopamine co-adsorbed with various ions interact with the silver surface, mainly via phenolic groups, and they adopt a perpendicular orientation versus the metal surface. An addition of electrolytes also significantly influences the intensity of the recorded SERS spectrum; for example, an addition of Na2SO4 to a final concentration of 1 M induces an increase in the intensity of the measured SERS spectrum by a factor of ca. 40. This means that the addition of electrolytes to the analyzed solution can reduce the limit of detection of dopamine by SERS spectroscopy. The abovementioned findings may facilitate the construction of dopamine SERS sensors.

A mechanistic model of ADHD as resulting from dopamine phasic/tonic imbalance during reinforcement learning.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in children. Although the involvement of dopamine in this disorder seems to be established, the nature of dopaminergic dysfunction remains controversial. The purpose of this study was to test whether the key response characteristics of ADHD could be simulated by a mechanistic model that combines a decrease in tonic dopaminergic activity with an increase in phasic responses in cortical-striatal loops during learning reinforcement. To this end, we combined a dynamic model of dopamine with a neurocomputational model of the basal ganglia with multiple action channels. We also included a dynamic model of tonic and phasic dopamine release and control, and a learning procedure driven by tonic and phasic dopamine levels. In the model, the dopamine imbalance is the result of impaired presynaptic regulation of dopamine at the terminal level. Using this model, virtual individuals from a dopamine imbalance group and a control group were trained to associate four stimuli with four actions with fully informative reinforcement feedback. In a second phase, they were tested without feedback. Subjects in the dopamine imbalance group showed poorer performance with more variable reaction times due to the presence of fast and very slow responses, difficulty in choosing between stimuli even when they were of high intensity, and greater sensitivity to noise. Learning history was also significantly more variable in the dopamine imbalance group, explaining 75% of the variability in reaction time using quadratic regression. The response profile of the virtual subjects varied as a function of the learning history variability index to produce increasingly severe impairment, beginning with an increase in response variability alone, then accumulating a decrease in performance and finally a learning deficit. Although ADHD is certainly a heterogeneous disorder, these results suggest that typical features of ADHD can be explained by a phasic/tonic imbalance in dopaminergic activity alone.

Overcoming reward deficiency syndrome by the induction of “dopamine homeostasis” instead of opioids for addiction: illusion or reality?

Many individuals in the United States are plagued by addiction, and the rate at which it is affecting people in the United States only seems to be increasing. Research shows that addiction is a preventable disorder rather than a flaw in one's moral fiber. It is driven by the imbalance of dopamine and the brain's reward system. Although medication-assisted treatment (MAT), the most common treatment for addiction, are effective in reducing harm, they provide minimal aid in addressing the root cause of this preventable disorder. The authors aim to convey that the proper treatment should help restore dopamine balance so the quality of life can be improved in the recovering community. Osteopathic principles emphasize the importance of homeostasis and allostasis in allowing the body to heal itself. Viewing reward deficiency syndrome (RDS) through this osteopathic lens can bring about treatments that aim to restore the dopamine homeostasis. The article discusses various potential therapeutic modalities that can provide dopamine homeostasis via activation of dopaminergic pathways.

Molecular Imaging of Central Dopamine in Obesity: A Qualitative Review across Substrates and Radiotracers.

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics.

Dopaminergic signaling regulates zebrafish larvae's response to electricity.

Electrical stimulation of brain or muscle activities has gained attention for studying the molecular and cellular mechanisms involved in electric-induced responses. We recently showed zebrafish's response to electricity. Here, we hypothesized that this response is affected by the dopaminergic signaling pathways. The effects of multiple dopamine agonists and antagonists on the electric response of 6 days-postfertilization zebrafish larvae were investigated using a microfluidic device with enhanced control of experimentation and throughput. All dopamine antagonists decreased locomotor activities, while dopamine agonists did not induce similar behaviors. The D2-selective dopamine agonist quinpirole enhanced the movement. Exposure to nonselective and D1-selective dopamine agonists apomorphine and SKF-81297 caused no significant change in the electric response. Exposing larvae that were pretreated with nonselective and D2-selective dopamine antagonists butaclamol and haloperidol to apomorphine and quinpirole, respectively, restored the electric locomotion. These results reveal a correlation between electric response and dopamine signaling pathway. Furthermore, they demonstrate that electric-induced zebrafish larvae locomotion can be conditioned by modulating dopamine receptor functions. Our electrofluidic assay has profound application potential for fundamental electric-induced response research and brain disorder studies especially those related to the dopamine imbalance and as a chemical screening method when investigating biological pathways and behaviors.

Improving Mood and Cognitive Symptoms in Huntington's Disease With Cariprazine Treatment.

In Huntington's disease (HD), the main clinical symptoms include depression, apathy, cognitive deficits, motor deficiencies and involuntary movements. Cognitive, mood and behavioral changes may precede motor symptoms by up to 15 years. The treatment of these diverse symptoms is challenging. Tetrabenazine and deutetrabenazine are the only medications specifically approved for Huntington's chorea, but they do not affect the non-motor symptoms. For these, antidepressants, antipsychotics, and benzodiazepines have demonstrated benefit in some cases and can be used off-label. These drugs, due to sedative side effects, may negatively influence cognition. Sixteen patients having HD received a 12-week off-label cariprazine (CAR) treatment (1.5–3 mg/day). Cognitive performance and behavioral changes were measured by the Addenbrooke Cognitive Examination (ACE) test, the Cognitive and Behavioral part of the Unified Huntington's Disease Rating Scale (UHDRS), and the Beck Depression Inventory (BDI). Mixed model for repeated measures was fitted to the data, with terms of visit, baseline (BL) and their interaction. Cariprazine treatment resulted in the following changes from BL to week 12, respectively: the mean score of BDI decreased from 17.7 ± 10.7 to 10.0 ± 10.7 (p <0.0097), while the Behavioral Assessment score of the UHDRS decreased from 54.9 ± 11.3 to 32.5 ± 15.4 (p < 0.0001); ACE score increased from 75.1 ± 11.0 to 89.0 ± 9.3 (p < 0.0001); Cognitive Verbal Fluency score from 6.2 ± 2.5 to 7.7 ± 2.7 (p < 0.0103); Symbol Digit Test from 9.2 ± 6.9 to 12.3 ± 8.9 (p < 0.0009). Mild akathisia was the most frequent side effect, presenting in 2 out of 16 patients (12.5%). We conclude that CAR had a positive effect on depressive mood, apathy and cognitive functions in patients with early stage of HD. Based on the neurobiological basis of these symptoms, CAR can improve the dopamine imbalance of the prefrontal cortex. This draws attention to the transdiagnostic approach which supports the further understanding of the similar symptomatology of different neuropsychiatric disorders and helps to identify new indications of pharmaceutical compounds.

Chemical imbalance and mental health

No chemical imbalances have been proven to exist in relation to any mental health condition, like serotonin deficiency in synapses in the so-called depressive disorders or dopamine imbalance and dopamine receptors distribution in socalled schizophrenia. No independent objective biological marker or current brain imagining science like fMRI exist to date in support of any psychiatric diagnosis, and finally yet importantly, no biological causes exist for any of the socalled psychiatric disorders. If we avoid Cartesian dualism, the claim that mental disorders are biological is obviously a tautology. Given the facts above, psychiatric diagnostic manuals, such as the DSM and ICD, are school examples of what evidence-based science is not and represent nothing but a failed attempt to build a legal road from Health Care to Hell Care by over-medicalization and by the suffering of human and non-human animals. Furthermore, psychiatric drugs can have long-lasting effects on the brain and the central nervous system, while, the withdrawal from them can cause a range of severe physical and psychological effects.

Striatal Acetylcholine-Dopamine Imbalance in Parkinson Disease: InVivo Neuroimaging Study with Dual-Tracer PET and Dopaminergic PET-Informed Correlational Tractography.

Previous studies of animal models of Parkinson disease (PD) suggest an imbalance between striatal acetylcholine and dopamine, although other studies have questioned this. To our knowledge, there are no previous invivo neuroimaging studies examining striatal acetylcholine-dopamine imbalance in PD patients. Using cholinergic and dopaminergic PET (18F-fluoroethoxybenzovesamicol [18F-FEOBV] and 11C-dihydrotetrabenazine [11C-DTBZ], respectively) and correlational tractography, our aim was to investigate the acetylcholine-dopamine interaction at 2 levels of dopaminergic loss in PD subjects: integrity loss of the nigrostriatal dopaminergic white matter tract and loss at the presynaptic-terminal level. Methods: The study involved 45 subjects with mild to moderate PD (36 men, 9 women; mean age, 66.3 ± 6.3 y, disease duration, 5.8 ± 3.6 y; Hoehn and Yahr stage, 2.2 ± 0.6) and 15 control subjects (9 men, 6 women; mean age, 69.1 ± 8.6 y). PET imaging was performed using standard protocols. We first estimated the integrity of the dopaminergic nigrostriatal white matter tracts in PD subjects by incorporating molecular information from striatal 11C-DTBZ PET into the fiber tracking process using correlational tractography (based on quantitative anisotropy [QA], a measure of tract integrity). Subsequently, we used voxel-based correlation to test the association of the mean QA of the nigrostriatal tract of each cerebral hemisphere with the striatal 18F-FEOBV distribution volume ratio (DVR) in PD subjects. The same analysis was performed for 11C-DTBZ DVR in 12 striatal subregions (presynaptic-terminal level). Results: Unlike 11C-DTBZ DVR in striatal subregions, the mean QA of the nigrostriatal tract of the most affected hemisphere showed a negative correlation with a striatal cluster of 18F-FEOBV DVR in PD subjects (corrected P = 0.039). We also found that the mean 18F-FEOBV DVR within this cluster was higher in the PD group than in the control group (P = 0.01). Cross-validation analyses confirmed these findings. We also found an increase in bradykinesia ratings associated with increased acetylcholine-dopamine imbalance in the most affected hemisphere (r = 0.41, P = 0.006). Conclusion: Our results provide evidence for the existence of striatal acetylcholine-dopamine imbalance in early PD and may provide an avenue for testing invivo effects of therapeutic strategies aimed at restoring striatal acetylcholine-dopamine balance in PD.

De Novo Movement Disorders and COVID-19: Exploring the Interface.

BackgroundNeurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) are being widely documented. However, movement disorders in the setting of 2019 coronavirus infectious disease (COVID‐19) have been a strikingly less discussed topic.ObjectivesTo summarize available pieces of evidence documenting de novo movement disorders in COVID‐19.MethodsWe used the existing PRISMA consensus statement. Data were collected from PubMed, EMBASE, Web of Science, and Scopus databases up to the 29th January, 2021, using pre‐specified searching strategies.ResultsTwenty‐two articles were selected for the qualitative synthesis. Among these, a total of 52 patients with de novo movement disorders were reported. Most of these had myoclonus, ataxia, tremor or a combination of these, while three had parkinsonism and one a functional disorder. In general, they were managed successfully by intravenous immunoglobulin or steroids. Some cases, primarily with myoclonus, could be ascribed to medication exposures, metabolic disturbances or severe hypoxia, meanwhile others to a post‐or para‐infectious immune‐mediated mechanism. SARS‐CoV‐2 could also invade the central nervous system, through vascular or retrograde axonal pathways, and cause movement disorders by two primary mechanisms. Firstly, through the downregulation of angiotensin‐converting enzyme 2 receptors, resulting in the imbalance of dopamine and norepinephrine; and secondly, the virus could cause cellular vacuolation, demyelination and gliosis, leading to encephalitis and associated movement disorders.ConclusionDe novo movement disorders are scantly reported in COVID‐19. The links between SARS‐CoV‐2 and movement disorders are not yet established. However, we should closely monitor COVID‐19 survivors for the possibility of post‐COVID movement disorders.