Parkinson's disease (PD) is associated with brain mitochondrial dysfunction. High-energy phosphates (HEPs), which rely on mitochondrial functioning, may be considered potential biomarkers for PD. ...Phosphorus magnetic resonance spectroscopy (
P-MRS) is a suitable tool to explore in vivo cerebral energetics. We considered 10
P-MRS studies in order to highlight the main findings about brain energetic compounds in patients affected by idiopathic PD and genetic PD. The studies investigated several brain areas such as frontal lobes, occipital lobes, temporoparietal cortex, visual cortex, midbrain, and basal ganglia. Resting-state studies reported contrasting results showing decreased as well as normal or increased HEPs levels in PD patients. Functional studies revealed abnormal PCr + βATP levels in PD subjects during the recovery phase and abnormal values at rest, during activation and recovery in one PD subject with PINK1 gene mutation suggesting that mitochondrial machinery is more impaired in PD patients with PINK1 gene mutation. PD is characterized by energetics impairment both in idiopathic PD as well as in genetic PD, suggesting that mitochondrial dysfunction underlies the disease. Studies are still sparse and sometimes contrasting, maybe due to different methodological approaches. Further studies are needed to better assess the role of mitochondria in the PD development.
Background
Lithium is recommended as a first line treatment for bipolar disorders. However, only 30% of patients show an optimal outcome and variability in lithium response and tolerability is poorly ...understood. It remains difficult for clinicians to reliably predict which patients will benefit without recourse to a lengthy treatment trial. Greater precision in the early identification of individuals who are likely to respond to lithium is a significant unmet clinical need.
Structure
The H2020-funded Response to Lithium Network (R-LiNK;
http://www.r-link.eu.com/
) will undertake a prospective cohort study of over 300 individuals with bipolar-I-disorder who have agreed to commence a trial of lithium treatment following a recommendation by their treating clinician. The study aims to examine the early prediction of lithium response, non-response and tolerability by combining systematic clinical syndrome subtyping with examination of multi-modal biomarkers (or biosignatures), including omics, neuroimaging, and actigraphy, etc. Individuals will be followed up for 24 months and an independent panel will assess and classify each participants’ response to lithium according to predefined criteria that consider evidence of relapse, recurrence, remission, changes in illness activity or treatment failure (e.g. stopping lithium; new prescriptions of other mood stabilizers) and exposure to lithium. Novel elements of this study include the recruitment of a large, multinational, clinically representative sample specifically for the purpose of studying candidate biomarkers and biosignatures; the application of lithium-7 magnetic resonance imaging to explore the distribution of lithium in the brain; development of a digital phenotype (using actigraphy and ecological momentary assessment) to monitor daily variability in symptoms; and economic modelling of the cost-effectiveness of introducing biomarker tests for the customisation of lithium treatment into clinical practice. Also, study participants with sub-optimal medication adherence will be offered brief interventions (which can be delivered via a clinician or smartphone app) to enhance treatment engagement and to minimize confounding of lithium non-response with non-adherence.
Conclusions
The paper outlines the rationale, design and methodology of the first study being undertaken by the newly established R-LiNK collaboration and describes how the project may help to refine the clinical response phenotype and could translate into the personalization of lithium treatment.
Symptoms of anxiety are present not only in panic disorder or other anxiety disorders, but are highly prevalent in the general population. Despite increasing biological research on anxiety disorders, ...there is little research on understanding subclinical or sub-threshold symptoms relating to anxiety in non-clinical community samples, which could give clues to factors relating to resilience or compensatory changes.
This study focused on brain structural correlates of subclinical anxiety/agoraphobia symptoms from a multi-center imaging study.
We obtained high-resolution structural T1 MRI scans of 409 healthy young participants and used the CAT12 toolbox for voxel-based morphometry (VBM) analysis. Subjects provided self-ratings of anxiety using the SCL-90-R, from which we used the phobia subscale, covering anxiety symptoms related to those of panic and agoraphobia spectrum.
We found significant (
< 0.05, FDR-corrected) correlations (mostly positive) of cortical volume with symptom severity, including the right lingual gyrus and calcarine sulcus, as well as left calcarine sulcus, superior, middle, and inferior temporal gyri. Uncorrected exploratory analysis also revealed positive correlations with GMV in orbitofrontal cortex, precuneus, and insula.
Our findings show brain structural associations of subclinical symptoms of anxiety, which overlap with those seen in panic disorder or agoraphobia. This is consistent with a dimensional model of anxiety, which is reflected not only functionally but also on the structural level.
Objectives:
To determine the effectiveness of an early intervention program in enhancing visual function in very preterm infants. Methods: We conducted a RCT. We included preterm infants born between ...25
+0
and 29
+6
weeks of gestational age (GA), without severe morbidities, and their families. Infants were randomized to either receive Standard Care (SC) or Early Intervention (EI). SC, according to NICU protocols, included Kangaroo Mother Care and minimal handling. EI included, in addition to routine care, parental training according to the PremieStart program, and multisensory stimulation (infant massage and visual interaction) performed by parents. Visual function was assessed at term equivalent age (TEA) using a prevalidated battery evaluating ocular spontaneous motility, ability to fix and follow a target, reaction to color, stripes discrimination and visual attention at distance.
Results:
Seventy preterm (EI
n
= 34, SC
n
= 36) infants were enrolled. Thirteen were excluded according to protocol. Fifty-seven infants (EI = 27, SC = 30) were assessed at TEA. The two groups were comparable for parental and infant characteristics. In total, 59% of infants in the EI group achieved the highest score in all the nine assessed items compared to 17% in the SC group (
p
= 0.001): all infants in both groups showed complete maturation in four items, but EI infants showed more mature findings in the other five items (ocular motility both spontaneous and with target, tracking arc, stripes discrimination and attention at distance).
Conclusions:
Our results suggest that EI has a positive effect on visual function maturation in preterm infants at TEA.
Trial Registration:
clinicalTrial.gov
(NCT02983513).
Despite various advances in the study of the neurobiological underpinnings of personality traits, the specific neural correlates associated with character and temperament traits are not yet fully ...understood. Therefore, this study aims to fill this gap by exploring the biochemical basis of personality, which is explored with the temperament and character inventory (TCI), during brain development in a sample of adolescents. Twenty-six healthy adolescents (aged between 13 and 21 years; 17 males and 9 females) with behavioral and emotional problems underwent a TCI evaluation and a 3T single-voxel proton magnetic resonance spectroscopy (
H MRS) acquisition of the anterior cingulate cortex (ACC). Absolute metabolite levels were estimated using LCModel: significant correlations between metabolite levels and selective TCI scales were identified. Specifically, phosphocreatine plus creatine (PCr+Cre) significantly correlated with self-directedness, positively, and with a self-transcendence (ST), negatively, while glycerophosphocholine plus phosphocholine (GPC+PC) and myo-inositol negatively correlated with ST. To the best of our knowledge, this is the first study reporting associations of brain metabolites with personality traits in adolescents. Therefore, our results represent a step forward for personality neuroscience within the study of biochemical systems and brain structures.
Nowadays, the lack of quantitative criteria to resolve the diagnostic heterogeneity of psychotic onsets limits the development of safer and more effective treatments. Therefore, the hypothesis to ...integrate multimodal data to uncover biological subtypes of psychosis has risen 1,2. Here we explored the existence of subgroups of patients affected by first episode psychosis (FEP) with a possible immunopathogenic basis.
To do this, we designed a computational model that use unsupervised machine learning to cluster a sample of 127 FEP patients and 117 healthy controls (HC), based on the peripheral blood concentrations of 12 immune gene transcripts which demonstrated to classify with high accuracy between FEP patients and healthy subjects in a previous study 3. To validate the model, we applied a resampling strategy based on the half-splitting of the total sample. Further, we tested the correlation between the subgroups and clinical, neuropsychological and brain structural variables.
In both the discovery and validation samples, the model identified a FEP cluster characterized by the high expression of inflammatory and immune-activating genes (IL1b, CCR7 and IL12a) and of a single immune counterregulatory gene (CCR3)4 and a further cluster consisting of equal number of FEP and HC subjects, which did not show a relative over or under expression of any immune marker (balanced subgroup). Also, none of the subgroups were related to specific symptoms dimensions or longitudinal diagnosis. FEP patients included in the balanced immune subgroup showed a reduced left hippocampal volume and a left supramarginal and lateroccipital cortexes’ thinning. These correlations seem to support an opposite pattern in the correspondent brain area of the inflammatory subgroup 5.
Our results demonstrated the existence of a FEP patients’ subgroup that present a prominent activation of the inflammatory response. This evidence may pave the way to sample stratification in future trials aiming to develop personalized diagnostic tools and therapies targeting specific immunopathogenic pathways of psychosis onsets.
Major Depressive Disorder (MDD) and Bipolar Disorder Depression (BDD) are common psychiatric illnesses characterized by structural and functional brain alterations and signs of neuroinflammation. In ...line with the neuroinflammatory pathogenesis of depressive syndromes, recent studies have demonstrated how white matter (WM) microstructural impairments detected by Diffusion Tensor Imaging, are correlated to peripheral immunomarkers in depressed patients. In this context, we performed a comprehensive systematic search on PubMed, Medline and Scopus of the original studies published till June 2022, exploring the association between immunomarkers and WM alteration patterns in patients affected by MDD or BDD. Overall, the studies included in this review showed a consistent association between blood proinflammatory and counter-regulatory immunomarkers, including regulatory T cells and natural killer cells markers, as well as measures of demyelination and dysmyelination in both MDD and BDD patients. These pathogenetic insights could outline an integrated clinical perspective to affective disorders, helping psychiatrists to develop novel biotype-to-phenotype models of depression and opening the way to tailored approaches in treatments.
•Plasma BDNF levels increase in parallel to the myelin inflammatory damage indicators in MDD patients.•The increase of pro-inflammatory cytokines is correlated to DT-MRI indicators of WM damage in MDD patients.•The correlation between the WM damage and IL-10 supports the involvement of the counter-regulatory immunity in BDD patients.•WM integrity is directly associated to Th17 and Treg levels in BDD patients.•NK cells play an important role in maintaining WM integrity in BDD patients.
Bipolar Disorder (BD) is a severe chronic psychiatric disorder whose aetiology is still largely unknown. However, increasing literature reported the involvement of neurovascular factors in the ...pathophysiology of BD, suggesting that a measure of Cerebral Blood Flow (CBF) could be an important biomarker of the illness. Therefore, since, to date, Magnetic Resonance Perfusion Weighted Imaging (PWI) techniques, such as Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labelling (ASL), are the most common approaches that allow non-invasive in-vivo perfusion measurements,this review aims to summarize the results from all PWI studies that evaluated the CBF in BD.
A bibliographic search in PubMed up until May 2021 was performed. 16 PWI studies that used DSC or ASL sequences met our inclusion criteria.
Overall, the results supported the presence of hyper-perfusion in the cingulate cortex and fronto-temporal regions, as well as the presence of hypo-perfusion in the cerebellum in BD, compared with both healthy controls and patients with unipolar depression. CBF changes after cognitive and aerobic training, as well as in relation with other physiological, clinical, and neurocognitive variables were also reported.
The heterogeneity across the studies, in terms of experimental designs, sample selection, and methodological approach employed, limited the studies' comparison.
These findings showed CBF alterations in the cingulate cortex, fronto-temporal regions, and cerebellum in BD, suggesting that CBF may be an important pathophysiological marker of BD that merits further investigation to clarify the extent of neurovascular alterations.
•BD showed higher CBF in the cingulate cortex and fronto-temporal regions compared to HC and UD patients.•BD showed lower CBF in the cerebellum compared to HC and UD patients.•In BD, CBF changes after cognitive and aerobic training.•Individual differences in CBF were associated with physiological, clinical, and neurocognitive variables.•CBF may be a pathophysiological marker of BD.
-Brain structure of bipolar disorder patients is affected by lithium intake.-The effect of lithium on hippocampus volumes seems to be normalizing.-Literature results are conflicting and further ...investigation is needed.
Lithium is one of the most effective medications for bipolar disorder episode prevention, but its mechanism of action is still largely unknown. The hippocampus is a subcortical cerebral structure involved in the formation of emotional responses, cognition and various primitive functions, altered during affective episodes. Deviations in the anatomy or physiology of the hippocampus would partially explain the symptomatology of bipolar subjects, and restoration may reflect treatment response.
In this mini review, we summarize the studies which have investigated the effect of lithium intake on the volume of hippocampus, measured using magnetic resonance imaging (MRI). We performed a bibliographic search on PubMed, using the terms terms “hippocampus”, “lithium”, “bipolar disorder”, “volume” and “MRI”. Only original studies were considered.
Thirteen studies met the inclusion criteria. Nine studies demonstrated increased total hippocampal volume or hippocampal subfield volumes in BD patients on lithium treatment (Li BD) compared to those not taking lithium (non-Li BD), while four failed to show significant differences between groups. When healthy controls were compared to either the Li subjects or the non-Li ones, the findings were more heterogeneous.
Heterogeneity in the methodology and definition of groups limits the comparison of study results.
Lithium may be associated with increased hippocampal volume in BD, potentially due to its putative neurotrophic action, but further research is needed better define the morphological alterations of hippocampus in BD and the longitudinal effects of lithium in the short and long-term.
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