Beyond Pain Relief: Unveiling the Multifaceted Impact of Anti-CGRP/R mAbs on Comorbid Symptoms in Resistant Migraine Patients.

The study aimed to evaluate the effects of monoclonal antibodies (mAbs) acting on the calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP/R mAbs) on migraine comorbidities of depression, anxiety, and fatigue in patients resistant to traditional therapies. The issue addressed in this study is pivotal to unveiling the role of this neurotransmitter beyond pain processing. We conducted an open-label prospective study assessing comorbidities in patients with high frequency (HFEM) and chronic migraine (CM), medication overuse headache (MOH), and resistance to traditional prophylaxis. All patients were treated with anti-CGRP/R mAbs for 3 months. Seventy-seven patients were enrolled with either HFEM (21%) or CM (79%) with or without MOH (56% and 44%, respectively). We identified 21 non-responders (27%) and 56 responders (73%), defined on the reduction ≥50% of headache frequency. The two groups were highly homogeneous for the investigated comorbidities. Disease severity in terms of headache frequency, migraine-related disability, and affective comorbid symptoms was reduced in both groups with different thresholds; allodynia and fatigue were ameliorated only in responders. We found that anti-CGRP/R antibodies improved pain together with affection, fatigue, and sensory sensitization in a cohort of migraine patients resistant to traditional prophylaxis. Our results offer novel perspectives on the early efficacy of anti-CGRP/R mAbs in difficult-to-treat patients focusing on clinical features other than pain relief.

Neuropeptides in the rat claustrum - An immunohistochemical detection.

Neuropeptides are involved in numerous brain activities and are responsible for a wide spectrum of higher mental functions. The main purpose of this outline structural qualitative study was to identify the possible immunoreactivity of classical neuropeptides, as well as novel ones such as nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU) and respective receptors within the rat claustrum for the first time. The study shows the novel identification of peptidergic neurotransmission in the rat claustrum which potentially implicates a contribution of this neuropeptide to numerous central neurosecretory mechanisms.

Sex matters: The impact of oxytocin on healthy conditions and psychiatric disorders.

Oxytocin (OT) is involved in the regulation of physiological processes and emotional states, with increasing evidence for its beneficial actions being mediated by the autonomic and immune systems. Growing evidence suggests that OT plays a role in the pathophysiology of different psychiatric disorders. Given the limited information in humans the aim of this study was to retrospectively explore plasma OT levels in psychiatric patients, particularly focusing on sex-related differences, as compared with healthy controls. The patients studied here were divided into three groups diagnosed with obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD) or major depressive disorder (MDD). Plasma OT levels were significantly different between healthy men and women, with the latter showing higher values, while none of the three psychiatric groups showed sex-related differences in the parameters measured here. The intergroup analyses showed that the OT levels were significantly higher in OCD, lower in PTSD and even more reduced in MDD patients than in healthy subjects. These differences were also confirmed when gender was considered, with the exception of PTSD men, in whom OT levels were similar to those of healthy men. The present results indicated that OT levels were higher amongst healthy women than men, while a sex difference was less apparent or reversed in psychiatric patients. Reductions in sex differences in psychopathologies may be related to differential vulnerabilities in processes associated with basic adaptive and social functions.

Decreased vitamin D levels in obsessive-compulsive disorder patients.

OBJECTIVE: The present paper compared vitamin D levels in adult patients with obsessive-compulsive disorder (OCD) and explored possible correlations with patients' characteristics. METHODS: Fifty outpatients with OCD, according to DSM-5 criteria, were included and assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HRDS). RESULTS: All the patients except one showed lower vitamin D levels than normative values (>30 nm/L). Vitamin D values of the whole sample were negatively correlated with Y-BOCS total, compulsion subscale, and some items' scores, specifically "interference from obsessions," "distress associated with obsessions," and "time spent on compulsions". The same relationships were detected in men, while women showed negative correlations between vitamin D levels and Y-BOCS compulsion subscale and "resistance to compulsions," "degree of control of compulsions," "insight" item scores. CONCLUSIONS: Our findings would indicate that vitamin D might be involved in the pathophysiology of OCD, and that it is possibly related to the severity of the disorder and to typical symptoms, with some sex-related peculiarities. Further studies are necessary to support or not our findings and to ascertain the effectiveness of vitamin D supplementation in patients with OCD.

Back to the Future: The Role of Infections in Psychopathology. Focus on OCD.

Objective: Recently, there has been a resurgence of interest in the relationship between infections and psychopathology, given the increasing data on the neurotropism and neurological/psychiatric morbidity of the SARS-COV2 virus, responsible for the current worldwide pandemic. Although the majority of observations were those obtained in mood and schizophrenic disorders, a few data are also available on the presence of bacterial or viral infections in patients suffering from obsessive-compulsive disorder (OCD). Therefore, given the limited information, the present paper aimed at reviewing the most updated evidence of infections in neuropsychiatric disorders and their possible mechanisms of actions, with a narrow focus on microbes in OCD. Method: This paper is a narrative review. The databases of PubMed, Scopus, Embase, PsycINFO and Google Scholar were accessed to research and collect English language papers published between 1 January 1980 and 31 December 2021. The data on PANDAS/PANS and those observed during severe brain infections were excluded. Results: Several pathogens have been associated with an increased risk to develop a broad spectrum of neuropsychiatric conditions, such as schizophrenia, mood disorders, autism, attention-deficit/hyperactivity disorder, anorexia nervosa, and post-traumatic stress disorder. Some evidence supported a possible role of infections also in the pathophysiology of OCD. Infections from Herpes simplex virus 1, Borna disease virus, Group A-Beta Hemolytic Streptococcus, Borrelia spp., and Toxoplasma gondii were actually found in patients with OCD. Although different mechanisms have been hypothesized, all would converge to trigger functional/structural alterations of specific circuits or immune processes, with cascade dysfunctions of several other systems. Conclusions: Based on the current evidence, a possible contribution of different types of microbes has been proposed for different neuropsychiatric disorders including OCD. However, the currently available literature is meager and heterogeneous in terms of sample characteristics and methods used. Therefore, further studies are needed to better understand the impact of infectious agents in neuropsychiatric disorders. Our opinion is that deeper insights in this field might contribute to a better definition of biological underpinnings of specific clinical pictures, as well as to promote psychiatric precision medicine, with treatments based on altered pathological pathways of single patients. This might be particularly relevant in OCD, a disorder with a high proportion of patients who are resistant or do not respond to conventional therapeutic strategies.

Escitalopram alters local expression of noncanonical stress-related neuropeptides in the rat brain via NPS receptor signaling.

BACKGROUND: Neuropeptide S (NPS) is a multifunctional regulatory factor that exhibits a potent anxiolytic activity in animal models. However, there are no reports dealing with the potential molecular relationships between the anxiolytic activity of selective serotonin reuptake inhibitors (SSRIs) and NPS signaling, especially in the context of novel stress-related neuropeptides action. The present work therefore focused on gene expression of novel stress neuropeptides in the rat brain after acute treatment with escitalopram and in combination with neuropeptide S receptor (NPSR) blockade. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into five groups: animals injected with saline (control) and experimental rats treated with escitalopram (at single dose 10 mg/kg daily), escitalopram and SHA-68, a selective NPSR antagonist (at a single dose of 40 mg/kg), SHA-68 alone and corresponding vehicle (solvent SHA-68) control. To measure anxiety-like behavior and locomotor activity the open field test was performed. All individuals were killed under anaesthesia and the whole brain was excised. Total mRNA was isolated from homogenized samples of the amygdala, hippocampus, hypothalamus, thalamus, cerebellum, and brainstem. Real-time PCR was used for estimation of related NPS, NPSR, neuromedin U (NMU), NMU receptor 2 (NMUR2) and nesfatin-1 precursor nucleobindin-2 (NUCB2) gene expression. RESULTS: Acute escitalopram administration affects the local expression of the examined neuropeptides mRNA in a varied manner depending on brain location. An increase in NPSR and NUCB2 mRNA expression in the hypothalamus and brainstem was abolished by SHA-68 coadministration, while NMU mRNA expression was upregulated after NPSR blockade in the hippocampus and cerebellum. CONCLUSIONS: The pharmacological effects of escitalopram may be connected with local NPSR-related alterations in NPS/NMU/NMUR2 and nesfatin-1 gene expression at the level of selected rat brain regions. A novel alternative mode of SSRI action can be therefore cautiously proposed.

GABA System in Depression: Impact on Pathophysiology and Psychopharmacology.

BACKGROUND: The pathophysiology of major depressive disorder (MDD), one of the major causes of worldwide disability, is still largely unclear, despite the increasing data reporting evidence of multiple alterations of different systems. Recently, there was a renewed interest in the signalling of gamma aminobutyric acid (GABA) - the main inhibitory neurotransmitter. OBJECTIVE: The aim of this study was to review and comment on the available literature about the involvement of GABA in MDD, as well as on novel GABAergic compounds possibly useful as antidepressants. METHODS: We carried out a narrative review through Pubmed, Google Scholar and Scopus, by using specific keywords. RESULTS: The results, derived from various research tools, strongly support the presence of a deficiency of the GABA system in MDD, which appears to be restored by common antidepressant treatments. More recent publications would indicate the complex interactions between GABA and all the other processes involved in MDD, such as monoamine neurotransmission, hypothalamus-pituitary adrenal axis functioning, neurotrophism, and immune response. Taken together, all these findings seem to further support the complexity of the pathophysiology of MDD, possibly reflecting the heterogeneity of the clinical pictures. CONCLUSION: Although further data are necessary to support the specificity of GABA deficiency in MDD, the available findings would suggest that novel GABAergic compounds might constitute innovative therapeutic strategies in MDD.

Decreased Plasma Oxytocin Levels in Patients With PTSD.

INTRODUCTION: Although the pathophysiology of post-traumatic stress disorder (PTSD) is still unclear, growing preclinical evidences suggest that oxytocin (OT), a pleiotropic hormone, is possibly involved. However, direct studies on OT levels or clinical trials with this exogenous hormone in patients with PTSD led to inconsistent findings. Therefore, the aim of the present study was at exploring and comparing the plasma OT levels in a group of patients with PTSD and matched healthy subjects as the control group. MATERIALS AND METHODS: Twenty-six outpatients (13 men, 13 women, mean age: 40.3 ± 11.5 years) suffering from PTSD, according to the Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5), and 26 healthy subjects (13 men, 13 women, mean age: 43.8 ± 12.7 years) were included. The patients were assessed through the structured clinical interview for DSM-5 research version, patient edition (SCID-I/P), and the Impact for Event Scale revised (IES-R). All fasting subjects underwent three venous blood samples for the subsequent oxytocin radioimmunoassay. We used unpaired Student's t-test to assess OT levels and the intergroup difference of demographic characteristics, while anxiety, avoidance, and hyperarousal scores were compared among groups adjusting for the effect of gender and age by means of analysis of covariance (ANCOVA). The correlations between different variables were investigated by Pearson's method. RESULTS: The most common traumatic events of patients with PTSD were the following: severe car accident, physical violence, sexual violence, sudden death of a loved one, and natural disaster. The IES total score was 55 ± 15. Student's t-test revealed that the patients showed significantly lower OT levels (mean ± SD, pg/ml) than healthy control subjects (4.37 ± 1.61 vs 5.64 ± 2.17, p < 0.001). We detected no correlation between the IES total score, subscales, or single items and OT plasma levels. Again, no difference between men and women was detected in the patients' group, while healthy control women showed higher OT levels than men. DISCUSSION: Our study, while reporting the presence of decreased plasma OT levels in outpatients with PTSD of both sexes, as compared with healthy control subjects, would support the possible involvement of OT in the pathophysiology of PTSD. However, given the complexity of the clinical picture, future investigations are necessary to better deepen the role and level of OT in PTSD.

Neuropeptides of the human magnocellular hypothalamus.

Hypothalamic magnocellular nuclei with their large secretory neurons are unique and phylogenetically conserved brain structures involved in the continual regulation of important homeostatic and autonomous functions in vertebrate species. Both canonical and newly identified neuropeptides have a broad spectrum of physiological activity at the hypothalamic neuronal circuit level located within the supraoptic (SON) and paraventricular (PVN) nuclei. Magnocellular neurons express a variety of receptors for neuropeptides and neurotransmitters and therefore receive numerous excitatory and inhibitory inputs from important subcortical neural areas such as limbic and brainstem populations. These unique cells are also densely innervated by axons from other hypothalamic nuclei. The vast majority of neurochemical maps pertain to animal models, mainly the rodent hypothalamus, however accumulating preliminary anatomical structural studies have revealed the presence and distribution of several neuropeptides in the human magnocellular nuclei. This review presents a novel and comprehensive evidence based evaluation of neuropeptide expression in the human SON and PVN. Collectively this review aims to cast a new, medically oriented light on hypothalamic neuroanatomy and contribute to a better understanding of the mechanisms responsible for neuropeptide-related physiology and the nature of possible neuroendocrinal interactions between local regulatory pathways.

Climate change, environment pollution, COVID-19 pandemic and mental health.

Converging data would indicate the existence of possible relationships between climate change, environmental pollution and epidemics/pandemics, such as the current one due to SARS-CoV-2 virus. Each of these phenomena has been supposed to provoke detrimental effects on mental health. Therefore, the purpose of this paper was to review the available scientific literature on these variables in order to suggest and comment on their eventual synergistic effects on mental health. The available literature report that climate change, air pollution and COVID-19 pandemic might influence mental health, with disturbances ranging from mild negative emotional responses to full-blown psychiatric conditions, specifically, anxiety and depression, stress/trauma-related disorders, and substance abuse. The most vulnerable groups include elderly, children, women, people with pre-existing health problems especially mental illnesses, subjects taking some types of medication including psychotropic drugs, individuals with low socio-economic status, and immigrants. It is evident that COVID-19 pandemic uncovers all the fragility and weakness of our ecosystem, and inability to protect ourselves from pollutants. Again, it underlines our faults and neglect towards disasters deriving from climate change or pollution, or the consequences of human activities irrespective of natural habitats and constantly increasing the probability of spillover of viruses from animals to humans. In conclusion, the psychological/psychiatric consequences of COVID-19 pandemic, that currently seem unavoidable, represent a sharp cue of our misconception and indifference towards the links between our behaviour and their influence on the "health" of our planet and of ourselves. It is time to move towards a deeper understanding of these relationships, not only for our survival, but for the maintenance of that balance among man, animals and environment at the basis of life in earth, otherwise there will be no future.

[Cariprazine: from receptor affinities to therapeutic effects. Review in schizophrenic spectrum disorders and expert opinion]. / Cariprazina: dalle affinità recettoriali agli effetti terapeutici. Rassegna nei disturbi dello spettro schizofrenico ed expert opinion.

INTRODUCTION: Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional and social adjustments. Antipsychotics (APs) are the first-line treatment for schizophrenia that may modify the course of the disease in most cases, by decreasing the institutionalization risk, although they may induce severe side effects. It is worth noting that APs may well control positive symptoms, while their efficacy on negative and cognitive symptoms is low. Cariprazine is one of the latest third-generation APs acting as a partial agonist at dopamine receptor of the type 2 and 3 with a broader spectrum of activities, recently approved for the treatment of adult schizophrenia. AIM: The aim of this paper was to review and comment on the available literature on the effectiveness and tolerability of cariprazine in schizophrenia, with a main focus on possibly specific symptoms, as well as in those peculiar patients' populations that could mostly benefit from this latest AP, when compared with previous APs. DISCUSSION: The current literature would indicate that cariprazine is significantly more effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative and cognitive symptoms, than other APs. In any case, cariprazine has a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its advantages over other APs, cariprazine appears to represent a promising treatment for schizophrenic spectrum disorders.

Modulatory effect of olanzapine on SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expressions in the rat brainstem.

BACKGROUND: Phoenixin, spexin and nesfatin-1 belong to a family of newly discovered multifunctional neuropeptides that play regulatory roles in several brain structures and modulate the activity of important neural networks. However, little is known about their expression and action at the level of brainstem. The present work was, therefore, focused on gene expression of the aforementioned peptides in the brainstem of rats chronically treated with olanzapine, a second generation antipsychotic drug. METHODS: Studies were carried out on adult, male Sprague-Dawley rats that were divided into 2 groups: control and experimental animals treated with olanzapine (28-day-long intraperitoneal injection, at dose 5 mg/kg daily). All individuals were killed under anesthesia and the brainstem excised. Total mRNA was isolated from homogenized samples of both structures and the RT-PCR method was used for estimation of related SMIM20/phoenixin, NPQ/spexin and NUCB2/nesfatin-1 gene expression. RESULTS: Long-term treatment with olanzapine is reflected in qualitatively different changes in expression of examined neuropeptides mRNA in the rat brainstem. Olanzapine significantly decreased NPQ/spexin mRNA expression, but increased SMIM20/phoenixin mRNA level in the rat brainstem; while NUCB2/nesfatin-1 mRNA expression remained unchanged. CONCLUSIONS: Olanzapine can affect novel peptidergic signaling in the rat brainstem. This may cautiously suggest the presence of an alternative mode of its action.

Progress regarding the context-of-use of tau as biomarker of Alzheimer's disease and other neurodegenerative diseases.

Introduction: Tau protein misfolding and accumulation in toxic species is a critical pathophysiological process of Alzheimer's disease (AD) and other neurodegenerative disorders (NDDs). Tau biomarkers, namely cerebrospinal fluid (CSF) total-tau (t-tau), 181-phosphorylated tau (p-tau), and tau-PET tracers, have been recently embedded in the diagnostic criteria for AD. Nevertheless, the role of tau as a diagnostic and prognostic biomarker for other NDDs remains controversial.Areas covered: We performed a systematical PubMed-based review of the most recent advances in tau-related biomarkers for NDDs. We focused on papers published from 2015 to 2020 assessing the diagnostic or prognostic value of each biomarker.Expert opinion: The assessment of tau biomarkers in alternative easily accessible matrices, through the development of ultrasensitive techniques, represents the most significant perspective for AD-biomarker research. In NDDs, novel tau isoforms (e.g. p-tau217) or proteolytic fragments (e.g. N-terminal fragments) may represent candidate diagnostic and prognostic biomarkers and may help monitoring disease progression. Protein misfolding amplification assays, allowing the identification of different tau strains (e.g. 3 R- vs. 4 R-tau) in CSF, may constitute a breakthrough for the in vivo stratification of NDDs. Tau-PET may help tracking the spatial-temporal evolution of tau pathophysiology in AD but its application outside the AD-spectrum deserves further studies.

Inflammatory and metabolic markers in patients with mood disorders.

OBJECTIVES: An increasing bulk of data underlined that mood disorders show alterations that are not confined to the brain, but involve several other systems. The aim of this retrospective study was to explore metabolic/inflammatory profiles, blood pressure, and BMI in patients affected by bipolar disorders (BDs) to better understand the role of peripheral biomarkers in mood disorders. METHODS: Different metabolic/inflammatory parameters and clinical characteristics were evaluated in 97 BD inpatients from Sicily, a southern Italian region, and compared with normative values from the same area. RESULTS: No difference was detected between the assessed parameters and the normative values, or between treated and untreated patients. Interestingly, the mean acid uric levels were at the lowest extreme of the normative values, with men showing higher concentrations than women. CONCLUSIONS: No metabolic nor inflammatory alterations emerged in BD patients, even if when obese. A possible explanation might be due to their geographical origin, with culinary traditions based on the Mediterranean diet. Therefore, it would be interesting to ascertain whether such a diet might improve the metabolic impairment often associated with mood disorders. Again, the routine assessment of different clinical/chemistry parameters might be helpful to improve the diagnostic stratification and the personalised treatment.

Impact of economic crisis on mental health: a 10-year challenge.

The worldwide economic crisis of the last decade, and still unresolved, led to a great recession involving all major economies. Since economic factors may influence mental wellbeing, not surprisingly a rise in poor mental health was observed in different countries, while representing a great challenge to psychiatric interventions. This paper aims at reviewing the available English literature focusing on the impact of the current economic crisis on mental health, with a special focus on depression and suicide. Available studies indicate that consequences of economic crisis, such as unemployment, increased workload or work reorganization, and reduced staff and wages, may constitute important stressing factors with a negative impact on mental health. Although data are not easily comparable in different countries, depression seems to be the most common psychiatric disorders especially in middle-aged men. Even suicide rates seem to be increased in men, mainly in countries with no public welfare or poor family relationships. All these findings require a careful attention from both governments that cut resources on public health instead of investing in it, and psychiatric associations that should implement appropriate strategies to face and to manage this sort of depression epidemic driven by economic crisis. Again, as available data suggest that the impact of the crisis might have been attenuated in countries with higher spending in social protection, they clearly urge policy makers to take into account possible health externalities associated to inadequate social protection systems.

Negative Air Ions in Neuropsychiatric Disorders.

BACKGROUND: Air ions (AIs) are clusters of ionized particles present in the atmosphere, carrying an electrical charge of negative or positive polarity. Past speculations suggested that exposure to positive air ions may be harmful, while exposure to negative air ions (NAIs) may be associated with beneficial health effects. Increasing attention has been directed towards investigating the potential effect of NAIs on human brain activities since initial observations of their beneficial effects on some cognitive processes and mood. AIMS: Given the paucity and scattered literature, our paper aims to review the available studies on potential positive effects of NAIs exposure on cognitive performances and depression. DISCUSSION: The review of the literature seems to confirm the effects of NAIs on several brain functions. Indeed, a significant association between NAIs exposure and both well-being and high cognitive performances has been described. Furthermore, exposure to high concentrations of NAIs could be related to the improvement of depressive symptoms. CONCLUSION: A growing evidence of data, although not yet conclusive, would suggest that NAIs might improve cognitive processes. These findings require specific and urgent controlled trials adopting systems based on AIs release to possibly prevent and treat cognitive dysfunctions present in a broad range of neuropsychiatric conditions.

Cariprazine as a therapeutic option for schizophrenia: a drug evaluation.

Introduction: Schizophrenia is a very disabling condition that may result in a significant impairment of individual, professional, and social adjustments. Antipsychotics (APs), the first-line treatment for schizophrenia, in many cases modify the course of the disease, by reducing the institutionalization risk, at the price of severe and invalidating side effects. Cariprazine is one of the latest second-generation APs (SGAs) acting as a partial agonist of type 2 and 3 dopamine receptors, which was recently approved for the treatment of adult schizophrenia.Areas covered: The authors provide a critical review and commentary on the currently available data on the effectiveness and tolerability of cariprazine in schizophrenic patients, with a particular focus on its specific target symptoms.Expert opinion: Cariprazine appears significantly effective on both acute and maintenance treatment of schizophrenia, and in improving positive, negative, and cognitive symptoms, slightly more than other SGAs. It shows a good safety and tolerability profile, with akathisia being its most common side effect. Although further independent studies are needed to clarify its precise advantages over other SGAs, cariprazine seems a promising compound not only in schizophrenia, but also in a broad range of psychiatric conditions, including perhaps bipolar and addictive disorders.

The role of synaptic biomarkers in the spectrum of neurodegenerative diseases.

INTRODUCTION: The quest for reliable fluid biomarkers tracking synaptic disruption is supported by the evidence of a tight association between synaptic density and cognitive performance in neurodegenerative diseases (NDD), especially Alzheimer's disease (AD). AREAS COVERED: Neurogranin (Ng) is a post-synaptic protein largely expressed in neurons involved in the memory networks. Currently, Ng measured in CSF is the most promising synaptic biomarker. Several studies show Ng elevated in AD dementia with a hippocampal phenotype as well as in MCI individuals who progress to AD. Ng concentrations are also increased in Creutzfeldt Jacob Disease where widespread and massive synaptic disintegration takes place. Ng does not discriminate Parkinson's disease from atypical parkinsonisms, nor is it altered in Huntington disease. CSF synaptosomal-associated protein 25 (SNAP-25) and synaptotagmin-1 (SYT-1) are emerging candidates. EXPERT OPINION: CSF Ng revealed a role as a diagnostic and prognostic biomarker in NDD. Ng increase seems to be very specific for typical AD phenotype, probably for a prevalent hippocampal involvement. Synaptic biomarkers may serve different context-of-use in AD and other NDD including prognosis, diagnosis, and tracking synaptic damage - a critical pathophysiological mechanism in NDD - thus representing reliable tools for a precision medicine-oriented approach to NDD.

Different Clinical Contexts of Use of Blood Neurofilament Light Chain Protein in the Spectrum of Neurodegenerative Diseases.

One of the most pressing challenges in the clinical research of neurodegenerative diseases (NDDs) is the validation and standardization of pathophysiological biomarkers for different contexts of use (CoUs), such as early detection, diagnosis, prognosis, and prediction of treatment response. Neurofilament light chain (NFL) concentration is a particularly promising candidate, an indicator of axonal degeneration, which can be analyzed in peripheral blood with advanced ultrasensitive methods. Serum/plasma NFL concentration is closely correlated with cerebrospinal fluid NFL and directly reflects neurodegeneration within the central nervous system. Here, we provide an update on the feasible CoU of blood NFL in NDDs and translate recent findings to potentially valuable clinical practice applications. As NFL is not a disease-specific biomarker, however, blood NFL is an easily accessible biomarker with promising different clinical applications for several NDDs: (1) early detection and diagnosis (i.e., amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, atypical parkinsonisms, sporadic late-onset ataxias), (2) prognosis (Huntington's disease and Parkinson's disease), and (3) prediction of time to symptom onset (presymptomatic mutation carriers in genetic Alzheimer's disease and spinocerebellar ataxia type 3).

State-of-the-Art: Inflammatory and Metabolic Markers in Mood Disorders.

Mounting evidence highlights the involvement of inflammatory/immune systems and their relationships with neurotransmitters and different metabolic processes in mood disorders. Nevertheless, there is a general agreement that available findings are still inconclusive. Therefore, further investigations are required, aimed at deepening the role of possible alterations of biomarkers in the pathophysiology of mood disorders that might lead to more focused and tailored treatments. The present study is a comprehensive review on these topics that seem to represent intriguing avenues for the development of real innovative therapeutic strategies of mood disorders.