The BDNF Val66Met Polymorphism Affects the Vulnerability of the Brain Structural Network

Val66Met, a naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF) gene resulting in a valine (Val) to methionine (Met) substitution at codon 66, plays an important role in neuroplasticity. While the effect of the BDNF Val66Met polymorphism on local brain structures has previously been examined, its impact on the configuration of the graph-based white matter structural networks is yet to be investigated. In the current study, we assessed the effect of the BDNF polymorphism on the network properties and robustness of the graph-based white matter structural networks. Graph theory was employed to investigate the structural connectivity derived from white matter tractography in two groups, Val homozygotes (n = 18) and Met-allele carriers (n = 55). Although there were no differences in the global network measures including global efficiency, local efficiency, and modularity between the two genotype groups, we found the effect of the BDNF Val66Met polymorphism on the robustness properties of the white matter structural networks. Specifically, the white matter structural networks of the Met-allele carrier group showed higher vulnerability to targeted removal of central nodes as compared with those of the Val homozygote group. These findings suggest that the central role of the BDNF Val66Met polymorphism in regards to neuroplasticity may be associated with inherent differences in the robustness of the white matter structural network according to the genetic variants. Furthermore, greater susceptibility to brain disorders in Met-allele carriers may be understood as being due to their limited stability in white matter structural connectivity

Alterations in Brain Morphometric Networks and Their Relationship with Memory Dysfunction in Patients with Type 2 Diabetes Mellitus

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM

Network-Level Structural Abnormalities of Cerebral Cortex in Type 1 Diabetes Mellitus

Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion. © 2013 Lyoo et al

The effect of internet video game play on clinical and extrapyramidal symptoms in patients with schizophrenia

This research was supported by a grant(M103KV010021-07K2201-02110) from Brain Research Center of the 21st Century Froniter Research Program(I.K.L.)

The neural substrates of affective processing toward positive and negative affective pictures in patients with major depressive disorder

Previous studies examining neural responses to emotional stimuli in individuals with major depressive disorder (MDD) have indicated increased responses within the left amygdala to sad faces, and increased activity within the visual cortex and striatum to expressions of happiness. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, positive and negative pictures of the International Affective Picture System in 15 healthy individuals and 15 patients with MDD. Depressed individuals demonstrated lower activity in the right hippocampus and the right insula to negative affective pictures, whereas they showed lower activity in the right anterior cingulate cortex and the left insula to positive pictures. However, within the MDD group, the severity of depression correlated with the activity of the left amygdala, bilateral inferior orbitofrontal areas, and the left insula to negative pictures, whereas there were no clear indications of association between specific cerebral regions and positive pictures. Our findings indicate that preferential decreases in the left amygdala in response to negative pictures might be involved in the processing of emotional stimuli in depressed individuals. Also, these findings suggest that the bilateral inferior orbitofrontal cortices and left amygdala may be preferentially recruited in MDD patients, but not in healthy individuals

Decreased glutamate/glutamine levels may mediate cytidine's efficacy in treating bipolar depression: a longitudinal proton magnetic resonance spectroscopy study

Targeting the glutamatergic system has been suggested as a promising new option for developing treatment strategies for bipolar depression. Cytidine, a pyrimidine, may exert therapeutic effects through a pathway that leads to altered neuronal-glial glutamate cycling. Pyrimidines are also known to exert beneficial effects on cerebral phospholipid metabolism, catecholamine synthesis, and mitochondrial function, which have each been linked to the pathophysiology of bipolar depression. This study was aimed at determining cytidine's efficacy in bipolar depression and at assessing the longitudinal effects of cytidine on cerebral glutamate/glutamine levels. Thirty-five patients with bipolar depression were randomly assigned to receive the mood-stabilizing drug valproate plus either cytidine or placebo for 12 weeks. Midfrontal cerebral glutamate/glutamine levels were measured using proton magnetic resonance spectroscopy before and after 2, 4, and 12 weeks of oral cytidine administration. Cytidine supplementation was associated with an earlier improvement in depressive symptoms (weeks 1-4; p=0.02, 0.001, 0.002, and 0.004, respectively) and also produced a greater reduction in cerebral glutamate/glutamine levels in patients with bipolar depression (weeks 2, 4, and 12; p=0.004, 0.004, and 0.02, respectively). Cytidine-related glutamate/glutamine decrements correlated with a reduction in depressive symptoms (p=0.001). In contrast, these relationships were not observed in the placebo add-on group. The study results suggest that cytidine supplementation of valproate is associated with an earlier treatment response in bipolar depression. Furthermore, cytidine's efficacy in bipolar depression may be mediated by decreased levels of cerebral glutamate and/or glutamine, consistent with alterations in excitatory neurotransmission

Increased efficiency of brain connectivity networks in veterans with suicide attempts

Background: Suicide is a public health concern for United States veterans and civilians. Prior research has shown neurobiological factors in suicide. However, studies of neuroimaging correlates of suicide risk have been limited. This study applied complex weighted network analyses to characterize the neural connectivity in white matter in veterans with suicide behavior. Methods: Twenty-eight veterans without suicide behavior (NS), 29 with a history of suicidal ideation only (SI), and 23 with prior suicide attempt (SA) completed diffusion tensor brain imaging, the Columbia Suicide Severity Rating Scale and Barratt Impulsiveness Scale (BIS). Structural connectivity networks among 82 parcellated brain regions were produced using whole-brain tractography. Global and nodal metrics of network topology have been calculated. Results: SA had shorter characteristic path length and greater global efficiency and mean weighted degree of global network metrics (p < 0.024). SA had more hub nodes than NS and SI. The left posterior cingulate cortex (PCC) showed significantly greater weighted degree in SA relative to others (p < 0.0003). Nonplanning subscale of BIS correlated with the weighted degrees of the left PCC within SA. In rich club connectivity, SA had higher local connections than others (p = 0.001). Conclusion: Veterans with prior suicide attempt had altered connectivity networks characteristics in the white matter. These findings may be distinctive neurobiological markers for individuals with suicide attempt. Strong connectivity in the left PCC may be implicated in impulsivity in veterans with suicide attempt. Keywords: Suicide, Veteran, Diffusion tensor imaging, White matter, Connectome, Cingulat

Psychosis of Alzheimer's disease: Gender differences in regional perfusion

We sought to determine whether the presence of psychotic symptoms in patients with Alzheimer's disease is associated with abnormal regional cerebral function. Perfusion single photon emission computed tomography images from 51 AD patients with psychotic symptoms were compared to images of 52 AD patients without such symptoms. Group comparisons were made with a voxel-based method, Statistical Parametric Mapping. We found that perfusion was lower in female patients with psychotic symptoms in right infero-lateral prefrontal cortex and in inferior temporal regions compared to female patients without such symptoms. In contrast, perfusion was higher in male patients with psychotic symptoms in the right striatum compared to male patients without such symptoms. Comparison groups did not differ in age or in dementia severity, as estimated by the Mini-Mental State Examination (MMSE). These results support the role of right hemisphere prefrontal and lateral temporal cortex in the psychosis of AD in women but not in men, and raise the possibility that these dysfunctional processes have a gender-specific regional pathophysiology in AD

A magnetic resonance imaging study of mood stabilizer- and neuroleptic-naïve first-episode mania

OBJECTIVES: Patients with bipolar disorder have changes in brain structures but it is unclear if these are present at disease onset and thus predispose subjects to develop the disorder, or whether they develop during the course of the disorder, either due to the effects of multiple episodes or as a consequence of treatment with psychotropic agents. Studies in first-episode (FE) manic patients have the potential to provide answers to these questions. METHODS: Voxel-based morphometry (VBM) was used to assess magnetic resonance imaging scans of 15 FE manic patients and 15 matched healthy controls. RESULTS: Using a priori defined statistical criteria, no significant differences in brain structures were noted between the two groups. However, there was approximately a 6% reduction in left anterior cingulate, left precuneus and right posterior cingulate volume in FE patients and these reductions were significant (p<or=0.002) at uncorrected levels. CONCLUSIONS: First-episode manic patients have reductions in left anterior, right posterior cingulate as well as left precuneus volumes, but these reductions are smaller and likely worsen with further mood episodes in bipolar patients

Patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder

AIMS: The purpose of the present study was to assess patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder (ADHD) and to investigate the relationship between patterns of temperament and character and the severity of ADHD symptoms. METHODS: Fifty-one children who met DSM-IV criteria for ADHD and 51 age- and sex-matched healthy comparison subjects completed the Junior Temperament and Character Inventory (JTCI) and the DuPaul's ADHD Rating Scale (ARS-IV). RESULTS: Children with ADHD had significantly higher scores of Novelty Seeking and lower scores of Self-directedness in both parents' rating and children's self-rating. In addition, low Self-directedness scores predicted higher total scores of ARS-IV. CONCLUSIONS: In a clinical sample of Korean children with ADHD, a distinct pattern of temperament and character was found. The current findings suggest that low Self-directedness may be related to the severity of ADHD symptoms