Die Bedeutung des Immunsystems in der Pathophysiologie von bipolaren Erkrankungen und Epilepsie ist ein aktueller Gegenstand der neuropsychoimmunologischen Forschung. Eine erhöhte Produktion von Zytokinen aufgrund von oxidativem Stress wurde dabei wiederholt als für die Pathophysiologie von Epilepsie und Bipolarer Störung relevant angesehen. In Hinblick auf Veränderungen der Zytokine Interleukin (IL)-1ß, IL-2, IL-4, IL-6 und Tumornekrosefaktor-alpha (TNF-α) wurden z. T. überlappende Ergebnisse bei beiden Erkrankungen beschrieben. Inwiefern diese Zytokine durch Stimmungsstabilisierer und Antiepileptika beeinflusst werden, wurde bisher jedoch nicht systematisch untersucht. In dieser Studie wurden systematisch in-vitro die Konzentrationen von IL-1ß, IL-2, IL-4, IL-6, IL-17, IL-22 und TNF-α im stimulierten Blut 14 gesunder Frauen mittels Vollblutverfahren (whole blood assay) nach Zugabe von Stimmungsstabilisierern bzw. Antiepileptika gemessen. Es wurden dabei die Stimmungsstabilisierer bzw. Antiepileptika Primidon, Carbamazepin, Levetiracetam, Lamotrigin, Valproat, Oxcarbazepin, Topiramat, Phenobarbital und Lithium untersucht. Die Ergebnisse lassen darauf schließen, dass der Mechanismus von erwünschter und unerwünschter anderer Wirkung von Stimmungsstabilisierern und Antiepileptika mit der Regulation von IL-1ß, IL-2, IL-22 und TNF-α in Zusammenhang stehen könnte. Getrennt nach den im Vollblutverfahren verwendeten Stimulanzien – Toxic-Shock-Syndrome-Toxin-1 (TSST-1) vs. monoklonaler Antikörper gegen das CD3-Oberflächenantigen (OKT3) in Kombination mit dem 5C3-Antikörper gegen CD40 (OKT3/CD40) – wurden die Ergebnisse in zwei unterschiedlichen Publikationen berichtet, die dieser Promotion zugrunde liegen.

Mood disorders are serious diseases. Nevertheless, their pathophysiology is not sufficiently clarified. Biological markers that would facilitate the diagnosis or successful prediction of pharmacotherapy are still being sought. The aim of the study was to find out whether mitochondrial functions are affected by antidepressants, mood stabilizers and depression. Our research is based on recent hypotheses of mood disorders, the advanced monoamine hypothesis, the neurotrophic hypothesis, and the mitochondrial dysfunction hypothesis. We assume that impaired function of mitochondria leads to neuronal damage and can be related to the origin of mood disorders. Effects of antidepressants and mood stabilizers on mitochondrial functions can be related to their therapeutic or side effects. In vitro effects of pharmacologically different antidepressants and mood stabilizers on the activities of mitochondrial enzymes were measured in mitochondria isolated from pig brains (in vitro model). Activity of monoamine oxidase (MAO) isoforms was determined radiochemically, activities of other mitochondrial enzymes were measured spectrophotometrically. Overall activity of the system of oxidative phosphorylation was measured electrochemically using high- resolution respirometry. Methods were modified to measure the same...

Psychopharmaca are a large group of drugs widely used not only in psychiatry. Their systemic administration affects both the main diagnosis and the organism as a whole. The subject of our experiments is the effect of psychopharmaca on the changes in mitochondrial functions, which is beneficial for understanding of molecular mechanisms of therapeutic and adverse effects of drugs. The aim of this thesis was to study the in vitro effects of selected drugs on the cell energy metabolism. Selected antipsychotics (chlorpromazine, levomepromazine, haloperidol, risperidone, ziprasidone, zotepine, aripiprazole, clozapine, olanzapine, and quetiapine), antidepressants (bupropion, fluoxetine, amitriptyline, imipramine) and mood stabilizers (lithium, valproate, valpromide, lamotrigine, carbamazepine) were tested. In vitro effects of selected psychopharmaca were measured on isolated pig brain mitochondria. The activities of citrate synthase (CS) and electron transport chain (ETC) complexes (I, II+III, IV) were measured spectrophotometrically. Drug-induced changes of mitochondrial respiration rates linked to complex I (supported by malate and pyruvate) and complex II (supported by succinate) were evaluated by high resolution respirometry. Complex I was significantly inhibited by lithium, carbamazepine, fluoxetine,...

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.

Background Polypharmacy is often prescribed for bipolar disorder, yet medication non-adherence remains a serious problem. This study investigated the regularity in the daily dosage taken of mood stabilizers and second generation antipsychotics. Methods Daily self-reported data on medications taken and mood were available from 241 patients with a diagnosis of bipolar disorder who received treatment as usual. Patients who took the same mood stabilizer or second generation antipsychotic for ≥ 100 days were included. Approximate entropy was used to determine serial regularity in daily dosage taken. Generalized estimating equations were used to estimate if demographic or clinical variables were associated with regularity. Results There were 422 analysis periods available from the 241 patients. Patients took drugs on 84.4% of days. Considerable irregularity was found, mostly due to single-day omissions and dosage changes. Drug holidays (missing 3 or more consecutive days) were found in 35.8% of the analysis periods. Irregularity was associated with an increasing total number of psychotropic drugs taken (p = 0.009), the pill burden (p = 0.026), and the percent of days depressed (p = 0.049). Conclusion Despite low missing percent of days, daily drug dosage may be irregular primarily due to single day omissions and dosage changes. Drug holidays are common. Physicians should expect to see partial adherence in clinical practice, especially with complex drug regimens. Daily dosage irregularity may impact the continuity of drug action, contribute to individual variation in treatment response, and needs further study.