Psychiatric disorders in women with polycystic ovary syndrome. / Wystepowanie zaburzen psychicznych u kobiet z zespolem policystycznych jajników.

Polycystic ovary syndrome (PCOS) is the most commonly diagnosed endocrine disorder in women of reproductive age, affecting approximately 5-8% of females in this group. It is characterized by hyperandrogenism, abnormal periods (rare periods or amenorrhea) and polycystic ovaries visualized through ultrasonography. The etiopathogenesis of polycystic ovary syndrome has not been elucidated in detail. There are numerous hypotheses on this subject which tend to complement one another. The most widely recognized hypothesis is that the development of PCOS is due to insulin resistance and hyperinsulinemia, which subsequently lead to hyperandrogenism. On the basis of an as of yet relatively small number of studies, an increased prevalence of various psychiatric disorders can be observed in women with PCOS. These include: depression, generalized anxiety disorder, personality disorders, social phobia, obsessive-compulsive disorder, attention deficit hyperactivity disorder (ADHD), and eating disorders. Bipolar affective disorder, schizophrenia and other psychotic disorders have also been reported in women with PCOS more often than in the general population. The higher prevalence of psychiatric disorders in patients with PCOS, especially depression and anxiety disorders, may be due to both hyperandrogenism and the resulting somatic symptoms. These symptoms can undoubtedly be stigmatizing for women and lower their quality of life. This article is intended to provide an overview of the literature regarding mental disorders associated with polycystic ovary syndrome and to present own research on depression and sexual dysfunction in this group.

Glutamate-Related Antibodies and Peripheral Insulin-Like Growth Factor in Bipolar Disorder and Lithium Prophylaxis.

AIMS: The aim of this study was to evaluate serum levels of the antineuronal antibodies anti-N-methyl-D-aspartate receptor (NMDAR) and anti-glutamic acid decarboxylase (GAD), and insulin-like growth factor 1 (IGF-1), in patients with bipolar disorder (BD), during manic and depressive episodes and in remission compared to euthymic patients receiving long-term lithium therapy. METHODS: Serum levels of anti-NMDAR and anti-GAD 450/620 antibodies, as well as IGF-1, were measured using the ELISA method in 19 manic and 17 depressed patients both in an acute episode and in remission after the episode. All of the subjects were under pharmacological treatment. The control group included 18 euthymic BD patients receiving lithium for 9-44 years (mean 22 ± 11) in whom a single measurement was performed. RESULTS: Serum levels of anti-NMDAR antibodies were higher in acute manic episodes than in lithium-treated patients. Serum levels of anti-GAD 450/620 antibodies were higher in acute manic and depressive episodes compared to remission after the respective episode. Their values in both acute manic and depressive episodes were higher than those in lithium-treated patients. Serum levels of IGF-1 were higher in acute manic episodes and in remission after mania than in lithium-treated patients. CONCLUSION: Higher levels of anti-NMDAR and anti-GAD antibodies during episodes may point to an abnormality in the glutamatergic system in BD. Increased levels of IGF-1 during an acute manic episode and in remission after mania may constitute a compensatory mechanism against excitotoxicity. Lower levels of anti-NMDAR, anti-GAD antibodies, and IGF-1 during long-term lithium treatment may reflect normalization of this processes, contributing to mood stabilization.

Stages of the clinical course of schizophrenia - staging concept. / Etapy przebiegu schizofrenii - koncepcja stagingu.

Clinical staging is a tool useful in medical sciences. It assumes the presence of three key elements. Firstly, pathologic indices are progressing in subsequent stages. Secondly, the patients in the individual stages present similar pathological changes. Thirdly, treatment should be most effective in the earlier stages. Such model is particularly well established in the treatment of malignancies. Staging is useful here to define prognosis, to evaluate the results of treatment, facilitate the exchange and comparison of information among treatment centres. There is much data describing a similar model for mental illnesses including schizophrenia. There are two theories supporting the staging model for schizophrenia: the neurodevelopmental hypothesis and allostatic load concept. Both theories make a theoretical premise for creating the staging model for schizophrenia. We can describe at least three stages in the development of a schizophrenic illness: the prodrome, the first episode and chronic phase. Each stage is reflected by anatomical and functional changes in the brain. Therefore, a clinical staging model can describe a development of schizophrenia over time, to help selecting adequate treatments that are particularly relevant to a given stage and to show the relations between known biological markers and psychosocial risk factors and the stage of the illness.

Extrapyramidal symptoms during treatment of first schizophrenia episode: results from EUFEST.

The European First Episode Schizophrenia Trial (EUFEST) included first-episode schizophrenia patients, assessing the efficacy of five antipsychotic drugs (haloperidol, amisulpride, olanzapine, quetiapine and ziprasidone) over one year. Baseline frequency of extrapyramidal symptoms (EPS) in this group of patients (n=490) was as follows: parkinsonism 10.8%, akathisia 10.0%, dystonia 1.8%, and dyskinesia 0.6%. The frequency of parkinsonism at baseline was greater in patients with a brief prior exposure to antipsychotics (≤2 weeks) compared with antipsychotic-naïve ones, and was positively correlated with the intensity of negative symptoms and negatively with depressive symptoms. After one month of treatment, the increase of parkinsonism was highest in patients receiving haloperidol (+13%), that of akathisia in patients treated with ziprasidone (+14%), and 10.1% of the patients were taking anticholinergic drugs, most frequently in the haloperidol group (24%). In 291 patients remaining on treatment after one year, both parkinsonism and akathisia had decreased: the frequency of parkinsonism was 3%, highest in the haloperidol group (9.1%), that of akathisia was 3%, highest in the quetiapine group (7.5%), and 4% of patients were taking anticholinergic drugs, most frequently those receiving haloperidol (10.5%). The results obtained suggest that in first-episode schizophrenia patients during the first year of antipsychotic treatment (in this case amisulpride, haloperidol in low doses, olanzapine, quetiapine and ziprasidone), EPS were present as manageable clinical problems.

[Staging of unipolar affective illness]. / Etapy przebiegu choroby afektywnej jednobiegunowej.

In this article, a concept of staging of unipolar affective illness (recurrent depression) is presented. In respective subchapters, three most important aspects of this issue have been discussed: 1) staging of unipolar affective illness; 2) staging of treatment-resistant depression; and 3) conversion of unipolar into bipolar affective illness. The evidence for so called neuroprogression of the illness, accumulated in recent years, has allowed for a classification of staging based on a concept of allostasis and allostatic load. In the course of illness, changes in neuroendocrine system (mainly hypothalamic pituitary-adrenal (HPA) axis), immunological system, mechanisms of oxidative stress, neurotransmitters, neurotrophic factors as well as structural and functional changes of the brain occur. In their paper of 2007, Fava and Tossani elaborated a concept of staging of unipolar affective illness presenting a continuum model of five consecutive stages with specific clinical features. In the present paper, a concept of treatment-resistant depression and staging of treatment resistance is presented in the context of several models. An important determinant of treatment-resistant depression is so called subthreshold bipolarity which is connected with worse efficacy of antidepressant drugs. In the course of illness, there is a possibility of changing diagnosis from recurrent depression into bipolar affective illness. The studies on this issue show that frequency of such diagnostic conversion is 1,5% of depressed patients per year.

Increased serum matrix metalloproteinase-9 (MMP-9) levels in young patients during bipolar depression.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is an enzyme implicated in a number of pathological conditions such as cardiovascular disease, cancer, and neuropsychiatric disorders. Increased blood levels of MMP-9 were found in cancer, heart disease and migraine. Molecular-genetic studies demonstrated an association of functional polymorphism of MMP-9 gene with predisposition to schizophrenia and bipolar illness. In this first study of serum MMP-9 in psychiatric illness, we estimated it in patients with bipolar mood disorder both during depression or mania as well as during immediate remission after these episodes. METHODS: The study was performed on 54 in-patients with bipolar mood disorder (19 males, 35 females), aged 42±14 years. Thirty were studied during acute episode and immediate remission after depression, and 24 during acute episode and immediate remission after mania. The control group consisted of 29 subjects (15 males, 14 females) aged 40±11 years. Serum MMP-9 was estimated by ELISA. RESULTS: In patients with bipolar illness, a significant correlation of MMP-9 levels was obtained with age. Younger patients with depression (below or equal 45 years of age), both during acute episode and in remission after depression had significantly higher MMP-9 levels compared to those with acute episode and remission after mania and control subjects. LIMITATIONS: Relatively small number of patients, who were receiving different antidepressant, antipsychotic and mood stabilizing drugs that might have influenced MMP-9 levels. CONCLUSIONS: Increased levels of serum MMP-9 during depression in young patients may indicate this phenomenon as a possible biochemical marker for staging of bipolar disorder.

[Activity of selected cytokines in bipolar patients during manic and depressive episodes]. / Ocena aktywnosci wybranych cytokin w epizodzie maniakalnym i depresyjnym choroby afektywnej dwubiegunowej.

AIM: The aim of the study was to examine the activity of selected cytokines in bipolar patients during manic and depressive episodes and in remission. METHOD: The cytokine status was assessed in 76 bipolar patients, 35 with mania- and 41 with depression. For cytokine measurements blood samples were drawn from each patient twice-- while in an acute episode and in remission. 78 healthy individuals were examined once. Serum samples were tested for concentrations of: IL-6, IL-10, IL-1beta, TNF-alpha, IFN-gamma using the cytometric method. The patients' mental status was assessed with Young Mania Rating Scale and Hamilton Depression Rating Scale. RESULTS: Concentration of IL-6 was higher during the manic state as compared to control group. Additionally, IL-6 level was higher in mania than in remission. Concentration of IL-10 was higher in patients in remission after manic episodes than in healthy controls. In manic patients raising of IFN-gamma level was accompanied by more severe symptoms evaluated with YMRS. In remission after mania there was a correlation between IL-6 concentration and the intensity of the manic state. IFN-gamma level was higher in depressed patients comparing to remission, as well as manic patients and subjects from control group. IFN-gamma in remission after depression was still higher than in the healthy controls. Concentration of IL-1beta was higher in depressed patients comparing to healthy subjects. CONCLUSION: The results obtained in this study show disturbances of the immune system in bipolar patients. These disturbances have features of either decrease or pathological increase of the immune response. Cytokines' profiles were different for mania and depression. Clinical improvement seems to be connected with immunomodulation process that results in changes of cytokine levels in bipolar patients in remission.

Selected cytokine profiles during remission in bipolar patients.

OBJECTIVES: The aim of the study was to examine the cytokine status in bipolar patients during immediate remission after acute episodes of mania or depression and in patients with sustained (≥6 months) remission, compared with healthy controls. METHODS: The study was performed on 121 bipolar patients, of whom 35 were in immediate remission after mania, 41 were in immediate remission after depression, and 45 were in >6-month remission on lithium monotherapy or lithium combined with other drugs. The control group consisted of 78 healthy individuals without any history of psychiatric or immunological illnesses. Serum concentrations of IL-1ß, IL-2, IL-6, IL-10, TNF-α and IFN-γ were determined using the Human Th1/Th2 Cytometric Bead Array method. RESULTS: The concentration of IL-10 was higher in patients in remission after mania and the concentration of IFN-γ was higher in those in remission after depression than in healthy controls. On the other hand, cytokine concentrations in patients with sustained remission were not different from those of healthy subjects. CONCLUSIONS: The results obtained in this study show that sustained remission in bipolar patients achieved mostly by lithium maintenance brings the cytokine status to a level similar to healthy control subjects.

[The role of oxytocin and vasopressin in central nervous system activity and mental disorders]. / Rola oksytocyny i wazopresyny w czynnosci osrodkowego ukladu nerwowego i w zaburzeniach psychicznych.

Oxytocin and vasopressin, "peptides of love and fear", except for their classic role in control of labor and breastfeeding and blood pressure regulation, are also implicated in various processes like sexual behaviours, social recognition and stress response. These hormones seems to be essential for appropriate and beneficial social interactions, play a very important role in maternal care and closeness, promote general trust and cooperation and prolong social memory. They also play a very important role in modulating fear and anxiety response, especially by regulating the hypothalamic-pituitary-adrenal axis and amygdala activity by its projections to the brain stem and hypothalamic structures. Both hormones, particularly oxytocin, appears to be activating sexual behaviour or is responsible for increased sexual arousal. Evidence from clinical trials suggests their potential role in pathogenesis of schizophrenia, depression, autism and addiction together with possible therapeutic use in the above conditions. In schizophrenia, patients with higher peripheral oxytocin levels showed less severe positive, general and social symptoms and better prosocial behaviours. Literature suggests that exogenous oxytocin may be effective as an adjunctive therapy for that illness. Some data suggest that naturally occurring autoantibodies reacting with oxytocin and vasopressin are involved in depression, eating disorders and conduct disorder genesis.

[Neuroimmunology of bipolar affective disorder]. / Neuroimmunologia choroby afektywnej dwubiegunowej.

Previous neuroimmunological studies focused mostly on depression, regardless of its diagnostic category. In this paper, the studies on the immunological system in patients with bipolar affective illness, including manic episode, have been presented. Research possibilities of neuroimmunology of affective disorders using molecular-genetic methods have also been shown. The studies on the neuroimmunology of depression have always been connected with studies on changes in the immunological system related to stress situations. Disturbances of the immunological system regulation have features of either decrease or pathological increase of the immunological system, with increased activity of pro-inflammatory cytokines (interleukin 1 and 6, interferon). Some pathogenic role for the disturbances of immunological system in depression is also played by viral infections (herpes, Borna viruses). The changes of the immunological system in mania are mostly similar to those observed during depression. An increase of activity of pro-inflammatory cytokines, connected with the lymphocyte Th1 system is especially evident. Like in depression, the role of viral infections has been pointed out (herpes, Borna, parvovirus B19). The oldest mood-stabilizing drug, lithium, has been shown to have strong action against herpes viruses. Molecular-genetic studies point to an association of some genes of the immunological system with both bipolar disorder and schizophrenia. An association of some genes with a predisposition to depression and efficacy of antidepressant drugs has also been shown.