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Neuroscience and Biobehavioral Reviews Aug 2022The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain... (Review)
Review
The serotonergic system is involved in diverse cognitive functions including memory. Of particular importance to daily life are declarative memories that contain information about personal experiences, general facts, and events. Several psychiatric or neurological diseases, such as depression, attention-deficit-hyperactivity disorder (ADHD), and dementia, show alterations in serotonergic signalling and attendant memory disorders. Nevertheless, understanding serotonergic neurotransmission and its influence on memory remained a challenge until today. In this systematic review, we summarize recent psychopharmacological studies in animals and humans from a psychological memory perspective, in consideration of task-specific requirements. This approach has the advantage that comparisons between serotonin (5-HT)-related neurochemical mechanisms and manipulations are each addressing specific mnemonic circuits. We conclude that applications of the same 5-HT-related treatments can differentially affect unrelated tasks of declarative memories. Moreover, the analysis of specific mnemonic phases (e.g., encoding vs. consolidation) reveals opposing impacts of increased or decreased 5-HT tones, with low 5-HT supporting spatial encoding but impairing the consolidation of objects and verbal memories. Promising targets for protein synthesis-dependent consolidation enhancements include 5-HT receptor agonists and 5-HT receptor antagonists, with the latter being of special interest for the treatment of age-related decline. Further implications are pointed out as base for the development of novel therapeutic targets for memory impairment of neuropsychiatric disorders.
Topics: Animals; Attention Deficit Disorder with Hyperactivity; Cognition; Humans; Memory; Memory Disorders; Serotonin
PubMed: 35691469
DOI: 10.1016/j.neubiorev.2022.104729 -
The Oncologist Jun 2022The dexamethasone (DEX)-sparing strategy, which limits administration of DEX to day one, is reportedly non-inferior to conventional antiemetic regimens comprising... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The dexamethasone (DEX)-sparing strategy, which limits administration of DEX to day one, is reportedly non-inferior to conventional antiemetic regimens comprising multiple-day DEX. However, the usefulness of the DEX-sparing strategy in triplet antiemetic prophylaxis (neurokinin-1 receptor antagonist [NK1RA] + serotonin receptor antagonist [5HT3RA] + DEX) for carboplatin and moderate emetogenic chemotherapy (MEC) has not been clarified.
PATIENTS AND METHODS
We systematically reviewed randomized controlled trials that examined the efficacy of antiemetics for preventing chemotherapy-induced nausea and vomiting associated with carboplatin and MEC. We conducted a network meta-analysis to compare the antiemesis efficacy of three-day DEX with NK1RA (3-DEX + NK1RA) and one-day DEX with NK1RA (1-DEX + NK1RA). The primary outcome was complete response during the delayed phase (CR-DP). The secondary outcome was no nausea during the delayed phase (NN-DP).
RESULTS
Seventeen trials involving 4534 patients were included. The proportion who experienced CR-DP was 82.5% (95% credible interval [CI], 73.9-88.6) and 73.5% (95% CI, 62.8-80.9) among those who received 3-DEX + NK1RA and 1-DEX + NK1RA, respectively. There was no significant difference between the two regimens. However, 3-DEX + NK1RA tended to be superior to 1-DEX + NK1RA, with an absolute risk difference of 9.0% (95% CI, -2.3 to 21.1) in CR-DP and 24.7% (95% CI: -14.9 to 54.6) in NN-DP. 3-DEX + NK1RA also tended to be superior to 1-DEX + NK1RA in patients who received carboplatin-based chemotherapy, for whom the absolute risk difference was 12.3% (95% CI, -3.2 to 30.7).
CONCLUSIONS
Care is needed when administering the DEX-sparing strategy in combination with NK1RA to patients receiving carboplatin and non-carboplatin MEC.
Topics: Antiemetics; Antineoplastic Agents; Carboplatin; Dexamethasone; Humans; Nausea; Network Meta-Analysis; Neurokinin-1 Receptor Antagonists; Vomiting
PubMed: 35427418
DOI: 10.1093/oncolo/oyac060 -
Therapeutic Advances in... 2021Many older adults experience a deterioration in cognitive function with aging, and this can have a negative impact on quality of life. Late-life depression has been... (Review)
Review
Many older adults experience a deterioration in cognitive function with aging, and this can have a negative impact on quality of life. Late-life depression has been linked to mild cognitive impairment and dementia, and treating depression with an agent that has procognitive effects could be beneficial. Vortioxetine is a novel antidepressant with a multimodal mechanism of action that works primarily serotonin transporter inhibition, 5-HT receptor agonism and 5-HT receptor antagonism. A recent systematic review demonstrated procognitive effects of vortioxetine when indirectly compared with selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors in adults aged 18-65 years with major depressive disorder. While this systematic review demonstrated promising procognitive effects from vortioxetine, the included studies did not enroll older adults, who are at the highest risk of cognitive impairment. Therefore, our systematic review sought to investigate the effects of vortioxetine on cognitive functioning in patients over the age of 65 years. Three studies met the prespecified search criteria and were evaluated. Overall, these preliminary data suggest that vortioxetine has promising effects in improving cognition in older adults with depressive symptoms and may have a place in therapy in older adults with depression and/or cognitive impairment, including Alzheimer's disease. Additional long-term studies that include more diverse populations with comorbidities and direct comparisons with other antidepressants are needed to fully understand the potential cognitive benefits in older adults.
PubMed: 35186260
DOI: 10.1177/20451253211026796 -
Journal of Applied Oral Science :... 2022This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are...
UNLABELLED
This study aimed to investigate if SNP rs6313, SNP rs2770304, SNP rs4941573, and SNP rs1923884 of the 5-HT2A receptor gene and SNP rs6295 of the 5-HT1A receptor gene are associated with bruxism etiology.
METHODOLOGY
This systematic review was registered in PROSPERO (CRD42018094561). A search was conducted for articles published in or before May 2021. To qualify for eligibility in this review, the studies had to be case-controls, cohort or cross-sectional. The inclusion criteria were the articles with a group of patients with bruxism and a control group in which the presence of these SNPs was evaluated. The exclusion criteria were the investigations of other polymorphisms, the studies that did not consider a control group for comparison, case reports, and reviews. The NOS and JBI were used to evaluate the methodological quality of studies.
RESULTS
We conducted this study with databases, such as Web of Science, Scopus, Embase, PubMed/MEDLINE, and ProQuest. We considered four studies eligible. A total of 672 participants were included,187 with sleep bruxism, 105 with awake bruxism, 89 with sleep and awake bruxism, and 291 controls. One study found a strong association between the SNPs rs6313, rs2770304 and rs4941573 of the 5-HT2A receptor gene and sleep bruxism. In one study, we considered the C allele of the SNP rs2770304 a risk factor for sleep bruxism. We found no significant results of other SNPs in sleep bruxers compared to controls. We found no positive association concerning the SNPs and groups of awake bruxism and sleep and awake bruxism.
CONCLUSION
The different results regarding the SNPs in sleep bruxers could be explained by the genetic distinction between Chilean, Mexican, Japanese, and Polish population. More clinical trials and prospective studies must be conducted with larger sample size and in different ethnicities to confirm the results of this review.
Topics: Humans; Polymorphism, Single Nucleotide; Receptor, Serotonin, 5-HT1A; Sleep Bruxism
PubMed: 35019025
DOI: 10.1590/1678-7757-2021-0262 -
Neuropsychopharmacology : Official... Mar 2022Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for...
Ondansetron is a selective serotonin (5HT3) receptor antagonist that is under evaluation as an adjunctive treatment for schizophrenia, and a novel treatment for hallucinations in Parkinson's disease. Ondansetron reverses sensory gating deficits and improves visuoperceptual processing in animal models of psychosis, but it is unclear to what extent preclinical findings have been replicated in humans. We systematically reviewed human studies that evaluated the effects of ondansetron and other 5HT3 receptor antagonists on sensory gating deficits or sensory processing. Of 11 eligible studies, eight included patients with schizophrenia who were chronically stable on antipsychotic medication; five measured sensory gating using the P50 suppression response to a repeated auditory stimulus; others included tests of visuoperceptual function. Three studies in healthy participants included tests of visuoperceptual and sensorimotor function. A consistent and robust finding (five studies) was that ondansetron and tropisetron (5HT3 antagonist and α7-nicotinic receptor partial agonist) improved sensory gating in patients with schizophrenia. Tropisetron also improved sustained visual attention in non-smoking patients. There was inconsistent evidence of the effects of 5HT3 antagonists on other measures of sensory processing, but interpretation was limited by the small number of studies, methodological heterogeneity and the potential confounding effects of concomitant medication in patients. Despite these limitations, we found strong evidence that selective 5HT3 antagonists (with or without direct α7-nicotinic partial agonist effects) improved sensory gating. Future studies should investigate how this relates to potential improvement in neurocognitive symptoms in antipsychotic naive patients with prodromal or milder symptoms, in order to understand the clinical implications.
Topics: Antipsychotic Agents; Humans; Perception; Schizophrenia; Sensory Gating; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 35017671
DOI: 10.1038/s41386-021-01255-4 -
European Journal of Psychotraumatology 2021: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all... (Meta-Analysis)
Meta-Analysis
: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. : A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. : Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. : Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antipsychotic Agents; Drug Synergism; Drug Therapy, Combination; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 34992738
DOI: 10.1080/20008198.2020.1802920 -
Neuropsychopharmacology : Official... Mar 2022We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published...
We searched PubMed for primary research quantifying drug modification of light-induced circadian phase-shifting in rodents. This search, conducted for work published between 1960 and 2018, yielded a total of 146 papers reporting results from 901 studies. Relevant articles were those with any extractable data on phase resetting in wildtype (non-trait selected) rodents administered a drug, alongside a vehicle/control group, near or at the time of exposure. Most circadian pharmacology experiments were done using drugs thought to act directly on either the brain's central pacemaker, the suprachiasmatic nucleus (SCN), the SCN's primary relay, the retinohypothalamic tract, secondary pathways originating from the medial/dorsal raphe nuclei and intergeniculate leaflet, or the brain's sleep-arousal centers. While the neurotransmitter systems underlying these circuits were of particular interest, including those involving glutamate, gamma-aminobutyric acid, serotonin, and acetylcholine, other signaling modalities have also been assessed, including agonists and antagonists of receptors linked to dopamine, histamine, endocannabinoids, adenosine, opioids, and second-messenger pathways downstream of glutamate receptor activation. In an effort to identify drugs that unduly influence circadian responses to light, we quantified the net effects of each drug class by ratioing the size of the phase-shift observed after administration to that observed with vehicle in a given experiment. This allowed us to organize data across the literature, compare the relative efficacy of one mechanism versus another, and clarify which drugs might best suppress or potentiate phase resetting. Aggregation of the available data in this manner suggested that several candidates might be clinically relevant as auxiliary treatments to suppress ectopic light responses during shiftwork or amplify the circadian effects of timed bright light therapy. Future empirical research will be necessary to validate these possibilities.
Topics: Circadian Rhythm; Pharmaceutical Preparations; S Phase; Serotonin; Suprachiasmatic Nucleus
PubMed: 34961774
DOI: 10.1038/s41386-021-01251-8 -
European Psychiatry : the Journal of... Nov 2021Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression,...
BACKGROUND
Mental disorders in comorbidity with chronic skin diseases may worsen disease outcome and patients' quality of life. We hypothesized the comorbidity of depression, anxiety syndromes, or symptoms as attributable to biological mechanisms that the combined diseases share.
METHODS
We conducted a systematic review based on the Preferred Reporting Items for Systematic Review and Meta-Analysis statement searching into PubMed, PsycInfo, and Scopus databases. We examined the literature regarding the comorbidity of psoriasis (Ps), atopic dermatitis (AD), or hidradenitis suppurativa with depression and/or anxiety in adults ≥18 years and the hypothetical shared underlying biological mechanisms.
RESULTS
Sixteen studies were analyzed, mostly regarding Ps and AD. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling and nuclear factor kappa-light-chain-enhancer of activated B cells/p38 mitogen-activated protein kinase pathways arose as shared mechanisms in Ps animal models with depression- and/or anxiety-like behaviors. Activated microglia and neuroinflammatory responses emerged in AD depressive models. As to genetic studies, atopic-dermatitis patients with comorbid anxiety traits carried the short variant of serotonin transporter and a polymorphism of the human translocator protein gene. A GA genotype of catechol-O-methyltransferase gene was instead associated with Ps. Reduced natural killer cell activity, IL-4, serotonin serum levels, and increased plasma cortisol and IgE levels were hypothesized in comorbid depressive AD patients. In Ps patients with comorbid depression, high serum concentrations of IL-6 and IL-18, as well as IL-17A, were presumed to act as shared inflammatory mechanisms.
CONCLUSIONS
Further studies should investigate mental disorders and chronic skin diseases concurrently across patients' life course and identify their temporal relation and biological correlates. Future research should also identify biological characteristics of individuals at high risk of the comorbid disorders and associated complications.
Topics: Animals; Anxiety; Catechol O-Methyltransferase; Comorbidity; Depression; Dermatitis, Atopic; Hidradenitis Suppurativa; Humans; Psoriasis; Quality of Life
PubMed: 34819201
DOI: 10.1192/j.eurpsy.2021.2249 -
Behavioral Sciences (Basel, Switzerland) Oct 2021Although blockade of dopamine receptors D2 and D3 appears to be the main mechanism of antipsychotic action, treatment response variability calls for an examination of... (Review)
Review
Dopamine, Serotonin, and Structure/Function Brain Defects as Biological Bases for Treatment Response in Delusional Disorder: A Systematic Review of Cases and Cohort Studies.
Although blockade of dopamine receptors D2 and D3 appears to be the main mechanism of antipsychotic action, treatment response variability calls for an examination of other biological systems. Our aim is to systematically review reports of treatment response in delusional disorder (DD) in order to help determine its biological bases. Computerized searches of ClinicalTrials.gov, PubMed, and Scopus databases (from 1999 to September 2021) were systematically reviewed, in keeping with PRISMA directives. We used the search terms: (treat * OR therap * AND (delusional disorder)). We included all studies that explored the biological mechanisms of treatment response in DD, as diagnosed by ICD or DSM criteria. A total of 4344 records were initially retrieved, from which 14 papers were included: case reports, case series, and cohort studies. Findings point to (1) dopaminergic dysfunction (based on biochemical and genetic studies), (2) serotonergic dysfunction (based on partial agonism/antagonism of drugs), and (3) brain structure/function impairment, especially in the temporal and parietal lobes, as crucial factors in treatment response. Further studies with higher levels of evidence are needed to help clinicians determine treatment.
PubMed: 34677234
DOI: 10.3390/bs11100141 -
Molecular Pain 2021Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions...
Chronic neuropathic pain is a debilitating ordeal for patients worldwide and pharmacological treatment efficacy is still limited. As many pharmacological interventions for neuropathic pain often fail, insights into the underlying mechanism and role of identified receptors is of utmost importance. An important target for improving treatment of neuropathic pain is the descending serotonergic system as these projections modulate nociceptive signaling in the dorsal horn. Also with use of last resort treatments like spinal cord stimulation (SCS), the descending serotonergic projections are known to be involved in the pain relieving effect. This systematic review summarizes the involvement of the serotonergic system on nociceptive modulation in the healthy adult rodent and the chronic neuropathic rodent and summarizes all available literature on the serotonergic system in the SCS-treated neuropathic rodent. Medline, Embase and Pubmed databases were used in the search for articles. Descending serotonergic modulation of nociceptive signaling in spinal dorsal horn in normal adult rat is mainly inhibitory and mediated by 5-HT1a, 5-HT1b, 5-HT2c, 5-HT3 and 5-HT4 receptors. Upon injury and in the neuropathic rat, this descending serotonergic modulation becomes facilitatory via activation of the 5-HT2a, 5-HT2b and 5-HT3 receptors. Analgesia due to neuromodulatory intervention like SCS restores the inhibitory function of the descending serotonergic system and involves 5-HT2, 5-HT3 and 5-HT4 receptors. The results of this systematic review provide insights and suggestions for further pharmacological and or neuromodulatory treatment of neuropathic pain based on targeting selected serotonergic receptors related to descending modulation of nociceptive signaling in spinal dorsal horn. With the novel developed SCS paradigms, the descending serotonergic system will be an important target for mechanism-based stimulation induced analgesia.
Topics: Animals; Humans; Neuralgia; Nociception; Rats; Receptors, Serotonin, 5-HT3; Spinal Cord; Spinal Cord Dorsal Horn; Spinal Cord Stimulation
PubMed: 34662215
DOI: 10.1177/17448069211043965