Pub Date : 2025-03-01DOI: 10.1016/j.bpsc.2024.07.011
Zachary Freyberg , Ana C. Andreazza , Colleen A. McClung , Mary L. Phillips
There is growing interest in the ketogenic diet as a treatment for bipolar disorder (BD), and there are promising anecdotal and small case study reports of efficacy. However, the neurobiological mechanisms by which diet-induced ketosis might ameliorate BD symptoms remain to be determined, particularly in manic and hypomanic states—defining features of BD. Identifying these mechanisms will provide new markers to guide personalized interventions and provide targets for novel treatment developments for individuals with BD. In this critical review, we describe recent findings highlighting 2 types of neurobiological abnormalities in BD: 1) mitochondrial dysfunction and 2) neurotransmitter and neural network functional abnormalities. We link these abnormalities to mania/hypomania and depression in BD and then describe the biological underpinnings by which the ketogenic diet may have a beneficial effect in individuals with BD. We end the review by describing approaches that can be employed in future studies to elucidate the neurobiology that underlies the therapeutic effect of the ketogenic diet in BD. Doing this may provide marker predictors to identify individuals who will respond well to the ketogenic diet, as well as offer neural targets for novel treatment developments for BD.
{"title":"Linking Mitochondrial Dysfunction, Neurotransmitter, and Neural Network Abnormalities and Mania: Elucidating Neurobiological Mechanisms of the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder","authors":"Zachary Freyberg , Ana C. Andreazza , Colleen A. McClung , Mary L. Phillips","doi":"10.1016/j.bpsc.2024.07.011","DOIUrl":"10.1016/j.bpsc.2024.07.011","url":null,"abstract":"<div><div>There is growing interest in the ketogenic diet as a treatment for bipolar disorder (BD), and there are promising anecdotal and small case study reports of efficacy. However, the neurobiological mechanisms by which diet-induced ketosis might ameliorate BD symptoms remain to be determined, particularly in manic and hypomanic states—defining features of BD. Identifying these mechanisms will provide new markers to guide personalized interventions and provide targets for novel treatment developments for individuals with BD. In this critical review, we describe recent findings highlighting 2 types of neurobiological abnormalities in BD: 1) mitochondrial dysfunction and 2) neurotransmitter and neural network functional abnormalities. We link these abnormalities to mania/hypomania and depression in BD and then describe the biological underpinnings by which the ketogenic diet may have a beneficial effect in individuals with BD. We end the review by describing approaches that can be employed in future studies to elucidate the neurobiology that underlies the therapeutic effect of the ketogenic diet in BD. Doing this may provide marker predictors to identify individuals who will respond well to the ketogenic diet, as well as offer neural targets for novel treatment developments for BD.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 3","pages":"Pages 267-277"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141763219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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.bpsc.2024.09.015
Cecilia A. Hinojosa , Sanne J.H. van Rooij , Negar Fani , Robyn A. Ellis , Nathaniel G. Harnett , Lauren A.M. Lebois , Timothy D. Ely , Tanja Jovanovic , Vishnu P. Murty , Stacey L. House , Francesca L. Beaudoin , Xinming An , Thomas C. Neylan , Gari D. Clifford , Sarah D. Linnstaedt , Laura T. Germine , Scott L. Rauch , John P. Haran , Alan B. Storrow , Christopher Lewandowski , Jennifer S. Stevens
Background
Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry posttrauma in humans. Neuroimaging markers may be particularly useful because they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. In this study, we aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure.
Methods
Participants were recruited from U.S. emergency departments for the AURORA study (n = 286; 178 female). Trauma-related change in alcohol use at 8 weeks posttrauma relative to pretrauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency measure. Reward-related neurocircuitry activation and functional connectivity were assessed 2 weeks posttrauma using functional magnetic resonance imaging during a monetary reward task using region of interest and whole-brain voxelwise analyses.
Results
Greater increase in alcohol use from pretrauma to 8 weeks posttrauma was predicted by 1) greater ventral tegmental area, 2) greater cerebellum activation during gain > loss trials measured 2 weeks posttrauma, and 3) greater seed-based functional connectivity between the ventral tegmental area and lateral occipital cortex and precuneus.
Conclusions
Altered ventral tegmental area activation and functional connectivity early posttrauma may be associated with reward seeking and processing, thereby contributing to greater alcohol use posttrauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early posttrauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use.
{"title":"Reward Neurocircuitry Predicts Longitudinal Changes in Alcohol Use Following Trauma Exposure","authors":"Cecilia A. Hinojosa , Sanne J.H. van Rooij , Negar Fani , Robyn A. Ellis , Nathaniel G. Harnett , Lauren A.M. Lebois , Timothy D. Ely , Tanja Jovanovic , Vishnu P. Murty , Stacey L. House , Francesca L. Beaudoin , Xinming An , Thomas C. Neylan , Gari D. Clifford , Sarah D. Linnstaedt , Laura T. Germine , Scott L. Rauch , John P. Haran , Alan B. Storrow , Christopher Lewandowski , Jennifer S. Stevens","doi":"10.1016/j.bpsc.2024.09.015","DOIUrl":"10.1016/j.bpsc.2024.09.015","url":null,"abstract":"<div><h3>Background</h3><div>Trauma is a risk factor for developing maladaptive alcohol use. Preclinical research has shown that stress alters the processing of midbrain and striatal reward and incentive signals. However, little research has been conducted on alterations in reward-related neurocircuitry posttrauma in humans. Neuroimaging markers may be particularly useful because they can provide insight into the mechanisms that may make an individual vulnerable to developing trauma-related psychopathologies. In this study, we aimed to identify reward-related neural correlates associated with changes in alcohol use after trauma exposure.</div></div><div><h3>Methods</h3><div>Participants were recruited from U.S. emergency departments for the AURORA study (<em>n</em> = 286; 178 female). Trauma-related change in alcohol use at 8 weeks posttrauma relative to pretrauma was quantified as a change in 30-day total drinking per the PhenX Toolkit Alcohol 30-Day Quantity and Frequency measure. Reward-related neurocircuitry activation and functional connectivity were assessed 2 weeks posttrauma using functional magnetic resonance imaging during a monetary reward task using region of interest and whole-brain voxelwise analyses.</div></div><div><h3>Results</h3><div>Greater increase in alcohol use from pretrauma to 8 weeks posttrauma was predicted by 1) greater ventral tegmental area, 2) greater cerebellum activation during gain > loss trials measured 2 weeks posttrauma, and 3) greater seed-based functional connectivity between the ventral tegmental area and lateral occipital cortex and precuneus.</div></div><div><h3>Conclusions</h3><div>Altered ventral tegmental area activation and functional connectivity early posttrauma may be associated with reward seeking and processing, thereby contributing to greater alcohol use posttrauma. These data provide novel evidence of neural correlates that underlie increased alcohol use early posttrauma that may be targeted via early interventions to prevent the development of maladaptive alcohol use.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 3","pages":"Pages 314-323"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142402322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.bpsc.2024.10.001
Emily Au , Kristoffer J. Panganiban , Sally Wu , Kira Sun , Bailey Humber , Gary Remington , Sri Mahavir Agarwal , Adria Giacca , Sandra Pereira , Margaret Hahn
The use of antipsychotic drugs is associated with adverse metabolic effects. Disruptions in glucose metabolism such as hyperglycemia and insulin resistance have been shown to occur with antipsychotic use, independent of changes in body weight or adiposity. The regulation of whole-body glucose metabolism is partly mediated by the central nervous system. In particular, the hypothalamus and brainstem are responsive to peripheral energy signals and subsequently mediate feedback mechanisms to maintain peripheral glucose homeostasis. In this scoping review of preclinical in vivo studies, we aimed to explore central mechanisms through which antipsychotics dysregulate glucose metabolism. A systematic search for animal studies identified 29 studies that met our eligibility criteria for qualitative synthesis. The studies suggest that antipsychotic-induced changes in autonomic nervous system activity, certain neurotransmitter systems, expression of neuropeptides, and central insulin action mediate impairments in glucose metabolism. These findings provide insight into potential targets for the mitigation of the adverse effects of antipsychotics on glucose metabolism.
{"title":"Antipsychotic-Induced Dysregulation of Glucose Metabolism Through the Central Nervous System: A Scoping Review of Animal Models","authors":"Emily Au , Kristoffer J. Panganiban , Sally Wu , Kira Sun , Bailey Humber , Gary Remington , Sri Mahavir Agarwal , Adria Giacca , Sandra Pereira , Margaret Hahn","doi":"10.1016/j.bpsc.2024.10.001","DOIUrl":"10.1016/j.bpsc.2024.10.001","url":null,"abstract":"<div><div>The use of antipsychotic drugs is associated with adverse metabolic effects. Disruptions in glucose metabolism such as hyperglycemia and insulin resistance have been shown to occur with antipsychotic use, independent of changes in body weight or adiposity. The regulation of whole-body glucose metabolism is partly mediated by the central nervous system. In particular, the hypothalamus and brainstem are responsive to peripheral energy signals and subsequently mediate feedback mechanisms to maintain peripheral glucose homeostasis. In this scoping review of preclinical in vivo studies, we aimed to explore central mechanisms through which antipsychotics dysregulate glucose metabolism. A systematic search for animal studies identified 29 studies that met our eligibility criteria for qualitative synthesis. The studies suggest that antipsychotic-induced changes in autonomic nervous system activity, certain neurotransmitter systems, expression of neuropeptides, and central insulin action mediate impairments in glucose metabolism. These findings provide insight into potential targets for the mitigation of the adverse effects of antipsychotics on glucose metabolism.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 3","pages":"Pages 244-257"},"PeriodicalIF":5.7,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.bpsc.2024.10.002
Omid Kardan , Alexander S. Weigard , Lora M. Cope , Meghan E. Martz , Mike Angstadt , Katherine L. McCurry , Cleanthis Michael , Jillian E. Hardee , Luke W. Hyde , Chandra Sripada , Mary M. Heitzeg
Background
Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI.
Methods
We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally during pre- and early adolescence, can predict future SUI. Next, in an independent subsample, we tested whether these patterns were associated with earlier environmental exposures, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the ABCD (Adolescent Brain Cognitive Development) Study. SUI was defined as first-time use of at least 1 full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (n = 228) of participants without SUI who were matched to the SUI group (n = 233) on age, sex, race/ethnicity, household income, and parental education.
Results
Multivariate analysis showed that whole-brain rsFC from 9–10 to 11–12 years of age (prior to SUI) prospectively differentiated the SUI and control groups. The SUI-related rsFC pattern was also related to aging in both groups, suggesting a pattern of accelerated maturation in the years prior to SUI. This same pattern of rsFC was predicted by higher pollution but not neighborhood disadvantage (adjusted for family socioeconomic factors) in an independent subsample (n = 2854).
Conclusions
Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation can predict SUI in youth and are associated with exposure to pollution.
背景：过早开始使用药物（SUI）会大大增加青少年日后出现药物使用障碍的风险。此外，青春期是大脑网络成熟的关键时期，而大脑网络成熟的速度和程度很容易受到环境的影响，并可能决定青少年罹患药物滥用症的风险：我们研究了在青春期前期和早期纵向测量的静息时大脑功能连接（rsFC）模式是否能预测未来的 SUI。接下来，我们在一个独立的子样本中测试了这些模式是否与早期的环境暴露有关，特别是邻里污染和社会经济因素。我们利用了青少年脑认知发展研究（ABCD）® 的数据。SUI 被定义为首次使用至少一次全剂量酒精、尼古丁、大麻或其他药物。我们设立了一个对照组（N = 228），由没有 SUI 的参与者组成，他们与 SUI 组（N = 233）在年龄、性别、种族/民族、父母收入和教育程度方面相匹配：多变量分析表明，从 9-10 岁到 11-12 岁（SUI 之前）的全脑 rsFC 可对 SUI 组和对照组进行前瞻性区分。与 SUI 相关的 rsFC 模式也与两组人的年龄增长有关，这表明在 SUI 之前的几年中，人的成熟速度加快。在一个独立的子样本（N = 2,854）中，污染程度越高，但邻里关系越差（根据家庭社会经济因素调整），也能预测出同样的rsFC模式：结论：与加速成熟有关的青春期早期大脑功能连接模式可以预测青少年的 SUI，并且与暴露于污染有关。
{"title":"Functional Brain Connectivity Predictors of Prospective Substance Use Initiation and Their Environmental Correlates","authors":"Omid Kardan , Alexander S. Weigard , Lora M. Cope , Meghan E. Martz , Mike Angstadt , Katherine L. McCurry , Cleanthis Michael , Jillian E. Hardee , Luke W. Hyde , Chandra Sripada , Mary M. Heitzeg","doi":"10.1016/j.bpsc.2024.10.002","DOIUrl":"10.1016/j.bpsc.2024.10.002","url":null,"abstract":"<div><h3>Background</h3><div>Early substance use initiation (SUI) places youth at substantially higher risk for later substance use disorders. Furthermore, adolescence is a critical period for the maturation of brain networks, the pace and magnitude of which are susceptible to environmental influences and may shape risk for SUI.</div></div><div><h3>Methods</h3><div>We examined whether patterns of functional brain connectivity during rest (rsFC), measured longitudinally during pre- and early adolescence, can predict future SUI. Next, in an independent subsample, we tested whether these patterns were associated with earlier environmental exposures, specifically neighborhood pollution and socioeconomic dimensions. We utilized data from the ABCD (Adolescent Brain Cognitive Development) Study. SUI was defined as first-time use of at least 1 full dose of alcohol, nicotine, cannabis, or other drugs. We created a control group (<em>n</em> = 228) of participants without SUI who were matched to the SUI group (<em>n</em> = 233) on age, sex, race/ethnicity, household income, and parental education.</div></div><div><h3>Results</h3><div>Multivariate analysis showed that whole-brain rsFC from 9–10 to 11–12 years of age (prior to SUI) prospectively differentiated the SUI and control groups. The SUI-related rsFC pattern was also related to aging in both groups, suggesting a pattern of accelerated maturation in the years prior to SUI. This same pattern of rsFC was predicted by higher pollution but not neighborhood disadvantage (adjusted for family socioeconomic factors) in an independent subsample (<em>n</em> = 2854).</div></div><div><h3>Conclusions</h3><div>Brain functional connectivity patterns in early adolescence that are linked to accelerated maturation can predict SUI in youth and are associated with exposure to pollution.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 2","pages":"Pages 203-212"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.bpsc.2024.07.023
Milena Radoman , K. Luan Phan , Olusola A. Ajilore , Stephanie M. Gorka
Background
A developing theory and recent research suggest that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidance-based coping and characterizes individuals with current and past alcohol use disorder (AUD). Neuroimaging studies of unpredictable threat processing have repeatedly demonstrated activation of the anterior insula, anteromedial thalamus, and dorsal anterior cingulate cortex. In the current study, we aimed to understand how these 3 regions function as a network during anticipation of unpredictable threat (and predictable threat).
Methods
Participants were 43 adults (ages 21–30) with AUD and 26 healthy control participants. Functional magnetic resonance imaging and dynamic causal modeling were used to study interregional effective connectivities and predictable and unpredictable threat-related modulations thereof within this network. Parametric empirical Bayesian modeling was used to conduct between-group comparisons in effective connectivities.
Results
During unpredictable threat trials, the increased projection from the right anteromedial thalamus to the right anterior insula was significantly present only in the AUD group. This directional influence was stronger among individuals who consumed more drinks per week on average. As expected, we found no group differences in modulatory changes to effective connectivities during predictable threat trials.
Conclusions
To our knowledge, this is the first study to examine directional interactions between key frontolimbic regions during anticipation of unpredictable and predictable threat and demonstrate the importance of bottom-up thalamic-insular projections during unpredictable threat processing in AUD. Prospective studies are warranted to determine whether this association is causal.
{"title":"Altered Effective Connectivity During Threat Anticipation in Individuals With Alcohol Use Disorder","authors":"Milena Radoman , K. Luan Phan , Olusola A. Ajilore , Stephanie M. Gorka","doi":"10.1016/j.bpsc.2024.07.023","DOIUrl":"10.1016/j.bpsc.2024.07.023","url":null,"abstract":"<div><h3>Background</h3><div>A developing theory and recent research suggest that heightened reactivity to uncertain stressors or threats may be an important individual difference factor that facilitates excessive drinking as a means of avoidance-based coping and characterizes individuals with current and past alcohol use disorder (AUD). Neuroimaging studies of unpredictable threat processing have repeatedly demonstrated activation of the anterior insula, anteromedial thalamus, and dorsal anterior cingulate cortex. In the current study, we aimed to understand how these 3 regions function as a network during anticipation of unpredictable threat (and predictable threat).</div></div><div><h3>Methods</h3><div>Participants were 43 adults (ages 21–30) with AUD and 26 healthy control participants. Functional magnetic resonance imaging and dynamic causal modeling were used to study interregional effective connectivities and predictable and unpredictable threat-related modulations thereof within this network. Parametric empirical Bayesian modeling was used to conduct between-group comparisons in effective connectivities.</div></div><div><h3>Results</h3><div>During unpredictable threat trials, the increased projection from the right anteromedial thalamus to the right anterior insula was significantly present only in the AUD group. This directional influence was stronger among individuals who consumed more drinks per week on average. As expected, we found no group differences in modulatory changes to effective connectivities during predictable threat trials.</div></div><div><h3>Conclusions</h3><div>To our knowledge, this is the first study to examine directional interactions between key frontolimbic regions during anticipation of unpredictable and predictable threat and demonstrate the importance of bottom-up thalamic-insular projections during unpredictable threat processing in AUD. Prospective studies are warranted to determine whether this association is causal.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 2","pages":"Pages 213-221"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.bpsc.2024.08.020
Wisteria Deng , Benjamin Chong , Jean Addington , Carrie E. Bearden , Kristin S. Cadenhead , Barbara A. Cornblatt , Matcheri Keshavan , Daniel H. Mathalon , Diana O. Perkins , William Stone , Elaine F. Walker , Scott W. Woods , Tyrone D. Cannon
Background
Although the clinical high risk for psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status defines a diagnostic construct in its own right. In a previous study, CHR-P nonconverters were observed to follow 3 distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity.
Methods
Here, we utilized the NAPLS3 (North American Prodrome Longitudinal Study phase 3) sample (N = 806) to determine whether 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy control participants and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes.
Results
Three distinctive subgroups within the CHR nonconverters were identified, largely paralleling those observed previously. Importantly, these extracted groups, together with non-CHR control participants and CHR converters, differed from each other significantly on putative etiological risk factors (e.g., predicted risk scores, physiological and self-report measures of stress), affective comorbidities, and functional outcomes, thus providing converging evidence supporting the validity of the identified trajectory groups.
Conclusions
This pattern, together with the fact that even the subgroup of CHR-P nonconverters who showed a remission trajectory deviated from healthy control participants, supports treating the CHR-P syndrome not only as a status that denotes risk for onset of full psychosis but also as a marker of ongoing distress for a population that is in need of interventions.
{"title":"Beyond the Descriptive: A Comprehensive, Multidomain Validation of Symptom Trajectories for Individuals at Clinical High Risk for Psychosis","authors":"Wisteria Deng , Benjamin Chong , Jean Addington , Carrie E. Bearden , Kristin S. Cadenhead , Barbara A. Cornblatt , Matcheri Keshavan , Daniel H. Mathalon , Diana O. Perkins , William Stone , Elaine F. Walker , Scott W. Woods , Tyrone D. Cannon","doi":"10.1016/j.bpsc.2024.08.020","DOIUrl":"10.1016/j.bpsc.2024.08.020","url":null,"abstract":"<div><h3>Background</h3><div>Although the clinical high risk for psychosis (CHR-P) criteria are widely used to ascertain individuals at heightened risk for imminent onset of psychosis, it remains controversial whether CHR-P status defines a diagnostic construct in its own right. In a previous study, CHR-P nonconverters were observed to follow 3 distinct trajectories in symptoms and functioning: remission, partial remission, and maintenance of symptoms and functional impairments at subthreshold levels of intensity.</div></div><div><h3>Methods</h3><div>Here, we utilized the NAPLS3 (North American Prodrome Longitudinal Study phase 3) sample (<em>N</em> = 806) to determine whether 1) the same trajectory groups can be detected when assessing symptoms at 2-month intervals over an 8-month period and 2) the resulting trajectory groups differ from each other and from healthy control participants and converting CHR-P cases in terms of risk factors, comorbidities, and functional outcomes.</div></div><div><h3>Results</h3><div>Three distinctive subgroups within the CHR nonconverters were identified, largely paralleling those observed previously. Importantly, these extracted groups, together with non-CHR control participants and CHR converters, differed from each other significantly on putative etiological risk factors (e.g., predicted risk scores, physiological and self-report measures of stress), affective comorbidities, and functional outcomes, thus providing converging evidence supporting the validity of the identified trajectory groups.</div></div><div><h3>Conclusions</h3><div>This pattern, together with the fact that even the subgroup of CHR-P nonconverters who showed a remission trajectory deviated from healthy control participants, supports treating the CHR-P syndrome not only as a status that denotes risk for onset of full psychosis but also as a marker of ongoing distress for a population that is in need of interventions.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 2","pages":"Pages 195-202"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.bpsc.2024.10.019
Carl Hacker , Madaline M. Mocchi , Jiayang Xiao , Brian Metzger , Joshua Adkinson , Bailey Pascuzzi , Raissa Mathura , Denise Oswalt , Andrew Watrous , Eleonora Bartoli , Anusha Allawala , Victoria Pirtle , Xiaoxu Fan , Isabel Danstrom , Ben Shofty , Garrett Banks , Yue Zhang , Michelle Armenta-Salas , Koorosh Mirpour , Nicole Provenza , Kelly R. Bijanki
Background
A reliable physiological biomarker for major depressive disorder is essential for developing and optimizing neuromodulatory treatment paradigms. In this study, we investigated a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours.
Methods
We analyzed brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human participants (nfemale = 3, nmale = 2). This surgical setting allowed for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric that reflects the balance of activity across all frequency bands and may serve as a proxy for excitatory/inhibitory balance in the brain.
Results
Our findings demonstrated that shifts in aperiodic slope correlated with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all 5 participants, particularly in the ventromedial prefrontal cortex.
Conclusions
This biomarker offers a new way to track patient responses to major depressive disorder treatment, thus paving the way for individualized therapies in both intracranial and noninvasive monitoring contexts.
{"title":"Aperiodic (1/f) Neural Activity Robustly Tracks Symptom Severity Changes in Treatment-Resistant Depression","authors":"Carl Hacker , Madaline M. Mocchi , Jiayang Xiao , Brian Metzger , Joshua Adkinson , Bailey Pascuzzi , Raissa Mathura , Denise Oswalt , Andrew Watrous , Eleonora Bartoli , Anusha Allawala , Victoria Pirtle , Xiaoxu Fan , Isabel Danstrom , Ben Shofty , Garrett Banks , Yue Zhang , Michelle Armenta-Salas , Koorosh Mirpour , Nicole Provenza , Kelly R. Bijanki","doi":"10.1016/j.bpsc.2024.10.019","DOIUrl":"10.1016/j.bpsc.2024.10.019","url":null,"abstract":"<div><h3>Background</h3><div>A reliable physiological biomarker for major depressive disorder is essential for developing and optimizing neuromodulatory treatment paradigms. In this study, we investigated a passive electrophysiologic biomarker that tracks changes in depressive symptom severity on the order of minutes to hours.</div></div><div><h3>Methods</h3><div>We analyzed brief recordings from intracranial electrodes implanted deep in the brain during a clinical trial of deep brain stimulation for treatment-resistant depression in 5 human participants (<em>n</em><sub>female</sub> = 3, <em>n</em><sub>male</sub> = 2). This surgical setting allowed for precise temporal and spatial sensitivity in the ventromedial prefrontal cortex, a challenging area to measure. We focused on the aperiodic slope of the power spectral density, a metric that reflects the balance of activity across all frequency bands and may serve as a proxy for excitatory/inhibitory balance in the brain.</div></div><div><h3>Results</h3><div>Our findings demonstrated that shifts in aperiodic slope correlated with depression severity, with flatter (less negative) slopes indicating reduced depression severity. This significant correlation was observed in all 5 participants, particularly in the ventromedial prefrontal cortex.</div></div><div><h3>Conclusions</h3><div>This biomarker offers a new way to track patient responses to major depressive disorder treatment, thus paving the way for individualized therapies in both intracranial and noninvasive monitoring contexts.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 2","pages":"Pages 186-194"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142640466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.bpsc.2024.09.008
James M. Gold , Sonia Bansal , Benjamin Robinson , Alan Anticevic , Steven J. Luck
Background
People with schizophrenia (PSZ) show impaired accuracy in spatial working memory (sWM), which is thought to reflect abnormalities in the sustained firing of feature selective neurons that are critical for successful encoding and maintenance processes. Recent research has documented a new source of variance in the accuracy of sWM: In healthy adults, sWM representations are unconsciously biased by previous trials such that current-trial responses are attracted to previous-trial responses (serial dependence). This opens a new window to examine how schizophrenia impacts both the sustained neural firing representing the current-trial target and the longer-term synaptic plasticity that stores previous-trial information.
Methods
We examined response accuracy in a single-item sWM test with delay intervals of 0, 2, 4, or 8 seconds in 41 PSZ and 32 demographically similar healthy control participants. Our main dependent variable was the bias index, which quantifies the extent to which the current-trial responses were biased toward or away from the previous-trial target.
Results
PSZ showed opposite-direction serial dependence bias effects: Healthy control participants showed an attractive bias that increased over increasing delays whereas PSZ showed a repulsion bias that increased over delays. In PSZ, the magnitude of the repulsion bias negatively correlated with broad measures of cognitive ability and WM capacity.
Conclusions
PSZ show opposite-direction effects of previous trials on WM. Such qualitatively distinct differences in performance are extremely rare in psychopathology and may index a fundamental alteration in neural processing that could serve as a valuable biomarker for pathophysiology and treatment development research.
{"title":"Opposite-Direction Spatial Working Memory Biases in People With Schizophrenia and Healthy Control Participants","authors":"James M. Gold , Sonia Bansal , Benjamin Robinson , Alan Anticevic , Steven J. Luck","doi":"10.1016/j.bpsc.2024.09.008","DOIUrl":"10.1016/j.bpsc.2024.09.008","url":null,"abstract":"<div><h3>Background</h3><div>People with schizophrenia (PSZ) show impaired accuracy in spatial working memory (sWM), which is thought to reflect abnormalities in the sustained firing of feature selective neurons that are critical for successful encoding and maintenance processes. Recent research has documented a new source of variance in the accuracy of sWM: In healthy adults, sWM representations are unconsciously biased by previous trials such that current-trial responses are attracted to previous-trial responses (serial dependence). This opens a new window to examine how schizophrenia impacts both the sustained neural firing representing the current-trial target and the longer-term synaptic plasticity that stores previous-trial information.</div></div><div><h3>Methods</h3><div>We examined response accuracy in a single-item sWM test with delay intervals of 0, 2, 4, or 8 seconds in 41 PSZ and 32 demographically similar healthy control participants. Our main dependent variable was the bias index, which quantifies the extent to which the current-trial responses were biased toward or away from the previous-trial target.</div></div><div><h3>Results</h3><div>PSZ showed opposite-direction serial dependence bias effects: Healthy control participants showed an attractive bias that increased over increasing delays whereas PSZ showed a repulsion bias that increased over delays. In PSZ, the magnitude of the repulsion bias negatively correlated with broad measures of cognitive ability and WM capacity.</div></div><div><h3>Conclusions</h3><div>PSZ show opposite-direction effects of previous trials on WM. Such qualitatively distinct differences in performance are extremely rare in psychopathology and may index a fundamental alteration in neural processing that could serve as a valuable biomarker for pathophysiology and treatment development research.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 2","pages":"Pages 167-174"},"PeriodicalIF":5.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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