MyMedR

Displaying all 7 publications

Abstract:

Sort:

Genetic association of LMAN2L gene in schizophrenia and bipolar disorder and its interaction with ANK3 gene polymorphism

Lim CH, Zain SM, Reynolds GP, Zain MA, Roffeei SN, Zainal NZ, et al.

Prog Neuropsychopharmacol Biol Psychiatry, 2014 Oct 3;54:157-62.
PMID: 24914473 DOI: 10.1016/j.pnpbp.2014.05.017

Recent studies have shown that bipolar disorder (BPD) and schizophrenia (SZ) share some common genetic risk factors. This study aimed to examine the association between candidate single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) and risk of BPD and SZ. A total of 715 patients (244 BPD and 471 SZ) and 593 controls were genotyped using the Sequenom MassARRAY platform. We showed a positive association between LMAN2L (rs6746896) and risk of both BPD and SZ in a pooled population (P-value=0.001 and 0.009, respectively). Following stratification by ethnicity, variants of the ANK3 gene (rs1938516 and rs10994336) were found to be associated with BPD in Malays (P-value=0.001 and 0.006, respectively). Furthermore, an association exists between another variant of LMAN2L (rs2271893) and SZ in the Malay and Indian ethnic groups (P-value=0.003 and 0.002, respectively). Gene-gene interaction analysis revealed a significant interaction between the ANK3 and LMAN2L genes (empirical P=0.0107). Significant differences were shown between patients and controls for two haplotype frequencies of LMAN2L: GA (P=0.015 and P=0.010, for BPD and SZ, respectively) and GG (P=0.013 for BPD). Our study showed a significant association between LMAN2L and risk of both BPD and SZ.
Effect of newer anti-epileptic drugs (AEDs) on the cognitive status in pentylenetetrazol induced seizures in a zebrafish model

Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.

Prog Neuropsychopharmacol Biol Psychiatry, 2019 06 08;92:483-493.
PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014

Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.
Repressor element 1 silencing transcription factor /neuron-restrictive silencing factor (REST/NRSF) in social stress and depression

Soga T, Nakajima S, Kawaguchi M, Parhar IS

Prog Neuropsychopharmacol Biol Psychiatry, 2021 01 10;104:110053.
PMID: 32739332 DOI: 10.1016/j.pnpbp.2020.110053

Extreme stress is closely linked with symptoms of depression. Chronic social stress can cause structural and functional changes in the brain. These changes are associated with dysfunction of neuroprotective signalling that is necessary for cell survival, growth, and maturation. Reduced neuronal numbers and volume of brain regions have been found in depressed patients, which may be caused by decreased cell survival and increased cell death. Elucidating the mechanism underlying the degeneration of the neuroprotective system in social stress-induced depression is important for developing neuroprotective measures. The Repressor Element 1 Silencing Transcription Factor (REST) also known as Neuron-Restrictive Silencing Factor (NRSF) has been reported as a neuroprotective molecule in certain neurological disorders. Decreased expression levels of REST/NRSF in the nucleus can induce death-related gene expression, leading to neuronal death. Under physiological stress conditions, REST/NRSF over expression is known to activate neuronal survival in the brain. Alterations in REST/NRSF expression in the brain has been reported in stressed animal models and in the post-mortem brain of patients with depression. Here, we highlight the neuroprotective function of REST/NRSF and discuss dysregulation of REST/NRSF and neuronal damage during social stress and depression.
Remote neurocognitive interventions for attention-deficit/hyperactivity disorder - Opportunities and challenges

Zhang DW, Johnstone SJ, Sauce B, Arns M, Sun L, Jiang H

Prog Neuropsychopharmacol Biol Psychiatry, 2023 Dec 20;127:110802.
PMID: 37257770 DOI: 10.1016/j.pnpbp.2023.110802

Improving neurocognitive functions through remote interventions has been a promising approach to developing new treatments for attention-deficit/hyperactivity disorder (AD/HD). Remote neurocognitive interventions may address the shortcomings of the current prevailing pharmacological therapies for AD/HD, e.g., side effects and access barriers. Here we review the current options for remote neurocognitive interventions to reduce AD/HD symptoms, including cognitive training, EEG neurofeedback training, transcranial electrical stimulation, and external cranial nerve stimulation. We begin with an overview of the neurocognitive deficits in AD/HD to identify the targets for developing interventions. The role of neuroplasticity in each intervention is then highlighted due to its essential role in facilitating neuropsychological adaptations. Following this, each intervention type is discussed in terms of the critical details of the intervention protocols, the role of neuroplasticity, and the available evidence. Finally, we offer suggestions for future directions in terms of optimizing the existing intervention protocols and developing novel protocols.
Fulltext The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies

Low ZXB, Ng WS, Lim ESY, Goh BH, Kumari Y

Prog Neuropsychopharmacol Biol Psychiatry, 2025 Jan 10;136:111139.
PMID: 39251080 DOI: 10.1016/j.pnpbp.2024.111139

Emerging evidence suggests that classical psychedelics possess immunomodulatory and anti-inflammatory properties; however, these effects are yet to be well-established. This systematic review aims to provide a timely and comprehensive overview of the immunomodulatory effects of classical psychedelics in preclinical studies. A systematic search was conducted on six databases, including CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus, and Web of Science. Eligible studies targeting classical psychedelics for evaluation of their effects on inflammatory markers and immunomodulation have been included for analysis. Data was extracted from 40 out of 2822 eligible articles, and their risk of bias was assessed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool and Quality Assessment Tool for In Vitro Studies (QUIN). Studies examined 2,5-dimethoxy-4-iodoamphetamine (DOI; n = 18); psilocybin (4-PO-DMT; n = 9); N,N-dimethyltryptamine (DMT; n = 8); lysergic acid diethylamide (LSD; n = 6); 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT; n = 3); psilocin (4-HO-DMT; n = 3); and mescaline (n = 2). In 36 studies where inflammatory cytokine levels were measured following psychedelic administration, a decrease in at least one inflammatory cytokine was observed in 29 studies. Immune cell activity was assessed in 10 studies and findings were mixed, with an equal number of studies (n = 5 out of 10) reporting either an increase or decrease in immune cell activity. Classical psychedelics were found to alleviate pre-existing inflammation but promote inflammation when administered under normal physiological conditions. This information is anticipated to inform future clinical trials, exploring classical psychedelics' potential to alleviate inflammation in various pathologies.
Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review

Low ZXB, Yong SJ, Alrasheed HA, Al-Subaie MF, Al Kaabi NA, Alfaresi M, et al.

Prog Neuropsychopharmacol Biol Psychiatry, 2025 Mar 20;137:111279.
PMID: 39909170 DOI: 10.1016/j.pnpbp.2025.111279

RATIONALE: In our ongoing battle against the coronavirus 2019 (COVID-19) pandemic, a major challenge is the enduring symptoms that continue after acute infection. Also known as Long COVID, post-COVID-19 syndrome (PCS) often comes with debilitating symptoms like fatigue, disordered sleep, olfactory dysfunction, and cognitive issues ("brain fog"). Currently, there are no approved treatments for PCS. Recent research has uncovered that the severity of PCS is inversely linked to circulating serotonin levels, highlighting the potential of serotonin-modulating therapeutics for PCS. Therefore, we propose that serotonergic psychedelics, acting mainly via the 5-HT2A serotonin receptor, hold promise for treating PCS.
OBJECTIVES: Our review aims to elucidate potential mechanisms by which serotonergic psychedelics may alleviate the symptoms of PCS.
RESULTS: Potential mechanisms through which serotonergic psychedelics may alleviate PCS symptoms are discussed, with emphasis on their effects on inflammation, neuroplasticity, and gastrointestinal function. Additionally, this review explores the potential of serotonergic psychedelics in mitigating endothelial dysfunction, a pivotal aspect of PCS pathophysiology implicated in organ dysfunction. This review also examines the potential role of serotonergic psychedelics in alleviating specific PCS symptoms, which include olfactory dysfunction, cognitive impairment, sleep disturbances, and mental health challenges.
CONCLUSIONS: Emerging evidence suggests that serotonergic psychedelics may alleviate PCS symptoms. However, further high-quality research is needed to thoroughly assess their safety and efficacy in treating patients with PCS.
Fulltext Fear conditioning: Insights into learning, memory and extinction and its relevance to clinical disorders

Trent S, Abdullah MH, Parwana K, Valdivieso MA, Hassan Z, Müller CP

Prog Neuropsychopharmacol Biol Psychiatry, 2025 Mar 06;138:111310.
PMID: 40056965 DOI: 10.1016/j.pnpbp.2025.111310

Fear, whether innate or learned, is an essential emotion required for survival. The learning, and subsequent memory, of fearful events enhances our ability to recognise and respond to threats, aiding adaptation to new, ever-changing environments. Considerable research has leveraged associative learning protocols such as contextual or auditory forms of fear conditioning in rodents, to understand fear learning, memory consolidation and extinction phases of memory. Such assays have led to detailed characterisation of the underlying neurocircuitry and neurobiology supporting fear learning processes. Given fear processing is conserved across rodents and humans, fear conditioning experiments provide translational insights into fundamental memory processes and fear-related pathologies. This review examines associative learning protocols used to measure fear learning, memory and extinction, before providing an overview on the underlying complex neurocircuitry including the amygdala, hippocampus and medial prefrontal cortex. This is followed by an in-depth commentary on the neurobiology, particularly synaptic plasticity mechanisms, which regulate fear learning, memory and extinction. Next, we consider how fear conditioning assays in rodents can inform our understanding of disrupted fear memory in human disorders such as post-traumatic stress disorder (PTSD), anxiety and psychiatric disorders including schizophrenia. Lastly, we critically evaluate fear conditioning protocols, highlighting some of the experimental and theoretical limitations and the considerations required when conducting such assays, alongside recent methodological advancements in the field. Overall, rodent-based fear conditioning assays remain central to making progress in uncovering fundamental memory phenomena and understanding the aetiological mechanisms that underpin fear associated disorders, alongside the development of effective therapeutic strategies.