Zexuan Li

Prefrontal white matter abnormalities in young adult with major depressive disorder: A diffusion tensor imaging study

Prefrontal impairments have been hypothesized to be most strongly associated with the cognitive and emotional dysfunction in depression. Recently, white matter microstructural abnormalities in prefrontal lobe have been reported in elderly patients with major depressive disorder (MDD) using diffusion tensor imaging (DTI). However, it is still unclear whether the same changes exist in younger patients. In the present study, we first utilized DTI to detect prefrontal white matter in young adults with MDD. Nineteen first-episode, untreated young adults with MDD and twenty age- and gender-matched healthy controls were recruited. DTI and localizing anatomic data were acquired. Then, the regions of interest (ROIs) were located in prefrontal white matter at 4 mm inferior, and 0, 4, 8, 12, 16 and 20 mm superior to the anterior commissure-posterior commissure (AC-PC) plane, respectively. Compared with healthy controls, patients with MDD showed significantly lower fractional anisotropy (FA) values in prefrontal white matter at bilateral 20 mm, right 16 mm and right 12 mm above the AC-PC. Furthermore, there was no significant correlation between the FA value of any ROI and illness course as well as severity of depression. Together with previous findings, the present results suggest that microstructural abnormalities in prefrontal white matter may occur early in the course of MDD and may be related to the neuropathology of depression throughout adulthood from young to elderly.

Overlapping and Segregated Resting-State Functional Connectivity in Patients with Major Depressive Disorder With and Without Childhood Neglect

Many studies have suggested that childhood maltreatment increase risk of adulthood major depressive disorder (MDD) and predict its unfavorable treatment outcome, yet the neural underpinnings associated with childhood maltreatment in MDD remain poorly understood. Here, we seek to investigate the whole‐brain functional connectivity patterns in MDD patients with childhood maltreatment. Resting‐state functional magnetic resonance imaging was used to explore intrinsic or spontaneous functional connectivity networks of 18 MDD patients with childhood neglect, 20 MDD patients without childhood neglect, and 20 healthy controls. Whole‐brain functional networks were constructed by measuring the temporal correlations of every pairs of brain voxels and were further analyzed by using graph‐theory approaches. Relative to the healthy control group, the two MDD patient groups showed overlapping reduced functional connectivity strength in bilateral ventral medial prefrontal cortex/ventral anterior cingulate cortex. However, compared with MDD patients without a history of childhood maltreatment, those patients with such a history displayed widespread reduction of functional connectivity strength primarily in brain regions within the prefrontal‐limbic‐thalamic‐cerebellar circuitry, and these reductions significantly correlated with measures of childhood neglect. Together, we showed that the MDD groups with and without childhood neglect exhibited overlapping and segregated functional connectivity patterns in the whole‐brain networks, providing empirical evidence for the contribution of early life stress to the pathophysiology of MDD. Hum Brain Mapp 35:1154–1166, 2014.

Altered resting-state functional connectivity of thalamus in earthquake-induced posttraumatic stress disorder: A functional magnetic resonance imaging study

BACKGROUND Thalamic dysfunction has been found in patients with posttraumatic stress disorder (PTSD), suggesting that the thalamus may be implicated in the etiology of PTSD. However, no studies have explored the functional connectivity between the thalamus and other brain regions during resting-state. The objective of the present study was to investigate the resting-state functional connectivity of the thalamus in recent onset medication-naive PTSD sufferers who went through an earthquake in the Sichuan province of China. METHODS Fifty-four participants with PTSD and seventy-two age and gender matched traumatized controls without PTSD recruited from the 2008 Sichuan earthquake were scanned by 3T functional magnetic resonance imaging (fMRI) in resting state. Region of interest (ROI)-based functional connectivity analysis was employed to identify the potential differences in the functional connectivity of the thalamus between the two groups. RESULTS In the PTSD group, the thalamus-ROIs showed decreased positive functional connectivity to particular brain regions including right medial frontal gyrus and left anterior cingulate cortex. Importantly, we also found increased positive functional connectivity of thalamus-ROIs with bilateral inferior frontal and left middle frontal gyri, left inferior parietal lobule as well as right precuneus in the PTSD participants when compared to traumatized controls without PTSD. CONCLUSION The results provide evidence that abnormal resting state functional connections linking the thalamus to cortical regions may be involved in the underlying pathology in PTSD.

Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

Different white matter abnormalities between the first-episode, treatment-naive patients with posttraumatic stress disorder and generalized anxiety disorder without comorbid conditions

BACKGROUND This study compared brain white matter integrity in two groups of patients with DSM-IV anxiety disorders. METHOD Seventeen patients with posttraumatic stress disorder (PTSD), 20 with generalized anxiety disorder (GAD), and 28 healthy controls were assessed on diffusion tensor imaging. RESULTS As compared to healthy controls, increased fractional anisotropy (FA) in left superior frontal gyrus in PTSD patients, and increased FA in right postcentral gyrus in GAD subjects were exhibited. Furthermore, patients with PTSD showed reduced FA in right anterior cingulate gyrus relative to GAD subjects. However, there was no significant correlation between the FA value of any altered region and the severity of PTSD or GAD. LIMITATIONS The sample studied can be considered small. Gender and educational level were not well-matched among the groups. CONCLUSIONS We tentatively speculate that abnormal white matter integrity of right anterior cingulate gyrus is an important neuroimaging marker of PTSD that distinguishes it from other anxiety disorders such as GAD.

Enriched environment treatment counteracts enhanced addictive and depressive-like behavior induced by prenatal chronic stress

Prenatal stress can cause many long-term behavior changes in offspring, but whether prenatal stress can alter addictive behavior in offspring and postnatal enriched environment treatment (EE) can restore these changes are unknown. We reported here that prenatal chronic stress (10 unpredictable, 1 s, 0.8 mA foot-shocks per day during gestational days 13-19) enhanced morphine-induced (10 mg/kg, s.c., per day, 6 consecutive days) place preference. Moreover, prenatal chronic stress caused higher depressive-like behavior in forced swimming test in adult offspring. However, enriched environment housing treatment on postnatal days 22-52 counteracted both the abnormal behaviors alterations. This work observed a phenomenon that might contribute to the understanding of clinically important interactions among addiction, prenatal stress and enriched environment treatment. Postnatal enriched environment treatment might be an important therapeutic intervention in preventing the prenatal stress-induced addictive disorders.

Abnormalities of cortical-limbic-cerebellar white matter networks may contribute to treatment-resistant depression: a diffusion tensor imaging study.

BackgroundWhite matter abnormalities can cause network dysfunction that underlies major depressive disorder (MDD). Diffusion tensor imaging (DTI) is used to examine the neural connectivity and integrity of the white matter. Previous studies have implicated frontolimbic neural networks in the pathophysiology of MDD. Approximately 30% of MDD patients demonstrate treatment-resistant depression (TRD). However, the neurobiology of TRD remains unclear.MethodsWe used a voxel-based analysis method to analyze DTI data in young patients with TRD (n = 30; 19 males, 11 females) compared with right-handed, age- and sex-matched healthy volunteers (n = 25; 14 males, 11 females).ResultsWe found a significant decrease in fractional anisotropy (FA) (corrected, cluster size >50) in the left middle frontal gyrus (peak coordinates [−18 46–14]), left limbic lobe uncus (peak coordinates [−18 2–22]), and right cerebellum posterior lobe (peak coordinates [26–34 -40]). There was no increase in FA in any brain region in patients. We also found a significant negative correlation between mean regional FA values in the three areas and Beck Depression Inventory symptom scores.ConclusionsWe found significant differences in white matter FA in the frontal lobe, limbic lobe and cerebellum between TRD patients and controls. These data suggest that abnormalities of cortical-limbic-cerebellar white matter networks may contribute to TRD in young patients.

High-frequency rTMS treatment increases white matter FA in the left middle frontal gyrus in young patients with treatment-resistant depression

BACKGROUND Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for treatment-resistant depression (TRD), but its therapeutic mechanisms are unclear. White matter abnormalities are thought to cause network dysfunction underlying TRD. Diffusion tensor imaging (DTI) is an ideal tool for examining neural connections and the integrity of white matter. Few studies have used DTI to investigate the impact of rTMS on alterations of whiter matter in TRD. METHOD 30 young treatment-resistant unipolar depression patients (19 males and 11 females) were enrolled in a double-blind, randomized high-frequency (15 Hz) rTMS treatment study. Seventeen patients were treated with real stimulation, and 13 were treated with sham stimulation. White-matter fractional anisotropy (FA) was evaluated using voxel-based analysis (VBA) of FA maps derived from DTI before and after treatment. Twenty-five age- and gender-matched subjects were examined as a control group. RESULTS In an exploratory VBA method, clusters of fifty voxels or greater that survived a family-wise error (FWE)-corrected threshold of p<0.05 were considered significant. The results revealed significantly reduced FA in the left middle frontal gyrus, with peak coordinates [-18 46 -14] in TRD patients. This reduced FA was significantly improved after active rTMS treatment, but not sham stimulation. FA increases were correlated with decreased depressive symptoms. LIMITATIONS This study requires replication and further clarification in a larger patient population, and optimization of stimulation locations and methods. CONCLUSIONS These results suggest that the efficacy of rTMS on TRD is related to increased white-matter FA in the left middle frontal gyrus.

High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

BACKGROUND Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS). METHOD Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study active ((n=19) vs. sham(n=15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls. RESULTS In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS (p<0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed. CONCLUSIONS Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.

Lower levels of whole blood serotonin in obsessive-compulsive disorder and in schizophrenia with obsessive-compulsive symptoms

It has been reported that some schizophrenic patients suffer from obsessive-compulsive symptoms (OCS), and clozapine treatment is quite often associated with an occurrence/increase of OCS in schizophrenic patients. The aim of the study was to explore whether differences would exist in the clinical symptomatology and the whole blood serotonin (5-HT) concentrations in patients with obsessive-compulsive disorder (OCD), schizophrenic patients with and without OCS (S+OCS, S-OCS), and clozapine-treated schizophrenic patients with and without clozapine-induced OCS (CLZ+OCS, CLZ-OCS). We found that S+OCS patients (n=15) showed significantly lower scores on the Hamilton Anxiety Scale (HAMA), but similar levels of compulsions and obsessions using Yale-Brown Obsessive-Compulsive Scale (YBOCS) as compared to the patients (n=35) with OCD. S+OCS patients scored significantly lower on the Positive and Negative Syndrome Scale (PANSS) but higher on the Hamilton Depression Scale (HAMD) compared with S-OCS patients (n=19). However, CLZ+OCS patients (n=15) suffered from dominant compulsions but fewer obsessions compared with the OCD and S+OCS patients. OCD, S+OCS and CLZ+OCS groups had significantly lower levels of whole blood 5-HT than did the healthy volunteers (n=15), S-OCS and CLZ-OCS groups. It suggests that alterations in serotonin metabolism may be a common biological characteristic of OCS in OCD as well as in schizophrenia.