Yüksek genetik risk taşıyan, erken başlangıçlı, yineleyici major depresif bozukluk hastaları ile sağlıklı kontrollerin hipokampüs hacimlerinin karşılaştırılması
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Dosyalar
Tarih
2018
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
GİRİŞ: Major depresif bozukluk (MDB) toplumda en yaygın görülen affektif bozukluktur. Toplumda ciddi düzeyde morbidite ve mortaliteye yol açmaktadır. Genetik ve çevresel faktörlerin etkileşimiyle ortaya çıkan MDB'nin patofizyolojisi henüz tam olarak aydınlatılamamıştır. Nörogörüntüleme çalışmalarında en çok hipokampüs hacminde azalma olduğu gösterilmiştir. Başta hipokampüs olmak üzere tüm beyinde oluşan değişiklikler aydınlatırılırsa patofizyoloji ile ilgili daha net bilgilere ulaşılacağı tahmin edilmektedir. Araştırma grubumuzun yaptığı bir çalışmada yüksek genetik risk taşıyan sağlıklı kadınlar ile kontrol grubunun hipokampüs hacimleri karşılaştırılmış, toplam hipokampüs hacmi açısından fark saptanmamış, subikulumda premorbid genetik yatkınlığı yansıttığı düşünülen değişiklikler olduğu gösterilmiştir. Bu çalışmada ise 19-25 yaş arasında olan ve bir tanesi 19 yaşından önce olmak üzere en az iki MDB epizodu geçirmiş yüksek ailesel riske sahip kadınlarla kontrol grubunun hipokampüs ve hipokampüs altbölüm hacimleri karşılaştırılmıştır. YÖNTEM: Çalışmaya 19-25 yaş arası, annelerinde depresyon öyküsü olan, kendileri de bir tanesi 19 yaş öncesinde olmak üzere en az 2 MDB epizodu geçiren 27 hasta ve hasta grubuna yaş ve eğitim düzeyi açısından eş 29 sağlıklı kontrol dahil edilmiştir. Kriterlere uyan ve çalışmaya katılamayı kabul eden gönüllülere bilgilendirilmiş onam formu imzalatılmış, ayrıntılı psikiyatrik muayene yapıldıktan sonra SCID-I (Structured Clinical Interview for DSM IV; DSM IV için yapılandırılmış klinik görüşme), Hamilton Depresyon Değerlendirme Ölçeği (HAM-D-17), Beck Depresyon Envanteri (BDE), Beck Anskiyete Envanteri (BAE), Durumluk-Sürekli Anksiyete Envanteri (STAI- State Trait Anxiety Inventory) ve Çocukluk Çağı Ruhsal Travma Ölçeği (Childhood Trauma Questionnaire CTQ) uygulanmıştır. Sonrasında 3 Tesla MR cihazı kullanılarak MR görüntüleri elde edilmiş ve 3D T1 ağırlıklı MP-RAGE sekanslarıyla elde edilen görüntüler ilgi alanı analizleri için kullanılmıştır. FreeSurfer (v6.0) yazılım paketi ile hipokampüs ve altbölümlerinin hacim ölçümleri yapılmıştır. BULGULAR: Çalışmada depresyon ve kontrol grubu arasında sol ve sağ total hipokampüs ve hipokampüs proper hacmi anlamlı fark bulunmamıştır. Sağ HPV hasta grubunda küçülme eğilimi göstermiştir. Tüm hacimler için yaş, eğitim düzeyi, total intrakraniyal volüm (TIV) ve grubun etkisi genel lineer model kullanılarak değerlendirilmiştir. Sağ CA1 bölgesinin gövdesi hacmi hastalarda kontrollere göre anlamlı düzeyde düşük bulunmuştur ( F(1,51)=7,160 p=0,010). Sağ presubiculumun gövdesi ve toplamı hastalarda anlamlı düzeyde büyük bulunmuştur (sırasıyla F(1,51)=5,222 p=0,026; F(1,51)=4,099 p=0,048). Hasta grubunda sağ CA2/3 bölgesi toplam hacmi anlamlı düzeyde düşük ( F(1,51)= 4,190 p=0,046); gövde kısmı ise azalma eğilimindedir ( F(1,51)=4,000 p=0,051). Diğer altbölüm hacimlerinde gruplar arasında anlamlı fark bulunmamıştır. Fark olduğu saptanan bölgeler için etkili olabileceği düşünülen faktörlerle regresyon analizi yapılmış ve buna göre; sağ CA1 gövde hacmi üzerine HAM-D skoru (p=0,012; r2=0,131) ve TIV (p=0,016; r2=0,97); sağ presubiculum gövde hacmi için TIV (p=0,004; r2=0,117) ve CTQ (p=0,06; r2=0,123); CA3 toplam hacmi için ise TIV (p<0,01; r2=0,340) ve yaş (p=0,047; r2=0,051) anlamlı derecede etkili bulunmuştur. TARTIŞMA ve SONUÇ: Çalışmamızın oldukça yüksek düzeyde hastalık yüküne neden olan MDB ile ilgili bilgilerimizi arttırmak, patofizyolojisini aydınlatmak, hangi hastada hangi tedavinin işe yarayacağını öngördürebilecek yöntemler geliştirmek açısından literatüre katkı sağladığı düşünülmektedir. Daha kesin bilgilere ulaşabilmek ve neden sonuç ilişkilerini açıklayabilmek, hatırlama faktörünün etkisini azaltabilmek için çok merkezli, daha geniş örneklemin dahil edildiği, uzun izlem çalışmalara ihtiyaç vardır.
INTRODUCTION: MDD is the most common affective disorder in society which can cause severe morbidity and even mortality. It is known that both genetic and environmental factors play role in MDD but the whole pathophysiology has not been clarified yet. In neuroimaging studies it has been shown that the most volume reduction occurs in hippocampus. It is supposed that clear information about pathophysiology would be reached by clarifying the changes in the whole brain, especially in hippocampus. In a study done by our research group, comparison of hippocampus volume in control group and a group of women who have high genetic risk for MDD. As a result, it has been shown that there is no difference in total hippocampus volume but some differences attract attention which are thought to be related to premorbid genetic predisposition. In this study, comparisons of hippocampus volume and hippocampus subsection volume have been done in two groups, one of them is a group of women whose ages are between 19 and 25, who have high genetic risk for MDD and have at least two MDD episodes and one of these episodes must occur under age 19, and the second group is control group. METHOD: 27 patients, with at least two MDD episodes, at least one episode under age of 19, with depressed mothers and 19-25 years of age and 29 healthy controls equal to the patient group in terms of age and education level have beeen included in this study. Informed consent form has been signed and detailed psychiatric examination has been done to the volunteers who agree with the criteria and agree to participate in the study. In addition to psychiatric examination, Structured Clinical Interview for DSM IV (SCID-I), Hamilton Depression Rating Scale(HAM-D-17), Beck Depression Inventory, Beck Anxiety Inventory, State Trait Anxiety Inventory (STAI) and Childhood Trauma Questionnaire (CTQ) have been conducted. Subsequently MR images have been obtained by using 3 Tesla MR devices and images obtained with 3D T1 weighted MP-RAGE sequences have been used for region of interest analysis. Volumes of hippocampus and hippocampus subsection have been measured with FreeSurfer software package. CONCLUSION: There has been no significant difference in left and right total hippocampus volume and hippocampus proper volume between depression group and control group. Right HPV has tended to shrink in depression group. Effects of age, education level, total intracranial volume and group on all volumes have been evaluated by using general linear model. The volume of the right CA1 body region has been found significantly lower in patient group comparing to control group (F(1,51)=7,160 p=0,010). Both total and body volumes of right presubiculum have been found significantly higher in patient group (F(1,51)=5,222 p=0,026; F(1,51)=4,099 p=0,048). Total volume of right CA2/3 region has been found significantly lower in patient group ( F(1,51)= 4,190 p=0,046), in addition to this body region has tended to shrink ( F(1,51)=4,000 p=0,051).Other subsection volumes has not been significantly different between groups. Regression analysis has been performed with the factors thought to be effective for the regions determined to be different and according to analysis HAM-D score (p = 0.012, r2 = 0.131) and TIV (p = 0.016, r2 = 0.97) have been significantly effective on right CA1 body volume; TIV (p = 0.004; r2 = 0.1117) and CTQ (p = 0.06; r2 = 0.123) have been significantly effective for the right presubiculum body volume; TIV (p <0,01, r2 = 0,340) and age (p = 0,047, r2 = 0,051) have been significantly effective for total volume of CA3. DISCUSSION AND CONCLUSION: It is believed that our study has contributed to literature not only by clarifying pathopysiology and improving our knowledge about MDD which has high disease burden, but also by developing methods which can predict which treatment work in which patient. Long-term follow-up studies with wider sampling in multiple centers should be done so as to get more precise information, explain cause-result relations and reduce the impact of recall factor.
INTRODUCTION: MDD is the most common affective disorder in society which can cause severe morbidity and even mortality. It is known that both genetic and environmental factors play role in MDD but the whole pathophysiology has not been clarified yet. In neuroimaging studies it has been shown that the most volume reduction occurs in hippocampus. It is supposed that clear information about pathophysiology would be reached by clarifying the changes in the whole brain, especially in hippocampus. In a study done by our research group, comparison of hippocampus volume in control group and a group of women who have high genetic risk for MDD. As a result, it has been shown that there is no difference in total hippocampus volume but some differences attract attention which are thought to be related to premorbid genetic predisposition. In this study, comparisons of hippocampus volume and hippocampus subsection volume have been done in two groups, one of them is a group of women whose ages are between 19 and 25, who have high genetic risk for MDD and have at least two MDD episodes and one of these episodes must occur under age 19, and the second group is control group. METHOD: 27 patients, with at least two MDD episodes, at least one episode under age of 19, with depressed mothers and 19-25 years of age and 29 healthy controls equal to the patient group in terms of age and education level have beeen included in this study. Informed consent form has been signed and detailed psychiatric examination has been done to the volunteers who agree with the criteria and agree to participate in the study. In addition to psychiatric examination, Structured Clinical Interview for DSM IV (SCID-I), Hamilton Depression Rating Scale(HAM-D-17), Beck Depression Inventory, Beck Anxiety Inventory, State Trait Anxiety Inventory (STAI) and Childhood Trauma Questionnaire (CTQ) have been conducted. Subsequently MR images have been obtained by using 3 Tesla MR devices and images obtained with 3D T1 weighted MP-RAGE sequences have been used for region of interest analysis. Volumes of hippocampus and hippocampus subsection have been measured with FreeSurfer software package. CONCLUSION: There has been no significant difference in left and right total hippocampus volume and hippocampus proper volume between depression group and control group. Right HPV has tended to shrink in depression group. Effects of age, education level, total intracranial volume and group on all volumes have been evaluated by using general linear model. The volume of the right CA1 body region has been found significantly lower in patient group comparing to control group (F(1,51)=7,160 p=0,010). Both total and body volumes of right presubiculum have been found significantly higher in patient group (F(1,51)=5,222 p=0,026; F(1,51)=4,099 p=0,048). Total volume of right CA2/3 region has been found significantly lower in patient group ( F(1,51)= 4,190 p=0,046), in addition to this body region has tended to shrink ( F(1,51)=4,000 p=0,051).Other subsection volumes has not been significantly different between groups. Regression analysis has been performed with the factors thought to be effective for the regions determined to be different and according to analysis HAM-D score (p = 0.012, r2 = 0.131) and TIV (p = 0.016, r2 = 0.97) have been significantly effective on right CA1 body volume; TIV (p = 0.004; r2 = 0.1117) and CTQ (p = 0.06; r2 = 0.123) have been significantly effective for the right presubiculum body volume; TIV (p <0,01, r2 = 0,340) and age (p = 0,047, r2 = 0,051) have been significantly effective for total volume of CA3. DISCUSSION AND CONCLUSION: It is believed that our study has contributed to literature not only by clarifying pathopysiology and improving our knowledge about MDD which has high disease burden, but also by developing methods which can predict which treatment work in which patient. Long-term follow-up studies with wider sampling in multiple centers should be done so as to get more precise information, explain cause-result relations and reduce the impact of recall factor.
Açıklama
Anahtar Kelimeler
Major Depresif Bozukluk, Hipokampüs, Hipokampüs Alt bölüm Hacimleri, Major Depressive Disorder, Hippocampus, Hippocampus Subsection Volumes
