Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder

Author(s):  
Richard J. Beninger

Schizophrenia, Parkinson’s disease, and attention deficit hyperactivity disorder (ADHD) discusses how hyperactive dopaminergic neurotransmission appears to underlie schizophrenia’s positive symptoms, loss of dopaminergic neurons in adulthood leads to Parkinson’s disease, and dopamine neuron hypofunction in childhood and adolescence may underlie ADHD. Positive schizophrenia symptoms may arise from excessive incentive learning that is gradually lost with antipsychotic treatment. Declarative learning and memory may contribute to delusions based on excessive incentive learning. Loss of responsiveness to environmental stimuli in Parkinson’s may result from a decrease of their conditioned incentive value and inverse incentive learning. Conditioned incentive stimuli not encountered while in a state of decreased dopaminergic neurotransmission may retain their incentive value, producing apparent kinesia paradoxa. Dopamine hypofunction in juveniles does not lead to hypokinesia but may result in loss of incentive learning that focuses attention. Pro-dopaminergic drugs have a calming effect in ADHD, presumably because they reinstate normal incentive learning.

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Juan Carlos Corona

Parkinson’s disease (PD) is the second most common neurodegenerative disorder with an unknown aetiology. The pathogenic mechanisms include oxidative stress, mitochondrial dysfunction, protein dysfunction, inflammation, autophagy, apoptosis, and abnormal deposition of α-synuclein. Currently, the existing pharmacological treatments for PD cannot improve fundamentally the degenerative process of dopaminergic neurons and have numerous side effects. On the other hand, attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood and is characterised by hyperactivity, impulsivity, and inattention. The aetiology of ADHD remains unknown, although it has been suggested that its pathophysiology involves abnormalities in several brain regions, disturbances of the catecholaminergic pathway, and oxidative stress. Psychostimulants and nonpsychostimulants are the drugs prescribed for the treatment of ADHD; however, they have been associated with increased risk of substance use and have several side effects. Today, there are very few tools available to prevent or to counteract the progression of such neurological disorders. Thus, therapeutic approaches with high efficiency and fewer side effects are needed. This review presents a brief overview of the two neurological disorders and their current treatments, followed by a discussion of the natural compounds which have been studied as therapeutic agents and the mechanisms underlying the beneficial effects, in particular, the decrease in oxidative stress.


2020 ◽  
Vol 29 ◽  
pp. 096368972094741
Author(s):  
Hueng-Chuen Fan ◽  
Yu-Kang Chang ◽  
Jeng-Dau Tsai ◽  
Kuo-Liang Chiang ◽  
Jui-Hu Shih ◽  
...  

While Parkinson’s disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan’s Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.


2019 ◽  
Author(s):  
Nina Roth Mota ◽  
Geert Poelmans ◽  
Marieke Klein ◽  
Bàrbara Torrico ◽  
Noèlia Fernàndez-Castillo ◽  
...  

ABSTRACTAttention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N=53,293, N=681,275, and N=98,697, respectively). We then conducted genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD-BMI overlapping genes with brain volumes (primary GWAS data N=10,720–10,928; replication data N=9,428). The dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), the circadian rhythm was associated with BMI (P=1.28×10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD-BMI and ADHD-obesity results. The ADHD-BMI overlapping genes were associated with putamen volume (P=7.7×10−3; replication data P=3.9×10−2) – a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.


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