Poststroke depression (PSD) is the most prevalent psychiatric disorder after stroke, which is independently correlated with negative clinical outcome. The identification of specific biomarkers could help to increase the sensitivity of PSD diagnosis and elucidate its pathophysiological mechanisms. The aim of current study was to review and summarize literature exploring potential biomarkers for PSD diagnosis. The PubMed database was searched for papers published in English from October 1977 to December 2017, 90 of which met inclusion criteria for clinical studies related to PSD biomarkers. PSD biomarkers were subdivided into neuroimaging, molecular, and neurophysiological. Some of them could be recommended to support PSD diagnosing. According to the data, lesions affecting the frontal-subcortical circles of mood regulation (prefrontal cortex, basal nuclei, and thalamus) predominantly in the left hemisphere can be considered as neuroimaging markers and predictors for PSD for at least 1 year after stroke. Additional pontine and lobar cerebral microbleeds in acute stroke patients, as well as severe microvascular lesions of the brain, increase the likelihood of PSD. The following molecular candidates can help to differentiate PSD patients from non-depressed stroke subjects: decreased serum BDNF concentrations; increased early markers of inflammation (high-sensitivity C-reactive protein, ferritin, neopterin, and glutamate), serum pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-18, IFN-γ), as well as pro-inflammatory/anti-inflammatory ratios (TNF-α/IL-10, IL-1β/IL-10, IL-6/IL-10, IL-18/IL-10, IFN-γ/IL-10); lowered complement expression; decreased serum vitamin D levels; hypercortisolemia and blunted cortisol awakening response; S/S 5-HTTLPR, STin2 9/12, and 12/12 genotypes of the serotonin transporter gene SLC6A4, 5-HTR2a 1438 A/A, and BDNF met/met genotypes; higher SLC6A4 promoter and BDNF promoter methylation status. Neurophysiological markers of PSD, that reflect a violation of perception and cognitive processing, are the elongation of the latency of N200, P300, and N400, as well as the decrease in the P300 and N400 amplitude of the event-related potentials. The selected panel of biomarkers may be useful for paraclinical underpinning of PSD diagnosis, clarifying various aspects of its multifactorial pathogenesis, optimizing therapeutic interventions, and assessing treatment effectiveness.

Depression and cognitive dysfunction share a common neuropathological platform. Abnormal neural plasticity in the frontolimbic circuits has been linked to changes in the expression of neurotrophic factors, including IGF-1. These changes may result in clinical abnormalities observed over the course of major depressive disorder (MDD), including cognitive dysfunction. The present review aimed to summarize evidence regarding abnormalities of peripheral IGF-1 in MDD patients and assess a marker and predictive role of the neurotrophin for emotional and cognitive disturbances, and treatment effectiveness. A literature search of the PubMed database was conducted for studies, in which peripheral IGF-1 levels were evaluated. Our analysis revealed four main findings: (1) IGF-1 levels in MDD patients mismatch across the studies, which may arise from various factors, e.g., age, gender, the course of the disease, presence of cognitive impairment, ongoing therapy, or general health conditions; (2) the initial peripheral IGF-1 levels may predict the occurrence of depression in future; (3) peripheral IGF-1 levels may reflect cognitive dysfunction, although the data is limited; (4) it is difficult to evaluate the influence of treatment on IGF-1 levels as there is discrepancy of this growth factor among the studies at baseline, although most of them showed a decrease in IGF-1 levels after treatment.

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Background: IGF-1 is an essential neurotrophin produced peripherally and in the brain. Impairments in the brain IGF-1 concentrations might be responsible for some aspects of major depressive disorder (MDD) pathogenesis, whereas peripheral IGF-1 could have the marker value. We aimed: 1) to compare serum IGF-1 levels in MDD patients and healthy controls (HC); 2) to elucidate possible associations between changes in IGF-1 expression and crucial characteristics of the current depressive episode, MDD course; 3) to evaluate IGF-1 dynamics after 8 weeksv ortioxetine treatment. Methods: Seventy-eight MDD patients (according to DSM-5) and 47 HC were enrolled. Serum IGF-1, psychopathological (MADRS, CGI) and neuropsychological parameters (PDQ-5, RAVLT, TMT-B, DSST) were analyzed in all subjects at admission and 48 patients after 8 weeks`vortioxetine treatment. AUC-ROCs were calculated to determine if the value of serum IGF-1 could separate MDD patients from HC. Multiple regression models were performed to explore relationships between IGF-1 and depressive episode's symptoms. Results: MDD patients had significantly higher serum IGF-1 levels than HC (228 (183-312) ng/ml vs 153 (129-186) ng/ml, p < 0.0001). IGF-1 had a good diagnostic value for predicting MDD in the whole sample with AUC of 0.820 (p < 0.0001). For a cutoff of 178.00 ng/ml, the sensitivity and specificity were 83 and 71%, respectively, and the number needed to misdiagnose was 5, indicating that only 1 of 5 tests give an invalid result. Among MADRS items, only reported sadness, inner tension, and concentration difficulties were significantly positively associated with serum IGF-1 concentrations. Vortioxetine treatment significantly attenuated IGF-1 levels and improved all psychopathological, neuropsychological parameters.

Decreased levels of brain-derived neurotrophic factor (BDNF) are assumed to play a crucial role in the pathophysiology of mild neurocognitive disorders (MNCDs). In this study, we compared plasma BDNF levels (at baseline and after two months of treatment with escitalopram) in patients with the main types of MNCDs and normal controls. 21 patients met the DSM-5 diagnostic criteria for possible MNCD due to Alzheimer's disease (MNCD-AD); 22 patients fulfilled the diagnostic criteria for subcortical vascular MNCD (ScVMNCD) according to Frisoni et al. (2002) and neuroimaging-supported probable diagnosis of vascular MNCD according to DSM-5; 16 subjects entered control group. At baseline, we detected lower BDNF levels in both MNCD groups, which was significant only in subjects with MNCD-AD. Moreover, plasma BDNF level of 21160 pg/mL showed high sensitivity (94%) to discriminate patients with MNCD-AD. Decreased plasma BDNF highly correlated with the severity of memory impairment and total MMSE score in MNCD-AD group. Escitalopram treatment in patients with MNCD-AD or ScVMNCD led to an increase of plasma BDNF concentrations and as a result to a decrease of cognitive, depressive, and anxiety symptom severity. In conclusion, plasma BDNF might be a reliable biomarker for the validation of MNCD-AD diagnosis and treatment efficacy.

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BackgroundThe diagnostic construct of mild neurocognitive disorders (MNCDs) is substantially congruent with previously proposed criteria for mild cognitive impairment (MCI). MNCD/MCI is associated with neuropsychiatric symptoms (NPS). Previous studies have examined the prevalence of NPS in amnestic and non-amnestic MCI subtypes; however, no studies exist for etiological types of MNCD. We aimed to estimate the prevalence of NPS in patients with MNCD due to Alzheimer’s disease (MNCD-AD) and subcortical vascular MNCD (ScVMNCD) and to determine whether NPS would expand these MNCD phenotypes.MethodsThe sample comprised 70 patients with MNCD-AD, 70 patients with ScVMNCD, and 55 cognitively normal elderly persons (CNEP). The diagnosis of MNCD-AD was made according to DSM-5 criteria for possible MNCD-AD. ScVMNCD patients fulfilled the DSM-5 criteria of the probable vascular MNCD and the diagnostic criteria for subcortical vascular MCI according to Frisoni et al. (1). The prevalence of NPS was based on the neuropsychiatric inventory. The statistical analyses included parametric and non-parametric tests, multivariate regression, and Spearman’s correlation coefficient.ResultsAbout 69.1% of CNEP, 97.1% of MNCD-AD, and 100% of ScVMNCD patients had one or more NPS. The prevalence of NPS in both MNCD groups was significantly higher than that in CNEP. The most prevalent NPS that had significant differential diagnostic value in separating MNCD-AD from ScVMNCD, as well as MNCD from CNEP, were anxiety (81.43%) and irritability (67.14%) in MNCD-AD and depression (81.43%) in ScVMNCD. In both MNCD groups, we observed significant (p < 0.05) correlations between all distinguishing NPS and the differential cognitive disturbances: the amnestic syndrome in MNCD-AD and executive dysfunction in ScVMNCD.ConclusionNPS occur in the majority of persons with MNCD-AD and ScVMNCD. Anxiety and irritability are the most prevalent NPS in MNCD-AD, as well as depression in ScVMNCD. The amnestic–anxious–irritable syndrome can be the main phenotype in MNCD-AD, on the other hand, the dysexecutive–depressive syndrome can be considered as the most prevalent clinical manifestation in ScVMNCD. Obtained data may be used for clinical differentiation of MNCD-AD and ScVMNCD patients.

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