scholarly journals A common molecular mechanism for cognitive deficits and craving in alcoholism

2020 ◽  
Author(s):  
Marcus W. Meinhardt ◽  
Simone Pfarr ◽  
Cathrin Rohleder ◽  
Valentina Vengeliene ◽  
Janet Barroso-Flores ◽  
...  

Alcohol-dependent patients commonly show impairments in executive functions that facilitate craving and can lead to relapse. The medial prefrontal cortex, a key brain region for executive control, is prone to alcohol-induced neuroadaptations. However, the molecular mechanisms leading to executive dysfunction in alcoholism are poorly understood. Here using a bi-directional neuromodulation approach we demonstrate a causal link for reduced prefrontal mGluR2 function and both impaired executive control and alcohol craving. By neuron-specific prefrontal knockdown of mGluR2 in rats, we generated a phenotype of reduced cognitive flexibility and excessive alcohol-seeking. Conversely, restoring prefrontal mGluR2 levels in alcohol-dependent rats rescued these pathological behaviors. Also targeting mGluR2 pharmacologically reduced relapse behavior. Finally, we developed a FDG-PET biomarker to identify those individuals that respond to mGluR2-based interventions. In conclusion, we identified a common molecular pathological mechanism for both executive dysfunction and alcohol craving, and provide a personalized mGluR2-mechanism-based intervention strategy for medication development of alcoholism.

2021 ◽  
Author(s):  
◽  
Sophie Hedley

<p>Creativity is hugely important in our everyday lives. Understanding what makes some people more creative than others is not just important in traditional creative fields. Creative problem solving is the key to solving all significant challenges we face as a society, including but not limited to technological, political and environmental challenges. Mental illness, in both popular culture and in psychological science, have long been linked to creative thought. Many eminent creatives, both past and current, attribute their success to their mental illness. For example, in schizophrenia, the grandiose thinking and florid hallucinations that characterise this disorder may be supportive of creative thinking.   However, schizophrenia is characterised by severe cognitive deficits that, according to models of creativity, would be disadvantageous to creative thinking. Schizotypy is a personality trait that is characterised by some features of schizophrenia (unusual thinking, poor interpersonal communication), but is not accompanied by the same severe cognitive deficits seen in schizophrenia. Based on this view, it is reasonable to assume that people high on schizotypal traits may be more creative than those who are low on schizotypal traits.   While there a number of studies examining this relationship, findings are inconsistent, with effect sizes ranging from -.42 to .8. In my thesis, I explored a) whether there was a relationship between schizotypy and creativity and b) whether that relationship could be explained by underlying differences in cognitive processing (associative processing and executive control). I predicted that positive schizotypy in particular (typified by unusual thinking, superstitious beliefs) would be positively correlated with schizotypy in three different measures of creativity (two performance based tasks and one self-report measure) in two different samples of participants.   In Chapters 3 + 4, I tested the relationship between schizotypy and creativity using two different methods. In chapter 3, I found no evidence for the predicted effect. In fact, I found a negative association between positive schizotypy and scores on one measure of creativity (the Remote Associates test) and a positive association between negative schizotypy (characterised by interpersonal deficits) and performance on the RAT. These effects did not replicate in the second sample. Finally, there was a positive association between disorganised schizotypy and creativity on the Alternate Uses task. The results of Chapter 4, using a latent profile analytic approach, mirrored the results of Chapter 3. Finally, Chapter 5 found no support for any relationship being mediated by associative processing or executive control; however, there was partial support for two models of creativity. Overall, evidence suggests that schizotypal traits are not helpful for creativity. These results shed light on some of the challenges when conducting research regarding both schizotypy and creativity.</p>


2014 ◽  
Vol 20 (10) ◽  
pp. 971-981 ◽  
Author(s):  
Tisha J. Ornstein ◽  
Sanya Sagar ◽  
Russell J. Schachar ◽  
Linda Ewing-Cobbs ◽  
Sandra B. Chapman ◽  
...  

AbstractThe present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6–16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions. (JINS, 2014,20, 971–981)


2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Yan-Fang Xian ◽  
Chang Qu ◽  
Yue Liu ◽  
Siu-Po Ip ◽  
Qiu-Ju Yuan ◽  
...  

Alzheimer’s disease (AD) is a common neurodegenerative disease characterized by progressive memory loss. Magnolol (MN), the main active ingredient of Magnolia officinalis, possesses anti-AD effects in several experimental models of AD. In this study, we aimed to explore whether MN could ameliorate the cognitive deficits in TgCRND8 transgenic mice and to elucidate its molecular mechanisms. Male TgCRND8 mice were orally administered with MN (20 and 40 mg/kg) daily for 4 consecutive months, followed by assessing the spatial learning and memory functions using the open-field, radial arm maze, and novel object recognition tests. The results demonstrated that MN (20 and 40 mg/kg) could markedly ameliorate the cognitive deficits in TgCRND8 mice. In addition, MN significantly increased the expression of postsynaptic density protein 93 (PSD93), PSD-95, synapsin-1, synaptotagmin-1, synaptophysin (SYN), and interleukin-10 (IL-10), while markedly reduced the protein levels of tumor necrosis factor alpha (TNF-α), IL-6, IL-1β, Aβ40, and Aβ42, and modulated the amyloid precursor protein (APP) processing and phosphorylation. Immunofluorescence showed that MN significantly suppressed the activation of microglia (Iba-1) and astrocytes (GFAP) in the hippocampus and cerebral cortex of TgCRND8 mice. Mechanistic studies revealed that MN could significantly increase the ratios of p-GSK-3β (Ser9)/GSK-3β, p-Akt (Ser473)/Akt, and p-NF-κB p65/NF-κB p65. These findings indicate that MN exerted cognitive deficits improving effects via suppressing neuroinflammation, amyloid pathology, and synaptic dysfunction through regulating the PI3K/Akt/GSK-3β and NF-κB pathways, suggesting that MN is a promising naturally occurring polyphenol worthy of further developing into a therapeutic agent for AD treatment.


2006 ◽  
Vol 11 (5) ◽  
pp. 323-332 ◽  
Author(s):  
E. E. Epstein ◽  
K. C. Rhines ◽  
S. Cook ◽  
B. Zdep‐Mattocks ◽  
N. K. Jensen ◽  
...  

2014 ◽  
Vol 76 (9) ◽  
pp. 734-741 ◽  
Author(s):  
Lorenzo Leggio ◽  
William H. Zywiak ◽  
Samuel R. Fricchione ◽  
Steven M. Edwards ◽  
Suzanne M. de la Monte ◽  
...  

Alcohol ◽  
2010 ◽  
Vol 44 (5) ◽  
pp. 401-406 ◽  
Author(s):  
Rachel D. Thompson ◽  
Jaimee L. Heffner ◽  
Judith A. Strong ◽  
Thomas J. Blom ◽  
Robert M. Anthenelli

2013 ◽  
Vol 132 (1-2) ◽  
pp. 395-398 ◽  
Author(s):  
Daniel S. Quintana ◽  
Adam J. Guastella ◽  
Iain S. McGregor ◽  
Ian B. Hickie ◽  
Andrew H. Kemp

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Erbao Chen ◽  
Xiaojing Xu ◽  
Ruiqi Liu ◽  
Tianshu Liu

Hepatocellular carcinoma (HCC), which accounts for 85–90% of primary liver cancer, is the fifth most common malignant tumor and the third leading cause of cancer-related deaths worldwide, but the pathological mechanism of HCC is still not fully elucidated. miRNAs are evolutionarily endogenous small noncoding RNAs that negatively regulate gene expression via posttranscriptional inhibition or target mRNA degradation in several diseases, especially human cancer. Therefore, discovering the roles of miRNAs is appealing to scientific researchers. Emerging evidence has shown that the aberrant expressions of numerous miRNAs are involved in many HCC biological processes. In hepatocarcinogenesis, miRNAs with dysregulated expression can exert their function as oncogenes or tumor suppressors depending on their cellular target during the cell cycle, and in tumor development, differentiation, apoptosis, angiogenesis, metastasis, and progression of the tumor microenvironment. In this review, we summarize current findings on miRNAs and assess their functions to explore the molecular mechanisms of tumor progression in HCC.


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