Reconciling Variable Findings of White Matter Integrity in Major Depressive Disorder

Diffusion tensor imaging (DTI) has been used to evaluate white matter (WM) integrity in major depressive disorder (MDD), with several studies reporting differences between depressed patients and controls. However, these findings are variable and taken from relatively small studies often using suboptimal analytic approaches. The presented DTI study examined WM integrity in large samples of medication-free MDD patients (n=134) and healthy controls (n=54) using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) approaches, and rigorous statistical thresholds. Compared with health control subjects, MDD patients show no significant differences in fractional anisotropy, radial diffusivity, mean diffusivity, and axonal diffusivity with either the VBM or the TBSS approach. Our findings suggest that disrupted WM integrity does not have a major role in the neurobiology of MDD in this relatively large study using optimal imaging acquisition and analysis; however, this does not eliminate the possibility that certain patient subgroups show WM disruption associated with depression.     

White Matter Disruptions in Adolescents Exposed to Childhood Maltreatment and Vulnerability to Psychopathology

Childhood maltreatment has been known to produce long-lasting impairments in behavioral, cognitive and social functioning, but their underlying mechanisms are not well-understood. A better understanding of their underlying mechanisms will aid in developing effective preventive interventions. Nineteen adolescent volunteers with no personal history of a psychiatric illness, but who were exposed to maltreatment during childhood, and 13 adolescent volunteers with no personal or family history of a psychiatric disorder (controls) underwent diffusion tensor imaging (DTI) studies. The participants were then followed longitudinally at 6-month intervals for up to 5 years to determine the onset of mood and substance use disorders. The associations among fractional anisotropy (FA) values obtained from the DTI scans at baseline and psychopathology at follow-up were examined. At baseline, adolescents exposed to childhood maltreatment had significantly lower FA values in the left and right superior longitudinal fasciculi, right cingulum bundle projecting to the hippocampus, left inferior fronto-occipital fasciculus, and splenium of the corpus callosum compared with controls. Adolescents who developed major depressive disorder at follow-up had significantly lower FA values in the superior longitudinal fasciculi and the right cingulum-hippocampal projection compared with their counterparts who did not develop the illness. Adolescents who developed substance use disorder during follow-up had significantly lower FA values in the right cingulum-hippocampal projection than their counterparts without the disorder. These preliminary results suggest that white matter disruptions observed in adolescents exposed to childhood maltreatment may be associated with increased vulnerability to psychopathology, specifically depressive and substance use disorders.     

The Influence of Acute SSRI Administration on White Matter Microstructure in Patients Suffering From Major Depressive Disorder and Healthy Controls

BackgroundSelective serotonin reuptake inhibitors (SSRIs) are predominantly prescribed for people suffering from major depressive disorder. These antidepressants exert their effects by blocking the serotonin transporter (SERT), leading to increased levels of serotonin in the synaptic cleft and subsequently to an attenuation of depressive symptoms and elevation in mood. Although long-term studies investigating white matter (WM) alterations after exposure to antidepressant treatment exist, results on the acute effects on the brain’s WM microstructure are lacking.MethodsIn this interventional longitudinal study, 81 participants were included (33 patients and 48 healthy controls). All participants underwent diffusion weighted imaging on 2 separate days, receiving either citalopram or placebo using a randomized, double-blind, cross-over design. Fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity were calculated within the FMRIB software library and analyzed using tract-based spatial statistics.ResultsThe repeated-measures ANOVA model revealed significant decreases after SSRI administration in mean diffusivity, axial diffusivity, and radial diffusivity regardless of the group (P < .05, family-wise error [FWE] corrected). Results were predominantly evident in frontal WM regions comprising the anterior corona radiata, corpus callosum, and external capsule and in distinct areas of the frontal blade. No increases in diffusivity were found, and no changes in fractional anisotropy were present.ConclusionsOur investigation provides the first evidence, to our knowledge, that fast WM microstructure adaptations within 1 hour after i.v. SSRI administration precede elevations in mood due to SSRI treatment. These results add a new facet to the complex mode of action of antidepressant therapy. This study was registered at clinicaltrials.gov with the identifier {"type":"clinical-trial","attrs":{"text":"NCT02711215","term_id":"NCT02711215"}}NCT02711215.     

草酸艾司西酞普兰与米安色林治疗老年抑郁症各46例对照研究

目的探讨草酸艾司西酞普兰与米安色林治疗老年抑郁症的疗效和安全性。方法 92例符合CCMD-3抑郁症诊断标准的老年患者,随机分为草酸艾司西酞普兰组和米安色林组,治疗观察8周,采用汉密尔顿抑郁量表（HAMD）评定临床疗效,副反应量表（TESS）评定不良反应。结果草酸艾司西酞普兰组与米安色林组疗效相当,治疗后HAMD总分均有显著减少。草酸艾司西酞普兰显效较快,不良反应更少。结论草酸艾司西酞普兰是治疗老年性抑郁症的理想药物。     

White Matter Tract Integrity of Anterior Limb of Internal Capsule in Major Depression and Type 2 Diabetes

A number of studies have shown an association between diabetes and depression. However, the underlying mechanisms are still unclear. Previous findings indicate a role for the prefrontal cortex and subcortical gray matter regions in type 2 diabetes and major depressive disorder (MDD). The purpose of this study was to examine the white matter integrity in the fibers that are part of the anterior limb of internal capsule (ALIC) in MDD and diabetic subjects using diffusion tensor imaging tractography. We studied 4 groups of subjects including 1) 42 healthy controls (HC), 2) 28 MDD subjects (MD), 3) 24 patients diagnosed with type 2 diabetes without depression (DC), and 4) 22 patients diagnosed with diabetes and depression (DD). Results revealed significantly decreased fractional anisotropy (FA; P=.021) and a trend towards significant increase in radial diffusivity (RD; P=.078) of the right ALIC in depressed subjects (MD+DD) compared to non-depressed subjects (HC+DC). While there were no significant diabetes effects or interactions between depression and diabetes, subjects with high depression ratings and high hemoglobin A1c levels had the lowest mean FA values in the right ALIC. In addition, we found a significant negative correlation between FA of the left ALIC with hemoglobin A1c in diabetic subjects (DC+DD; P=.016). Our study demonstrated novel findings of white matter abnormalities of the ALIC in depression and diabetes. These findings have implications for clinical manifestations of depression and diabetes as well as their pathophysiology.     

Alterations of Superficial White Matter in Schizophrenia and Relationship to Cognitive Performance

Post-mortem studies have demonstrated alterations in superficial white matter (SWM) in schizophrenia patients. Diffusion tensor imaging (DTI) can be used to assess SWM in vivo, and compare SWM fractional anisotropy (FA) in schizophrenia patients vs healthy controls. The assessment of SWM in vivo also provides an opportunity to identify novel neural correlates of cognitive performance, and potential cognitive impairment in schizophrenia patients. Forty-four patients with schizophrenia and 44 matched healthy controls underwent neuroimaging and cognitive protocols. Using an SWM mask and tract-based spatial statistics, differences in SWM-FA were examined between groups. SWM-FA clusters different between groups were then used to predict cognitive performance with multiple linear regression. The relative contribution of SWM fiber subtypes (deep white matter extensions vs U-fibers and intraregional fibers) from significantly different clusters was examined. Compared to controls, patients with schizophrenia had reduced FA in five SWM clusters: the largest a left posterior parieto-occipital cluster, followed by four clusters in the left frontal lobe. SWM-FA in the frontal lobe clusters predicted attention, working memory, and processing speed performance in healthy controls, but not in patients with schizophrenia. The majority of streamlines tracked from these clusters were restricted to U-fibers and intraregional fibers, rather than deep white matter extensions. Our analyses revealed prominent SWM disruption in patients with schizophrenia compared to controls. SWM–cognition relationships shown in healthy individuals were disrupted in patients with schizophrenia. SWM may be an important neurobiological substrate of cognitive performance and a novel cortical treatment target for cognitive deficits in schizophrenia patients.     

DHF-7 Ameliorates Behavioral Disorders and White Matter Lesions by Regulating BDNF and Fyn in a Mouse Model of Schizophrenia Induced by Cuprizone and MK-801

BackgroundSchizophrenia is a psychiatric disorder including multiple clinical symptoms such as severe psychosis and cognitive dysfunction. DHF-7 is a novel dihydroflavanone derivative that was designed and synthesized to treat schizophrenia. This study aimed to investigate the effects and mechanisms of DHF-7 in a mouse model of schizophrenia induced by a combination of cuprizone and MK-801.MethodsAfter intragastric administration of DHF-7 for 7 weeks, open field, Y-maze, and novel object recognition tests were performed to detect behavioral changes in the mouse model. White matter lesions and myelin loss were determined using transmission electron microscopy and oil red O staining. Western blotting and immunohistochemistry were used to detect the expression of the related proteins.ResultsThe results showed that DHF-7 treatment significantly improved cognitive impairment and positive symptoms in the model mice. Moreover, DHF-7 alleviated white matter lesions and demyelination and promoted the differentiation and maturation of oligodendrocytes for remyelination in the corpus callosum of model mice. The mechanistic study showed that DHF-7 increased the expression of brain-derived neurotrophic factor and phosphorylated Fyn, thus activating the tyrosine kinase receptor B (Trk B)/Fyn/N-methyl-D-aspartate receptor subunit 2 B (NMDAR2B) and Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-related kinase (ERK) signaling pathways.ConclusionsOur results provide an experimental basis for the development of DHF-7 as a novel therapeutic agent for schizophrenia.     

重组人脑利钠肽治疗急性心肌梗死继发心力衰竭老年患者效果及对其心功能影响分析

目的:分析重组人脑利钠肽治疗急性心肌梗死继发心力衰竭老年患者效果及对其心功能影响。方法:选择某院2015年10月~2018年10月收治的80例急性心肌梗死继发心力衰竭患者作为研究对象,随机分为对照组与观察组各40例,对照组患者使用硝酸甘油,观察组患者在上述治疗方法的前提下,使用重组人脑利纳肽进行注射治疗,比较两组患者治疗前治疗后心功能指标、治疗疗效、治疗前后的肾功能指标。结果:(1)与对照组对比,观察组治疗后LVEF明显更高,LVEDD和LVESD明显更低,数据差异存在统计学意义(P<0.05);和治疗前对比,两组治疗后LVEF明显提高,LVEDD、LVESD明显下降,数据差异存在统计学意义(P<0.05)。(2)观察组治疗疗效可达95%,对照组治疗疗效仅达75%,观察组治疗疗效明显优于对照组,数据差异存在统计学意义(P<0.05)。(3)对照组治疗前后谷丙转氨酶、尿素氮、肌酐水平变化显著(P<0.05);观察组治疗前后谷丙转氨酶、尿素氮、肌酐水平变化无明显差异,不具有统计学意义(P>0.05)。结论:重组人脑利钠肽治疗急性心肌梗死继发心力衰竭老年患者效果满意确切,可以有效地改善患者的心功能,从而提高了治疗有效率,安全可靠,值得广泛应用于急性心肌梗死的治疗中。