Liwen Tan

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.

Decrease in Temporal Gyrus Gray Matter Volume in First-Episode, Early Onset Schizophrenia: An MRI Study

Background Loss of gray matter has been previously found in early-onset schizophrenic patients. However, there are no consistent findings between studies due to different methods used to measure grey matter volume/density and influences of confounding factors. Methods The volume of gray matter (GM) was measured in 29 first episode early-onset schizophrenia (EOS) and 34 well-matched healthy controls by using voxel-based morphometry (VBM). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The correlations between the GM volume and PANSS scores, age of psychosis onset, duration of psychosis, and chlorpromazine (CPZ) equivalent value were investigated. Results Relative to healthy subjects, the patients with first episode EOS showed significantly lower GM volume in the left middle and superior temporal gyrus. The loss of GM volume negatively correlated with PANSS-positive symptoms (p = 0.002), but not with PANSS-negative symptoms, PANSS-general psychopathology, and PANSS-total score. No significant correlation was found between GM volume and age of psychosis onset, duration of psychosis, and CPZ equivalent value. Conclusion Patients with first episode EOS have evidence of reduced GM in the left middle and superior temporal gyrus. Structural abnormalities in the left middle and superior temporal gyrus may contribute to the pathophysiology of schizophrenia.

A resting-state functional magnetic resonance imaging study on the first-degree relatives of persons with schizophrenia

In this study, resting state fMRI images and BOLD signals were recorded from 13 first-degree relatives of schizophrenic patients and 13 healthy controls. The data were analyzed with the ReHo approach after realignment, registration, and normalization in statistical parametric mapping 2 (SPM2). A two-sample t-test was used to analyze the ReHo differences between first-degree relatives and healthy controls in a voxel by voxel manner. A combined threshold of p < 0.005 and number of voxels >5 was designated as statistically significant. To evaluate cognitive deficits in first-degree relatives, attention/vigilance and verbal/visual memory were measured. Significant impairments in attention were observed in first-degree relatives compared to healthy controls. Significant abnormalities in ReHo were observed in resting brain in first-degree relatives. Decreased ReHo was found to be distributed over the bilateral middle frontal, middle temporal, cingulate gyrus and cerebellar tonsil; the left inferior frontal gyrus, inferior parietal lobule and dorsolateral prefrontal cortex; the right superior frontal gyrus and dorsolateral prefrontal cortex. Increased ReHo was found to be distributed in the right precuneus and superior temporal gyrus. These changes in ReHo suggest abnormality in the resting state brain function of first-degree relatives of schizophrenic patients and may be early signs for the development of schizophrenia.

White matter integrity alterations in first episode, treatment-naive generalized anxiety disorder

BACKGROUND Several neurobiological models of anxiety disorder posit a primary role for dysfunction of the amygdala and anterior cingulate cortex (ACC). This study tests the hypothesis that patients with generalized anxiety disorder (GAD) have abnormal white matter microstructure in the amygdala and ACC, as inferred from diffusion tensor imaging, compared with healthy controls. METHODS Subjects were 16 right-handed, first-episode, treatment-naive GAD patients without comorbid disorders and 26 matched, healthy comparison controls. All subjects underwent diffusion tensor imaging and structural magnetic resonance imaging brain scanning. Fractional anisotropy (FA), a robust intravoxel measure of water self-diffusion, was compared between groups on a voxel-by-voxel basis. Associations between clinical ratings of symptom severity (i.e., the Hamilton Anxiety Scale and the Penn State Worry Questionnaire) and FA were assessed. RESULTS Compared with healthy volunteers, patients demonstrated significantly higher FA in the right amygdala white matter and lower FA in the caudal ACC/mid-cingulate cortex white matter. Higher right amygdala FA correlated significantly with higher Hamilton Anxiety Scale scores and higher Penn State Worry Questionnaire scores. LIMITATIONS The sample size was modest and may contribute to false positive effects. CONCLUSIONS These findings provide the first evidence of an abnormality in white matter microstructure that involves the amygdala and the cingulate cortex in the pathogenesis of GAD, and are consistent with neurobiological models that posit a defect in emotion-related brain regions.

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.

Leukocyte Mitochondrial DNA Copy Number in Blood Is Not Associated with Major Depressive Disorder in Young Adults

Background Major depressive disorder (MDD) is the leading cause of disability worldwide, and has significant genetic predisposition. Mitochondria may have a role in MDD and so mitochondrial DNA (mtDNA) has been suggested as a possible biomarker for this disease. We aimed to test whether the mtDNA copy number of peripheral blood leukocytes is related to MDD in young adults. Methods A case-control study was conducted with 210 MDD patients and 217 healthy controls (HC). The mtDNA copy number was measured by quantitative polymerase chain reaction (qPCR) method. Depression severity was assessed by the Hamilton-17 Depression Rating Scale (HDRS-17). Results We found no significant differences in mtDNA copy number between MDD patients and HC, though the power analysis showed that our sample size has enough power to detect the difference. There were also no significant correlations between mtDNA copy number and the clinical characteristics (such as age, age of onset, episodes, Hamilton Depression Rating Scale (HDRS) score and Global Assessment of Function Scale (GAF) score) in MDD patients. Conclusion Our study suggests that leukocyte mtDNA copy number is unlikely to contribute to MDD, but it doesn’t mean that we can exclude the possibility of involvement of mitochondria in the disease. Further studies are required to elucidate whether mtDNA can be a biomarker of MDD.

Three dysconnectivity patterns in treatment-resistant schizophrenia patients and their unaffected siblings

Among individuals diagnosed with schizophrenia, approximately 20%–33% are recognized as treatment-resistant schizophrenia (TRS) patients. These TRS patients suffer more severely from the disease but struggle to benefit from existing antipsychotic treatments. A few recent studies suggested that schizophrenia may be caused by impaired synaptic plasticity that manifests as functional dysconnectivity in the brain, however, few of those studies focused on the functional connectivity changes in the brains of TRS groups. In this study, we compared the whole brain connectivity variations in TRS patients, their unaffected siblings, and healthy controls. Connectivity network features between and within the 116 automated anatomical labeling (AAL) brain regions were calculated and compared using maps created with three contrasts: patient vs. control, patient vs. sibling, and sibling vs. control. To evaluate the predictive power of the selected features, we performed a multivariate classification approach. We also evaluated the influence of six important clinical measures (e.g. age, education level) on the connectivity features. This study identified abnormal significant connectivity changes of three patterns in TRS patients and their unaffected siblings: 1) 69 patient-specific connectivity (PCN); 2) 102 shared connectivity (SCN); and 3) 457 unshared connectivity (UCN). While the first two patterns were widely reported by previous non-TRS specific studies, we were among the first to report widespread significant connectivity differences between TRS patient groups and their healthy sibling groups. Observations of this study may provide new insights for the understanding of the neurophysiological mechanisms of TRS.

Brain structure in post-traumatic stress disorder: A voxel-based morphometry analysis.

This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.

Common promoter variants of the NDUFV2 gene do not confer susceptibility to schizophrenia in Han Chinese

BackgroundThe NADH-ubiquinone oxidoreductase flavoprotein gene (NDUFV2), which encodes a 24 kD mitochondrial complex I subunit, has been reported to be positively associated with schizophrenia and bipolar disorder in different populations.MethodsWe genotyped the promoter variants of this gene (rs6506640 and rs1156044) by direct sequencing in 529 unrelated Han Chinese schizophrenia patients and 505 matched controls. Fishers Exact test was performed to assess whether these two reported single nucleotide polymorphisms (SNPs) confer susceptibility to schizophrenia in Chinese.ResultsAllele, genotype and haplotype comparison between the case and control groups showed no statistical significance, suggesting no association between the NDUFV2 gene promoter variants and schizophrenia in Han Chinese.ConclusionThe role of NDUFV2 played in schizophrenia needs to be further studied. Different racial background and/or population substructure might account for the inconsistent results between studies.