Pub Date : 2025-03-06DOI: 10.1016/j.neubiorev.2025.106089
Yumeng Ma, Nilofar Vafaie, Philip A. Kragel
Emotion knowledge is organized in a two-dimensional space known as the affective circumplex, which is thought to develop from core affective feelings and the co-occurrence of emotional events. Neural studies reveal that emotion concepts and cognitive maps of space and abstract concepts are represented in hippocampal-prefrontal systems. We propose that the circumplex is formed by learning the transitions between emotion concepts, a process mediated by a reciprocal network involving hippocampal cells that encode emotion concepts and grid cells in medial entorhinal and ventral prefrontal cortices that encode the relations between them. We anticipate that testing this hypothesis will shed light on the debate about whether emotions are biologically basic or constructed from core affective dimensions.
{"title":"Embedding emotion concepts in cognitive maps","authors":"Yumeng Ma, Nilofar Vafaie, Philip A. Kragel","doi":"10.1016/j.neubiorev.2025.106089","DOIUrl":"10.1016/j.neubiorev.2025.106089","url":null,"abstract":"<div><div>Emotion knowledge is organized in a two-dimensional space known as the affective circumplex, which is thought to develop from core affective feelings and the co-occurrence of emotional events. Neural studies reveal that emotion concepts and cognitive maps of space and abstract concepts are represented in hippocampal-prefrontal systems. We propose that the circumplex is formed by learning the transitions between emotion concepts, a process mediated by a reciprocal network involving hippocampal cells that encode emotion concepts and grid cells in medial entorhinal and ventral prefrontal cortices that encode the relations between them. We anticipate that testing this hypothesis will shed light on the debate about whether emotions are biologically basic or constructed from core affective dimensions.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106089"},"PeriodicalIF":7.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-06DOI: 10.1016/j.neubiorev.2025.106092
C. Schiemer , M.J. Summers , K.B. Stefanidis
Background/rationale
Electroencephalography (EEG) has potential to provide a sensitive measure of the acute neurophysiological response to cannabis administration. As delta-9-tetrahydrocannabinol (THC; the psychoactive constituent of cannabis) can induce transient neurocognitive impairments that differ as a function of tolerance and dose, understanding the neural profile related to intoxication would be of great benefit in the wake of increasing recreational and medicinal use. Accordingly, the present systematic review examined the current research literature related to acute cannabis administration and EEG measures.
Methods
Peer-reviewed articles published from 2000 were assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that administered non-synthetic cannabis, containing THC (orally or inhaled) and reported differences in EEG outcomes within the acute time frame (<6 hours post-administration) as compared to baseline or placebo, were eligible for inclusion.
Results/discussion
A total of 16 studies were eligible for inclusion, of which 11 reported differences in the amplitude/latency of event-related potentials (ERPs) and 9 reported changes in frequency band power. Of the ERPs, the P3 was identified as a potential indicator of recent cannabis consumption, as demonstrated by decreased P3 amplitude across various doses (generally exhibiting small-to-moderate magnitude effects where effect sizes were reported). Oscillatory activity in the theta frequency band power range (typically 4–7 Hz) was impacted following cannabis administration, with some support for a dose-dependent change in power. The present results highlight the potential utility of some EEG measures as markers of recent cannabis consumption, although great heterogeneity in participant characteristics and reported data limits conclusions from these results. It is also evident that EEG changes in highly tolerant user groups (such as those who use cannabis medicinally), require further exploration.
{"title":"Identifying EEG markers related to acute cannabis consumption: A systematic review","authors":"C. Schiemer , M.J. Summers , K.B. Stefanidis","doi":"10.1016/j.neubiorev.2025.106092","DOIUrl":"10.1016/j.neubiorev.2025.106092","url":null,"abstract":"<div><h3>Background/rationale</h3><div>Electroencephalography (EEG) has potential to provide a sensitive measure of the acute neurophysiological response to cannabis administration. As delta-9-tetrahydrocannabinol (THC; the psychoactive constituent of cannabis) can induce transient neurocognitive impairments that differ as a function of tolerance and dose, understanding the neural profile related to intoxication would be of great benefit in the wake of increasing recreational and medicinal use. Accordingly, the present systematic review examined the current research literature related to acute cannabis administration and EEG measures.</div></div><div><h3>Methods</h3><div>Peer-reviewed articles published from 2000 were assessed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that administered non-synthetic cannabis, containing THC (orally or inhaled) and reported differences in EEG outcomes within the acute time frame (<6 hours post-administration) as compared to baseline or placebo, were eligible for inclusion.</div></div><div><h3>Results/discussion</h3><div>A total of 16 studies were eligible for inclusion, of which 11 reported differences in the amplitude/latency of event-related potentials (ERPs) and 9 reported changes in frequency band power. Of the ERPs, the P3 was identified as a potential indicator of recent cannabis consumption, as demonstrated by decreased P3 amplitude across various doses (generally exhibiting small-to-moderate magnitude effects where effect sizes were reported). Oscillatory activity in the theta frequency band power range (typically 4–7 Hz) was impacted following cannabis administration, with some support for a dose-dependent change in power. The present results highlight the potential utility of some EEG measures as markers of recent cannabis consumption, although great heterogeneity in participant characteristics and reported data limits conclusions from these results. It is also evident that EEG changes in highly tolerant user groups (such as those who use cannabis medicinally), require further exploration.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106092"},"PeriodicalIF":7.5,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-04DOI: 10.1016/j.neubiorev.2025.106090
Emily K. Wall , Elizabeth A. Virakorn , Kathryn D. Baker , E. Myfanwy Cohen , Rick Richardson
Adolescence is a window of vulnerability for the development of anxiety disorders but also a window of opportunity for treatments to minimize the long-term impact of such disorders. Current first-line treatments, primarily exposure-based cognitive-behavioral therapy (CBT), have limited long-term efficacy in adolescents. The urgent need for more effective interventions is underscored by the frequent reports of extinction impairments in adolescents as well as the rising anxiety rates in youth, particularly post-COVID-19. Preclinical research on the extinction of learned fear in adolescents may contribute to developing better treatment approaches to anxiety in this age group. Unfortunately, this is still a largely under-explored area. However, both pharmacological and behavioral augmentation strategies can be used to enhance extinction learning and consolidation. Here we describe work exploring such adjuncts, focusing on pre-clinical work with rodents. Much of the research to date shows striking developmental differences in response to various pharmacological treatments, with only a few shown to be effective in adolescents. Further, recent experience of stress reduces the efficacy of these treatments in adolescence. This review highlights the necessity for tailored strategies, especially when it comes to pharmacological adjuncts, that address developmental differences in drug responses as well as the impact of stressful experiences on treatment efficacy.
{"title":"Preclinical behavioral and pharmacological treatments for enhancing fear extinction in adolescence","authors":"Emily K. Wall , Elizabeth A. Virakorn , Kathryn D. Baker , E. Myfanwy Cohen , Rick Richardson","doi":"10.1016/j.neubiorev.2025.106090","DOIUrl":"10.1016/j.neubiorev.2025.106090","url":null,"abstract":"<div><div>Adolescence is a window of vulnerability for the development of anxiety disorders but also a window of opportunity for treatments to minimize the long-term impact of such disorders. Current first-line treatments, primarily exposure-based cognitive-behavioral therapy (CBT), have limited long-term efficacy in adolescents. The urgent need for more effective interventions is underscored by the frequent reports of extinction impairments in adolescents as well as the rising anxiety rates in youth, particularly post-COVID-19. Preclinical research on the extinction of learned fear in adolescents may contribute to developing better treatment approaches to anxiety in this age group. Unfortunately, this is still a largely under-explored area. However, both pharmacological and behavioral augmentation strategies can be used to enhance extinction learning and consolidation. Here we describe work exploring such adjuncts, focusing on pre-clinical work with rodents. Much of the research to date shows striking developmental differences in response to various pharmacological treatments, with only a few shown to be effective in adolescents. Further, recent experience of stress reduces the efficacy of these treatments in adolescence. This review highlights the necessity for tailored strategies, especially when it comes to pharmacological adjuncts, that address developmental differences in drug responses as well as the impact of stressful experiences on treatment efficacy.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106090"},"PeriodicalIF":7.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-04DOI: 10.1016/j.neubiorev.2025.106091
Marcus Augusto-Oliveira , Gabriela de Paula Arrifano , Caio Gustavo Leal-Nazaré , Adriano Chaves-Filho , Leticia Santos-Sacramento , Amanda Lopes-Araujo , Marie-Ève Tremblay , Maria Elena Crespo-Lopez
Microglia are the brain resident macrophages that respond rapidly to any insult. These non-neuroectodermal cells are decorated with plenty of receptors allowing them to recognise and respond precisely to a multitude of stimuli. To do so, microglia undergo structural and functional changes aiming to actively keep the brain’s homeostasis. However, some microglial responses, when sustained or exacerbated, can contribute to neuropathology and neurodegeneration. Many microglial molecular and cellular changes were identified that display a strong correlation with neuronal damage and neuroinflammation/disease status, as well as present key sex-related differences that modulate microglial outcomes. Nevertheless, the relationship between microglial structural and functional features is just beginning to be unravelled. Several reports show that microglia undergo soma and branch remodelling in response to environmental stimuli, ageing, neurodegenerative diseases, trauma, and systemic inflammation, suggesting a complex form and function link. Also, it is reasonable overall to suppose that microglia diminishing their process length and ramification also reduce their monitoring activity of synapses, which is critical for detecting any synaptic disturbance and performing synaptic remodelling. Elucidating the complex interactions between microglial morphological plasticity and its functional implications appears essential for the understanding of complex cognitive and behavioural processes in health and neuropathological conditions.
{"title":"Morphological diversity of microglia: Implications for learning, environmental adaptation, ageing, sex differences and neuropathology","authors":"Marcus Augusto-Oliveira , Gabriela de Paula Arrifano , Caio Gustavo Leal-Nazaré , Adriano Chaves-Filho , Leticia Santos-Sacramento , Amanda Lopes-Araujo , Marie-Ève Tremblay , Maria Elena Crespo-Lopez","doi":"10.1016/j.neubiorev.2025.106091","DOIUrl":"10.1016/j.neubiorev.2025.106091","url":null,"abstract":"<div><div>Microglia are the brain resident macrophages that respond rapidly to any insult. These non-neuroectodermal cells are decorated with plenty of receptors allowing them to recognise and respond precisely to a multitude of stimuli. To do so, microglia undergo structural and functional changes aiming to actively keep the brain’s homeostasis. However, some microglial responses, when sustained or exacerbated, can contribute to neuropathology and neurodegeneration. Many microglial molecular and cellular changes were identified that display a strong correlation with neuronal damage and neuroinflammation/disease status, as well as present key sex-related differences that modulate microglial outcomes. Nevertheless, the relationship between microglial structural and functional features is just beginning to be unravelled. Several reports show that microglia undergo soma and branch remodelling in response to environmental stimuli, ageing, neurodegenerative diseases, trauma, and systemic inflammation, suggesting a complex form and function link. Also, it is reasonable overall to suppose that microglia diminishing their process length and ramification also reduce their monitoring activity of synapses, which is critical for detecting any synaptic disturbance and performing synaptic remodelling. Elucidating the complex interactions between microglial morphological plasticity and its functional implications appears essential for the understanding of complex cognitive and behavioural processes in health and neuropathological conditions.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106091"},"PeriodicalIF":7.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.neubiorev.2025.106088
Yanan Wu , Hanbin Wang , Xu Hui , Zetao Qian , Mingming Wang , Fenfen E , Meng Xu , Liying Zhou , Xinxin Deng , Xiuxia Li , Kehu Yang
Background
Preventing the occurrence of prenatal depression is one of the most important possibilities for reducing the disease burden of maternal depression. The preventive effects of various non-pharmacological interventions on prenatal depression remain insufficiently understood.
Aims
To assess the efficacy of different non-pharmacological measures in preventing prenatal depression via a network analysis.
Method
We conducted a systematic review and network meta-analysis to examine the most effective non-pharmacological interventions for preventing prenatal depression in randomised controlled trials (RCTs). We searched databases including PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, Wanfang, CBM, and VIP from their inception to July 18, 2024, for RCTs. The Cochrane and PRISMA guidelines were used. Network meta-analysis was conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol has been registered in PROSPERO (CRD42024594188).
Results
We included 20 RCTs involving 3,051 participants. The results indicated that, compared to usual care, yoga was the most effective in preventing prenatal depression (SMD = -2.72; 95% CI, -4.39 to -1.05); CINeMA: Low certainty, followed by cognitive behavioral therapy (SMD = -1.92; 95% CI, -3.78 to -0.06); CINeMA: Low certainty. The surface under the cumulative ranking curve (SUCRA) value indicated that yoga has the highest likelihood of being the best intervention for preventing prenatal depression (89.1%).
Conclusions
Yoga was the most effective in preventing prenatal depression, followed by cognitive behavioral therapy. Due to the low quality of evidence, further well-designed trials are needed to confirm these findings.
{"title":"Efficacy of non-pharmacological interventions for the prevention of antenatal depression: A systematic review and network meta-analysis","authors":"Yanan Wu , Hanbin Wang , Xu Hui , Zetao Qian , Mingming Wang , Fenfen E , Meng Xu , Liying Zhou , Xinxin Deng , Xiuxia Li , Kehu Yang","doi":"10.1016/j.neubiorev.2025.106088","DOIUrl":"10.1016/j.neubiorev.2025.106088","url":null,"abstract":"<div><h3>Background</h3><div>Preventing the occurrence of prenatal depression is one of the most important possibilities for reducing the disease burden of maternal depression. The preventive effects of various non-pharmacological interventions on prenatal depression remain insufficiently understood.</div></div><div><h3>Aims</h3><div>To assess the efficacy of different non-pharmacological measures in preventing prenatal depression via a network analysis.</div></div><div><h3>Method</h3><div>We conducted a systematic review and network meta-analysis to examine the most effective non-pharmacological interventions for preventing prenatal depression in randomised controlled trials (RCTs). We searched databases including PubMed, Cochrane Library, Web of Science, EMBASE, CNKI, Wanfang, CBM, and VIP from their inception to July 18, 2024, for RCTs. The Cochrane and PRISMA guidelines were used. Network meta-analysis was conducted using a random-effects model. Confidence in the evidence was assessed using Confidence in Network Meta-Analysis (CINeMA). The protocol has been registered in PROSPERO (CRD42024594188).</div></div><div><h3>Results</h3><div>We included 20 RCTs involving 3,051 participants. The results indicated that, compared to usual care, yoga was the most effective in preventing prenatal depression (SMD = -2.72; 95% CI, -4.39 to -1.05); CINeMA: Low certainty, followed by cognitive behavioral therapy (SMD = -1.92; 95% CI, -3.78 to -0.06); CINeMA: Low certainty. The surface under the cumulative ranking curve (SUCRA) value indicated that yoga has the highest likelihood of being the best intervention for preventing prenatal depression (89.1%).</div></div><div><h3>Conclusions</h3><div>Yoga was the most effective in preventing prenatal depression, followed by cognitive behavioral therapy. Due to the low quality of evidence, further well-designed trials are needed to confirm these findings.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106088"},"PeriodicalIF":7.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.neubiorev.2025.106087
Maohui Yang , Xuemei Qin , Xiaojie Liu
Depression is a prevalent mental disorder with high morbidity and mortality and its pathogenesis remains exactly unclarified. However, mitochondria and endoplasmic reticulum (ER) are two highly dynamic organelles that perform an indispensable role in the development of depression. Mitochondrial dysfunction and ER stress are recognized as vital pathological hallmarks in depression. The changes of intracellular activities such as mitochondrial dynamics, mitophagy, energy metabolism and ER stress are closely correlated with the progression of depression. Moreover, organelles interactions are conducive to homeostasis and cellular functions, and mitochondrial-associated endoplasmic reticulum membranes (MAMs) serve as signaling hubs of the two organelles and the coupling of the pathological progression. The main roles of MAMs are involved in metabolism, signal transduction, lipid transport, and maintenance of its structure and function. At present, accumulating studies elucidated that MAMs have gradually become a novel therapeutic target in treatment of depression. In the review, we focus on influence of mitochondria dysfunction and ER stress on depression. Furthermore, we discuss the underlying role of MAMs in depression and highlight natural products targeting MAMs as potential antidepressants to treat depression.
{"title":"The effect of mitochondrial-associated endoplasmic reticulum membranes (MAMs) modulation: New insights into therapeutic targets for depression","authors":"Maohui Yang , Xuemei Qin , Xiaojie Liu","doi":"10.1016/j.neubiorev.2025.106087","DOIUrl":"10.1016/j.neubiorev.2025.106087","url":null,"abstract":"<div><div>Depression is a prevalent mental disorder with high morbidity and mortality and its pathogenesis remains exactly unclarified. However, mitochondria and endoplasmic reticulum (ER) are two highly dynamic organelles that perform an indispensable role in the development of depression. Mitochondrial dysfunction and ER stress are recognized as vital pathological hallmarks in depression. The changes of intracellular activities such as mitochondrial dynamics, mitophagy, energy metabolism and ER stress are closely correlated with the progression of depression. Moreover, organelles interactions are conducive to homeostasis and cellular functions, and mitochondrial-associated endoplasmic reticulum membranes (MAMs) serve as signaling hubs of the two organelles and the coupling of the pathological progression. The main roles of MAMs are involved in metabolism, signal transduction, lipid transport, and maintenance of its structure and function. At present, accumulating studies elucidated that MAMs have gradually become a novel therapeutic target in treatment of depression. In the review, we focus on influence of mitochondria dysfunction and ER stress on depression. Furthermore, we discuss the underlying role of MAMs in depression and highlight natural products targeting MAMs as potential antidepressants to treat depression.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106087"},"PeriodicalIF":7.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.neubiorev.2025.106086
B. Romeo , E. Kervadec , B. Fauvel , L. Strika-Bruneau , A. Amirouche , Aurore Bezo , P. Piolino , A. Benyamina
Background
Psychedelic-assisted therapies have demonstrated promising results in treating mental disorders, with results suggesting that the subjective intensity and quality of psychedelic experiences plays a significant role in mediating therapeutic effects. However, the strength of this association across diagnoses and treatment settings remains underexplored.
Methods
We searched MEDLINE, Embase, and PsycINFO databases for studies examining the correlation between the intensity of the psychedelic experience and clinical outcomes in patients treated with classical psychedelics. Meta-correlations were performed, and standardized mean differences of psychedelic experience intensity scores were compared between clinical responders and non-responders using random-effects models. Subgroup analyses were conducted based on diagnosis, study design, setting (clinical vs. naturalistic), and substance used.
Results
A significant positive correlation was found between the intensity of mystical experiences and clinical improvement across all studies (r = .33, p < .0001). Subgroup analyses revealed a stronger association (p = .02) for mood disorders (r = .41) compared to addictions (r = .19). The effect was greater (p < .01) in protocol-based clinical settings (r = .50) than in naturalistic use (r = .14). Prospective designs showed stronger (p < .01) correlations (r = .43) compared to retrospective designs (r = .14).
Conclusion
The intensity of psychedelic experiences is significantly and reliably associated with therapeutic outcomes, particularly in mood disorders. Clinical settings and prospective study designs strengthen this relationship, emphasizing the importance of controlled environments and therapeutic support to fully benefit from the therapeutic potential of psychedelics.
{"title":"The intensity of the psychedelic experience is reliably associated with clinical improvements: A systematic review and meta-analysis","authors":"B. Romeo , E. Kervadec , B. Fauvel , L. Strika-Bruneau , A. Amirouche , Aurore Bezo , P. Piolino , A. Benyamina","doi":"10.1016/j.neubiorev.2025.106086","DOIUrl":"10.1016/j.neubiorev.2025.106086","url":null,"abstract":"<div><h3>Background</h3><div>Psychedelic-assisted therapies have demonstrated promising results in treating mental disorders, with results suggesting that the subjective intensity and quality of psychedelic experiences plays a significant role in mediating therapeutic effects. However, the strength of this association across diagnoses and treatment settings remains underexplored.</div></div><div><h3>Methods</h3><div>We searched MEDLINE, Embase, and PsycINFO databases for studies examining the correlation between the intensity of the psychedelic experience and clinical outcomes in patients treated with classical psychedelics. Meta-correlations were performed, and standardized mean differences of psychedelic experience intensity scores were compared between clinical responders and non-responders using random-effects models. Subgroup analyses were conducted based on diagnosis, study design, setting (clinical vs. naturalistic), and substance used.</div></div><div><h3>Results</h3><div>A significant positive correlation was found between the intensity of mystical experiences and clinical improvement across all studies (r = .33, <em>p</em> < .0001). Subgroup analyses revealed a stronger association (<em>p</em> = .02) for mood disorders (r = .41) compared to addictions (r = .19). The effect was greater (<em>p</em> < .01) in <em>p</em>rotocol-based clinical settings (r = .50) than in naturalistic use (r = .14). Prospective designs showed stronger (<em>p</em> < .01) correlations (r = .43) compared to retrospective designs (r = .14).</div></div><div><h3>Conclusion</h3><div>The intensity of psychedelic experiences is significantly and reliably associated with therapeutic outcomes, particularly in mood disorders. Clinical settings and prospective study designs strengthen this relationship, emphasizing the importance of controlled environments and therapeutic support to fully benefit from the therapeutic potential of psychedelics.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106086"},"PeriodicalIF":7.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143544600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-28DOI: 10.1016/j.neubiorev.2025.106085
Graziano Pinna , Olga Ponomareva , George L. Stalcup , Ann M. Rasmusson
Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that arises after acute or chronic exposure to threatened death, serious injury, or sexual violence. The pathophysiology of PTSD is complex and involves dysregulation of multiple interacting brain regions and neurobiological systems including the sympathetic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system. Deficient biosynthesis of neurosteroids that positively modulate GABAA receptor function, including allopregnanolone (Allo) and its equipotent stereoisomer pregnanolone (PA), also affects a subpopulation of individuals with PTSD and is associated with increased PTSD risk, severity, chronicity and treatment resistance. The synthesis of these neuroactive steroids by the brain, adrenal glands, and gonads may be influenced by stress, drugs, social isolation and other factors with impact on the balance of inhibitory versus excitatory (I/E) neurotransmission in brain. These neuroactive steroids are thus considered a potential target for new PTSD therapeutics. In this review, we first present studies in humans and rodents performed over the past 20 years that have shaped our current understanding of the role of Allo and PA in the pathophysiology of PTSD. We will also discuss the means by which rigorous measurement of neurosteroids can be used to identify individually-variable dysfunctional patterns of neurosteroidogenesis that could be targeted to prevent or treat PTSD. This broadened precision medicine approach to diagnosis of neuroendocrinopathies associated with PTSD may aid in reducing PTSD risk and facilitating the effective prescribing of PTSD therapeutics. We hope that such an approach will also forestall development of individually variable but common psychiatric, substance abuse, and medical PTSD-comorbidities.
{"title":"Neuroactive steroids and the pathophysiology of PTSD: Biomarkers for treatment targeting","authors":"Graziano Pinna , Olga Ponomareva , George L. Stalcup , Ann M. Rasmusson","doi":"10.1016/j.neubiorev.2025.106085","DOIUrl":"10.1016/j.neubiorev.2025.106085","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that arises after acute or chronic exposure to threatened death, serious injury, or sexual violence. The pathophysiology of PTSD is complex and involves dysregulation of multiple interacting brain regions and neurobiological systems including the sympathetic nervous system, the hypothalamic-pituitary-adrenal (HPA) axis, and the immune system. Deficient biosynthesis of neurosteroids that positively modulate GABA<sub>A</sub> receptor function, including allopregnanolone (Allo) and its equipotent stereoisomer pregnanolone (PA), also affects a subpopulation of individuals with PTSD and is associated with increased PTSD risk, severity, chronicity and treatment resistance. The synthesis of these neuroactive steroids by the brain, adrenal glands, and gonads may be influenced by stress, drugs, social isolation and other factors with impact on the balance of inhibitory versus excitatory (I/E) neurotransmission in brain. These neuroactive steroids are thus considered a potential target for new PTSD therapeutics. In this review, we first present studies in humans and rodents performed over the past 20 years that have shaped our current understanding of the role of Allo and PA in the pathophysiology of PTSD. We will also discuss the means by which rigorous measurement of neurosteroids can be used to identify <em>individually-variable dysfunctional patterns of neurosteroidogenesis</em> that could be targeted to prevent or treat PTSD. This broadened precision medicine approach to diagnosis of neuroendocrinopathies associated with PTSD may aid in reducing PTSD risk and facilitating the effective prescribing of PTSD therapeutics. We hope that such an approach will also forestall development of individually variable but common psychiatric, substance abuse, and medical PTSD-comorbidities.</div></div>","PeriodicalId":56105,"journal":{"name":"Neuroscience and Biobehavioral Reviews","volume":"172 ","pages":"Article 106085"},"PeriodicalIF":7.5,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1016/j.neubiorev.2025.106063
Shinsuke Koike , Saori C. Tanaka , Takuya Hayashi
Recent magnetic resonance imaging (MRI) research has advanced our understanding of brain pathophysiology in psychiatric disorders. This progress necessitates re-evaluation of the diagnostic system for psychiatric disorders based on MRI-based biomarkers, with implications for precise clinical diagnosis and optimal therapeutics. To achieve this goal, large-scale multi-site studies are essential to develop a standardized MRI database, with the analysis of several thousands of images and the incorporation of new data. A critical challenge in these studies is to minimize sampling and measurement biases in MRI studies to accurately capture the diversity of disease-derived biomarkers. Various techniques have been employed to consolidate datasets from multiple sites in case-control studies. Traveling subject harmonization stands out as a powerful tool that can differentiate measurement bias from sample variety and sampling bias. A non-linear statistical model for a normative trajectory across the lifespan also strengthens the database to mitigate sampling bias from known factors such as age and sex. These approaches can enhance the alterations between psychiatric disorders and integrate new data and follow-up scans into existing life-course trajectory, enhancing the reliability of machine learning classification and subtyping. Although this approach has been developed using T1-weighted structural image features, future research may extend this framework to other modalities and measures. The required sample size and methodological establishment are needed for future investigations, leading to novel insights into the brain pathophysiology of psychiatric disorders and the development of optimal therapeutics for bedside clinical applications. Sharing big data and their findings also need to be considered.
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