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Molecular Psychiatry Jul 2023Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains... (Meta-Analysis)
Meta-Analysis
Impairment of insulin action and metabolic dysregulation have traditionally been associated with schizophrenia, although the molecular basis of such association remains still elusive. The present meta-analysis aims to assess the impact of insulin action manipulations (i.e., hyperinsulinemia, hypoinsulinemia, systemic or brain insulin resistance) on glutamatergic, dopaminergic, γ-aminobutyric acid (GABA)ergic, and serotonergic pathways in the central nervous system. More than one hundred outcomes, including transcript or protein levels, kinetic parameters, and other components of the neurotransmitter pathways, were collected from cultured cells, animals, or humans, and meta-analyzed by applying a random-effects model and adopting Hedges'g to compare means. Two hundred fifteen studies met the inclusion criteria, of which 180 entered the quantitative synthesis. Significant impairments in key regulators of synaptic plasticity processes were detected as the result of insulin handlings. Specifically, protein levels of N-methyl-D-aspartate receptor (NMDAR) subunits including type 2A (NR2A) (Hedges' g = -0.95, 95%C.I. = -1.50, -0.39; p = 0.001; I = 47.46%) and 2B (NR2B) (Hedges'g = -0.69, 95%C.I. = -1.35, -0.02; p = 0.043; I = 62.09%), and Postsynaptic density protein 95 (PSD-95) (Hedges'g = -0.91, 95%C.I. = -1.51, -0.32; p = 0.003; I = 77.81%) were found reduced in insulin-resistant animal models. Moreover, insulin-resistant animals showed significantly impaired dopamine transporter activity, whereas the dopamine D2 receptor mRNA expression (Hedges'g = 3.259; 95%C.I. = 0.497, 6.020; p = 0.021; I = 90.61%) increased under insulin deficiency conditions. Insulin action modulated glutamate and GABA release, as well as several enzymes involved in GABA and serotonin synthesis. These results suggest that brain neurotransmitter systems are susceptible to insulin signaling abnormalities, resembling the discrete psychotic disorders' neurobiology and possibly contributing to the development of neurobiological hallmarks of treatment-resistant schizophrenia.
Topics: Humans; Animals; Schizophrenia; Insulin; Neurobiology; Disks Large Homolog 4 Protein; Receptors, N-Methyl-D-Aspartate; gamma-Aminobutyric Acid; Neurotransmitter Agents
PubMed: 37085712
DOI: 10.1038/s41380-023-02065-4 -
Movement Disorders Clinical Practice Apr 2023Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional... (Review)
Review
BACKGROUND
Neuropathological studies, based on small samples, suggest that symptoms of Parkinson's disease (PD) emerge when dopamine/nigrostriatal loss is around 50-80%. Functional neuroimaging can be applied in larger numbers during life, which allows analysis of the extent of dopamine loss more directly.
OBJECTIVE
To quantify dopamine transporter (DaT) activity by neuroimaging in early PD.
METHODS
Systematic review and novel analysis of DaT imaging studies in early PD.
RESULTS
In our systematic review, in 423 unique cases from 27 studies with disease duration of less than 6 years, mean age 58.0 (SD 11.5) years, and mean disease duration 1.8 (SD 1.2) years, striatal loss was 43.5% (95% CI 41.6, 45.4) contralaterally, and 36.0% (95% CI 33.6, 38.3) ipsilaterally. For unilateral PD, in 436 unique cases, mean age 57.5 (SD 10.2) years, and mean disease duration 1.8 (SD 1.4) years, striatal loss was 40.6% (95% CI 38.8, 42.4) contralaterally, and 31.6% (95% CI 29.4, 33.8) ipsilaterally. In our novel analysis of the Parkinson's Progressive Marker Initiative study, 413 cases had 1436 scans performed. For a disease duration of less than 1 year, age was 61.8 (SD 9.8) years, and striatal loss was 51.2% (95% CI 49.1, 53.3) contralaterally and 39.5% (36.9, 42.1) ipsilaterally, giving an overall striatal loss of 45.3% (43.0, 47.6).
CONCLUSIONS
Loss of striatal DaT activity in early PD is less at 35-45%, rather than the 50-80% striatal dopamine loss estimated to be present at the time of symptom onset, based on backwards extrapolation from autopsy studies.
PubMed: 37070042
DOI: 10.1002/mdc3.13687 -
Cureus Mar 2023Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This... (Review)
Review
Parkinson's disease (PD) is a prevalent neurodegenerative disorder that occurs in old age due to a decrease in dopamine, which causes nerve cell destruction. This disease is difficult to diagnose since its symptoms are similar to those of the aging process. Those with PD have impaired motor control and function, dyskinesia, and tremors. To treat PD, drugs that enhance the amount of dopamine given to the brain are administered to alleviate symptoms. This inquiry examines the prescription of rotigotine to achieve this objective. The primary objective of this review is to examine the usage of rotigotine in both the late and early stages of PD. The statistical model utilized in the review found that there was not a significant difference in the dosage of rotigotine prescribed to late and early-stage PD patients, however, there were some confounding variables that may have skewed this result; therefore, further research is necessary to validate or nullify this hypothesis.
PubMed: 37069881
DOI: 10.7759/cureus.36211 -
Healthcare (Basel, Switzerland) Apr 2023Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This... (Review)
Review
Temporal discounting is a phenomenon where a reward loses its value as a function of time (e.g., a reward is more valuable immediately than when it delays in time). This is a type of intertemporal decision-making that has an association with impulsivity and self-control. Many pathologies exhibit higher discounting rates, meaning they discount more the values of rewards, such as addictive behaviors, bipolar disorder, attention-deficit/hyperactivity disorders, social anxiety disorders, and major depressive disorder, among others; thus, many studies look for the mechanism and neuromodulators of these decisions. This systematic review aims to investigate the association between pharmacological administration and changes in temporal discounting. A search was conducted in PubMed, Scopus, Web of Science, Science Direct and Cochrane. We used the PICO strategy: healthy humans (P-Participants) that received a pharmacological administration (I-Intervention) and the absence of a pharmacological administration or placebo (C-Comparison) to analyze the relationship between the pharmacological administration and the temporal discounting (O-outcome). Nineteen studies fulfilled the inclusion criteria. The most important findings were the involvement of dopamine modulation in a U-shape for choosing the delayed outcome (metoclopradime, haloperidol, and amisulpride). Furthermore, administration of tolcapone and high doses of d-amphetamine produced a preference for the delayed option. There was a time-dependent hydrocortisone effect in the preference for the immediate reward. Thus, it can be concluded that dopamine is a crucial modulator for temporal discounting, especially the D2 receptor, and cortisol also has an important time-dependent role in this type of decision. One of the limitations of this systematic review is the heterogeneity of the drugs used to assess the effect of temporal discounting.
PubMed: 37046974
DOI: 10.3390/healthcare11071046 -
The Cochrane Database of Systematic... Apr 2023Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of... (Review)
Review
BACKGROUND
Vestibular migraine is a form of migraine where one of the main features is recurrent attacks of vertigo. These episodes are often associated with other features of migraine, including headache and sensitivity to light or sound. The unpredictable and severe attacks of vertigo can lead to a considerable reduction in quality of life. The condition is estimated to affect just under 1% of the population, although many people remain undiagnosed. A number of pharmacological interventions have been used, or proposed to be used, at the time of a vestibular migraine attack to help reduce the severity or resolve the symptoms. These are predominantly based on treatments that are in use for headache migraine, with the belief that the underlying pathophysiology of these conditions is similar. OBJECTIVES: To assess the benefits and harms of pharmacological interventions used to relieve acute attacks of vestibular migraine.
SEARCH METHODS
The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 23 September 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs in adults with definite or probable vestibular migraine comparing triptans, ergot alkaloids, dopamine antagonists, antihistamines, 5-HT3 receptor antagonists, gepants (CGRP receptor antagonists), magnesium, paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) with either placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) improvement in headache, 6) improvement in other migrainous symptoms and 7) other adverse effects. We considered outcomes reported at three time points: < 2 hours, 2 to 12 hours, > 12 to 72 hours. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included two RCTs with a total of 133 participants, both of which compared the use of triptans to placebo for an acute attack of vestibular migraine. One study was a parallel-group RCT (of 114 participants, 75% female). This compared the use of 10 mg rizatriptan to placebo. The second study was a smaller, cross-over RCT (of 19 participants, 70% female). This compared the use of 2.5 mg zolmitriptan to placebo. Triptans may result in little or no difference in the proportion of people whose vertigo improves at up to two hours after taking the medication. However, the evidence was very uncertain (risk ratio 0.84, 95% confidence interval 0.66 to 1.07; 2 studies; based on 262 attacks of vestibular migraine treated in 124 participants; very low-certainty evidence). We did not identify any evidence on the change in vertigo using a continuous scale. Only one of the studies assessed serious adverse events. No events were noted in either group, but as the sample size was small we cannot be sure if there are risks associated with taking triptans for this condition (0/75 receiving triptans, 0/39 receiving placebo; 1 study; 114 participants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The evidence for interventions used to treat acute attacks of vestibular migraine is very sparse. We identified only two studies, both of which assessed the use of triptans. We rated all the evidence as very low-certainty, meaning that we have little confidence in the effect estimates and cannot be sure if triptans have any effect on the symptoms of vestibular migraine. Although we identified sparse information on potential harms of treatment in this review, the use of triptans for other conditions (such as headache migraine) is known to be associated with some adverse effects. We did not identify any placebo-controlled randomised trials for other interventions that may be used for this condition. Further research is needed to identify whether any interventions help to improve the symptoms of vestibular migraine attacks and to determine if there are side effects associated with their use.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Anti-Inflammatory Agents, Non-Steroidal; Vertigo; Headache; Tryptamines
PubMed: 37042545
DOI: 10.1002/14651858.CD015322.pub2 -
The Cochrane Database of Systematic... Apr 2023Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical... (Review)
Review
BACKGROUND
Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non-pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA.
OBJECTIVES
To summarise Cochrane Neonatal evidence on interventions (pharmacological or surgical) for the prevention of PDA and related complications, and interventions for the management of asymptomatic and symptomatic PDA in preterm infants.
METHODS
We searched the Cochrane Database of Systematic Reviews on 20 October 2022 for ongoing and published Cochrane Reviews on the prevention and treatment of PDA in preterm (< 37 weeks' gestation) or low birthweight (< 2500 g) infants. We included all published Cochrane Reviews assessing the following categories of interventions: pharmacological therapy using prostaglandin inhibitor drugs (indomethacin, ibuprofen, and acetaminophen), adjunctive pharmacological interventions, invasive PDA closure procedures, and non-pharmacological interventions. Two overview authors independently checked the eligibility of the reviews retrieved by the search, and extracted data from the included reviews using a predefined data extraction form. Any disagreements were resolved by discussion with a third overview author. Two overview authors independently assessed the methodological quality of the included reviews using the AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews) tool. We reported the GRADE certainty of evidence as assessed by the respective review authors using summary of findings tables.
MAIN RESULTS
We included 16 Cochrane Reviews, corresponding to 138 randomised clinical trials (RCT) and 11,856 preterm infants, on the prevention and treatment of PDA in preterm infants. One of the 16 reviews had no included studies, and therefore, did not contribute to the results. Six reviews reported on prophylactic interventions for the prevention of PDA and included pharmacological prophylaxis with prostaglandin inhibitor drugs, prophylactic surgical PDA ligation, and non-pharmacologic interventions (chest shielding during phototherapy and restriction of fluid intake); one review reported on the use of indomethacin for the management of asymptomatic PDA; nine reviews reported on interventions for the management of symptomatic PDA, and included pharmacotherapy with prostaglandin inhibitor drugs in various routes and dosages, surgical PDA ligation, and adjunct therapies (use of furosemide and dopamine in conjunction with indomethacin). The quality of reviews varied. Two reviews were assessed to be high quality, seven reviews were of moderate quality, five of low quality, while two reviews were deemed to be of critically low quality. For prevention of PDA, prophylactic indomethacin reduces severe intraventricular haemorrhage (IVH; relative risk (RR) 0.66, 95% confidence interval (CI) 0.53 to 0.82; 14 RCTs, 2588 infants), and the need for invasive PDA closure (RR 0.51, 95% CI 0.37 to 0.71; 8 RCTs, 1791 infants), but it does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability (RR 1.02, 95% CI 0.90 to 1.15; 3 RCTs, 1491 infants). Prophylactic ibuprofen probably marginally reduces severe IVH (RR 0.67, 95% CI 0.45 to 1.00; 7 RCTs, 925 infants; moderate-certainty evidence), and the need for invasive PDA closure (RR 0.46, 95% CI 0.22 to 0.96; 7 RCTs, 925 infants; moderate-certainty evidence). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (RR 1.09, 95% CI 0.07 to 16.39; 1 RCT, 48 infants). Necrotising enterocolitis (NEC) was lower with both prophylactic surgical ligation (RR 0.25, 95% CI 0.08 to 0.83; 1 RCT, 84 infants), and fluid restriction (RR 0.43, 95% CI 0.21 to 0.87; 4 RCTs, 526 infants). For treatment of asymptomatic PDA, indomethacin appears to reduce the development of symptomatic PDA post-treatment (RR 0.36, 95% CI 0.19 to 0.68; 3 RCTs, 97 infants; quality of source review: critically low). For treatment of symptomatic PDA, all available prostaglandin inhibitor drugs appear to be more effective in closing a PDA than placebo or no treatment (indomethacin: RR 0.30, 95% CI 0.23 to 0.38; 10 RCTs, 654 infants; high-certainty evidence; ibuprofen: RR 0.62, 95% CI 0.44 to 0.86; 2 RCTs, 206 infants; moderate-certainty evidence; early administration of acetaminophen: RR 0.35, 95% CI 0.23 to 0.53; 2 RCTs, 127 infants; low-certainty evidence). Oral ibuprofen appears to be more effective in PDA closure than intravenous (IV) ibuprofen (RR 0.38, 95% CI 0.26 to 0.56; 5 RCTs, 406 infants; moderate-certainty evidence). High-dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (RR 0.37, 95% CI 0.22 to 0.61; 3 RCTs, 190 infants; moderate-certainty evidence). With respect to adverse outcomes, compared to indomethacin administration, NEC appears to be lower with ibuprofen (any route; RR 0.68, 95% CI 0.49 to 0.94; 18 RCTs, 1292 infants; moderate-certainty evidence), oral ibuprofen (RR 0.41, 95% CI 0.23 to 0.73; 7 RCTs, 249 infants; low-certainty evidence), and with acetaminophen (RR 0.42, 95% CI 0.19 to 0.96; 4 RCTs, 384 infants; low-certainty evidence). However, NEC appears to be increased with a prolonged course of indomethacin versus a shorter course (RR 1.87, 95% CI 1.07 to 3.27; 4 RCTs, 310 infants).
AUTHORS' CONCLUSIONS
This overview summarised the evidence from 16 Cochrane Reviews of RCTs regarding the effects of interventions for the prevention and treatment of PDA in preterm infants. Prophylactic indomethacin reduces severe IVH, but does not appear to affect the composite outcome of death or moderate/severe neurodevelopmental disability. Prophylactic ibuprofen probably marginally reduces severe IVH (moderate-certainty evidence), while the evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH. All available prostaglandin inhibitor drugs appear to be effective in symptomatic PDA closure compared to no treatment (high-certainty evidence for indomethacin; moderate-certainty evidence for ibuprofen; low-certainty evidence for early administration of acetaminophen). Oral ibuprofen appears to be more effective in PDA closure than IV ibuprofen (moderate-certainty evidence). High dose ibuprofen appears to be more effective in PDA closure than standard-dose ibuprofen (moderate-certainty evidence). There are currently two ongoing reviews, one on fluid restriction for symptomatic PDA, and the other on invasive management of PDA in preterm infants.
Topics: Infant, Newborn; Humans; Ductus Arteriosus, Patent; Ibuprofen; Cyclooxygenase Inhibitors; Acetaminophen; Prostaglandin Antagonists; Systematic Reviews as Topic; Infant, Premature; Indomethacin
PubMed: 37039501
DOI: 10.1002/14651858.CD013588.pub2 -
Tremor and Other Hyperkinetic Movements... 2023The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs... (Review)
Review
OBJECTIVES
The objective of this review is to provide updated information on the epidemiology, correlating factors and treatment of chronic kidney disease associated restless legs syndrome (CKD-A-RLS) in both adult and pediatric population.
MATERIALS AND METHODS
We have reviewed the Medline search and Google Scholar search up to May 2022, using key words restless legs syndrome, chronic kidney disease and hemodialysis and kidney transplant. The reviewed articles were studied for epidemiology, correlating factors, as well as pharmacologic and non-pharmacologic treatment options.
RESULTS
Our search revealed 175 articles, 111 were clinical trials or cross- sectional studies and 64 were review articles. All 111 articles were retrieved and studied in detail. Of these, 105 focused on adults and 6 on children. A majority of studies on dialysis patients reported a prevalence between 15-30%, which is notably higher than prevalence of RLS in general population (5-10%). The correlation between presence of CKD-A-RLS with age, gender, abnormalities of hemogram, iron, ferritin, serum lipids, electrolytes and parathyroid hormones were also reviewed. The results were inconsistent and controversial. Limited studies have reported on the treatment of CKD-A-RLS. Non-pharmacological treatment focused on the effect(s) of exercise, acupuncture, massage with different oils and infra-red light whereas, pharmacologic treatment options include the effects of dopaminergic drugs, Alpha2-Delta ligands (gabapentin and pregabalin), vitamins E and C, and intravenous iron infusion.
CONCLUSION
This updated review showed that RLS is two to three times more common in patients with CKD compared to the general population. More patients with CKD-A-RLS demonstrated increased mortality, increased incidence of cardiovascular accident, depression, insomnia and impaired quality of life than those with CKD without RLS. Dopaminergic drugs such as levodopa, ropinirole, pramipexole and rotigotine as well as calcium channel blockers (gabapentin and pregabalin) are helpful for treatment of RLS. High quality studies with these agents are currently underway and hopefully confirm the efficacy and practicality of using these drugs in CKD-A-RLS. Some studies have shown that aerobic exercise and massage with lavender oil can improve symptoms of CKD-A- RLS suggesting that these measures can be useful as adjunct therapy.
Topics: Humans; Child; Gabapentin; Restless Legs Syndrome; Pregabalin; Quality of Life; Dopamine Agents; Renal Insufficiency, Chronic; Iron
PubMed: 37008995
DOI: 10.5334/tohm.752 -
International Journal of Molecular... Mar 2023Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain... (Review)
Review
Canonical and Non-Canonical Antipsychotics' Dopamine-Related Mechanisms of Present and Next Generation Molecules: A Systematic Review on Translational Highlights for Treatment Response and Treatment-Resistant Schizophrenia.
Schizophrenia is a severe psychiatric illness affecting almost 25 million people worldwide and is conceptualized as a disorder of synaptic plasticity and brain connectivity. Antipsychotics are the primary pharmacological treatment after more than sixty years after their introduction in therapy. Two findings hold true for all presently available antipsychotics. First, all antipsychotics occupy the dopamine D2 receptor (D2R) as an antagonist or partial agonist, even if with different affinity; second, D2R occupancy is the necessary and probably the sufficient mechanism for antipsychotic effect despite the complexity of antipsychotics' receptor profile. D2R occupancy is followed by coincident or divergent intracellular mechanisms, implying the contribution of cAMP regulation, β-arrestin recruitment, and phospholipase A activation, to quote some of the mechanisms considered canonical. However, in recent years, novel mechanisms related to dopamine function beyond or together with D2R occupancy have emerged. Among these potentially non-canonical mechanisms, the role of Na channels at the dopamine at the presynaptic site, dopamine transporter (DAT) involvement as the main regulator of dopamine concentration at synaptic clefts, and the putative role of antipsychotics as chaperones for intracellular D2R sequestration, should be included. These mechanisms expand the fundamental role of dopamine in schizophrenia therapy and may have relevance to considering putatively new strategies for treatment-resistant schizophrenia (TRS), an extremely severe condition epidemiologically relevant and affecting almost 30% of schizophrenia patients. Here, we performed a critical evaluation of the role of antipsychotics in synaptic plasticity, focusing on their canonical and non-canonical mechanisms of action relevant to the treatment of schizophrenia and their subsequent implication for the pathophysiology and potential therapy of TRS.
Topics: Humans; Antipsychotic Agents; Dopamine; Schizophrenia; Schizophrenia, Treatment-Resistant; beta-Arrestins
PubMed: 36983018
DOI: 10.3390/ijms24065945 -
Biomedicines Mar 2023Treatment resistant schizophrenia (TRS) is characterized by a lack of, or suboptimal response to, antipsychotic agents. The biological underpinnings of this clinical... (Review)
Review
Treatment resistant schizophrenia (TRS) is characterized by a lack of, or suboptimal response to, antipsychotic agents. The biological underpinnings of this clinical condition are still scarcely understood. Since all antipsychotics block dopamine D2 receptors (D2R), dopamine-related mechanisms should be considered the main candidates in the neurobiology of antipsychotic non-response, although other neurotransmitter systems play a role. The aims of this review are: (i) to recapitulate and critically appraise the relevant literature on dopamine-related mechanisms of TRS; (ii) to discuss the methodological limitations of the studies so far conducted and delineate a theoretical framework on dopamine mechanisms of TRS; and (iii) to highlight future perspectives of research and unmet needs. Dopamine-related neurobiological mechanisms of TRS may be multiple and putatively subdivided into three biological points: (1) D2R-related, including increased D2R levels; increased density of D2Rs in the high-affinity state; aberrant D2R dimer or heteromer formation; imbalance between D2R short and long variants; extrastriatal D2Rs; (2) presynaptic dopamine, including low or normal dopamine synthesis and/or release compared to responder patients; and (3) exaggerated postsynaptic D2R-mediated neurotransmission. Future points to be addressed are: (i) a more neurobiologically-oriented phenotypic categorization of TRS; (ii) implementation of neurobiological studies by directly comparing treatment resistant vs. treatment responder patients; (iii) development of a reliable animal model of non-response to antipsychotics.
PubMed: 36979877
DOI: 10.3390/biomedicines11030895 -
Scientific Reports Mar 2023There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and... (Meta-Analysis)
Meta-Analysis
There is significant evidence linking a 'reward deficiency syndrome' (RDS), comprising decreased availability of striatal dopamine D2-like receptors (DD2lR) and addiction-like behaviors underlying substance use disorders and obesity. Regarding obesity, a systematic review of the literature with a meta-analysis of such data is lacking. Following a systematic review of the literature, we performed random-effects meta-analyses to determine group differences in case-control studies comparing DD2lR between individuals with obesity and non-obese controls and prospective studies of pre- to post-bariatric surgery DD2lR changes. Cohen's d was used to measure effect size. Additionally, we explored factors potentially associated with group differences in DD2lR availability, such as obesity severity, using univariate meta-regression. In a meta-analysis including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies, striatal DD2lR availability did not significantly differ between obesity and controls. However, in studies comprising patients with class III obesity or higher, group differences were significant, favoring lower DD2lR availability in the obesity group. This effect of obesity severity was corroborated by meta-regressions showing inverse associations between the body mass index (BMI) of the obesity group and DD2lR availability. Post-bariatric changes in DD2lR availability were not found, although a limited number of studies were included in this meta-analysis. These results support lower DD2lR in higher classes of obesity which is a more targeted population to explore unanswered questions regarding the RDS.
Topics: Humans; Receptors, Dopamine D2; Dopamine; Prospective Studies; Tomography, X-Ray Computed; Obesity; Positron-Emission Tomography; Bariatric Surgery
PubMed: 36973321
DOI: 10.1038/s41598-023-31250-2