[Changes in sleep patterns and the doom-scrolling (doom-surfing) phenomenon as modifiable risk factors for anxiety due to continuous stress of the COVID-19 pandemic]. / Izmeneniya rezhima sna i potreblenie informatsii s negativnym kontentom v internete («dumskrolling¼, «dumserfing¼) kak upravlyaemye faktory riska razvitiya trevogi v usloviyakh stressa pandemii COVID-19.

OBJECTIVE: To evaluate the modifiable daily behavior patterns associated with increased anxiety indicators in the general population in response to the COVID-19 pandemic. MATERIAL AND METHODS: The study examined the characteristics of the Russian population (n=7777) of the international multicenter project COMET-G. In particular, variables were targeted to describe deviations in the behavior of adults during the period of application of measures of social isolation in connection with the pandemic, and revealing a relationship with the total score on the Spielberger State Anxiety Scale (STAI-S). Among these variables, experts selected those that could potentially be subject to change in the short term, that is, act as manageable or modifiable risk factors for the development of anxiety. The selected variables were analyzed in a statistical PLS-model to identify indicators that make the most significant contribution to the increase in the total anxiety score. RESULTS: Our statistical model explained 48.4% of the variability in the STAI-S anxiety total scores related to changes in daily life habits. In particular, doom-scrolling/doom-surfing about the spread of the virus and the COVID-19 pandemic, changes in sleep patterns and usual daily life activities due to social isolation measures presented as factors significantly contributing to the increase of state anxiety. CONCLUSION: Given the manageable or modifiable risk factors that we have identified, public awareness and therapeutic recommendations, pointing to the need to (I) control the amount of time spent in the internet and monitor their internet-based content consumption, (II) regulate sleep-wake patterns, (III) maintain daily habits and household activities, may reduce the likelihood of developing anxiety disorders in the context of the impact of a global chronic stress due to the COVID-19 pandemic and associated social isolation measures.

Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression.

Current understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs1106634 of the ATPV1B2 gene encoding the vacuolar H+ATPase on lifetime and current depression and the possible mediating role of neuroticism by logistic and linear regression in a white European general sample of 2226 subjects. Association of rs1106634 with performance on frontal (Stockings of Cambridge (SOC)) and hippocampal-dependent (paired associates learning (PAL)) cognitive tasks was investigated in multivariate general linear models in a smaller subsample. The ATP6V1B2 rs1106634 A allele had a significant effect on lifetime but not on current depression. The effect of the A allele on lifetime depression was not mediated by neuroticism. The A allele influenced performance on the PAL but not on the SOC test. We conclude that the effects of variation in the vacuolar ATPase may point to a new molecular mechanism that influences the long-term development of depression. This mechanism may involve dysfunction specifically in hippocampal circuitry and cognitive impairment that characterizes recurrent and chronic depression.

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms.

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings.

Distinct effects of folate pathway genes MTHFR and MTHFD1L on ruminative response style: a potential risk mechanism for depression.

Alterations in the folate pathway have been related to both major depression and cognitive inflexibility; however, they have not been investigated in the genetic background of ruminative response style, which is a form of perseverative cognition and a risk factor for depression. In the present study, we explored the association of rumination (measured by the Ruminative Responses Scale) with polymorphisms of two distinct folate pathway genes, MTHFR rs1801133 (C677T) and MTHFD1L rs11754661, in a combined European white sample from Budapest, Hungary (n=895) and Manchester, United Kingdom (n=1309). Post hoc analysis investigated whether the association could be replicated in each of the two samples, and the relationship between folate pathway genes, rumination, lifetime depression and Brief Symptom Inventory depression score. Despite its functional effect on folate metabolism, the MTHFR rs1801133 showed no effect on rumination. However, the A allele of MTHFD1L rs11754661 was significantly associated with greater rumination, and this effect was replicated in both the Budapest and Manchester samples. In addition, rumination completely mediated the effects of MTHFD1L rs11754661 on depression phenotypes. These findings suggest that the MTHFD1L gene, and thus the C1-THF synthase enzyme of the folate pathway localized in mitochondria, has an important effect on the pathophysiology of depression through rumination, and maybe via this cognitive intermediate phenotype on other mental and physical disorders. Further research should unravel whether the reversible metabolic effect of MTHFD1L is responsible for increased rumination or other long-term effects on brain development.

CB1 receptor antagonists: new discoveries leading to new perspectives.

CB(1) receptor antagonists were among the most promising drug targets in the last decade. They have been explored and found to be effective as therapeutic agents for obesity and related cardiometabolic problems; however, use of rimonabant, the first marketed CB(1) receptor antagonist, has been suspended because of its anxiogenic and depressogenic side effects. Because some other antiobesity drugs, like dexfenfluramine or sibutramine, were also suspended, the unmet need for drugs that reduce body weight became enormous. One approach that emerged was the use of CB(1) receptor antagonists that poorly cross the blood brain barrier, the second, the development of neutral antagonists instead of inverse agonists, and the third, use of personalized medicine, namely the selection of the patient population without psychiatric side effects. In this review, we dissect the peripheral and central mechanisms involved in the effects of CB(1) receptor antagonists and argue that central mechanisms are more or less involved in most cardiometabolic therapeutic effects and thus, among patients with unsatisfactory therapeutic response to compounds with peripheral action, centrally acting antagonists may be needed. An analysis of pharmacogenetic factors may help to identify persons who are at no or low risk for psychiatric adverse effects. Here, we present the models and identify molecular mechanisms and receptors involved in the effects of stress-, anxiety- and depression-related neurocircuitries sensitive to CB(1) receptor antagonists, like the serotonergic, noradrenergic and dopaminergic systems, which are not only regulated by CB(1) receptors, but also regulate the synthesis of the endocannabinoid 2-arachidonoyl-glycerol.

[Development of the Risk Assessment Suicidality Scale (RASS): a population-based study].

Suicide and suicide attempts are significant and costly public health problems. In order to prevent suicidal and other self-injurious behavior, research on the multiple factors involved in these behaviors with comprehensive and user-friendly instruments is necessary. The aim of the current study was to construct a self-report instrument with emphasis on the items which describe suicide-related behavior itself rather than strongly related clinical features on the basis of a general population study. Twelve items comprising a new scale were applied to 734 subjects from the general population (40.6% males and 59.4% females) aged 40.8 +/- 11.5, along with the STAI and the CES-D. The scoring method was developed on the basis of frequency table of responses to the individual scale items. The factor analysis returned 3 factors explaining 59.19% of total variance (Intention, Life, and History). The Cronbach's alpha was 0.85 for the Intention, 0.69 for the Life and 0.52 for the History subscale. The RASS is a reliable and valid instrument which might prove valuable in the assessment of suicidal risk in the general population as well as in mental patients.

Is anticonvulsant treatment of mania a class effect? Data from randomized clinical trials.

Our aim was to evaluate the efficacy and tolerability of anticonvulsant agents for the treatment of acute bipolar mania and ascertain if their effects on mania are a "class" effect. We conducted a systematic review of randomized controlled trials (RCTs) with placebo or active comparator, in acute bipolar mania in order to summarize available data on anticonvulsant treatment of mania/mixed episodes. We searched (PubMed/MEDLINE) with the combination of the words "acute mania" and "clinical trials" with each one of the following words: "anticonvulsants/antiepileptics,""valproic/valproate/divalproex,""carbamazepine,""oxcarbazepine,""lamotrigine,""gabapentin,""topiramate,""phenytoin,""zonisamide,""retigabine,""pregabalin,""tiagabine,""levetiracetam,""licarbazepine,""felbamate," and "vigabatrin." Original articles were found until November 1, 2008. Data from 35 randomized clinical trials suggested that not all anticonvulsants are efficacious for the treatment of acute mania. Valproate showed greater efficacy in reducing manic symptoms, with response rates around 50% compared to a placebo effect of 20-30%. It appears to have a more robust antimanic effect than lithium in rapid cycling and mixed episodes. As valproate, the antimanic effects of carbamazepine have been demonstrated. Evidences did not support the efficacy of the gabapentin, topiramate as well as lamotrigine as monotherapy in acute mania and mixed episodes. Oxcarbazepine data are inconclusive and data regarding other anticonvulsants are not available. Anticonvulsants are not a class when treating mania. While valproate and carbamazepine are significantly more effective than placebo, gabapentin, topiramate, and lamotrigine are not. However, some anticonvulsants may be efficacious in treating some psychiatric comorbidities that are commonly associated to bipolar illness.

Hyperthymic temperament may protect against suicidal ideation.

BACKGROUND: The aim of this study was to investigate the role of hyperthymic temperament in suicidal ideation between a sample of patients with affective disorders (unipolar and bipolar). METHOD: We investigated affective disorders outpatients (unipolar, bipolar I, II and NOS) treated in eleven participating centres during at least a six-month period. DSM-IV diagnosis was made by psychiatrists experienced in mood disorders, using the corresponding modules of the Mini International Neuropsychiatric Interview (MINI). In addition, bipolar NOS diagnoses were extended by guidelines for bipolar spectrum symptoms as proposed by Akiskal and Pinto in 1999. Thereby we also identified NOS III (switch by antidepressants) and NOS IV (hyperthymic temperament) bipolar subtypes. All patients completed the Beck Depression Inventory (BDI). We screened a total sample of 411 patients (69% bipolar), 352 completed all the clinical scales without missing any item. RESULTS: No statistical significant difference in suicidal ideation (measure by BDI item 9 responses) was found between bipolar and unipolar patients (4.5% vs. 9.1%, respectively). On the group of bipolar patients, suicidal ideation was slightly more frequent among bipolar NOS compared with bipolar I and II (p value 0.094 and 0.086, respectively), interestingly we found a statistical significant less common suicidal ideation among bipolar subtype IV (with hyperthymic temperament) compared with bipolar NOS patients (p value 0.048). CONCLUSIONS: Our results indicate that those subjects with hyperthymic temperament displayed less suicidal ideation. This finding supports the hypothesis that this particular affective temperament could be a protective factor against suicide among affective patients. LIMITATION: The original objective of the national study was the cross validation between MDQ and BSDS in patients with affective disorders in our country. This report arises from a secondary analysis of the original data.

Towards a genetically validated new affective temperament scale: a delineation of the temperament phenotype of 5-HTTLPR using the TEMPS-A.

BACKGROUND: Although it has been described that affective temperaments are associated with the 5-HTTLPR, less attention was paid to the association between this polymorphism and subscales and items related to each affective temperament. The aim of our study was to investigate the association of affective temperament subscales and individual items with the s allele of the 5-HTTLPR. METHOD: 138 psychiatrically healthy women completed the TEMPS-A questionnaire and were genotyped for 5-HTTLPR. Scores of subjects on the temperament scales, subscales and items in the three genotype and the two phenotype groups were compared using ANOVA. We selected items with significantly different mean scores between the three genotype groups and the two phenotype groups separately and performed item analysis. RESULTS: Subjects in the different 5-HTTLPR genotype and phenotype groups have significantly different score on scales measuring depressive, cyclothymic, irritable and anxious temperaments, and several subscales composing these temperamental scales. Subjects in the three genotype groups scored significantly different on 11 items, 8 of these remained in a derived genotype scale after item analysis. Subjects in the two phenotype groups had significantly different scores on 12 items, 9 of them were retained in a derived phenotype scale after item analysis. LIMITATIONS: Our sample was relatively small and included only women. CONCLUSIONS: Our data provide support for the association of affective temperaments with the s allele. Although the cyclothymic temperament shows the strongest association, all temperaments within the depressive superfactor have a similar share in this association. The newly derived 5-HTTLPR Phenotype Scale shows strong association with 5-HTTLPR genotype and phenotype, therefore this scale should be further investigated in relation to psychiatric disorders, as well as psychological traits and temperaments.

Patterns of mood changes throughout the reproductive cycle in healthy women without premenstrual dysphoric disorders.

OBJECTIVE: The cyclic nature of female reproductive function is a natural part of life accompanied by changes in several physical and psychological phenomena. The aim of our study was to investigate the fluctuation of psychological symptoms throughout the female reproductive cycle in healthy, non-PMDD (premenstrual dysphoric disorder) women. METHOD: 63 psychiatrically healthy, non-PMDD women with normal regular menstrual cycles and not using hormonal contraceptive methods participated in the study. Participants completed the PRISM (Prospective Record of the Impact and Severity of Menstrual Symptoms) calendar every night for three cycles and in addition they completed several other psychometric measures (Symptom Distress Checklist-SCL-51, State Trait Anxiety Inventory-STAI, Zung Self-rating Depression Scale-ZSDS, Eating Attitude Test-EAT, Mind and Body Cathexis Scale) at three predefined days of the first cycle. Based on an at least 66% increase in physical symptoms from the late follicular to the late luteal phase on the PRISM, subjects were assigned to luteal phase physical symptoms (LPPS) and no luteal phase physical symptoms (nonLPPS) groups. The association of psychometric scores with timing within the cycle and with physical symptoms was analysed. RESULTS: Significant changes in psychometric scores over time were observed for STAI state anxiety, SCL anxiety, SCL somatization, SCL depression, SCL obsessive-compulsive, SCL interpersonal sensitivity, SCL total, and ZSDS. A significant timexLPPS grouping interaction emerged in case of the SCL somatization subscale and the ZSDS. LPPS grouping was associated with only the interpersonal sensitivity subscale of the SCL51. CONCLUSION: Our results indicate that there is a significant increase in psychological symptoms related to neuroticism and depression from the late follicular to the late luteal phase in a healthy, non-PMDD female population. Although our results may not have direct clinical significance, since the statistically significant increases in psychometric scores are still small, it is an important finding that there is a consistent pattern observable in the fluctuation of psychological symptoms accompanying the female reproductive cycle.

Cigarette smoking and psychiatric disorders in Hungary.

Data from the United States and from several European countries show that patients with major mood disorders, schizophrenia and social phobia smoke at significantly higher rates than the general population. However, there are no published results on this field from Central Europe, including Hungary. In the present study, the rate of current and lifetime smoking of the consecutively screened outpatients with DSM-IV unipolar major depression (n=92), bipolar disorder (n=60), schizophrenia (n=80), schizoaffective disorder (n=42) and panic disorder without major depression (n=60) were assessed and the data were compared to the controls (n=5503), representative for the general population of Hungary. The results showed that, compared to controls, the rates of current and lifetime smoking were significantly higher among patients with unipolar major depression, bipolar disorder, schizophrenia and schizoaffective disorder, but not among patients with panic disorder without major depression. The findings support previous findings from other countries on the strong relationship between cigarette smoking and major mood and schizophrenic spectrum disorders.