Attention-deficit/hyperactivity disorder (ADHD) affects 2.5% of adults and is associated with cognitive decline and dementia. The neurobiological mechanisms contributing to adverse outcomes in ADHD are poorly understood. ADHD-related brain alterations may persist into later life and interact with ageing-related processes, potentially increasing susceptibility to neuropathology. This preregistered systematic review synthesised neuroimaging findings in adults aged 35 years and older with clinical, symptomatic, or genetic risk for ADHD, and summarised cognitive and clinical correlates. A search of five databases produced 13 included studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. Most studies (11/13) had low risk of bias. Compared to controls, ADHD groups exhibited alterations in fronto-striatal, fronto-parietal, and limbic systems implicated in executive control and attention. Middle-aged adults with clinical ADHD showed more widespread cortical structural differences, whereas older adults demonstrated abnormalities primarily in frontal regions, possibly reflecting attenuation of differences through ageing. Two functional studies in those with clinical ADHD reported frontal hypoactivation alongside parietal hyperactivation, consistent with compensatory recruitment. Among undiagnosed samples, there were interactions between genetic risk for ADHD and Alzheimer's disease-related pathology affecting brain and cognitive outcomes. Overall, ADHD-associated neurobiological alterations appear to persist into older age. Longitudinal investigations are needed to clarify these relationships.
Introduction Depression is a highly heterogeneous disorder with a similarly heterogeneous neurobiological background. Understanding separate depressive phenotypes, driven by distinct aetiological pathways like early trauma and neurobiological contributors, can improve treatment. Furthermore, sex differences must be considered, as both the development and treatment of depression may be sex-specific. We aimed to investigate the sex-dependent association between polygenic risk for chronotypes, childhood traumas, and depression.Methods In a discovery sample of 273,033 participants GWASs were ran and polygenic risk scores (PRS) were calculated in a target sample of 25,476 participants, separately for morning and evening chronotypes. Effects of chronotype-PRS in interaction with childhood adversities were analysed.Results We identified 39 significant lead-SPNs (single nucleotide polymorphisms) and 44 genes associated with morning chronotype, and 69 significant lead-SNPs and 76 genes for evening chronotype. Heritability was comparable, at 12.1% for morning and 11.8% for evening chronotypes. No significant main effect of either chronotype-PRS was found on depressive symptom scores, however, in interaction with childhood traumas, morningness-PRS showed a significant effect on depressive symptom scores in women.Discussion Our findings highlight important sex differences in the aetiological role of known risk factors for depression, such as chronotype or early trauma, and may have implications in the prevention of mood disorders in those genetically vulnerable and exposed to early risk factors.
Introduction Disrupted structural connectivity is recognized as a key pathophysiological feature of schizophrenia (SCZ). However, the relationship between cortical similarity network alterations and gene expression remains poorly understood.Methods We applied the Morphometric INverse Divergence framework to T1-weighted MRI from 1,216 participants. Cortical similarity networks were constructed, and global and nodal metrics were computed. Case-control comparisons were performed using linear models. Partial least squares (PLS) regression identified genes associated with spatial patterns of network alterations using Allen Human Brain Atlas data.Results Among global metrics, only the rich-club coefficient differed between groups, with a negligible effect size. Nodal metrics showed reduced eigenvector centrality and k-coreness centrality in left temporal/insular (somatomotor), lateral occipital (visual), anterior cingulate (salience/ventral attention), and posterior cingulate (default mode) regions. Participation coefficient was widely reduced in SCZ. For each nodal metric, we identified PLS2-positive and PLS2-negative gene sets. Across degree, eigenvector centrality, and k-coreness centrality, PLS2-negative genes were enriched for metal ion transport, linked to manic and nonorganic psychosis, and upregulated in adolescence and early adulthood. PLS2-positive genes were enriched for neuron projection development and learning or memory, but not psychotic disorders.Conclusions These findings highlight synaptic and neurodevelopmental mechanisms underlying structural dysconnectivity in SCZ.
INTRODUCTION:Sleep disturbances and impaired bed mobility are common in Parkinson's disease (PD). We examined whether objectively measured sleep efficiency is associated with axial motor impairment and explored its potential relationship with cognitive and mood profiles. METHODS:Twenty-eight patients with PD underwent single-night EEG-based sleep monitoring and assessment of nocturnal turning. Partial correlations between sleep metrics and scores on motor, cognitive and mood outcomes were analysed, controlling for age, sex and the MDS-UPDRS 3. Family-wise error (FWE) correction was applied within each sleep predictor. RESULTS:Poor sleep efficiency correlated with higher MDS-UPDRS axial subscore (rpartial = -.615) and this association survived stringent correction for multiple comparisons (FWE-p = .018). However, its associations with PIGD and clinically rated freezing of gait did not remain significant after the correction. Exploratory analyses showed the relationships of N1 percentage with mood disturbances and REM latency with self-reported freezing of gait, of which only the relationship of N1 percentage with depression score showed a trend towards significance after the correction (rpartial =.551, FWE-p = .074). CONCLUSION:Poor objective sleep quality was robustly associated with axial motor severity in PD, independent of overall motor burden. Sleep efficiency may represent a clinically accessible marker of shared brainstem-related pathology underlying axial dysfunction.
The present review summarises recommendations for the management of posttraumatic stress disorder (PTSD) based on a consensus among international experts in the field.Cognitive-behavioural therapy (CBT) has the best evidence base as a psychotherapy modality. Virtual reality exposure therapy appears to be an emerging treatment option for PTSD. Eye Movement Desensitisation and Reprocessing (EMDR) therapy and digital CBT-based interventions did not demonstrate superiority compared to controls. Controlled studies supporting the use of psychodynamic therapy are lacking. Early prophylactic psychotherapy for trauma victims is ineffective and may be harmful.First-line pharmacotherapy includes selective serotonin reuptake inhibitors (SSRIs) and the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine. Several second- and third-line medications are available for treatment-refractory patients. Currently, no medications can be recommended for prophylactic use in trauma victims.Although evidence is incomplete regarding combined psychotherapy and pharmacotherapy, available studies generally favour combination treatments over monotherapy. Repetitive transcranial magnetic stimulation (rTMS) showed efficacy in one study. In children and adolescents with PTSD, CBT demonstrated a medium effect size compared to active controls, while studies on SSRI treatment in this population yielded inconsistent results.
INTRODUCTION:Gender dysphoria (GD) causes distress from gender-sex incongruence with elevated suicide risk, yet its neuropathology remains unclear. The thalamic-cortical functional connectivity (FC) in transgender women (TW) is unexplored. We investigated thalamo-cortical FC and its mediating role in TW's symptom-cognition relationships. METHODS:We retrospectively analysed resting-state fMRI from 44 TW, 40 cisgender men (CM), and 42 cisgender women (CW), between October 2021 and January 2024. Clinical symptoms (GIDYQ-AA) and cognition (MCCB) were assessed. Seed-based thalamic subregion FC and mediation analyses were performed. RESULTS:Relative to CW, TW and CM exhibited increased FC in multiple thalamo-prefrontal circuits. Compared to CM, TW showed decreased left mPFtha-left DLPFC FC (p = 0.026), and right rTtha-left DLPFC FC (p = 0.025). Compared to CM, right PPtha-right MOG FC (p = 0.023; p < 0.001), and right cTtha-right SOG FC (p = 0.008; p < 0.001) were increased in TW and CW. In TW, left rTtha-bilateral MPFC FC correlated with GIDYQ-AA scores, attention/vigilance, and composite. This FC fully mediated relationships between GD symptoms and both attention/vigilance (bootstrapped 95% CI = 1.861-11.688) and composite (bootstrapped 95% CI = 1.025-12.283). CONCLUSIONS:TW exhibit thalamo-cortical FC abnormalities and cognitive dysfunction. Critically, thalamus-MPFC dysconnectivity mediates GD symptom-related cognitive dysfunction, revealing a novel neural pathway. Validation in larger, diverse samples is needed.
Introduction Disruptive behaviours of children with intellectual disabilities predispose mothers to mental and physical morbidities, leading to caregiving burnout, lower childcare quality, and poor child progress.Methods This cross-sectional study investigated the psychometrics of the Arabic version of the Generalised Anxiety Disorder 2-item scale (GAD-2) among 85 Saudi mothers of children with intellectual disabilities through latent variable model and receiver-operating characteristic curve analyses.Results The unidimensional GAD-2 demonstrated good construct validity, invariance at the configural, metric, and scalar levels across age groups, and adequate convergent/divergent validity—It was negatively predicted by high mood and happiness and positively predicted by stress, and it mediated the effect of stress and happiness on depression. Its known-group validity was determined by elevated anxiety levels among mothers using psychotropic drugs. Two cut-offs (≥2.5 and ≥3.5) flagged the best trade-off between sensitivity and specificity for predicting low mood, poor sleep quality, nightmares, high stress, low general physical health, and willingness to join a psychological support program. The positive predictive value for the cut-off ≥3.5 was higher for all outcomes than that of the cut-off ≥2.5.Discussion The GAD-2 is a valid and reliable tool, which at thresholds ≥3.5 can identify anxious mothers, aiding early diagnosis and intervention.
Introduction This work investigated brain dynamics underlying manic and depressive states in bipolar disorder.Methods Resting-state fMRI data were obtained from 69 bipolar patients—34 manic, 35 depressed—and 73 healthy controls. Intrinsic brain activity was modelled as a temporal sequence of discrete quasi-stationary states (co-activation patterns), which were compared between groups and related to symptomatology.Results Mania was associated with increased occurrence of a co-activation pattern encompassing sensorimotor network areas, which positively correlated with manic symptomatology (hyperactivity and mood elevation) and manic polarity, and negatively correlated with depressive symptomatology (retardation and apathy). Depression was associated with increased occurrence of a co-activation pattern encompassing default-mode network areas, negatively correlating with manic symptomatology (hyperactivity and mood elevation).Conclusions These findings suggest that polarisation of brain dynamics towards low-order sensorimotor/insular systems—subserving perception and modulation of the outer and inner/body environments—may reshape subjective experience and behaviour promoting immediate interaction with the environment, manifesting as mania. Conversely, polarisation towards high-order associative systems—subserving stimulus-independent associative processing—may reshape experience and behaviour favouring detachment from the environment, manifesting as depression. This framework illustrates how changes in the functional brain architecture may alter the structure of phenomenal experience and behaviour in physiology and psychopathology.
BACKGROUND:Current pharmacological treatments offer only limited benefits in altering the course of Alzheimer's disease (AD). Given these limitations, nonpharmacological interventions have emerged as potential therapeutic strategies. This study investigates the therapeutic effects of 40 Hz light stimulation in AD and analyzes blood biomarkers to explore its potential disease-modifying effects. METHODS:This longitudinal study examined the effects of 40 Hz light stimulation on clinical symptoms and blood biomarkers in AD patients. Fourteen individuals were enrolled, with 11 completing the 3-month light stimulation, and 6 continuing to 6 months for the final blood biomarker analysis, including amyloid beta (Aβ) oligomers, Aβ-40, Aβ-42, tau phosphorylated at threonine 181 (p-tau181) and 217 (p-tau217), and neurofilament light chain. RESULTS:At 3 months, cognitive function remained stable or improved in 63.6% of participants, depressive symptoms improved in 54.5%, caregiver burden decreased in 72.7%, and sleep quality improved in 90.9% (p = .014). At 6 months, cognitive function and neuropsychiatric symptoms remained stable or improved in 33.3% and 66.7% of participants, respectively. Biomarker analysis showed decreased Aβ oligomers, increased Aβ-42 and reduced p-tau, suggesting potential disease-modifying effects. CONCLUSIONS:40 Hz light stimulation demonstrated short-term benefits in cognitive stability, caregiver burden relief, and sleep improvement, with biomarker findings indicating possible neuroprotective effects.
Introduction Gratitude plays a crucial role in promoting affective well-being, yet the neural mechanisms underlying their relationship remains unclear. Given the central role of the nucleus accumbens (NAcc) and amygdala in emotion and reward processing, this study investigated whether resting-state functional connectivity (RSFC) of these subcortical regions correlates with trait gratitude and mediates its association with affective well-being.Methods Resting-state fMRI data were collected from 363 young adults. Seed-based connectivity analyses identified NAcc and amygdala connectivity patterns associated with trait gratitude. Mediation analyses tested whether these patterns explained the association between gratitude and affective well-being.Results Trait gratitude was linked to stronger connectivity between the left NAcc and dorsomedial prefrontal cortex and left posterior superior temporal sulcus; between the right NAcc and left dorsolateral prefrontal cortex (DLPFC), right inferior temporal gyrus and bilateral fusiform; and between the right amygdala and right DLPFC, superior temporal gyrus, cerebellum, and putamen. Critically, the right amygdala-putamen connectivity mediated the relationship between gratitude and positive affective well-being.Conclusions The right amygdala-putamen RSFC links gratitude to greater affective well-being. This finding identifies a specific subcortical pathway through which grateful dispositions translate into emotional benefit and suggests a potential target for interventions aimed at improving mental health.
Introduction Reproductive health impacts mental health. Consequently, reproductive factors should be assessed in psychotherapy to ensure correct differential diagnosis, precise case conceptualisation and efficient treatment. It has not been analysed to which extent psychotherapists assess reproductive factors in routine care.Methods Analyses were based on data from Germany-wide surveys with n = 390 psychotherapists and n = 291 patients. From their respective perspective, we examined how frequently psychotherapists proactively assessed whether patients experienced a menstrual cycle, menopause, used hormonal contraception, experienced a pregnancy, fertility treatment, or birth, whether these factors were associated with patients’ symptoms, and how relevant they were perceived to be. Further, we examined how psychotherapists acquired knowledge about the reproductive factors and which psychotherapist characteristics increased the likelihood of considering them.Results We identified a gap between low proactive assessment and high perceived relevance of reproductive factors. Psychotherapists acquired their knowledge through personal experience rather than clinical training or further education. Greater knowledge and perceived relevance increased the likelihood of proactively assessing reproductive factors.Conclusions There is a clear need to incorporate a standardised, proactive assessment of reproductive factors into routine care. The responsibility to disclose them should not be left to the patients. Developing appropriate teaching content and tailored anamnestic instruments can help to overcome the neglect.
OBJECTIVE:Internet addiction (IA) is often associated with impaired attention control. Nevertheless, ways to improve this deficit are lacking, and so is the understanding of the mechanisms that such interventions might impact. To address this gap, this study seeks to examine the efficacy of Solution-Focused Group Counselling (SFGC) in enhancing attention networks among individuals with IA. METHODS:A total of 32 college students with high IA scores were recruited, with 26 participants (16 females and 10 males; mean age 19.42 ± 1.10) completing a five-week SFGC intervention. Assessments conducted pre- and post-intervention included the Attention Network Test (ANT) and electroencephalogram (EEG). RESULTS:Results demonstrated a significant reduction in executive network reaction times (RT) following the intervention. Neurophysiological analyses revealed an increase in P3 amplitude and a decrease in alpha-band event-related desynchronisation (ERD) in the central parietal lobe, suggesting altered executive control. Moreover, a novel event-related potential (ERP) component, termed the Executive Efficiency Difference Wave (EED), was identified. It negatively correlated with executive network RT post-intervention, but not pre-intervention. CONCLUSIONS:Preliminary findings in a small sample suggest that SFGC effectively enhances both behavioural performance and neural indices associated with attention in individuals with IA. We call for future research to examine the broader applicability and long-term efficacy of SFGC.
Second-generation antipsychotics are frequently linked to weight gain and metabolic dysfunction, yet the mechanisms driving these effects remain elusive. The gut microbiome has been proposed as a potential mediator of these adverse outcomes. This study aimed to investigate the role of the gut microbiota in antipsychotic-induced weight gain. A systematic search of PubMed and Embase was conducted. In total, 24 publications were included in this review, including clinical and preclinical observational and intervention studies. Collectively, there is strong evidence that atypical antipsychotic-induced weight gain and metabolic dysfunction is accompanied by microbiota alterations. However, there is a lack of consensus with regards to the exact mechanisms and involvement of the microbiome in antipsychotic-induced weight gain. Nevertheless, a few patterns and common observations were found across studies, such as reduced diversity, increased Firmicutes/Bacteroidetes ratio and a reduction in Akkermansia species. While microbiota-targeted interventions had generally weak effects on weight gain and metabolic dysfunction in clinical cohorts, the use of specific probiotic strains and microbiota metabolites showed promise in preclinical studies. Thus, while the relationship between antipsychotic-induced weight gain, metabolic dysfunction, and changes in the gut microbiome are evident, further research is warranted to establish definitive causal relationships and to aid in the development of precision microbiota-targeted interventions to counteract these adverse effects.
Introduction Brain fog (i.e., subjective cognitive deficits) is one of the most common long-lasting symptoms post-COVID-19. Cognitive deficits and psychological factors (such as depression) are possible causes of brain fog. This study is to determine whether brain fog post-COVID-19 results from cognitive deficits or depression induced by COVID-19 infection.Methods We implemented psychological (depression scale) and behavioural measures (dual task: subtraction while walking) with simultaneous functional near-infrared spectroscopy (fNIRS) recording in 25 healthy young adults pre-, 3, 7 and 14 weeks post-COVID-19. Depression level, dual task performance and fNIRS results were compared among sessions. The relationships between brain fog severity, depression and dual task performance were assessed.Results Depression level and dual task performance remained unchanged post-COVID-19. Brain fog severity was positively correlated depression at all sessions (p’s < 0.05). Brain activation was significantly reduced at all sessions post-COVID-19 (p’s < 0.001), while global efficiency was significantly reduced at 7 weeks post-COVID-19 (p = 0.003). Changes in left somatosensory and motor cortices activation were inversely correlated with changes in walking cost (p’s = 0.005 and 0.007, respectively), while changes in global efficiency were associated with changes in walking cost (p = 0.006) from pre- to 7 weeks post-COVID-19.Conclusions Mild COVID-19 infection does not lead to apparent cognitive deficits or depression, although brain activation and global efficiency are reduced post-COVID-19. Brain fog is likely to result from depression rather than cognitive deficits induced by COVID-19. People should pay attention to their psychological states during COVID-19 pandemic.
BACKGROUND:Cognitive impairment is widely reported in migraineurs. A Mendelian randomisation (MR) approach, similar to a randomised-controlled trial, employs single-nucleotide polymorphisms (SNPs) to investigate causal relationships. METHODS:This study comprised one- and two-sample MR analyses of the Taiwan Biobank. Three strategies were used to obtain causal estimates: (1) a polygenic risk score (PRS) method-several SNPs associated with migraines were constructed as a single instrument variable; (2) a meta-analysis of genome-wide association study (GWAS) statistics for traits of migraines and cognitive impairment in the framework of a one-sample MR; and (3) a two-sample MR analysis with a meta-analysis of GWAS statistics in two distinct datasets (IEU GWAS database and the Taiwan Biobank). RESULTS:In strategy 1, the PRS constructed by 18 selected SNPs exhibited a causal association with cognitive impairment (β = -2.31, 95% confidence interval [CI]: -4.56 to -0.06). In strategy 2, a one-sample MR showed migraines were causally associated with cognitive impairment (inverse-variance weighted [IVW] estimator β = 2.90; 95% CI: 0.90-4.89). In strategy 3, a two-sample MR validated migraines to be causally associated with cognitive impairment (IVW estimator β = 2.43; 95% CI: 1.08-3.78). CONCLUSIONS:Migraine, a polygenic disorder, is causally associated with cognitive impairment.
OBJECTIVES:This study explored the plasma metabolites' mediation effect between gut microbiomes and insomnia through Mendelian randomisation (MR). METHODS:Using publicly accessible GWAS data from 5959 individuals for gut microbiota and 8299 individuals for plasma metabolites, we employed MR analysis to explore their causal effects on insomnia. Insomnia outcome data were obtained from Pan-UKB, GERA, and FinnGen, covering 9007 cases and 871,802 controls. Mediation effects of identified bacterial taxa on insomnia through plasma metabolites were computed using the product of coefficients approach. RESULTS:Our MR analysis included participants with a mean age of 45.7 years (SD = 11.5) for gut microbiota and 63 years (range 45-85) for plasma metabolites. The analysis identified 10 gut microbiomes and 35 plasma metabolites potentially associated with insomnia respectively. Specifically, increased abundances of certain gut microbiomes, such as species CAG-145 sp000435615, were linked to a higher risk of insomnia. Mediation analysis revealed that the plasma metabolite 3-ethylcatechol sulphate levels significantly mediated the effects of these microbiomes on insomnia, explaining up to 31.49% of the total effect. CONCLUSION:This study highlights the role of gut microbiota in influencing insomnia risk, mediated through specific plasma metabolites. These findings provide valuable insights into the gut-brain axis and may inform the development of therapeutic targets for managing sleep disorders.
Introduction Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS) are several common neurodegenerative diseases (NDs). At present, is the lack of effective diagnosis, progression, prognosis and therapeutic biomarkers. it is a urgent demand to search the relevant confident biomarkers.Area covered This review systematically analysed the potential biomarkers of blood, cerebrospinal fluid, neuroimaing and emerging non-invasive indicators, and synthesises current evidences on the biomarkers of AD, PD and ALS about diagnosis, progression, prognosis and therapeutic, especially diagnosis biomarkers.Expert commentary In this review, we focus on discussing relevant diagnosis, progression, prognosis and therapeutic biomarkers for AD, PD and ALS in recent years, and prospecting the possible future directions of relevant biomarkers.
Introduction Sexual dysfunctions are prevalent public health issues with understudied neurobiological correlates. This study explores structural brain differences in individuals with DSM-5 sexual dysfunctions vs. matched controls.Methods This cross-sectional study employed voxel-based morphometry (VBM) to analyse structural brain scans from the Hamburg City Health Study. Participants with erectile disorder (ED; n = 20), premature ejaculation (PE; n = 20), genito-pelvic pain/penetration disorder (GPPPD; n = 8), and female sexual interest/arousal disorder (FSIAD; n = 32) were compared with matched controls (n = 40,40,24,32, respectively). Whole-brain VBM analyses used SPM12 and CAT12. Statistical parametric maps were thresholded at uncorrected voxel-level (p < .001) and false discovery rate (FDR) correction (p_FDR < .05).Results ED showed clusters in right putamen with reduced rGMV and left postcentral gyrus with higher rGMV. PE displayed lower rGMV in cerebellar lobe VI/Crus I and left superior/medial temporal gyrus. GPPPD exhibited higher rGMV in right middle frontal gyrus. FSIAD showed no differences. No clusters survived FDR correction, underscoring the exploratory and hypothesis-generating nature of the reported findings.Conclusions This study identifies potential associations between sexual dysfunctions and structural brain differences in regions related to sexual function, arousal, inhibition, motor coordination, and pain processing. Results require cautious interpretation due to small sample sizes, but provide hypothesis-generating evidence for future research .
Objective The aim of our study was to investigate neurobiological markers and gender difference for diagnosing anxious major depressive disorder (aMDD) through a meta-analysis.Methods We systematically searched multiple databases for whole-brain neuroimaging studies comparing anxious major depression disorder (aMDD), pure MDD, and healthy controls, with publication dates through December 2024. We extracted brain coordinates and their corresponding peaks, for further analysis using the Seed-based d Mapping software package.Results A total of 11 studies were included in this study, encompassing 829 aMDD patients, 681 MDD patients, and 865 healthy controls. The meta-analysis revealed that aMDD patients exhibited increased functional alteration in the left middle temporal gyrus compared to individuals diagnosed with MDD. In the comparison between individuals with aMDD and healthy controls, the meta-analysis revealed increased functional alteration in the anterior commissure and decreased functional alteration the right middle frontal gyrus. Furthermore, the meta-regression analysis revealed heightened neural activity of the left middle cingulate gyrus and right anterior thalamic regions, as well as weakened neural activity of the left rolandic operculum in females with aMDD compared to the control group.Conclusions We identified specific functional alterations in brain regions that may serve as potential neurobiological markers for aMDD and associated differences.
