Peter Dome

Smoking, nicotine and neuropsychiatric disorders

Tobacco smoking is an extremely addictive and harmful form of nicotine (NIC) consumption, but unfortunately also the most prevalent. Although disproportionately high frequencies of smoking and its health consequences among psychiatric patients are widely known, the neurobiological background of this epidemiological association is still obscure. The diverse neuroactive effects of NIC and some other major tobacco smoke constituents in the central nervous system may underlie this association. This present paper summarizes the pharmacology of NIC and its receptors (nAChR) based on a systematic review of the literature. The role of the brains reward system(s) in NIC addiction and the results of functional and structural neuroimaging studies on smoking-related states and behaviors (i.e. dependence, craving, withdrawal) are also discussed. In addition, the epidemiological, neurobiological, and genetic aspects of smoking in several specific neuropsychiatric disorders are reviewed and the clinical relevance of smoking in these disease states addressed.

Suicidal behavior in bipolar disorder: Epidemiology, characteristics and major risk factors

BACKGROUND Suicide is one of the leading causes of death and a major public health problem worldwide, and the majority of suicide attempters and completers suffer from some major affective disorder at the time of their death, which, in the majority of cases is unrecognized, under- or misdiagnosed and untreated. METHODS Based on a systematic literature search, the authors give a detailed and critical overview of established risk factors of suicide in bipolar disorder. RESULTS Among affective disorders, bipolar disorder carries the highest risk of suicide, yet not all bipolar patients commit or even attempt suicide during their illness. While the general suicide risk factors also apply for bipolar disorders, there are several disease-specific risk factors as well which should be taken into account when evaluating suicide risk in case of patients. CONCLUSION It is crucial to identify suicide risk factors in bipolar disorder to be able to differentiate those patients within this already increased-risk illness group who are at especially high risk and therefore to allow for better prediction and prevention of suicidal acts.

Circulating endothelial cells, bone marrow-derived endothelial progenitor cells and proangiogenic hematopoietic cells in cancer: From biology to therapy

Vascularization, a hallmark of tumorigenesis, is classically thought to occur exclusively through angiogenesis (i.e. endothelial sprouting). However, there is a growing body of evidence that endothelial progenitor cells (EPCs) and proangiogenic hematopoietic cells (HCs) are able to support the vascularization of tumors and may therefore play a synergistic role with angiogenesis. An additional cell type being studied in the field of tumor vascularization is the circulating endothelial cell (CEC), whose presence in elevated numbers reflects vascular injury. Levels of EPCs and CECs are reported to correlate with tumor stage and have been evaluated as biomarkers of the efficacy of anticancer/antiangiogenic treatments. Furthermore, because EPCs and subtypes of proangiogenic HCs are actively participating in capillary growth, these cells are attractive potential vehicles for delivering therapeutic molecules. The current paper provides an update on the biology of CECs, EPCs and proangiogenic HCs, and explores the utility of these cell populations for clinical oncology.

The role of cognitive dysfunction in the symptoms and remission from depression.

The disability and burden associated with major depression comes only in part from its affective symptoms; cognitive dysfunctions associated with depression also play a crucial role. Furthermore, these cognitive impairments during depression are manifold and multilevel affecting elementary and more complex cognitive processes equally. Several models from different directions tried to evaluate, conceptualize and understand the depth and magnitude of cognitive dysfunctions in depression and their bidirectional interactions with other types of depressive symptomatology including mood symptoms. In the current review, we briefly overview different types of cognitive symptoms and deficits related to major depression including hot and cold as well as trait- and state-like cognitive alterations and we also describe current knowledge related to the impact of cognitive impairments on the course and outcomes of depression including remission, residual symptoms, function, and response to treatment. We also emphasize shortcomings of currently available treatments for depression in sufficiently improving cognitive dysfunctions and point out the need for newer pharmacological approaches especially in cooperation with psychotherapeutic interventions.

Relationship of suicide rates to economic variables in Europe: 2000-2011

BACKGROUND It is unclear whether there is a direct link between economic crises and changes in suicide rates. AIMS The Lopez-Ibor Foundation launched an initiative to study the possible impact of the economic crisis on European suicide rates. METHOD Data was gathered and analysed from 29 European countries and included the number of deaths by suicide in men and women, the unemployment rate, the gross domestic product (GDP) per capita, the annual economic growth rate and inflation. RESULTS There was a strong correlation between suicide rates and all economic indices except GPD per capita in men but only a correlation with unemployment in women. However, the increase in suicide rates occurred several months before the economic crisis emerged. CONCLUSIONS Overall, this study confirms a general relationship between the economic environment and suicide rates; however, it does not support there being a clear causal relationship between the current economic crisis and an increase in the suicide rate.

Season of birth is significantly associated with the risk of completed suicide.

BACKGROUND Previous studies have provided somewhat inconsistent results about the effects of season of birth on the risk of suicidal behavior. Therefore, we decided to investigate this question in a large sample of suicide completers. METHODS We determined the season of birth-associated risk of completed suicide between the years 1970 and 2008 among all individuals who were born in the area of todays Hungary between 1930 and 1939, 1941 and 1942, and 1944 and 1969. RESULTS The final sample of participants included around six and a half million people. About 80,000 completed suicides occurred among participants during the period investigated (the number of suicide completers in our study greatly exceeds the number of suicide completers in any previous studies). A significantly (p < .05) elevated risk of completed suicide was found among those individuals who were born in the high-risk period (spring and summer). Quantitatively, the biggest increase (7.6% [95% confidence interval: 5.4-9.9]) in suicide risk was detected among those who were born in July compared with the average risk of suicide in the population investigated. The associations between season of birth and the risk of completed suicide were stronger among male subjects than among female subjects and among those who committed suicide using violent methods than among those who chose nonviolent methods. CONCLUSIONS Our results from a large sample of suicide completers from Hungary--a country with one of the highest suicide rates in the world over the last century--strongly support the concept that the season of birth is significantly associated with the risk of completed suicide.

Peripheral vascular endothelial growth factor level is associated with antidepressant treatment response: Results of a preliminary study

BACKGROUND Recent investigations have revealed multiple actions of vascular endothelial growth factor (VEGF) in the nervous system. The role of VEGF in the molecular background of mood disorders has also been proposed. In this study we were interested in investigating a possible association between VEGF levels and treatment response in patients with a current episode of major depression (MDE). METHODS 34 patients with MDE were enrolled in our study. Depressive symptoms were monitored by the Montgomery-Åsberg Depression Rating Scale at baseline (V(1)) and after a 4-week treatment period (V(2)). Patients with less than a 50% improvement in MADRS total scores during this period were regarded as non-responders. RESULTS Plasma VEGF levels did not change during the treatment period in either the total sample or in the responder and non-responder subsamples. There was a strong trend for higher baseline VEGF levels in the non-responder group than in the responder group (p=0.055) and this difference-as a weak trend-was still detectable at the end of the treatment period (p=0.097). Regression analysis revealed that the baseline VEGF level was a significant predictor for the endpoint MADRS score (p=0.02). LIMITATIONS Sample size was relatively small; sample consists of both patients with MDD and bipolar disorder. CONCLUSIONS Our preliminary results raise the possibility that baseline levels of peripheral VEGF may predict treatment response in patients with mood disorders. Considering the limitations of our study, further investigations should resolve whether VEGF is a useful biomarker for treatment response in depression in clinical practice.

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.

Investigation of circulating endothelial progenitor cells and angiogenic and inflammatory cytokines during recovery from an episode of major depression

BACKGROUND Epidemiological studies strongly suggest a bidirectional positive relationship between mood and cardiovascular disorders (CVD). Reduced numbers of circulating endothelial progenitor cells (cEPCs) are associated with elevated risks of CVD. Previously we demonstrated that patients with a current episode of major depression (MDE) have a decreased number of cEPCs. The role of vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF) has been demonstrated in the etiopathogenesis of depression. In addition these cytokines are also involved in regulation of the vascular system. This suggests that VEGF and/or TNF may also mediate the elevated risk of CVD associated with mood disorders. METHODS In the current investigation, which has a self-controlled study design, we examined changes in VEGF and TNF levels and--for the first time--changes in cEPC number during recovery from MDE. RESULTS Twenty-four patients with MDE were enrolled. The severity of their depressive symptoms improved significantly during the one-month treatment period (~50% decrease in MADRS score; P≤0.001). We did not find significant differences between baseline and end-point levels of VEGF, TNF and the number of cEPCs. CONCLUSION Our negative result for alteration in the number of cEPCs in the course of recovery from MDE raises several questions. Before discarding the number of cEPCs as a possible marker of depression--and/or elevated CV risk associated with it--our results would require confirmation in larger samples. Our results for TNF and VEGF do not contradict the findings of prior studies, since these were controversial.

Suicide in Hungary-epidemiological and clinical perspectives.

Annual suicide rates of Hungary were unexpectedly high in the previous century. In our narrative review, we try to depict, with presentation of the raw data, the main descriptive epidemiological features of the Hungarian suicide scene of the past decades. Accordingly, we present the annual suicide rates of the period mentioned and also data on how they varied by gender, age, urban vs. rural living, seasons, marital status, etc. Furthermore, the overview of trends of other factors that may have influenced suicidal behavior (e.g., alcohol and tobacco consumption, antidepressant prescription, unemployment rate) in the past decades is appended as well. Based on raw data and also on results of the relevant papers of Hungarian suicidology we tried to explain the observable trends of the Hungarian suicide rate. Eventually, we discuss the results, the possibilities, and the future tasks of suicide prevention in Hungary.