Introduction
Non-suicidal self-injury (NSSI) – the deliberate, self-directed damage of body tissue without suicidal intent and for purposes not socially or culturally sanctioned – is a highly ...prevalent phenomenon in adolescents and young adults. Motivation for the NSSI is known to be heterogenous in different patients. However, biological and especially genetic markers associated with different motivation for the NSSI have not been studied to date. One of the possible candidates are mu- (
OPRM1
) and kappa-opioid receptor (
OPRK1
) genes, since opioid system is known to be involved in the NSSI. Another perspective candidate is the
DCC
gene, encoding the netrin 1 receptor, which plays vital part in the formation of the prefrontal cortex.
Objectives
We conducted a pilot cross-sectional study to test the impact of the rs1779971
OPRM1,
rs6473797
OPRK1
and rs8084280
DCC
gene polymorphisms on the characteristics and motivations for the NSSI in young adults.
Methods
28 patients of European ancestry with NSSI (89,3%; n=25) women, median age (Q1-Q3) – 23 (21,25-25) years) were included in the pilot sample. The majority of the sample had a diagnosis of bipolar disorder (78,6%; n=20). Characteristics and motivation for the NSSI were measured by the Inventory of Statements about Self-Injury (ISAS). The Childhood Trauma Questionnaire (CTQ) was used to control for adverse childhood experiences, a potent environmental factor, associated with NSSI. Genotyping was performed using RT-PCR. The genetic effect was evaluated using the dominant model. For statistical analysis multiple linear regression with the presence of minor alleles, different types of childhood trauma, diagnosis, age and sex as factors and ISAS scores as dependent variables were used.
Results
Multiple linear regression showed that minor C allele of rs6473796
OPRK1
gene polymorphism was associated with an increase of the “Affect regulation” (B=2,23; CI95% 0,39–4,06; p=0,022), “Anti-dissociation” (B=3,31; CI95% 0,18–6,44; p=0,039) subscales of ISAS scores. Moreover, the minor T allele of the rs8082480
DCC
gene polymorphism was associated with a decrease of the “Affect regulation” subscale score (B=-1,74; CI95% -3,30 – -0,18; p=0,032).
Conclusions
To our knowledge, this is the first study on the genetic markers of motivations for NSSI. Our pilot results showed that, controlling for diagnosis, age, sex and childhood trauma,
OPRK1
and
DCC
gene polymorphisms may be associated with the heterogeneity of motivations for NSSI. However, these results require confirmation on the larger samples.
Disclosure of Interest
None Declared
Various aspects of folate and tetrahydrobiopterin (BH4) metabolism disturbances have been detected in patients with schizophrenia.Data were obtained that disturbances in the pterins (folates and BH4) ...metabolism can be associated with oxidative stress and inflammation, but has not yet been confirmed in clinical studies in schizophrenia. Within the framework of this study, a correlation and factor analysis of biochemical markersof pterin metabolism, inflammation and redox imbalance in patients with schizophrenia was performed in order to test the hypothesis of the single etiopathogenetic node, including the studied biochemical processes. Methods: 125 patients with schizophrenia and 95 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, B12, homocysteine, C-reactive protein, interleukin-6, reduced glutathione levels in the blood serum; activity of superoxide dismutase and catalase - in erythrocytes; malondialdehyde - in blood plasma. All patients underwent an examination using standardized psychopathology rating scales. Spearman rank coefficient (ρ) with Benjamini-Hochberg correction was used for the correlation analysis. The principal components analysis (PCA) was used as a factor analysis. Results: Significant correlations were found within groups of pterin metabolism, inflammatory markers and redox-imbalance, and also between separate inflammation, oxidative stress and markers of pterin metabolism. The performed factor analysis made it possible to distinguish two components: 1 — pterin metabolism, 2 — oxidativeinflammatory markers. Despite the weak statistical associations and, possibly, functional relationships between pterin metabolism and oxidative/inflammation markers, each of the components has its own clinical correlates and, probably, a separate contribution to the pathology of schizophrenia.
•Weak correlations between pterin metabolism, inflammation and redox markers were revealed.•It may indicate functional relationships between studied 3 groups of biomarkers.•Factor analysis identified pterin metabolism and oxidative-inflammatory components.•Each of distinguished components has its own clinical correlates.•Hypothetically, each component has its own contribution to schizophrenia pathology.
It was reported that the levels of tetrahydrobiopterin (BH4) are reduced in schizophrenia. However, mechanisms of BH4 deficiency in schizophrenia had not been studied precisely. Objective: the search ...of the association between BH4 deficiency in schizophrenia and a range of biochemical and clinical parameters for the evaluation of the possible mechanisms of BH4 loss and its role in the development of the symptoms. Methods: 93 patients with schizophrenia and 60 healthy volunteers were randomly selected and evaluated with a biochemical examination of BH4, folate, cobalamin (B12), homocysteine, C-reactive protein (CRP), reduced glutathione (GSH) levels in the blood serum.Patients underwent standardized psychopathological examination. Results: In patients, the levels of BH4 and folate were lower (p = 0.001 and p = 0.054, respectively), and the levels of homocysteine were higher (p = 0.012) compared to the control group. BH4 levels directly moderately correlated with folate (ρ = 0.43; p = 0.0029) and B12 levels (ρ = 0.43; p = 0.0020) and inversely moderately correlated with homocysteine levels (ρ = −0.54; p = 0.00015) in patients. Cluster analysis identified schizophrenia biotype characterized by a deficiency of BH4, folate, B12, and hyperhomocysteinemia. The clinical characteristics of this biotype were not specific. CRP and GSH were higher in patients compared to controls, but their association with serum BH4 was not confirmed.
Objective
. To assess the impact of polymorphisms rs1779971 of the
OPRM1
gene, rs6473797 of the
OPRK1
gene, and rs8084280 of the
DCC
gene on the characteristics and motivators of non-suicidal ...self-harm (NSSH) in adults.
Materials and methods
. The pilot sample studied here consisted of 28 patients with NSSH (25 women (89.3%), median Q
1
–Q
3
age 23 21.25–25 years). The majority of patients (
n
= 20, 78.6%) had bipolar disorder. The characteristics and motivators of NSSH were assessed using the Inventory of Statements about Self-Injury (ISAS) scale. The Childhood Trauma Questionnaire (CTQ) was used to measure childhood trauma, which is the most important environmental factor associated with NSSH. The Baratt Impulsivity Scale (BIS) and Buss–Perry Aggression Questionnaire (BPAQ) were also used, to assess impulsivity and aggressiveness respectively. Genotyping was performed using real-time PCR and genetic effects were assessed using a dominance model. Statistical analysis used the Mann–Whitney
U
test, Pearson’s χ
2
test, and multiple linear regression.
Results
. Carriers of the minor G allele at rs1799971 of the
OPRM1
gene had a higher level of aggression on the BPAQ scale (
p
= 0.02). The presence of the minor C allele of the rs6473797 polymorphism of the
OPRK1
gene was associated with an increase in the severity of the NSSH motivators
Affect regulation
(B = 2.23; 95% CI (0.39–4.06);
p
= 0.022) and
Antidissociation
(B = 3.31; 95% CI (0.18–6.44);
p
= 0.039), while the minor T allele of rs8084280 of the
DCC
gene, conversely, reduced the level of the motivator
Affect regulation
(B = –1.74; 95% CI (–3.30 –0.18);
p
= 0.032). These effects were found after adjustment for diagnosis, gender, age, and the presence of childhood trauma.
Conclusions
. To our knowledge, this is the first study of the association of genetic markers with motivators of NSSH. The results of this pilot study demonstrate that polymorphisms in the
OPRK1
and
DCC
genes may determine differences in motivation to self-harm, but the results require confirmation in larger samples.
Anhedonia is a pathogenetically important clinical phenotype and a potential endophenotype for depressive symptoms with very high contributions from biological and genetic factors. The ...neurobiological mechanisms of anhedonia consist of impairments to the functioning of the brain “reward” system, which has been confirmed by a significant number of neuroimaging, genetic, and experimental studies. Anhedonia is transnosological in nature and is a complex phenomenon; its correct assessment in the context of one or another investigation paradigm is important. The optimum approach is to form a set of mutually supplementing investigation strategies assessing the most important facets of anhedonia, regardless of the relationship with the nosological form of the illness, in the framework of a single study using various methods to seek appropriate biomarkers for the severity of anhedonia (genetic, neuroimaging, biochemical). High-quality organization of studies of this type based on correct evidence-based medicine methodology should produce valuable systems of biomarkers in the near future, which when validated on independent cohorts will be useful for personalizing the diagnosis and treatment of depression.
This article discusses studies of the pathophysiological bases of the depressive state reflecting the significance of the third component of signal transmission in the pathogenesis of depression. ...Published data are summarized and the characteristics of tryptophan metabolism, impairments to serotonin and noradrenaline metabolism, and dysfunction of serotoninergic, noradrenergic, and dopaminergic neurotransmission in depression are discussed. The role of neurotrophins as first messengers regulating cellular functional activity is analyzed. Impairments to neurotrophin functions lead to a shift between the processes of proliferation and apoptosis towards the latter, which causes a reduction in neurogenesis and the development of neurodegeneration in pathological states, particularly depressive disorder.
The introduction of information technologies is inextricably linked with improving the quality and accessibility of medical care, as well as reducing the cost of medical services. Digital ...phenotyping is one of the clinical tools in the field of information technology that allows you to evaluate a person’s phenotype using various personal information devices, such as a smartphone, tablet, smartwatch, various sensors and other computer tools. The advantage of digital phenotyping is the ability to receive information about the patient’s condition in real time, without inpatient and outpatient monitoring and even without the active participation of the patient himself. This fact significantly expands the possibilities of screening and diagnosis of mental disorders, and also helps to track the risks of relapses and take timely measures to prevent an exacerbation of the disease. Information technologies have great prospects for use for scientific purposes — they provide an opportunity to conduct research online that does not require visiting research centers, while at the same time reducing the time and costs of ongoing clinical trials. However, the use of digital phenotyping for scientific and clinical purposes has a number of limitations. For further improvement of digital phenotyping in order to screen psychopathology and subsequent assessment of the condition of patients, it is necessary to develop new psychometric tools used in electronic form and devoid of the shortcomings of questionnaires that are currently being used. This critical review provides data on the current opportunities and problems of digital phenotyping, as well as the prospects for its development.
Interleukin-6 (IL-6) is one of the most important pro-inflammatory markers with immunomodulatory activity associated with schizophrenia. The possible involvement of interleukin-6 in the ...etiopathogenesis of schizophrenia and the development of different clusters of symptoms remains debatable; the relationship between an increase in interleukin-6 and a number of possible confounding factors, including smoking, has not yet been studied. The aim of this work was the pilot evaluation of the serum IL-6 level in patients with schizophrenia compared with healthy controls, as well as its association with clinical symptoms, socio-demographic factors and smoking. Materials and methods: 43 patients with schizophrenia and 24 healthy volunteers were examined. The determination of IL-6 was carried out by enzyme immunoassay. All patients were assessed using the Positive and Negative Schizophrenia Syndrome Scale (PANSS), The UKUSERS-Clin Therapeutic Side Effects Scale (UKU), Simpson-Angus Scale (SAS), the Abnormal Involuntary Movements Scale (AIMS), Barnes Akathisia Scale (BARS), Personal and Social Functioning Scale (PSP). Results: In patients with schizophrenia in a Russian sample, serum IL-6 levels were significantly associated with smoking status (p = 0.0017), the severity of negative symptoms and symptoms of the PANSS general psychopathology scale (p=0.014 and p=0.038, respectively), disorders of personal and social functioning (PSP, p=0.011), as well as side effects measured using the UKU scale (general, p=0.038, 0041 and extrapyramidal, p=0.018), as well as drug-induced parkinsonism (p=0.043), dyskinesia (p=0.0084) and akathisia (p=0.043). All scores are worse in patients with nicotine addiction. The occurrence of extrapyramidal symptoms (EPS) in response to standard doses of antipsychotics (AP) can serve as a clinical marker of possible immune-inflammatory disturbances in patients with schizophrenia, and the smoking status can act as a provocing factor for increasing of latent inflammation. Replication of the study is required to confirm the findings.
The article is devoted to modern concepts of cognitive disorders in schizophrenia. Neurocognitive deficits can be expressed in impaired attention, auditory memory, motor skills, working memory, ...processing speed and executive function. The attention of researchers is currently being paid to the violation of the speed of information processing and character encoding that can lead to impaired social functioning in patients with schizophrenia. Two hypotheses about the dynamics of neurocognitive impairments in schizophrenia are also considered: the theory of «static encephalopathy» and progressive impairment of cognitive functions.
This review evaluates the results of a comparative analysis of the effectiveness of first and second generation antipsychotics in the treatment of cognitive dysfunction. As a result of the analysis of the available data, it was concluded that first-generation antipsychotics most likely do not directly impair cognitive abilities, but they can do so indirectly, due to the simultaneous use of anticholinergic drugs that compromise some neurocognitive abilities. Second-generation antipsychotics have an advantage over first-generation drugs, however, it has been argued that most antipsychotics lead to a slight improvement in cognitive functioning, and there is no specific effect on its specific domains.
An analysis of data on the relationship between oxidative stress markers and psychopathological characteristics and cognitive profile of patients with schizophrenia was carried out. In particular, the mechanism of stress-induced cell death in the prefrontal and anterior frontal regions and a decrease in brain volume in these regions, leading to a decrease in cognitive and executive functions, are considered. In addition, the mechanisms of association of redox imbalance with brain-derived neurotrophic factor (BDNF) depletion, hypofunction of the NMDA receptor, changes in the level of pro-inflammatory cytokines, neurogenesis, and cell apoptosis were considered.
A wide range of studies have demonstrated that hyperhomocysteinemia is associated with the risk of schizophrenia, but currently available assumptions about the direct involvement of homocysteine ...(Hcy) in the pathogenesis of schizophrenia are hypothetical. It is possible that in vivo Hcy is only a marker of folate metabolism disturbances (which are involved in methylation processes) and is not a pathogenetic factor per se. Only one study has been conducted in which associations of hyperhomocysteinemia with oxidative stress in schizophrenia (oxidative damage to protein and lipids) have been found, and it has been suggested that the oxidative stress may be induced by the elevated Hcy in schizophrenic patients. But the authors did not study the level of reduced glutathione (GSH), as well as possible causes of hyperhomocysteinemia—disturbances of folate metabolism. The aim of this work is to analyze the association of Hcy levels with the following: (1) redox markers in schizophrenia GSH, markers of oxidative damage of proteins and lipids, and the activity of antioxidant enzymes in blood serum; (2) with the level of folate and cobalamin (В12); and (3) with clinical features of schizophrenia measured using the Positive and Negative Syndrome Scale (PANSS). 50 patients with schizophrenia and 36 healthy volunteers, matched by sex and age, were examined. Hcy in patients is higher than in healthy subjects (p=0.0041), and this may be due to the lower folate level in patients (p=0.0072). In patients, negative correlation was found between the level of Hcy both with the level of folate (ρ=−0.38, p=0.0063) and with the level of B12 (ρ=−0.36, p=0.0082). At the same time, patients showed higher levels of oxidative modification of serum proteins (p=0.00046) and lower catalase (CAT) activity (p=0.014). However, Hcy is not associated with the studied markers of oxidative stress in patients. In the group of patients with an increased level of Hcy (>10 μmol/l, n=42) compared with other patients (n=8), some negative symptoms (PANSS) were statistically significantly more pronounced: difficulty in abstract thinking (N5, p=0.019), lack of spontaneity and flow in conversation (N6, p=0.022), stereotyped thinking (N7, p=0.013), and motor retardation (G7, p=0.050). Thus, in patients with schizophrenia, hyperhomocysteinemia caused by deficiency of folate and B12 is confirmed and can be considered a marker of disturbances of vitamin metabolism. The redox imbalance is probably not directly related to hyperhomocysteinemia and is hypothetically caused by other pathological processes or by an indirect effect of Hcy, for example, on the enzymatic antioxidant defence system (CAT activity), which requires further exploration. Further study of the role of Hcy in the pathogenesis of schizophrenia is relevant, since the proportion of patients with hyperhomocysteinemia is high and correlations of its level with negative symptoms of schizophrenia are noted.
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