The Studies Of HPA Axis Activity And The Features Of Brain MRI In Depressive Patients With Childhood Neglect

Background:Depression is a heterogeneous disease, and in order to explore the pathogenesis, different scholars classified depression from different aspects,different kinds of depression may have different biological basis, treatment method, curative effect and prognosis. Therefore the scientific and rational classification of depression is important for understanding the pathogenesis of the different types of of depression, which can have profit to guide the treatment, improve treatment reponse and promote the recovery of patients. Childhood trauma is considered to be one of the risk factor of depression, the western studies support depression with childhood trauma may be a kind of functional subtype, which respond better to psychological treatment than antidepressant. Therefore, we classified depression acoording to absence or presence of childhood trauna. Childhood trauma have many different types, of which child neglect is considered to be one of the most common form of childhood trauma, in this study, we assume that the depression with child neglect is a kind of functional subtype of depression with specific biological change. To date, very few studies have explored this subtype.Objective:To find some evidences about depression with childhood neglect as a kind of functional subtype of depression, we explore the distinct biologic features of depression with child neglect by neuroimaging and HPA axis activity methodsMethods:115depressive patients were included randomly from September2010to July2011in the second Xiangya Hospital of Central South University.103healthy people were recruited from the local community. Childhood Trauma Questionnaire (CTQ), ZUNG self-rating depression scale, HAMD depression scale, HAMD anxiety scale, ZUNG self-rating anxiety scale, dysfunctional attitudes questionnaire (DAS) scale combined face-to-face interviews with the first class relatives of patients were used to assess childhood trauma and related clinical psychology. According to CTQ Scale total scores and subscale cutoff point, to learn the distribution of various types of child maltreatment, we mainly focused on depression with child neglect. Childhood neglect includes emotional neglect and physical neglect, emotional neglect scores≥15or physical neglect scores≥10, or the total scores of both neglects≥20in our studies.Nineteen sex-, age-matched depressive patients with child neglect were compared to21depressive patients without any form of childhood trauma (any subscale in CTQ was lower than8),20healthy controls without childhood trauma and11healthy controls with child neglect.3D structure imaging, DTI,’H-MRS were performed for each subject.Cortisol awakening response (CAR) was as an indicator of measurement of HPA axis activity, HPA axis activity is defined as the difference between the concentration at30minutes after awakening and the one at awakening. Results:1. Clinical featuresIn these115depressive patients,11(9.6%) existed childhood emotional abuse,10(8.7%) existed physical abuse,11(9.6%) existed sexual abuse and40(34.8%) existed physical neglect,31people (30%) existed emotional neglect; in103heathy controls,3(2.9%) existed childhood emotional abuse,6(5.8%) existed physical abuse,0(0%) existed sexual abuse and9(8.7%) existed physical neglect,12people (11.7%) existed emotional neglect; Dysfunctional attitudes scores in healthy control were significantly lower than the two depressive subtypes and the healthy control with child neglect, and the dysfunctional attitudes scores in depressive patients with child neglect was significant higher than the depressive group without childhood trauma (p=0.000) and the healthy control with child neglect (p=0.006). Child neglect scores were significantly positively correlated with dysfunctional attitudes (r=0.599, p=0.000). The total scores and subscores of Social support were significantly negtively correlated with HAMD scores.2. Neuroimaging2.1.3DCompared to controls, the depressive group with childhood neglect showed significant decreased white matter densities in bilateral inferior parietal lobe [43-3224][-42-4225], and the decreased white matter densities were negatively correlated with the CTQ neglect total scores, HAMD, and DAS scores. But the depression without any form of childhood trauma showed significant decreased densities in bilateral sub-lobar extra-nuclear white matters [27-1516][-27324], and the decreased densities were only negatively correlated with HAMD, but not with the CTQ and DAS scores.2.2. DTIBrain regions with significant lower fractional anisotropy in depressive patients without childhood trauma than in depressive patients with child neglect include left Medial Frontal Gyru [-8,2648], Parietal Sub-Gyral [-28,-38,32], Sub-lobar Extra-Nuclear [-30,-14,18] Insula [-34,-12,10], Limbic Lobe Parahippocampa Gyrus [-20,-32,-12], Brainstem Midbrain [-14,-24,-20]; The FA was significant decreased in right Sub-lobar Extra-Nuclear white matter in depressive patients without childhood trauma.2.3. HPA axis activityThe HPA axis activity in depression with childhood negect was signiffcant higher (p=0.000) than the depression without childhood trauma (p=0.000); The HPA axis activity in healthy control with childhood neglect was higher than depression without childhood trauma(p=0.006). There were significant differences in cortisol concentrations at awakening among the four groups, only no significant differences between the two healthy controls.The total scores of neglect were positively related to HPA axis activity (p=0.033).2.4.^-MRSCompared with the control group, depressive patients showed decreased NAA/Cr (left p<0.01; right p<0.001), Glx/Cr (left p<0.05; right p<0.005) in ACC; the two depressive subgroups showed decreased bilateral NAA/Cr (left right p<0.05; p<0.005),but decreased Glx/Cr was only found in right ACC (p<0.001) in depression with child neglect; NAA/Cr was significantly lower (p<0.005p<0.01, left, right) in depressive group than the one without childhood trauma.2.5. The relationship between HPA axis activity and ACC1H-MRS.Both high and low HPA axis activity group showed decreased NAA/Cr and Glx/Cr, Increased Cho/Cr were only found in right ACC in high activity HPA group. We found significant decreased NAA/Cr in left ACC and increased Cho/Cr in right ACC, when high HPA activity group were compared to low HPA activity group.Conclusion:1. The descriptive data from our study found the prevalence of childhood abuse was higher in depressive group than in the normal group, and the physical neglect had the highest prevalence in childhood trauma, followed by emotional neglect, and sexual abuse had the lowest incidence.2. The depression with childhood neglect has higher DAS scores, which are not related to the severity of depression.3. The depression with childhood neglect and without childhood trauma might be two different functional subtypes of depression. The former showed reduced white matter densities located at inferior parietal lobe (IPL) involving the dorsal brain cognitive control executive system; the latter mainly located at subcortical level which may be correlated with ventral brain affective processing system. The dysfunction of cognition in depression with childhood neglect may be related to the abnormalities of white matter microstructure in IPL.4. The depression with childhood neglect show significant different white matter FA from the patients without childhood traum, and the main different brain regions located at left cortical-subcortical circuits. 5. Childhood neglect is related to the HPA axis activity and the severity of depression6. Patients with depression showed metabolic abnormalities in bilateral ACC, involving N-acetyl aspartic acid, glutamic acid metabolic disorders; the depressive patients with child neglect showed decreased bilateral NAA/Cr than that in depressive patients without childhood trauma.7. Depressive patients showed metabolic abnormalities in bilateral ACC, involving N-acetyl aspartic acid, glutamic acid and choline metabolism; HPA axis function levels are related to decreased NAA/Cr in left ACC, and increased Cho/Cr in right ACC.In a word, our results support that the depression with childhood neglect has distinct biological features, which may mean that the depression with childhood neglect is one kind of functional subtype of depression.