Pub Date : 2024-03-14DOI: 10.1007/s44192-024-00062-9
Prashin Unadkat, Joao Quevedo, Jair Soares, Albert Fenoy
Major Depressive Disorder continues to remain one of the most prevalent psychiatric diseases globally. Despite multiple trials of conventional therapies, a subset of patients fail to have adequate benefit to treatment. Deep brain stimulation (DBS) is a promising treatment in this difficult to treat population and has shown strong antidepressant effects across multiple cohorts. Nearly two decades of work have provided insights into the potential for chronic focal stimulation in precise brain targets to modulate pathological brain circuits that are implicated in the pathogenesis of depression. In this paper we review the rationale that prompted the selection of various brain targets for DBS, their subsequent clinical outcomes and common adverse events reported. We additionally discuss some of the pitfalls and challenges that have prevented more widespread adoption of this technology as well as future directions that have shown promise in improving therapeutic efficacy of DBS in the treatment of depression.
{"title":"Opportunities and challenges for the use of deep brain stimulation in the treatment of refractory major depression.","authors":"Prashin Unadkat, Joao Quevedo, Jair Soares, Albert Fenoy","doi":"10.1007/s44192-024-00062-9","DOIUrl":"10.1007/s44192-024-00062-9","url":null,"abstract":"<p><p>Major Depressive Disorder continues to remain one of the most prevalent psychiatric diseases globally. Despite multiple trials of conventional therapies, a subset of patients fail to have adequate benefit to treatment. Deep brain stimulation (DBS) is a promising treatment in this difficult to treat population and has shown strong antidepressant effects across multiple cohorts. Nearly two decades of work have provided insights into the potential for chronic focal stimulation in precise brain targets to modulate pathological brain circuits that are implicated in the pathogenesis of depression. In this paper we review the rationale that prompted the selection of various brain targets for DBS, their subsequent clinical outcomes and common adverse events reported. We additionally discuss some of the pitfalls and challenges that have prevented more widespread adoption of this technology as well as future directions that have shown promise in improving therapeutic efficacy of DBS in the treatment of depression.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10940557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140133370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-08DOI: 10.1007/s44192-024-00061-w
Jacob D King, Thomas Elliott, Alexandra Pitman
Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.
{"title":"Steroid-induced mania in a patient with previously well-controlled organic bipolar 1-like affective disorder secondary to acquired brain injury: case report and literature review.","authors":"Jacob D King, Thomas Elliott, Alexandra Pitman","doi":"10.1007/s44192-024-00061-w","DOIUrl":"10.1007/s44192-024-00061-w","url":null,"abstract":"<p><p>Steroid-induced neuropsychiatric sequelae are common, and pose significant risks to people usually receiving glucocorticoids in the context of physical illness. Steroid-induced mania and hypomania are the most common of the acute complications, yet despite great progress in understandings in neurophysiology there are no recent studies which review the factors which might predict who will experience this severe complication, nor are there consensus guidelines on management. We report the unusual case of a woman in her 50s admitted to a psychiatric unit with steroid-induced mania despite compliance with two mood stabilisers, several days after the administration of a Dexamethasone and Docetaxel chemotherapy regime adjunctive to lumpectomy for breast cancer. She had previously been diagnosed with an organic affective disorder (with classical bipolar 1 pattern) following severe ventriculitis related to ventricular drain insertion for obstructive hydrocephalus secondary to a colloid cyst. She had no psychiatric illness before this brain injury, but has a maternal history of idiopathic bipolar 1 affective disorder. Her episode of steroid-induced mania resolved following use of sedative medications, continuation of her existing mood stabilisers, and reductions of the steroid dosing in collaboration with her oncology team, which also protected her from further manic relapses during continued chemotherapy. Established mental illness, a family history, and acquired brain injury may reflect risk factors for steroid-induced mania through currently unclear pathways. Future epidemiological studies could better confirm these observations, and basic neuroscience may look to further explore the role of extrinsic glucocorticoids in the pathophysiology of affective disorders.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10920485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-04DOI: 10.1007/s44192-024-00060-x
Hassan Mohammed Sonbol, Youmna Sabri, Mohamed Shahda, Eman Abdallah Shouman
Background: Adolescent substance use is a major problem that has serious medical, psychological, and legal consequences later in life. Substance use disorder is closely linked to deficits in executive functions. Impaired executive functions (EFs) have been linked to all stages of the substance use disorder (SUD) life cycle, increasing the likelihood of commencing use, escalating use more quickly, and increasing the likelihood of relapsing following treatment. The current study aimed at evaluating of the executive functions and quality of life in a sample of adolescent Egyptian males with substance use disorder.
Results: A significantly higher mean Trail Making Test-A, B (TMT-A and TMT-B) scores among studied cases than the control group (equals lower executive functions) with a mean score of TMT-A is 74.38 versus 63.2 among controls and for TMT-B; the mean score for control is 97.22 versus 142.04 among cases. A statistically significant difference between the case and control groups on all quality of life scores measuring the following domains: general health and well-being, physical health, psychological health, social interactions, and the environment, also there has been a negative correlation between TMT-A and the environmental domain (r = - 0.279) and TMT-B with the same variable (r = - 0.414).
Conclusions: Substance use disorders are a major health problem among youth. Deficits in executive functions are strongly associated with adolescent substance use. The more affected executive functions are associated with more affected quality of life of these patients.
{"title":"Evaluation of the executive functions and quality of life in a sample of Egyptian male adolescents with substance use disorder: A case-control study.","authors":"Hassan Mohammed Sonbol, Youmna Sabri, Mohamed Shahda, Eman Abdallah Shouman","doi":"10.1007/s44192-024-00060-x","DOIUrl":"10.1007/s44192-024-00060-x","url":null,"abstract":"<p><strong>Background: </strong>Adolescent substance use is a major problem that has serious medical, psychological, and legal consequences later in life. Substance use disorder is closely linked to deficits in executive functions. Impaired executive functions (EFs) have been linked to all stages of the substance use disorder (SUD) life cycle, increasing the likelihood of commencing use, escalating use more quickly, and increasing the likelihood of relapsing following treatment. The current study aimed at evaluating of the executive functions and quality of life in a sample of adolescent Egyptian males with substance use disorder.</p><p><strong>Results: </strong>A significantly higher mean Trail Making Test-A, B (TMT-A and TMT-B) scores among studied cases than the control group (equals lower executive functions) with a mean score of TMT-A is 74.38 versus 63.2 among controls and for TMT-B; the mean score for control is 97.22 versus 142.04 among cases. A statistically significant difference between the case and control groups on all quality of life scores measuring the following domains: general health and well-being, physical health, psychological health, social interactions, and the environment, also there has been a negative correlation between TMT-A and the environmental domain (r = - 0.279) and TMT-B with the same variable (r = - 0.414).</p><p><strong>Conclusions: </strong>Substance use disorders are a major health problem among youth. Deficits in executive functions are strongly associated with adolescent substance use. The more affected executive functions are associated with more affected quality of life of these patients.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140023504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-22DOI: 10.1007/s44192-024-00059-4
Adam P Natoli, Chloe M Rodriguez
Personality functioning impairment is at the center of many dimensional models of personality. Available measures of personality functioning impairment are limited to self-report, clinician-/informant-rated, and interview methods. Although researchers have begun investigating established performance-based instruments' potential for assessing personality functioning impairment, administration and scoring of these instruments is complex and the latent variables they measure diverge from personality functioning impairment as described in the ICD-11 and the Alternative Model for Personality Disorders (AMPD) of the DSM. We address this absence by developing and psychometrically evaluating the Level of Personality Functioning Scale-Questionnaire-based Implicit Association Test (LPFS-qIAT). The LPFS-qIAT's psychometric properties were evaluated across four studies, producing initial evidence supporting the new instrument's reliability as well as its convergent, discriminant, and criterion-related validity. As the first performance-based measure of personality functioning impairment that aligns with the AMPD and, to a degree the ICD-11, that is easily administered, scored, and interpreted, the LPFS-qIAT shows potential to become a valuable tool in both research and clinical practice.
{"title":"A new performance-based measure of personality functioning impairment: development and preliminary evaluation of reliability and validity.","authors":"Adam P Natoli, Chloe M Rodriguez","doi":"10.1007/s44192-024-00059-4","DOIUrl":"10.1007/s44192-024-00059-4","url":null,"abstract":"<p><p>Personality functioning impairment is at the center of many dimensional models of personality. Available measures of personality functioning impairment are limited to self-report, clinician-/informant-rated, and interview methods. Although researchers have begun investigating established performance-based instruments' potential for assessing personality functioning impairment, administration and scoring of these instruments is complex and the latent variables they measure diverge from personality functioning impairment as described in the ICD-11 and the Alternative Model for Personality Disorders (AMPD) of the DSM. We address this absence by developing and psychometrically evaluating the Level of Personality Functioning Scale-Questionnaire-based Implicit Association Test (LPFS-qIAT). The LPFS-qIAT's psychometric properties were evaluated across four studies, producing initial evidence supporting the new instrument's reliability as well as its convergent, discriminant, and criterion-related validity. As the first performance-based measure of personality functioning impairment that aligns with the AMPD and, to a degree the ICD-11, that is easily administered, scored, and interpreted, the LPFS-qIAT shows potential to become a valuable tool in both research and clinical practice.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139934556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-18DOI: 10.1007/s44192-023-00058-x
Jonathon R Howlett, Martin P Paulus
Control theory, which has played a central role in technological progress over the last 150 years, has also yielded critical insights into biology and neuroscience. Recently, there has been a surging interest in integrating control theory with computational psychiatry. Here, we review the state of the field of using control theory approaches in computational psychiatry and show that recent research has mapped a neural control circuit consisting of frontal cortex, parietal cortex, and the cerebellum. This basic feedback control circuit is modulated by estimates of reward and cost via the basal ganglia as well as by arousal states coordinated by the insula, dorsal anterior cingulate cortex, amygdala, and locus coeruleus. One major approach within the broader field of control theory, known as proportion-integral-derivative (PID) control, has shown promise as a model of human behavior which enables precise and reliable estimates of underlying control parameters at the individual level. These control parameters correlate with self-reported fear and with both structural and functional variation in affect-related brain regions. This suggests that dysfunctional engagement of stress and arousal systems may suboptimally modulate parameters of domain-general goal-directed control algorithms, impairing performance in complex tasks involving movement, cognition, and affect. Future directions include clarifying the causal role of control deficits in stress- and anxiety-related disorders and developing clinically useful tools based on insights from control theory.
{"title":"Out of control: computational dynamic control dysfunction in stress- and anxiety-related disorders.","authors":"Jonathon R Howlett, Martin P Paulus","doi":"10.1007/s44192-023-00058-x","DOIUrl":"10.1007/s44192-023-00058-x","url":null,"abstract":"<p><p>Control theory, which has played a central role in technological progress over the last 150 years, has also yielded critical insights into biology and neuroscience. Recently, there has been a surging interest in integrating control theory with computational psychiatry. Here, we review the state of the field of using control theory approaches in computational psychiatry and show that recent research has mapped a neural control circuit consisting of frontal cortex, parietal cortex, and the cerebellum. This basic feedback control circuit is modulated by estimates of reward and cost via the basal ganglia as well as by arousal states coordinated by the insula, dorsal anterior cingulate cortex, amygdala, and locus coeruleus. One major approach within the broader field of control theory, known as proportion-integral-derivative (PID) control, has shown promise as a model of human behavior which enables precise and reliable estimates of underlying control parameters at the individual level. These control parameters correlate with self-reported fear and with both structural and functional variation in affect-related brain regions. This suggests that dysfunctional engagement of stress and arousal systems may suboptimally modulate parameters of domain-general goal-directed control algorithms, impairing performance in complex tasks involving movement, cognition, and affect. Future directions include clarifying the causal role of control deficits in stress- and anxiety-related disorders and developing clinically useful tools based on insights from control theory.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10796870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139486656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-04DOI: 10.1007/s44192-023-00057-y
Daniel W Fisher, Jeffrey T Dunn, Hongxin Dong
Depression is a common and devastating neuropsychiatric symptom in the elderly and in patients with dementia. In particular, nearly 80% of patients with Alzheimer's Disease dementia experience depression during disease development and progression. However, it is unknown whether the depression in patients with dementia shares the same molecular mechanisms as depression presenting as primary psychiatric disease or occurs and persists through alternative mechanisms. In this review, we discuss how the clinical presentation and treatment differ between depression in dementia and as a primary psychiatric disease, with a focus on major depressive disorder. Then, we hypothesize several molecular mechanisms that may be unique to depression in dementia such as neuropathological changes, inflammation, and vascular events. Finally, we discuss existing issues and future directions for investigation and treatment of depression in dementia.
{"title":"Distinguishing features of depression in dementia from primary psychiatric disease.","authors":"Daniel W Fisher, Jeffrey T Dunn, Hongxin Dong","doi":"10.1007/s44192-023-00057-y","DOIUrl":"10.1007/s44192-023-00057-y","url":null,"abstract":"<p><p>Depression is a common and devastating neuropsychiatric symptom in the elderly and in patients with dementia. In particular, nearly 80% of patients with Alzheimer's Disease dementia experience depression during disease development and progression. However, it is unknown whether the depression in patients with dementia shares the same molecular mechanisms as depression presenting as primary psychiatric disease or occurs and persists through alternative mechanisms. In this review, we discuss how the clinical presentation and treatment differ between depression in dementia and as a primary psychiatric disease, with a focus on major depressive disorder. Then, we hypothesize several molecular mechanisms that may be unique to depression in dementia such as neuropathological changes, inflammation, and vascular events. Finally, we discuss existing issues and future directions for investigation and treatment of depression in dementia.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10767128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-04DOI: 10.1007/s44192-023-00054-1
Kate Lamont, Hugo C van Woerden, Emma King, Charlotte Wendelboe-Nelson, Roger W Humphry, Cameron Stark, Chris Williams, Margaret Maxwell
Background: The farming community have high rates of poor mental health, and are relatively 'hard to reach' with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based 'Living Life to the Full for Farming Communities' (LLTTF-F; www.llttf.com ), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation.
Methods: This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of > = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and 'Social and emotional support'. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began.
Results: Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the 'combined intervention' mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). 'Social and emotional support' mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). 'LLTTF-F CBT-based intervention only' mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback.
Conclusions: Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores. Trial Registration Number ISRCTN27173711, submitted 25/08/2023, confirmed 22/092023.
{"title":"Improving the mental health of farmers: what types of remote support are acceptable, feasible, and improve outcomes? A feasibility RCT.","authors":"Kate Lamont, Hugo C van Woerden, Emma King, Charlotte Wendelboe-Nelson, Roger W Humphry, Cameron Stark, Chris Williams, Margaret Maxwell","doi":"10.1007/s44192-023-00054-1","DOIUrl":"10.1007/s44192-023-00054-1","url":null,"abstract":"<p><strong>Background: </strong>The farming community have high rates of poor mental health, and are relatively 'hard to reach' with mental health services. The aim of this study was therefore to undertake a feasibility RCT, based on two mental health interventions. These were (1) CBT based 'Living Life to the Full for Farming Communities' (LLTTF-F; www.llttf.com ), and (2) a holistic social and emotional support service delivered by the Royal Scottish Agricultural Benevolent Institution (RSABI). The feasibility was supplemented by process evaluation.</p><p><strong>Methods: </strong>This feasibility study aimed to recruit 40 individuals from the farming community who were experiencing a common health problem defined as a score of > = 8 on PHQ-9. A snowball approach was used to recruit interested individuals who had an association with farming. An initial telephone call screened for eligibility and obtained consent to randomisation to the two specified interventions, or to a thirdly group receiving a combination of both LLTTF-F and 'Social and emotional support'. Participants were permitted to override the randomised option if they expressed a strong preference before the interventions began.</p><p><strong>Results: </strong>Thirty-two participants provided baseline and three-month data. All three interventions showed positive improvements on PHQ-9 scores as follows: the 'combined intervention' mean baseline score was 18.1 compared to 12.0 at 3-month follow-up (mean change 6.1). 'Social and emotional support' mean baseline score was 11.3 compared to 6.7 at 3-month follow-up (mean change 4.6). 'LLTTF-F CBT-based intervention only' mean baseline score was 11.8 compared to 4.5 at 3-month follow-up (mean change 7.3). The retention rate was 81% at three months. In a sub-group of the LLTTF-F CBT-based intervention online materials were supplemented by telephone guided support. This approach received very positive feedback.</p><p><strong>Conclusions: </strong>Recruitment from the farming community required intense effort, and good engagement can then be retained for at least three months. There is evidence that the interventions used were feasible, and tentative evidence that they had a demonstrable effect on mental wellbeing, with the LLTTFF providing the largest effect on PHQ-9 scores. Trial Registration Number ISRCTN27173711, submitted 25/08/2023, confirmed 22/092023.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2024-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10766572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-02DOI: 10.1007/s44192-023-00056-z
Benedetta Bigio, Shofiul Azam, Aleksander A Mathé, Carla Nasca
Mitochondrial metabolism can contribute to nuclear histone acetylation among other epigenetic mechanisms. A central aspect of this signaling pathway is acetyl-L-carnitine (LAC), a pivotal mitochondrial metabolite best known for its role in fatty acid oxidation. Work from our and other groups suggested LAC as a novel epigenetic modulator of brain plasticity and a therapeutic target for clinical phenotypes of depression linked to childhood trauma. Aberrant mitochondrial metabolism of LAC has also been implicated in the pathophysiology of Alzheimer's disease. Furthermore, mitochondrial dysfunction is linked to other processes implicated in the pathophysiology of both major depressive disorders and Alzheimer's disease, such as oxidative stress, inflammation, and insulin resistance. In addition to the rapid epigenetic modulation of glutamatergic function, preclinical studies showed that boosting mitochondrial metabolism of LAC protects against oxidative stress, rapidly ameliorates insulin resistance, and reduces neuroinflammation by decreasing proinflammatory pathways such as NFkB in hippocampal and cortical neurons. These basic and translational neuroscience findings point to this mitochondrial signaling pathway as a potential target to identify novel mechanisms of brain plasticity and potential unique targets for therapeutic intervention targeted to specific clinical phenotypes.
{"title":"The neuropsychopharmacology of acetyl-L-carnitine (LAC): basic, translational and therapeutic implications.","authors":"Benedetta Bigio, Shofiul Azam, Aleksander A Mathé, Carla Nasca","doi":"10.1007/s44192-023-00056-z","DOIUrl":"10.1007/s44192-023-00056-z","url":null,"abstract":"<p><p>Mitochondrial metabolism can contribute to nuclear histone acetylation among other epigenetic mechanisms. A central aspect of this signaling pathway is acetyl-L-carnitine (LAC), a pivotal mitochondrial metabolite best known for its role in fatty acid oxidation. Work from our and other groups suggested LAC as a novel epigenetic modulator of brain plasticity and a therapeutic target for clinical phenotypes of depression linked to childhood trauma. Aberrant mitochondrial metabolism of LAC has also been implicated in the pathophysiology of Alzheimer's disease. Furthermore, mitochondrial dysfunction is linked to other processes implicated in the pathophysiology of both major depressive disorders and Alzheimer's disease, such as oxidative stress, inflammation, and insulin resistance. In addition to the rapid epigenetic modulation of glutamatergic function, preclinical studies showed that boosting mitochondrial metabolism of LAC protects against oxidative stress, rapidly ameliorates insulin resistance, and reduces neuroinflammation by decreasing proinflammatory pathways such as NFkB in hippocampal and cortical neurons. These basic and translational neuroscience findings point to this mitochondrial signaling pathway as a potential target to identify novel mechanisms of brain plasticity and potential unique targets for therapeutic intervention targeted to specific clinical phenotypes.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-02DOI: 10.1007/s44192-023-00055-0
Kelly Sewell, Sudeshna Paul, Kelley De Polt, Maggie M Sugg, Ronald D Leeper, Douglas Rao, Jennifer D Runkle
Background: Concurrent heatwave and drought events may have larger health impacts than each event separately; however, no US-based studies have examined differential mental health impacts of compound drought and heatwave events in pediatric populations.
Objective: To examine the spatial patterns of mood disorders and suicide-related emergency department (ED) visits in children during heatwave, drought, and compound heatwave and drought events. We tested whether the occurrence of compound heatwave and drought events have a synergistic (multiplicative) effect on the risk of mental health related outcomes in children as compared to the additive effect of each individual climate hazard. Lastly, we identified household and community-level determinants of geographic variability of high psychiatric burden.
Methods: Daily counts of psychiatric ED visits in North Carolina from 2016 to 2019 (May to Sept) for pediatric populations were aggregated at the county scale. Bernoulli cluster analyses identified high-risk spatial clusters of psychiatric morbidity during heatwave, drought, or compound heatwave and drought periods. Multivariate adaptive regression models examined the individual importance of household and community-level determinants in predicting high-risk clustering of mood disorders or suicidality across the three climate threats.
Results: Results showed significant spatial clustering of suicide and mood disorder risks in children during heatwave, drought, and compound event periods. Periods of drought were associated with the highest likelihood of spatial clustering for suicide and mood disorders, where the risk of an ED visit was 4.48 and 6.32 times higher, respectively, compared to non-drought periods. Compounding events were associated with a threefold increase in both suicide and mood disorder-related ED visits. Community and household vulnerability factors that most contributed to spatial clustering varied across climate hazards, but consistent determinants included residential segregation, green space availability, low English proficiency, overcrowding, no broadband access, no vehicle access, housing vacancy, and availability of housing units.
Conclusion: Findings advance understanding on the locations of vulnerable pediatric populations who are disproportionately exposed to compounding climate stressors and identify community resilience factors to target in public health adaptation strategies.
{"title":"Impacts of compounding drought and heatwave events on child mental health: insights from a spatial clustering analysis.","authors":"Kelly Sewell, Sudeshna Paul, Kelley De Polt, Maggie M Sugg, Ronald D Leeper, Douglas Rao, Jennifer D Runkle","doi":"10.1007/s44192-023-00055-0","DOIUrl":"10.1007/s44192-023-00055-0","url":null,"abstract":"<p><strong>Background: </strong>Concurrent heatwave and drought events may have larger health impacts than each event separately; however, no US-based studies have examined differential mental health impacts of compound drought and heatwave events in pediatric populations.</p><p><strong>Objective: </strong>To examine the spatial patterns of mood disorders and suicide-related emergency department (ED) visits in children during heatwave, drought, and compound heatwave and drought events. We tested whether the occurrence of compound heatwave and drought events have a synergistic (multiplicative) effect on the risk of mental health related outcomes in children as compared to the additive effect of each individual climate hazard. Lastly, we identified household and community-level determinants of geographic variability of high psychiatric burden.</p><p><strong>Methods: </strong>Daily counts of psychiatric ED visits in North Carolina from 2016 to 2019 (May to Sept) for pediatric populations were aggregated at the county scale. Bernoulli cluster analyses identified high-risk spatial clusters of psychiatric morbidity during heatwave, drought, or compound heatwave and drought periods. Multivariate adaptive regression models examined the individual importance of household and community-level determinants in predicting high-risk clustering of mood disorders or suicidality across the three climate threats.</p><p><strong>Results: </strong>Results showed significant spatial clustering of suicide and mood disorder risks in children during heatwave, drought, and compound event periods. Periods of drought were associated with the highest likelihood of spatial clustering for suicide and mood disorders, where the risk of an ED visit was 4.48 and 6.32 times higher, respectively, compared to non-drought periods. Compounding events were associated with a threefold increase in both suicide and mood disorder-related ED visits. Community and household vulnerability factors that most contributed to spatial clustering varied across climate hazards, but consistent determinants included residential segregation, green space availability, low English proficiency, overcrowding, no broadband access, no vehicle access, housing vacancy, and availability of housing units.</p><p><strong>Conclusion: </strong>Findings advance understanding on the locations of vulnerable pediatric populations who are disproportionately exposed to compounding climate stressors and identify community resilience factors to target in public health adaptation strategies.</p>","PeriodicalId":72827,"journal":{"name":"Discover mental health","volume":"4 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761644/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139089595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}