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Objective: We have investigated BDNF levels in pre- and post-treatment serum in patients with bipolar disorder manic episode.
Methods: The patient group was formed by 29 patients (14 females, 15 males), with diagnosis of bipolar disorder manic episode and the control group was formed by 29 healthy subjects (14 females, 15 males) who were similar to the patient group, in terms of age and educational level. Blood samples were collected from the healthy controls and patients before, and at the 30th day of treatment. Patients included in the study were evaluated for their autobiography, family history, and sociodemographics, and were applied the Young Mania Rating Scale (YMRS). After collecting venous blood samples, serums were separated by centrifugation. Removed serums were incubated at -70 oC for 2-6 months. Based on the sandwich enzyme immunoassay principle, the microElisa system was applied for the detection of BDNF levels. In the study, Quantikine Human BDNF Kit was used. The test was performed properly according to the kit instructions. Due to small sample size and non-normal distribution, nonparametric tests (Mann-Whitney U and Wilcoxon Signed Ranks Test for continuous variables, Fisher’s exact test for categoricalvariables) were used. The effects of medications, age and educational status on pre- and posttreatment changes in BDNF levels were examined by Kruskall Wallis Test and multiple regression analysis.
Results: Mean age of bipolar patients was 32.62 ± 8.32 (18-45) years and their mean lengt of education was 8.79 ± 4.08 (0-18) grades. Mean age of control subjects was 33.83 ± 6.65 (17-45) years and mean length of education was 8.31 ± 4.22 (0-17) grades. No significant difference was found between the two groups in terms of age distribution (p=0.483) and educational status (p=0.550).The patients were ill for 9.68±8.92 years and, the mean duration of last manic episode prior to admission was 36.68±29.36 days. Two patients had their first episode. Previously used medications included valproate in 11 patients, lithium in 2, carbamazepine in 1 patient and atypical antipsychotics in 5 patients. None of the patients used a psychotropic medication in the last two months prior to the study. Lithium was administered to 10 patients and valproate to 17. Two patients did not receive mood stabilizers. Additionally, a typical antipsychotic was administered to 14 patients, and atypical antipsychotic to 12 patients. At baseline, mean BDNF levels were 14.35±5.85 pg/ml in patients and 40.17±9.74 pg/ml in controls. The difference was statistically significant. A statistically significant reduction of mean YMRS score was noticed from baseline 35.86±9.36 to 5.18±8.07, after the 30th day of treatment (p0.001). Mean BDNF levels were increased from baseline 14.35±5.85 pg/ml to 20.48±7.33 pg/ml after the 30th day, which was also statistically significant (p0.001). When the effects of each treatment to the change in YMRS and BDNF level were examined neither type of the antipsychotic (p=0.111), type of mood stabilizer (p=0.514), the presence of family history (p=0.512) (kruskall wallis test) nor the severity of manic symptoms (p=0.705), frequency of manic episodes (p= 0.460) and the length of the disease (p=0.776) were found to be effecting the BDNF levels.
Conclusions: Lower BDNF levels in manic patients compared to healthy controls suggest the significance of this neurotrophic factor in mania. However, long-term follow-up studies with large sample sizes and investigating different periods of bipolar disorder (mania, depression and euthymic) are needed in order to evaluate the effects of mood stabilizer and antipsychotic treatments on BDNF levels in mania.
Bipolar bozukluk manik epizotta serum BDNF düzeyleri ve tedavi ile de¤iflimi
Amaç: Biz çal›flmam›zda BDNF’nin, bipolar bozukluk manik epizottaki hastalarda tedavi öncesi ve sonras› serum düzeylerini araflt›rd›k.
Yöntem: Çal›flma grubu bipolar bozukluk manik epizot tan›s› alm›fl 29 hastadan (14 kad›n, 15 erkek), kontrol grubu ise e¤itim ve yafl aç›s›ndan benzer 29 sa¤l›kl› denekten (14 kad›n, 15 erkek) oluflturuldu. Kan örnekleri, tedavi öncesinde ve tedavinin 30. gününde hastalardan ve sa¤l›kl› kontrollerden al›nd›. Hastalar çal›flmaya al›n›rken, özgeçmifl ve soygeçmifl bilgilerini, sosyodemografik bilgilerini sorgulayan bir form ve Young Mani De¤erlendirme Ölçe¤i uyguland›. Venöz kan örnekleri al›nd›ktan sonra santrifüj edilerek serumlar ayr›ld›. Elde edilen serumlar 2-6 ay -70 C’de bekletildi. BDNF düzeylerinin saptanmas›nda sandwich enzim immunoassey prensibine dayal› mikroeliza yöntemi kullan›ld›. Çal›flmada Quantikine Human BDNF kiti kullan›ld›. Test kit prensibine uygun olarak çal›fl›ld›. Grup say›lar› düflük ve da¤›l›mlar›n›n normal olmamas› nedeni ile nonparametrik testler (sürekli de¤iflkenleri karfl›laflt›rmak için Mann- Whitney U ve Wilcoxon Signed Ranks Test, kategorik de¤iflkenleri karfl›laflt›rmak için Fisher’in kesinlik testi) kullan›ld›. Bu araflt›rmada BDNF düzeylerindeki tedavi öncesi ve sonras›ndaki de¤iflimlere kullan›lan ilaçlar›n yafl›n ve e¤itimin etkisini, multinominal lojistik regresyon analizi ile araflt›r›ld›.
Bulgular: Bipolar bozukluk manik epizot tan›s› alan hastalar›n yafl ortalamas› 32.62 ± 8.32 (18-45) ortalama e¤itim süreleri; 8.79 ± 4.08 (0-18) y›l olarak saptand›. Kontrol grubunun yafl ortalamas› 33.83 ± 6.65 (17-45) ve ortalama e¤itim süreleri 8.31 ± 4.22 (0-17) y›l olarak bulundu. Yafl (p=0.483) ve e¤itim süresi (p=0.550) aç›s›ndan iki grup aras›nda istatistiksel olarak anlaml› fark bulunmad›. Hasta grubunun ortalama hastal›k süresi 9.68±8.92 y›l ve yat›fltan önceki son manik epizodun süresi de 36.68±29.36 gün olarak saptand›. Yaln›zca 2 hastan›n ilk epizodu idi. Çal›flma grubundaki hiçbir hasta, baflvurudan önceki iki ay boyunca duygudurum düzenleyici veya antipsikotik kullanmam›flt›. ‹lk de¤erlendirme sonras›nda 10 hastaya lityum 17 hastaya Na-valproat baflland›. 2 hastaya duygudurum düzenleyici verilmedi Duygudurum düzenleyicilerin yan›nda 14 hastaya tipik ve 12 hastaya atipik antipsikotik verildi. Hasta grubunda bazal BDNF 14.35±5.85 pg/ml ve sa¤l›kl› kontrollerde 40.17±9.74 pg/ml olarak ölçüldü, aradaki fark istatistiksel olarak anlaml› bulundu. 30 günlük tedavi sonras›nda YMRS skorlar›nda 35.86±9.36 dan 5.18±8.07 ya istatistiksel olarak anlaml› bir düflüfl saptand› (p0.001). Ayn› sürede ortalama BDNF düzeyleri de istatistiksel olarak anlaml› bir flekilde (p0.001), 14.35±5.85 pg/ml’den 20.48±7.33 pg/ml’ye yükseldi. Uygulanan tedavilerin ve di¤er de¤iflkenlerin BDNF de¤iflimine etkisi araflt›r›ld›¤›nda antipsikotiklerin türünün (p=0.111), duygudurum düzenleyicilerin türünün (p=0.514) aile öyküsünün varl›¤›n›n (p=0.512) manik belirtilerin fliddetinin (p=0.705), manik epizodlar›n s›kl›¤›n›n (p= 0.460) ve hastal›k süresinin (p=0.776) BDNF düzeylerini etkilemedi¤i saptand›.
Sonuçlar: Manik hastalarda sa¤l›kl› kontrollere göre düflük BDNF düzeyleri, bu nörotrofik faktörün manideki önemine iflaret etmektedir. Ancak duygudurum düzenleyici ve antipsikotik tedavilerin manide BDNF düzeyine etkisini ölçmek için daha büyük say›da ve de¤iflik bipolar bozukluk dönemlerini yans›tan gruplar (mani, depresyon ve ötimik) ile daha uzun izlem çal›flmalar›na gereksinim vard