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Frontiers in Psychiatry 2024Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a...
INTRODUCTION
Suicide is a current leading cause of death in adolescents and young adults. The neurobiological underpinnings of suicide risk in youth, however, remain unclear and a brain-based model is lacking. In adult samples, current models highlight deficient serotonin release as a potential suicide biomarker, and in particular, involvement of serotonergic dysfunction in relation to the putamen and suicidal behavior. Less is known about associations among striatal regions and relative suicidal risk across development. The current study examined putamen connectivity in depressed adolescents with (AT) and without history of a suicide attempt (NAT), specifically using resting-state functional magnetic resonance imaging (fMRI) to evaluate patterns in resting-state functional connectivity (RSFC). We hypothesized the AT group would exhibit lower striatal RSFC compared to the NAT group, and lower striatal RSFC would associate with greater suicidal ideation severity and/or lethality of attempt.
METHODS
We examined whole-brain RSFC of six putamen regions in 17 adolescents with depression and NAT (M [SD] = 16.4[0.3], 41% male) and 13 with AT (M [SD] = 16.2[0.3], 31% male).
RESULTS
Only the dorsal rostral striatum showed a statistically significant bilateral between-group difference in RSFC with the superior frontal gyrus and supplementary motor area, with higher RSFC in the group without a suicide attempt compared to those with attempt history (voxel-wise <.001, cluster-wise <.01). No significant associations were found between any putamen RSFC patterns and suicidal ideation severity or lethality of attempts among those who had attempted.
DISCUSSION
The results align with recent adult literature and have interesting theoretical and clinical implications. A possible interpretation of the results is a mismatch of the serotonin transport to putamen and to the supplementary motor area and the resulting reduced functional connectivity between the two areas in adolescents with attempt history. The obtained results can be used to enhance the diathesis-stress model and the Emotional paiN and social Disconnect (END) model of adolescent suicidality by adding the putamen. We also speculate that connectivity between putamen and the supplementary motor area may in the future be used as a valuable biomarker of treatment efficacy and possibly prediction of treatment outcome.
PubMed: 38903634
DOI: 10.3389/fpsyt.2024.1364271 -
Frontiers in Neuroscience 2024VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms,...
VPS13A disease and Huntington's disease (HD) are two basal ganglia disorders that may be difficult to distinguish clinically because they have similar symptoms, neuropathological features, and cellular dysfunctions with selective degeneration of the medium spiny neurons of the striatum. However, their etiology is different. VPS13A disease is caused by a mutation in the VPS13A gene leading to a lack of protein in the cells, while HD is due to an expansion of CAG repeat in the huntingtin (Htt) gene, leading to aberrant accumulation of mutant Htt. Considering the similarities of both diseases regarding the selective degeneration of striatal medium spiny neurons, the involvement of VPS13A in the molecular mechanisms of HD pathophysiology cannot be discarded. We analyzed the VPS13A distribution in the striatum, cortex, hippocampus, and cerebellum of a transgenic mouse model of HD. We also quantified the VPS13A levels in the human cortex and putamen nucleus; and compared data on mutant Htt-induced changes in VPS13A expression from differential expression datasets. We found that VPS13A brain distribution or expression was unaltered in most situations with a decrease in the putamen of HD patients and small mRNA changes in the striatum and cerebellum of HD mice. We concluded that the selective susceptibility of the striatum in VPS13A disease and HD may be a consequence of disturbances in different cellular processes with convergent molecular mechanisms already to be elucidated.
PubMed: 38903599
DOI: 10.3389/fnins.2024.1394478 -
General Psychiatry 2024Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains...
BACKGROUND
Understanding synaptic alteration in obsessive-compulsive disorder (OCD) is crucial for elucidating its pathological mechanisms, but research on this topic remains limited.
AIMS
This study aimed to identify the synaptic density indicators in OCD and explore the relationship between cognitive dysfunction and synaptic density changes in OCD.
METHODS
This study enrolled 28 drug-naive adults with OCD aged 18-40 years and 16 healthy controls (HCs). Three-dimensional T1-weighted structural magnetic resonance imaging and F-SynVesT-1 positron emission tomography were conducted. Cognitive function was assessed using the Wisconsin Cart Sorting Test (WCST) in patients with OCD and HCs. Correlative analysis was performed to examine the association between synaptic density reduction and cognitive dysfunction.
RESULTS
Compared with HCs, patients with OCD showed reduced synaptic density in regions of the cortico-striato-thalamo-cortical circuit such as the bilateral putamen, left caudate, left parahippocampal gyrus, left insula, left parahippocampal gyrus and left middle occipital lobe (voxel p<0.001, uncorrected, with cluster level above 50 contiguous voxels). The per cent conceptual-level responses of WCST were positively associated with the synaptic density reduction in the left middle occipital gyrus (R=0.1690, p=0.030), left parahippocampal gyrus (R=0.1464, p=0.045) and left putamen (R=0.1967, p=0.018) in patients with OCD.
CONCLUSIONS
Adults with OCD demonstrated lower F-labelled difluoro analogue of F-SynVesT-1 compared with HCs, indicating potentially lower synaptic density. This is the first study to explore the synaptic density in patients with OCD and provides insights into potential biological targets for cognitive dysfunctions in OCD.
PubMed: 38894874
DOI: 10.1136/gpsych-2023-101208 -
CNS Neuroscience & Therapeutics Jun 2024The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering...
AIMS
The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from F-labeled-fluorodeoxyglucose positron emission tomography (F-FDG-PET) in distinguishing between UWS and MCS.
METHODS
Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes.
RESULTS
UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients.
CONCLUSION
UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.
Topics: Humans; Female; Male; Middle Aged; Adult; Glucose; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography; Persistent Vegetative State; Aged; Prospective Studies; Young Adult
PubMed: 38894559
DOI: 10.1111/cns.14787 -
Neurotoxicology Jun 2024This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of...
This study aimed to assess associations between prenatal and postnatal exposure to lead (Pb), mercury (Hg) and polychlorinated biphenyls (PCBs) and gray matter volume of key regions of the brain reward circuit, namely the caudate nucleus, putamen, nucleus accumbens (nAcc), the amygdala, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC). Structural magnetic resonance imaging (MRI) was conducted in 77 Inuit adolescents (mean age = 18.39) from Nunavik, Canada, who also completed the Brief Sensation Seeking Scale (BSSS-4) and Sensation Seeking - 2 (SS-2), two self-report questionnaires evaluating the tendency toward sensation seeking, which is a proxy of reward-related behaviors. Exposures to Pb, Hg and PCBs were measured in cord blood at birth, in blood samples at 11 years old and at time of testing (18 years old). Multivariate linear regressions were corrected for multiple comparisons and adjusted for potential confounders, such as participants' sociodemographic characteristics and nutrient fish intake. Results showed that higher cord blood Pb levels predicted smaller gray matter volume in the bilateral nAcc, caudate nucleus, amygdala and OFC as well as in left ACC. A moderating effect of sex was identified, indicating that the Pb-related reduction in volume in the nAcc and caudate nucleus was more pronounced in female. Higher blood Hg levels at age 11 predicted smaller right amygdala independently of sex. No significant associations were found between blood PCBs levels at all three times of exposure. This study provides scientific support for the detrimental effects of prenatal Pb and childhood Hg blood concentrations on gray matter volume in key reward-related brain structures.
PubMed: 38880197
DOI: 10.1016/j.neuro.2024.06.009 -
Altered brain perfusion and oxygen levels relate to sleepiness and attention in post-COVID syndrome.Annals of Clinical and Translational... Jun 2024Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated...
OBJECTIVE
Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS).
METHODS
Using resting-state functional magnetic resonance imaging, we investigated brain perfusion and oxygen level estimates in 47 patients (44.4 ± 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants. Group differences were calculated using two-sample t-tests. Multivariable linear regression was used for associations of each regional perfusion and oxygen level measure with cognition and sleepiness measures. Exploratory hazard ratios were calculated for each brain metric with clinical measures.
RESULTS
Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%). We found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-) = 0.038) and cortical grey matter (p- = 0.015). Brain perfusion did not differ between patients and healthy participants. However, delayed patient caudate nucleus perfusion was associated with better executive function (p- = 0.008). Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034). Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019). Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017).
INTERPRETATION
Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function. These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.
PubMed: 38874398
DOI: 10.1002/acn3.52121 -
Brain Communications 2024The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior...
The functional connectivity of the default mode network is important in understanding the neuro-pathophysiological abnormalities in patients with non-arteritic anterior ischaemic optic neuropathy. Independent component analysis can effectively determine within and between network connectivity of different brain components. Therefore, in order to explore the association between the default mode network and other brain regions, we utilized independent component analysis to investigate the alteration of functional connectivity of the default mode network. Thirty-one patients with non-arteritic anterior ischaemic optic neuropathy and 31 healthy controls, matched for age, sex and years of education, were recruited. For patients and healthy controls, functional connectivity within and between the default mode network and other brain regions were evaluated by independent component analysis. Compared with healthy controls, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity within the default mode network in the right cerebellar tonsil and left cerebellum posterior lobe and increased functional connectivity in the left inferior temporal and right middle frontal gyri. Furthermore, patients with non-arteritic anterior ischaemic optic neuropathy showed reduced functional connectivity between the default mode network and other brain regions in the left cerebellar tonsil and increased functional connectivity in the right putamen, left thalamus, right middle temporal and left middle frontal gyri. In conclusion, negative correlations between several clinical parameters and functional connectivity of the default mode network were observed. The study contributes to understanding the mechanism of functional reorganization in non-arteritic anterior ischaemic optic neuropathy.
PubMed: 38873004
DOI: 10.1093/braincomms/fcae186 -
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 -
Developmental Cognitive Neuroscience Jun 2024There is an imminent need to identify neural markers during preadolescence that are linked to developing depression during adolescence, especially among youth at...
Familial risk for depression moderates neural circuitry in healthy preadolescents to predict adolescent depression symptoms in the Adolescent Brain Cognitive Development (ABCD) Study.
BACKGROUND
There is an imminent need to identify neural markers during preadolescence that are linked to developing depression during adolescence, especially among youth at elevated familial risk. However, longitudinal studies remain scarce and exhibit mixed findings. Here we aimed to elucidate functional connectivity (FC) patterns among preadolescents that interact with familial depression risk to predict depression two years later.
METHODS
9-10 year-olds in the Adolescent Brain Cognitive Development (ABCD) Study were classified as healthy (i.e., no lifetime psychiatric diagnoses) at high familial risk for depression (HR; n=559) or at low familial risk for psychopathology (LR; n=1203). Whole-brain seed-to-voxel resting-state FC patterns with the amygdala, putamen, nucleus accumbens, and caudate were calculated. Multi-level, mixed-effects regression analyses were conducted to test whether FC at ages 9-10 interacted with familial risk to predict depression symptoms at ages 11-12.
RESULTS
HR youth demonstrated stronger associations between preadolescent FC and adolescent depression symptoms (ps<0.001) as compared to LR youth (ps>0.001), primarily among amygdala/striatal FC with visual and sensory/somatomotor networks.
CONCLUSIONS
Preadolescent amygdala and striatal FC may be useful biomarkers of adolescent-onset depression, particularly for youth with family histories of depression. This research may point to neurobiologically-informed approaches to prevention and intervention for depression in adolescents.
PubMed: 38870601
DOI: 10.1016/j.dcn.2024.101400 -
PCN Reports : Psychiatry and Clinical... Mar 2024To date, only a few reports of anti-LGI1 encephalitis with isolated psychiatric symptoms in the initial phase have been reported. We present a relatively rare case of...
BACKGROUND
To date, only a few reports of anti-LGI1 encephalitis with isolated psychiatric symptoms in the initial phase have been reported. We present a relatively rare case of antileucine-rich glioma-inactivated 1 (LGI1) encephalitis that developed only psychiatric symptoms at the onset.
CASE PRESENTATION
The patient was a male in his 40s who developed anxiety and panic symptoms and was started on antidepressants after being diagnosed with panic disorder by a psychiatrist. He visited our hospital 2 months later presenting with hallucinations, delusions, mild cognitive decline, and faciobrachial dystonic seizures in the left upper extremity and face. Fluid-attenuated inversion recovery magnetic resonance imaging revealed swelling and hyperintensities in the right caudate nucleus and putamen. Cerebrospinal fluid analysis did not show increased protein levels or cell counts and revealed positive oligoclonal bands. Subsequently, positive results for anti-LGI1 antibodies were observed in the cerebrospinal fluid. Therefore, the patient was diagnosed with anti-LGI1 encephalitis.
CONCLUSION
This case highlights the need to consider anti-LGI1 encephalitis therapy in patients with acute-onset psychiatric symptoms.
PubMed: 38868479
DOI: 10.1002/pcn5.181