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Annals of Clinical and Translational... Jun 2024Cognitive and affective symptoms in multiple sclerosis (MS) can be independently impaired and have different pathways of progression. Cognitive alterations have been...
OBJECTIVE
Cognitive and affective symptoms in multiple sclerosis (MS) can be independently impaired and have different pathways of progression. Cognitive alterations have been described since the earliest MS stages; by contrast, the social cognition (SC) domain has never been investigated in the first year from MS diagnosis. We aimed to evaluate SC and unravel its neural bases in newly diagnosed MS patients.
METHODS
Seventy MS patients underwent at diagnosis a 3 T-MRI and a neuropsychological/SC assessment (median time between diagnosis and MRI/cognitive evaluation = 0 months). We tested two matched reference samples: 31 relapsing-remitting MS patients with longer course (mean ± SD disease duration = 7.0 ± 4.5 years) and 38 healthy controls (HCs). Cortical thicknesses (CTh) and volumes of brain regions were calculated.
RESULTS
Newly diagnosed MS patients performed significantly lower than HCs in facial emotion recognition (global: p < 0.001; happiness: p = 0.041, anger: p = 0.007; fear: p < 0.001; disgust: p = 0.004) and theory of mind (p = 0.005), while no difference was found between newly diagnosed and longer MS patients. Compared to lower performers, higher performers in facial emotion recognition showed greater volume of amygdala (p = 0.032) and caudate (p = 0.036); higher performers in theory of mind showed greater CTh in lingual gyrus (p = 0.006), cuneus (p = 0.024), isthmus cingulate (p = 0.038), greater volumes of putamen (p = 0.016), pallidum (p = 0.029), and amygdala (p = 0.032); patients with higher empathy showed lower cuneus CTh (p = 0.042) and putamen volume (p = 0.007).
INTERPRETATIONS
SC deficits are present in MS patients since the time of diagnosis and remain persistent along the disease course. Specific basal, limbic, and occipital areas play a significant role in the pathogenesis of these alterations.
PubMed: 38872257
DOI: 10.1002/acn3.52085 -
Nature Communications Jun 2024Mood disorders are an enigmatic class of debilitating illnesses that affect millions of individuals worldwide. While chronic stress clearly increases incidence levels of...
Mood disorders are an enigmatic class of debilitating illnesses that affect millions of individuals worldwide. While chronic stress clearly increases incidence levels of mood disorders, including major depressive disorder (MDD), stress-mediated disruptions in brain function that precipitate these illnesses remain largely elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding direct roles for serotonin in the precipitation and treatment of affective disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this non-canonical phenomenon has not yet been explored following stress and/or AD exposures. Here, we employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress, as well as in DRN of human MDD patients, to examine the impact of stress exposures/MDD diagnosis on H3K4me3Q5ser dynamics, as well as associations between the mark and depression-related gene expression. We additionally assessed stress-induced/MDD-associated regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy in mice to reduce H3K4me3Q5ser levels in DRN and examine its impact on stress-associated gene expression and behavior. We found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to attenuate stress-mediated gene expression and behavior. Corresponding patterns of H3K4me3Q5ser regulation were observed in MDD subjects on vs. off ADs at their time of death. These findings thus establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity, observations of which may be of clinical relevance to human MDD and its treatment.
Topics: Animals; Dorsal Raphe Nucleus; Histones; Male; Female; Stress, Psychological; Humans; Antidepressive Agents; Depressive Disorder, Major; Mice; Serotonin; Mice, Inbred C57BL; Epigenesis, Genetic; Behavior, Animal; Gene Expression Regulation; Social Defeat
PubMed: 38871707
DOI: 10.1038/s41467-024-49336-4 -
JAMA Network Open Jun 2024The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these...
IMPORTANCE
The use of evidence-based standardized outcome measures is increasingly recognized as key to guiding clinical decision-making in mental health. Implementation of these measures into clinical practice has been hampered by lack of clarity on what to measure and how to do this in a reliable and standardized way.
OBJECTIVE
To develop a core set of outcome measures for specific neurodevelopmental disorders (NDDs), such as attention-deficit/hyperactivity disorder (ADHD), communication disorders, specific learning disorders, and motor disorders, that may be used across a range of geographic and cultural settings.
EVIDENCE REVIEW
An international working group composed of clinical and research experts and service users (n = 27) was convened to develop a standard core set of accessible, valid, and reliable outcome measures for children and adolescents with NDDs. The working group participated in 9 video conference calls and 8 surveys between March 1, 2021, and June 30, 2022. A modified Delphi approach defined the scope, outcomes, included measures, case-mix variables, and measurement time points. After development, the NDD set was distributed to professionals and service users for open review, feedback, and external validation.
FINDINGS
The final set recommends measuring 12 outcomes across 3 key domains: (1) core symptoms related to the diagnosis; (2) impact, functioning, and quality of life; and (3) common coexisting problems. The following 14 measures should be administered at least every 6 months to monitor these outcomes: ADHD Rating Scale 5, Vanderbilt ADHD Diagnostic Rating Scale, or Swanson, Nolan, and Pelham Rating Scale IV; Affective Reactivity Index; Children's Communication Checklist 2; Colorado Learning Disabilities Questionnaire; Children's Sleep Habits Questionnaire; Developmental-Disability Children's Global Assessment Scale; Developmental Coordination Disorder Questionnaire; Family Strain Index; Intelligibility in Context Scale; Vineland Adaptive Behavior Scale or Repetitive Behavior Scale-Revised and Social Responsiveness Scale; Revised Child Anxiety and Depression Scales; and Yale Global Tic Severity Scale. The external review survey was completed by 32 professionals and 40 service users. The NDD set items were endorsed by more than 70% of professionals and service users in the open review survey.
CONCLUSIONS AND RELEVANCE
The NDD set covers outcomes of most concern to patients and caregivers. Use of the NDD set has the potential to improve clinical practice and research.
Topics: Humans; Neurodevelopmental Disorders; Child; Consensus; Outcome Assessment, Health Care; Adolescent; Delphi Technique; Attention Deficit Disorder with Hyperactivity; Female
PubMed: 38869906
DOI: 10.1001/jamanetworkopen.2024.16760 -
PCN Reports : Psychiatry and Clinical... Mar 2024We present a case report on the efficacy of the short-term application of vortioxetine in managing winter depression in patients with seasonal bipolar disorder (BP)....
BACKGROUND
We present a case report on the efficacy of the short-term application of vortioxetine in managing winter depression in patients with seasonal bipolar disorder (BP). Standard treatment strategies for BP may not adequately address seasonal depressive symptoms during winter in patients with seasonal BP patterns. Depressive symptoms during winter may be linked to seasonal changes in serotonin transporter binding, such as a decrease in synaptic serotonin levels, necessitating alternative approaches. Although antidepressants, including vortioxetine, are effective in treating seasonal monopolar depression, their efficacy and safety in treating depression in patients with seasonal BP patterns remain unclear.
CASE PRESENTATION
This case report focuses on a 44-year-old male patient diagnosed with seasonal BP who had recurrent depressive episodes, specifically during winter. Notably, the patient had a significant decrease in recurrent episodes after short-term seasonal vortioxetine use without inducing mania or rapid cycling.
CONCLUSION
Our study highlights the potential effectiveness of a seasonal, short-term treatment strategy with antidepressants, including vortioxetine, for winter depression in individuals with BP.
PubMed: 38868466
DOI: 10.1002/pcn5.163 -
PCN Reports : Psychiatry and Clinical... Sep 2023Hyperthymic temperament is a cheerful action orientation that is suggested to have a protective effect on depressive symptoms. We recently reported that hyperthymic...
AIM
Hyperthymic temperament is a cheerful action orientation that is suggested to have a protective effect on depressive symptoms. We recently reported that hyperthymic temperament can positively predict activation of reward-related brain areas in anticipation of monetary rewards, which could serve as a biomarker of hyperthymic temperament. However, the relationship between hyperthymic temperament and neural responsiveness to nonmonetary rewards (i.e., feedback indicating success in a task) remains unclear.
METHODS
Healthy participants performed a modified monetary incentive delay task inside a functional magnetic resonance imaging scanner. To examine the effect of nonmonetary positive feedback, the participants performed feedback and no-feedback trials. We explored brain regions whose neural responsiveness to nonmonetary rewards was predicted by hyperthymic temperament.
RESULTS
There was premotor area activation in anticipation of a nonmonetary reward, which was negatively predicted by hyperthymic temperament. Moreover, brain areas located mainly in the primary somatosensory area and somatosensory association area were activated by performance feedback, which was positively predicted by hyperthymic temperament.
CONCLUSION
We found that hyperthymic temperament is related to neural responsiveness to both monetary and nonmonetary rewards. This may be related to the process of affective regulation in the somatosensory area.
PubMed: 38867834
DOI: 10.1002/pcn5.140 -
Scientific Reports Jun 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower... (Clinical Trial)
Clinical Trial
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower health-related quality of life (HRQoL). PCOS is closely associated with obesity, which per se can lead to symptoms of anxiety and depression and lower HRQoL. The first-line treatment for PCOS is weight loss through lifestyle intervention, which has been shown to improve all symptoms of the syndrome. The aim of this study was to investigate symptoms of anxiety and depression and HRQoL in women with severe obesity (BMI ≥ 35) with and without PCOS, and to evaluate the effect of a one-year structured weight loss intervention. A total of 246 women with severe obesity (PCOS n = 63, non-PCOS n = 183) were included. The comprehensive psychopathological rating scale self-rating scale for affective symptoms (CPRS-S-A) and the short form-36 (SF-36) were used to assess symptoms of anxiety and depression and HRQoL. In total 72 women of the 246 women with severe obesity completed a one-year weight loss programme and were followed up and compared with baseline data. In women with severe obesity, there were no differences in symptoms of anxiety and depression and HRQoL between women with and without PCOS at baseline. Clinically relevant anxiety symptoms were present in 71.3% (PCOS) and 65.6% (non-PCOS), and depression symptoms were present in 56.4% (PCOS) and 52.2% (non-PCOS). Significant weight loss improved physical HRQoL in all women, but reduced symptoms of anxiety and depression only in women without PCOS. There were no differences when comparing the changes between the groups. Women with severe obesity are severely affected by symptoms of anxiety and depression, independent of PCOS. Weight loss improved symptoms of anxiety and depression in women without PCOS, but there were no differences between groups in change from baseline to follow-up.Trial registration number: Clinical trial.gov: NCT01319162, March 18, 2011. Date of registration and enrolment of the first subject September 2011.
Topics: Adult; Female; Humans; Anxiety; Depression; Obesity, Morbid; Polycystic Ovary Syndrome; Quality of Life; Weight Loss; Weight Reduction Programs
PubMed: 38866860
DOI: 10.1038/s41598-024-63166-w -
JAMA Network Open Jun 2024Racial discrimination is a psychosocial stressor associated with youths' risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation...
IMPORTANCE
Racial discrimination is a psychosocial stressor associated with youths' risk for psychiatric symptoms. Scarce data exist on the moderating role of amygdalar activation patterns among Black youths in the US.
OBJECTIVE
To investigate the association between racial discrimination and risk for psychopathology moderated by neuroaffective processing.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used longitudinal self-report and functional magnetic resonance imaging (fMRI) data from Black youth participants in the US from the Adolescent Brain Cognitive Development (ABCD) study. Data were analyzed from January 2023 to May 2024.
EXPOSURES
At time 1 of the current study (12 months after baseline), youths self-reported on their experiences of interpersonal racial discrimination and their feelings of marginalization. Amygdalar response was measured during an emotionally valenced task that included blocks of faces expressing either neutral or negative emotion.
MAIN OUTCOMES AND MEASURES
At 24 and 36 months after baseline, youths reported their internalizing (anxiety and depressive symptoms) and externalizing symptoms (aggression and rule-breaking symptoms).
RESULTS
A total of 1596 youths were a mean (SD) age of 10.92 (0.63) years, and 803 were female (50.3%). Families in the study had a mean annual income range of $25 000 to $34 999. Two factors were derived from factor analysis: interpersonal racial discrimination and feelings of marginalization (FoM). Using structural equation modeling in a linear regression, standardized β coefficients were obtained. Neural response to faces expressing negative emotion within the right amygdala significantly moderated the association between FoM and changes in internalizing symptoms (β = -0.20; 95% CI, -0.32 to -0.07; P < .001). The response to negative facial emotion within the right amygdala significantly moderated the association between FoM and changes in externalizing symptoms (β = 0.24; 95% CI, 0.04 to 0.43; P = .02). Left amygdala response to negative emotion significantly moderated the association between FoM and changes in externalizing symptoms (β = -0.16; 95% CI, -0.32 to -0.01; P = .04).
CONCLUSIONS AND RELEVANCE
In this cohort study of Black adolescents in the US, findings suggest that amygdala function in response to emotional stimuli can both protect and intensify the affective outcomes of feeling marginalized on risk for psychopathology, informing preventive interventions aimed at reducing the adverse effects of racism on internalizing and externalizing symptoms among Black youths.
Topics: Humans; Female; Male; Racism; Black or African American; Child; Magnetic Resonance Imaging; Amygdala; Adolescent; Longitudinal Studies; United States; Depression; Anxiety; Cohort Studies; Self Report
PubMed: 38865126
DOI: 10.1001/jamanetworkopen.2024.16491 -
International Journal of Bipolar... Jun 2024Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide...
BACKGROUND
Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II.
RESULTS
We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism.
CONCLUSIONS
Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.
PubMed: 38865039
DOI: 10.1186/s40345-024-00341-y -
Cureus May 2024Neuropathic pain (NP), resulting from damage to the somatosensory system, is characterized by either spontaneous or evoked pain. In the context of NP, wherein aberrant... (Review)
Review
Neuropathic pain (NP), resulting from damage to the somatosensory system, is characterized by either spontaneous or evoked pain. In the context of NP, wherein aberrant signaling pathways contribute to the perception of pain, the thalamus emerges as a key player. This structure is integral to the pain network that includes connections to the dorsal horn of the spinal cord, highlighting its role in the affective-motivational aspects of pain perception. Given its significant involvement, the thalamus is targeted in advanced treatments such as thalamotomy and deep brain stimulation (DBS) when traditional therapies fail, emphasizing the need to understand its function in NP to improve management strategies. This review aimed to provide an overview of the role of the thalamus in the transmission of nociceptive information in NP by discussing the existing evidence, including the effectiveness and safety of current techniques in the management and treatment of NP. This is an integrative review involving the qualitative analysis of scientific articles published in PubMed/MEDLINE, Embase, Scopus, and Web of Science. A total of 687 articles were identified, and after selection, 15 articles were included in this study. All studies reviewed demonstrated varying degrees of effectiveness of DBS and thalamotomy in alleviating painful symptoms, although the relief was often temporary. Many studies noted a reduction in pain perception at the conclusion of treatment compared to pre-treatment levels, with this decrease maintained throughout patient follow-ups. However, adverse events associated with these treatments were also reported. In conclusion, there are some benefits, albeit temporary, to using thalamotomy and DBS to alleviate the painful symptoms of NP. Both procedures are considered advanced forms of surgical intervention that aim to modulate pain pathways in the brain, providing significant relief for patients suffering from chronic pain resistant to conventional treatment. Despite limitations, these surgical interventions offer renewed hope for patients facing disabling chronic pain and can provide a significant improvement in quality of life.
PubMed: 38864037
DOI: 10.7759/cureus.60130 -
BMJ Neurology Open 2024Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness....
INTRODUCTION
Dissociative seizures often occur in the context of dysregulated affective arousal and entail dissociative symptoms such as a disintegration of bodily awareness. However, the interplay between affective arousal and changes in interoceptive processing at the onset of dissociative seizures is not well understood.
METHODS
Using retrospective routine data obtained from video-electroencephalography telemetry in a university hospital epilepsy monitoring unit, we investigate ictal changes in cardiac indices of autonomic arousal and heartbeat evoked potentials (HEPs) in 24 patients with dissociative seizures.
RESULTS
Results show autonomic arousal during seizures with increased heart rate and a shift towards sympathetic activity. Compared with baseline, ictal HEP amplitudes over central and right prefrontal electrodes (F8, Fz) were significantly less pronounced during seizures, suggesting diminished cortical representation of interoceptive information. Significant correlations between heart rate variability measures and HEPs were observed at baseline, with more sympathetic and less parasympathetic activity related to less pronounced HEPs. Interestingly, these relationships weakened during seizures, suggesting a disintegration of autonomic arousal and interoceptive processing during dissociative seizures. In a subgroup of 16 patients, MRI-based cortical thickness analysis found a correlation with HEP amplitudes in the left somatosensory association cortex.
CONCLUSIONS
These findings possibly represent an electrophysiological hint of how autonomic arousal could negatively impact bodily awareness in dissociative seizures, and how these processes might be related to underlying brain structure.
PubMed: 38860229
DOI: 10.1136/bmjno-2024-000665