Higher Seasonal Variation of Systemic Inflammation in Bipolar Disorder.

Seasonal rhythms affect the immune system. Evidence supports the involvement of immuno-inflammatory mechanisms in bipolar disorder (BD), with the neutrophil to lymphocyte ratio (NLR), and the systemic immune-inflammatory index (SII; platelets × neutrophils/lymphocytes) consistently reported to be higher in patients with BD than in HC, but seasonal rhythms of innate and adaptive immunity have never been studied. We retrospectively studied NLR and SII in 824 participants divided into three groups: 321 consecutively admitted inpatients affected by a major depressive episode in course of BD, and 255 consecutively admitted inpatients affected by obsessive-compulsive disorder (OCD; positive psychiatric control), and 248 healthy controls (HC). Patients with BD showed markedly higher markers of systemic inflammation in autumn and winter, but not in spring and summer, in respect to both HC and patients with OCD, thus suggesting a specific effect of season on inflammatory markers in BD, independent of a shared hospital setting and drug treatment. Given that systemic inflammation is emerging as a new marker and as target for treatment in depressive disorders, we suggest that seasonal rhythms should be considered for tailoring antidepressant immuno-modulatory treatments in a precision medicine approach.

Inflammatory Markers Predict Blood Neurofilament Light Chain Levels in Acute COVID-19 Patients.

Acute coronavirus disease 2019 (COVID-19) is paralleled by a rise in the peripheral levels of neurofilament light chain (NfL), suggesting early nervous system damage. In a cohort of 103 COVID-19 patients, we studied the relationship between the NfL and peripheral inflammatory markers. We found that the NfL levels are significantly predicted by a panel of circulating cytokines/chemokines, including CRP, IL-4, IL-8, IL-9, Eotaxin, and MIP-1ß, which are highly up-regulated during COVID-19 and are associated with clinical outcomes. Our findings show that peripheral cytokines influence the plasma levels of the NfL, suggesting a potential role of the NfL as a marker of neuronal damage associated with COVID-19 inflammation.

Cognitive remediation therapy for post-acute persistent cognitive deficits in COVID-19 survivors: A proof-of-concept study.

Cognitive impairments figure prominently in COVID-19 survivors. Cognitive remediation therapy (CRT) improves functional outcomes reducing long-term cognitive deficits in several neurological and psychiatric conditions. Our case-control study investigates the efficacy of a CRT programme administered to COVID-19 survivors in the post-acute phase of the illness. Seventy-three COVID-19 survivors presenting cognitive impairments at one-month follow-up were enrolled. Among them, 15 patients were treated with a two-month CRT programme, and 30 non-treated patients were matched conditional to their baseline cognitive functioning. Cognitive functions were assessed before and after treatment. Depression and quality of life were also evaluated. Mixed model ANOVA revealed a significant effect over time of the CRT programme on global cognitive functioning (F = 4.56, p = 0.039), while no significant effect was observed in the untreated group. We observed a significant effect of the improvement in verbal fluency (χ2 = 7.20, p = 0.007) and executive functions (χ2 = 13.63, p < 0.001) on quality of life. A positive significant correlation was found between depressive symptomatology and verbal fluency (r = -0.35), working memory (r = -0.44), psychomotor coordination (r = -0.42), and executive functions (r = -0.33). Our results could pave the way to a plausible innovative treatment targeting cognitive impairments and ameliorating the quality of life of COVID-19 survivors.

Long-term consequences of COVID-19 on cognitive functioning up to 6 months after discharge: role of depression and impact on quality of life.

Neurologic and psychiatric symptoms have been reported in the months following the infection with COVID-19. A low-grade inflammation has been associated both with depression and cognitive symptoms, suggesting a link between these disorders. The aim of the study is to investigate cognitive functioning 6 months following hospital discharge for COVID-19, the impact of depression, and the consequences on quality of life. Ninety-two COVID-19 survivors evaluated at 1-month follow-up, 122 evaluated at 3 months and 98 evaluated at 6 months performed neuropsychological and psychiatric evaluations and were compared with a healthy comparison group (HC) of 165 subjects and 165 patients with major depression (MDD). Cognitive performances were adjusted for age, sex, and education. Seventy-nine percent of COVID-19 survivors at 1 month and 75% at 3- and 6-month follow-up showed cognitive impairment in at least one cognitive function. No significant difference in cognitive performances was observed between 1-, 3-, and 6-months follow-up. COVID-19 patients performed worse than HC but better than MDD in psychomotor coordination and speed of information processing. No difference between COVID-19 survivors and MDD was observed for verbal fluency, and executive functions, which were lower than in HC. Finally, COVID-19 survivors performed the same as HC in working memory and verbal memory. The factor that most affected cognitive performance was depressive psychopathology which, in turn, interact with cognitive functions in determining quality of life. Our results confirm that COVID-19 sequelae include signs of cognitive impairment which persist up to 6 months after hospital discharge and affect quality of life.

Persistent psychopathology and neurocognitive impairment in COVID-19 survivors: Effect of inflammatory biomarkers at three-month follow-up.

COVID-19 outbreak is associated with mental health implications during viral infection and at short-term follow-up. Data on psychiatric and cognitive sequelae at medium-term follow-up are still lacking. During an ongoing prospective cohort study, the psychopathological and cognitive status of 226 COVID-19 pneumonia survivors (149 male, mean age 58) were prospectively evaluated one and three months after hospital discharge. Psychiatric clinical interview, self-report questionnaires, and neuropsychological profiling of verbal memory, working memory, psychomotor coordination, executive functions, attention and information processing, and verbal fluency were performed. Three months after discharge from the hospital, 35.8% still self-rated symptoms in the clinical range in at least one psychopathological dimension. We observed persistent depressive symptomatology, while PTSD, anxiety, and insomnia decreased during follow-up. Sex, previous psychiatric history, and the presence of depression at one month affected the depressive symptomatology at three months. Regardless of clinical physical severity, 78% of the sample showed poor performances in at least one cognitive domain, with executive functions and psychomotor coordination being impaired in 50% and 57% of the sample. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, predicted self-rated depressive symptomatology and cognitive impairment at three-months follow-up; and changes of SII predicted changes of depression during follow-up. Neurocognitive impairments associated with severity of depressive psychopathology, and processing speed, verbal memory and fluency, and psychomotor coordination were predicted by baseline SII. We hypothesize that COVID-19 could result in prolonged systemic inflammation that predisposes patients to persistent depression and associated neurocognitive dysfunction. The linkage between inflammation, depression, and neurocognition in patients with COVID-19 should be investigated in long-term longitudinal studies, to better personalize treatment options for COVID-19 survivors.

Diabetes Mellitus and Acute Myocardial Infarction: Impact on Short and Long-Term Mortality.

Diabetes mellitus (DM) is an important risk factor for acute myocardial infarction (AMI) and a frequent co-morbidity in patients hospitalized with AMI, being present in about 30% of cases. Although current treatment of AMI has considerably improved survival in both patients with and without DM, the presence of DM still doubles the case fatality rate during both the acute phase of AMI and at long-term follow-up. This higher mortality risk of DM patients strongly indicates a particular need for better treatment options in these patients and suggests that intensive medical treatment, prolonged surveillance, and stringent control of other risk factors should be carefully pursued and maintained for as long as possible in them.In this review, we will focus on the close association between DM and in-hospital and long-term mortality in AMI patients. We will also aim at providing current evidence on the mechanisms underlying this association and on emerging therapeutic strategies, which may reduce the traditional mortality gap that still differentiates AMI patients with DM from those without.

Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors.

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors. We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels. A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up. PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Monocyte count in schizophrenia and related disorders: a systematic review and meta-analysis.

OBJECTIVE: Increasing evidence suggests that immunological and inflammatory dysfunctions may play an important role in predisposition, onset, and progression of schizophrenia and related psychosis. The activation of cells of the mononuclear phagocyte system, especially microglia and monocytes, has been reported in schizophrenia. We carried out this systematic review and meta-analysis to investigate if there are significant differences in monocyte count comparing healthy controls with people suffering from schizophrenia and related disorders. METHODS: We searched main electronic databases; nine records met all our criteria and were included in the meta-analysis. Meta-analyses based on random effects models have been carried out generating pooled standardised mean differences (SMDs) of monocyte count in peripheral blood between schizophrenia and related psychosis and healthy controls. Heterogeneity was estimated. Relevant sensitivity and subgroup analyses were conducted. RESULTS: Patients showed higher monocyte count as compared with healthy control (SMD = 0.393; p = 0.001). Heterogeneity across studies was from moderate to high (I2 = 65.952%); sensitivity analysis leaving out two studies responsible for most of the heterogeneity showed a slightly higher SMD. Subgroup analyses confirmed this result, showing no significant differences in the effect size across different study characteristics. CONCLUSIONS: Monocyte count can be considered an indirect marker of microglia activation in the central nervous system. Thus, the observed higher monocyte count in patients could be considered as a possible peripheral marker of microglia's activation in schizophrenia disorder.

Prevalence of co-occurring psychiatric disorders in adults and adolescents with intellectual disability: A systematic review and meta-analysis.

BACKGROUND: Subjects with intellectual disability (ID) are vulnerable to experience psychiatric disorders. The present authors performed a systematic review and meta-analysis to estimate the prevalence of co-occurring psychiatric disorders, excluding co-occurring autism spectrum disorders, in subjects with intellectual disability. METHOD: The present authors performed a random-effects meta-analysis of the prevalence of psychiatric disorders in adults and adolescents with intellectual disability. RESULTS: Twenty-two studies were included. The pooled prevalence of any co-occurring psychiatric disorders in intellectual disability was 33.6% (95% CI: 25.2%-43.1%) with high heterogeneity but no publication bias. Prevalence was lower in population-based studies, in studies that used ICD criteria for the psychopathology and in studies with low risk of bias. The prevalence was higher in mild, moderate and severe intellectual disability than in profound intellectual disability. CONCLUSIONS: Psychiatric disorders are common in subjects with intellectual disability, and the present authors found that clinical and methodological moderators affect the pooled prevalence.

[The experience of the reading group in the psychiatric inpatient unit of Desio (Lombardy Region, Northern Italy)]. / L'esperienza del gruppo lettura nel Servizio psichiatrico di diagnosi e cura di Desio.

OBJECTIVES: to evaluate the possible advantages secondary to the introduction of a reading group in an acute psychiatric inpatient unit. DESIGN: before-after study. SETTING AND PARTICIPANTS: the study was conducted at the acute psychiatric inpatient unit of Desio (Lombardy Region, Northern Italy). Each admitted patients was included in the study. The patients were stratified as follow: the group of patients admitted between 01.03.2016 and 28.02.2017 (No. 472; before the introduction of the reading group) and the group of patients admitted between 01.03.2017 and 01.03.2018 (No. 515; after the introduction of the reading group). MAIN OUTCOME MEASURES: the following objective parameters were analysed: mean length of stay, number and mean length of the involuntary treatment, number and mean length of the physical restraint. We also analysed the results of the Maslach Burnout Inventory administered to the nursing staff (No. 20) before and after the introduction of the reading group to evaluate emotional exhaustion, depersonalization, and personal accomplishment of the staff members. RESULTS: we observed a significant statistical reduction of the mean length of stay (3 days), of the mean length of the involuntary treatment (2 days), of the mean length and number of the physical restraint (16 hours and 30 episodes). Analysing the results of the Maslach Burnout Inventory, we also observed a reduction of emotional exhaustion and depersonalization and an increase of personal accomplishment. CONCLUSION: a cheap, easy, reproducible, versatile intervention such as the reading group generated objective and subjective improvements explained by the creation of an atmosphere of active participation and sharing and by the increment in the satisfaction for the received care.

White matter alterations associate with onset symptom dimension in obsessive-compulsive disorder.

AIM: The high heterogeneity of obsessive-compulsive disorder (OCD) is best described by a multidimensional model involving symptom dimensions. We aimed to investigate white matter alterations associated with OCD, focusing on the impact of long-lasting effect of symptom dimensions assessed at onset of illness. Furthermore, we investigated white matter alterations associated with this disorder, controlling for the impact of medications and for the prevailing current symptom dimension. METHODS: We studied 58 patients affected by OCD and 58 age- and sex-matched healthy controls. We divided patients according to symptom dimension at onset of illness, assessed with the five-factor model. T-tests were performed in order to investigate differences between subgroups. Similar analyses were performed considering the prevailing current symptom dimension. Analyses were conducted with tract-based spatial statistics on diffusion tensor imaging. RESULTS: Doubt/checking and rituals/superstition symptom dimensions at onset and symmetry/perfectionism current symptom dimensions were characterized by significant alterations in diffusion tensor imaging measures. An association of white matter alterations and symmetry/perfectionism current dimension was found only when controlling for the effect of doubt/checking dimension at onset. Finally, results pointed out that the observed differences between patients and healthy controls were carried by the effect of previous and current medications. CONCLUSION: Our findings evidenced that onset symptom dimensions are associated with enduring alterations of white matter microstructure. Onset symptom dimensions may reflect underlying endophenotypes. In addition, present results confirm the effect of medications on white matter in OCD, showing a large effect of current treatment on myelination.

Inflammatory mediators in major depression and bipolar disorder.

Major depressive disorder (MDD) and bipolar disorder (BD) are highly disabling illnesses defined by different psychopathological, neuroimaging, and cognitive profiles. In the last decades, immune dysregulation has received increasing attention as a central factor in the pathophysiology of these disorders. Several aspects of immune dysregulations have been investigated, including, low-grade inflammation cytokines, chemokines, cell populations, gene expression, and markers of both peripheral and central immune activation. Understanding the distinct immune profiles characterizing the two disorders is indeed of crucial importance for differential diagnosis and the implementation of personalized treatment strategies. In this paper, we reviewed the current literature on the dysregulation of the immune response system focusing our attention on studies using inflammatory markers to discriminate between MDD and BD. High heterogeneity characterized the available literature, reflecting the heterogeneity of the disorders. Common alterations in the immune response system include high pro-inflammatory cytokines such as IL-6 and TNF-α. On the contrary, a greater involvement of chemokines and markers associated with innate immunity has been reported in BD together with dynamic changes in T cells with differentiation defects during childhood which normalize in adulthood, whereas classic mediators of immune responses such as IL-4 and IL-10 are present in MDD together with signs of immune-senescence.

Preferential and sustained platelet activation in COVID-19 survivors with mental disorders.

Pre-existing mental disorders are considered a risk factor for severe COVID-19 outcomes, possibly because of higher vascular burden. Moreover, an unconventional platelet activation characterizes COVID-19 and contributes to inflammatory and thrombotic manifestations. In the light of the inflammation theory of mental disorders, we hypothesized that patients with mental disorders could be sensitive to the SARS-CoV-2 elicited platelet activation. We investigated platelet activation in 141 COVID-19 survivors at one month after clearance of the virus, comparing subjects with or without an established pre-existing diagnosis of mental disorder according to the DSM-5. We found that platelets from patients with a positive history of psychiatric disorder underwent unconventional activation more frequently than conventional activation or no activation at all. Such preferential activation was not detected when platelets from patients without a previous psychiatric diagnosis were studied. When testing the effects of age, sex, and psychiatric history on the platelet activation, GLZM multivariate analysis confirmed the significant effect of diagnosis only. These findings suggest a preferential platelet activation during acute COVID-19 in patients with a pre-existing psychiatric disorder, mediated by mechanisms associated with thromboinflammation. This event could have contributed to the higher risk of severe outcome in the psychiatric population.

Post-COVID Trajectory of Pentraxin 3 Plasma Levels Over 6 Months and Their Association with the Risk of Developing Post-Acute Depression and Anxiety.

BACKGROUND AND OBJECTIVES: Clinical manifestations of coronavirus disease 2019 (COVID-19) often persist after acute disease resolution. Underlying molecular mechanisms are unclear. The objective of this original article was to longitudinally measure plasma levels of markers of the innate immune response to investigate whether they associate with and predict post-COVID symptomatology. METHODS: Adult patients with previous severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection during the first pandemic wave who underwent the 6-month multidisciplinary follow-up were included. Plasma levels of pentraxin 3 (PTX3), the complement components C3a and C5a, and chitinase-3 like-protein-1 (CHI3L1) were measured at hospital admission during acute disease (baseline) and at 1 and 6 months after hospital discharge. Associations with post-COVID-19 sequelae at 6 months were investigated using descriptive statistic and multiple regression models. RESULTS: Ninety-four COVID-19 patients were included. Baseline PTX3, C5a, C3a, and CHI3L1 did not predict post-COVID-19 sequelae. The extent of the reduction of PTX3 over time (delta PTX3) was associated with lower depressive and anxiety symptoms at 6 months (both p < 0.05). When entering sex, age, need for intensive care unit or non-invasive ventilation during hospital stay, psychiatric history, and baseline PTX3 as nuisance covariates into a generalized linear model (GLM), the difference between baseline and 6-month PTX3 levels (delta PTX3) significantly predicted depression (χ2 = 4.66, p = 0.031) and anxiety (χ2 = 4.68, p = 0.031) at 6 months. No differences in PTX3 levels or PTX3 delta were found in patients with or without persistent or new-onset other COVID-19 symptoms or signs at 6 months. Plasma levels of C3a, C5a, and CHI3L1 did not correlate with PTX3 levels at either time point and failed to associate with residual or de novo respiratory or systemic clinical manifestations of the disease at 6 months. CONCLUSIONS: A lower reduction of plasma PTX3 after acute COVID-19 associates with the presence of depression and anxiety, suggesting an involvement of inflammation in post-COVID-19 psychopathology and a potential role of PTX3 as a biomarker.

Micronized/ultramicronized palmitoylethanolamide improves depression and fatigue in coronavirus disease 2019 (COVID-19) survivors.

Coronavirus disease 2019 (COVID-19) may lead to neuropsychiatric sequelae. Palmitoylethanolamide (PEA) is an anti-inflammatory and neuroprotective amide used in depressive syndromes. Here we investigate whether micronized/ultramicronized (m/um) PEA improves neuropsychiatric sequelae in COVID-19 survivors. Patients evaluated at our post-COVID-19 outpatient clinic between February and August 2021 and presenting neuropsychiatric manifestations (n = 98) were offered treatment with m/umPEA 600 mg twice daily for 3 months. Those accepting m/umPEA therapy (n = 57) were compared with those who did not (n = 41), in terms of depression, fatigue, chronic pain and subjective well-being, through validated scales administered pre- and posttreatment. The two groups did not differ in terms of demographics, comorbidities, psychiatric history, antidepressant therapy, acute COVID-19 severity and baseline neuropsychiatric status. Patients receiving m/umPEA showed a greater improvement in depression and fatigue (both P < 0.05). Conversely, no association was found with changes in chronic pain or subjective well-being. At multivariable logistic regression, m/umPEA predicted neuropsychiatric improvement independently of age, sex and baseline neuropsychiatric status. Worse pretreatment fatigue and subjective well-being identified those who most likely benefited from treatment. In conclusion, despite its retrospective nature, our study suggests that m/umPEA may improve depression and fatigue in COVID-19 survivors, justifying future research in this setting.

Prevalence of depression in SARS-CoV-2 infected patients: An umbrella review of meta-analyses.

OBJECTIVE: The COVID-19 pandemic is still spreading worldwide two years after its outbreak. Depression has been reported in around 30% of SARS-CoV-2 infected patients. We aim to synthesize the available meta-analytical evidence in an umbrella review exploring the prevalence of depression during and after SARS-CoV-2 infection. METHODS: First, we performed a narrative umbrella review including only meta-analyses providing a quantitative summary of the prevalence of depression during or after SARS-CoV-2 infection. Then we extracted the prevalence and sample size from the original studies included in each meta-analysis, and after removing duplicate studies, we performed a random-effects model meta-analysis based on single original study estimates. Heterogeneity, publication bias, leave-one-out sensitivity, and subgroup analyses were performed. RESULTS: 14 meta-analyses were included in the umbrella review. The prevalence of depression ranged from 12% to 55% in the presence of high heterogeneity. The meta-analysis based on 85 original studies derived from the included 14 meta-analyses showed a pooled prevalence of depression of 31% (95% CI:25-38%) in the presence of high and significant heterogeneity (Q = 8988; p < 10-6; I2 = 99%) and publication bias (p < 0.001). CONCLUSION: The burden of post-COVID depression substantially exceeds the pre-pandemic prevalence. Health care services for COVID-19 survivors should monitor and treat emergent depression, reducing its potential detrimental long-term effects.

In Between the Psychological and Physiological Self - The Impact of Covid-19 Pandemic on the Neuro-Socio-Ecological and Inflammatory Mind-Body-Brain System.

The COVID-19 pandemic has had a profound impact on individuals' sense of self perturbating the sense of connectedness with the others, touching upon deep existential fears and deep intersubjective and cultural layers, emphasizing the importance of a neuro-socio-ecological alignment for the sense of security of psychological self. We can still observe after years how social distancing measures, quarantines, and lockdowns have disrupted social connections and routines, leading to feelings of isolation, anxiety and depressive symptomatology. Furthermore, from a physiological perspective, some people continue to experience health problems long after having COVID-19, and these ongoing health problems are sometimes called post-COVID-19 syndrome or post-COVID conditions (PASC). In this complex scenario, through the operationalization of the sense of self and its psychological and physiological baseline, our aim is to try to shed some new light on elements of resilience vs. vulnerability. Here we intend the self and its baseline as the crossroads between psychology and physiology and we show how COVID-19 pandemic, especially in post-COVID-19 syndrome (PACS), left traces in the mind-body-brain system at a neuro-socio-ecological and inflammatory level.

The Burden of Survivorship: Survivor Guilt and Its Association with Psychiatric Sequelae in COVID-19 Patients.

COVID-19 survivors struggle with intense depressive and post-traumatic symptoms in sub-acute stages. Survivor guilt may affect post-acute psychopathology. Herein, we aim to unveil the potential affective mechanism underpinning post-COVID psychiatric implications by focusing on the association of survivor guilt with psychopathology and maladaptive attributional style. At one month after discharge, we evaluated symptoms of depression on The Zung Severity Rating Scale (ZSDS), post-traumatic distress on Impact of Event Scale-Revised (IES-R), and sleep disturbances on the Women's Health Initiative Insomnia Rating Scale (WHIIRS) in 195 COVID-19 survivors. Interpersonal Guilt Rating Scale (IGRS-15) rated survivor guilt. A discrepancy score between the burden of depression and post-traumatic distress symptoms was computed individually. Dysfunctional depressive attributions were assessed through the Cognition Questionnaire (CQ). Survivor guilt significantly predicts all evaluated psychopathological dimensions. Moreover, higher rates of survivor guilt were associated with an overlap between post-traumatic and depressive symptomatology, thus suggesting that survivor guilt equally sustains both psychiatric manifestations. Finally, survivor guilt fully mediated the relationship between dysfunctional depressive attributions and the discrepancy index. Our results confirm survivor guilt as a clinically relevant form of suffering related to psychopathological dimensions of post COVID-19 infection, gaining the status of a specific phenomenon and a promising treatment target.

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness's resolution, mainly related to neurological and neuropsychiatric consequences. Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach. Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest. Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.