Major Depressive Disorder With Anger Attacks and Subcortical MRI White Matter Hyperintensities

Iosifescu, Dan V.,Renshaw, Perry F.,Dougherty, Darin D.,Lyoo, In Kyoon,Lee, Ho Kyu,Fraguas, Renerio,Cassano, Paolo,Nierenberg, Andrew A.,Fava, Maurizio Lippincott Williams Wilkins, Inc. 2007 The Journal of nervous and mental disease Vol.195 No.2

Previous reports of increased rates of cardiovascular risk factors in major depressive disorder (MDD) with anger attacks led the authors to hypothesize that MDD with anger attacks may be associated with brain vascular changes (magnetic resonance imaging white matter hyperintensities [WMHs]). Sixty-five subjects meeting DSM-III-R criteria for major depressive disorder were administered brain magnetic resonance imaging scans at 1.5T to detect T2 WMH. The severity of brain WMH was classified with the Fazekas scale. We used standardized scales to assess melancholic MDD, atypical MDD, and MDD with anger attacks. In logistic regression analyses, MDD with anger attacks was associated with higher severity of subcortical WMH and of total WMH, but not with periventricular WMH. Atypical and melancholic MDD subtypes were not significantly associated with brain WMH. In conclusion, subcortical brain vascular lesions may be more prevalent or severe in MDD with anger attacks.

Altitude May Contribute to Regional Variation in Methamphetamine Use in the United States: A Population Database Study

김태석,Douglas G Kondo,Namkug Kim,Perry F Renshaw 대한신경정신의학회 2014 PSYCHIATRY INVESTIGATION Vol.11 No.4

Objective Methamphetamine (MA) use rates in the United States (US) have consistently demonstrated geographical variation and have been higher in the West and Midwest. This uneven pattern of use could be explained by regional differences in MA manufacturing and distribution, but may also result from differences in altitude. The hypobaric hypoxia found at high altitude alters neurotransmitter synthesis in the brain, which may contribute to MA use. The present study investigated the relationship between mean altitude and MA use rate in the 48 contiguous US states and the District of Columbia. Methods State-level estimates of past year MA use were extracted from the National Survey on Drug Use and Health report. The mean altitude of each state was calculated using the Shuttle Radar Topography Mission altitude data set. Results There was a significant positive correlation between mean state altitude and MA use rate (r=0.66, p<0.0001). Multivariate linear regression analysis showed that altitude remained a significant predictor for MA use rate (β=0.36, p=0.02), after adjusting for age, ethnicity, education, socioeconomic level, employment, MA laboratory incidents, subpopulations, and other substance use. Conclusion Altitude appears to a possible contributing factor for regional variation of MA use in the US. Further studies will be required to determine biological changes in neurotransmission resulting from chronic mild hypoxia at high altitude in MA users.

Exposure to Environmental Toxins in Mothers of Children with Autism Spectrum Disorder

김선미,한덕현,민경준,Hang Sik Lyoo,Perry Renshaw,김경호 대한신경정신의학회 2010 PSYCHIATRY INVESTIGATION Vol.7 No.2

Objective Environmental pollutants, especially environmental toxins (ET), may have the potential to disrupt neurodevelopmental pathways during early brain development. This study was designed to test our hypothesis that mothers with autism spectrum disorder (ASD) children would have less knowledge about ET and more chance to be exposed to ET than mothers with healthy children (MHC). MethodsaaOne hundred and six biologic mothers with ASD children (MASD) and three hundred twenty four biologic mothers with healthy children MHC were assessed using two questionnaires asking about ET. ResultsaaThe total score in response to questions related to knowledge about ET in MHC was higher than that in MASD. The possibility of exposure to ET was higher in MASD than MHC. MASD showed higher sub-scale scores in terms of exposures to canned food, plastics, waste incinerators, old electronics, microwavable food, and textiles. ConclusionaaThe current results show that reduced knowledge about ET and greater exposure to ET may be associated with autism spectrum disorder.

Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder : Brain connectivity and Internet gaming

Han, Doug Hyun,Kim, Sun Mi,Bae, Sujin,Renshaw, Perry F.,Anderson, Jeffrey S. Wiley Blackwell (Blackwell Publishing) 2017 Addiction Biology Vol.22 No.3

Comparison of brain connectivity between Internet gambling disorder and Internet gaming disorder: A preliminary study

Bae, Sujin,Han, Doug Hyun,Jung, Jaebum,Nam, Ki Chun,Renshaw, Perry F. Akadémiai Kiadó 2017 JOURNAL OF BEHAVIOURAL ADDICTIONS Vol.6 No.4

<P><B>Background and aims</B></P><P>Given the similarities in clinical symptoms, Internet gaming disorder (IGD) is thought to be diagnostically similar to Internet-based gambling disorder (ibGD). However, cognitive enhancement and educational use of Internet gaming suggest that the two disorders derive from different neurobiological mechanisms. The goal of this study was to compare subjects with ibGD to those with IGD.</P><P><B>Methods</B></P><P>Fifteen patients with IGD, 14 patients with ibGD, and 15 healthy control subjects were included in this study. Resting-state functional magnetic resonance imaging data for all participants were acquired using a 3.0 Tesla MRI scanner (Philips, Eindhoven, The Netherlands). Seed-based analyses, the three brain networks of default mode, cognitive control, and reward circuitry, were performed.</P><P><B>Results</B></P><P>Both IGD and ibGD groups demonstrated decreased functional connectivity (FC) within the default-mode network (DMN) (family-wise error <I>p</I> < .001) compared with healthy control subjects. However, the IGD group demonstrated increased FC within the cognitive network compared with both the ibGD (<I>p</I> < .01) and healthy control groups (<I>p</I> < .01). In contrast, the ibGD group demonstrated increased FC within the reward circuitry compared with both IGD (<I>p</I> < .01) and healthy control subjects (<I>p</I> < .01).</P><P><B>Discussion and conclusions</B></P><P>The IGD and ibGD groups shared the characteristic of decreased FC in the DMN. However, the IGD group demonstrated increased FC within the cognitive network compared with both ibGD and healthy comparison groups.</P>

Aerobic Exercise and Attention Deficit Hyperactivity Disorder: Brain Research

CHOI, JAE WON,HAN, DOUG HYUN,KANG, KYUNG DOO,JUNG, HYE YEON,RENSHAW, PERRY F. American College of Sports Medicine 2015 Medicine and science in sports and exercise Vol.47 No.1

PURPOSE: As adjuvant therapy for enhancing the effects of stimulants and thereby minimizing medication doses, we hypothesized that aerobic exercise might be an effective adjunctive therapy for enhancing the effects of methylphenidate on the clinical symptoms, cognitive function, and brain activity of adolescents with attention deficit hyperactivity disorder (ADHD). METHODS: Thirty-five adolescents with ADHD were randomly assigned to one of two groups in a 1/1 ratio; methylphenidate treatment + 6-wk exercise (sports-ADHD) or methylphenidate treatment + 6-wk education (edu-ADHD). At baseline and after 6 wk of treatment, symptoms of ADHD, cognitive function, and brain activity were evaluated using the Dupaul attention deficit hyperactivity disorder rating scale--Korean version (K-ARS), the Wisconsin Card Sorting Test, and 3-T functional magnetic resonance imaging, respectively. RESULTS: The K-ARS total score and perseverative errors in the sports-ADHD group decreased compared with those in the edu-ADHD group. After the 6-wk treatment period, the mean &bgr; value of the right frontal lobe in the sports-ADHD group increased compared with that in the edu-ADHD group. The mean &bgr; value of the right temporal lobe in the sports-ADHD group decreased. However, the mean &bgr; value of the right temporal lobe in the edu-ADHD group did not change. The change in activity within the right prefrontal cortex in all adolescents with ADHD was negatively correlated with the change in K-ARS scores and perseverative errors. CONCLUSIONS: The current results indicate that aerobic exercise increased the effectiveness of methylphenidate on clinical symptoms, perseverative errors, and brain activity within the right frontal and temporal cortices in response to the Wisconsin card sorting test stimulation.

Lithium-Induced Gray Matter Volume Increase As a Neural Correlate of Treatment Response in Bipolar Disorder: A Longitudinal Brain Imaging Study

Lyoo, In Kyoon,Dager, Stephen R,Kim, Jieun E,Yoon, Sujung J,Friedman, Seth D,Dunner, David L,Renshaw, Perry F American College of Neuropsychopharmacology 2010 Neuropsychopharmacology Vol.35 No.8

Preclinical studies suggest that lithium may exert neurotrophic effects that counteract pathological processes in the brain of patients with bipolar disorder (BD). To describe and compare the course and magnitude of gray matter volume changes in patients with BD who are treated with lithium or valproic acid (VPA) compared to healthy comparison subjects, and to assess clinical relationships to gray matter volume changes induced by lithium in patients with BD, we conducted longitudinal brain imaging and clinical evaluations of treatment response in 22 mood-stabilizing and antipsychotic medications-naive patients with BD who were randomly assigned to either lithium or VPA treatment after baseline assessment. Fourteen healthy comparison subjects did not take any psychotropic medications during follow-up. Longitudinal data analyses of 93 serial magnetic resonance images revealed lithium-induced increases in gray matter volume, which peaked at week 10–12 and were maintained through 16 weeks of treatment. This increase was associated with positive clinical response. In contrast, VPA-treated patients with BD or healthy comparison subjects did not show gray matter volume changes over time. Results suggest that lithium induces sustained increases in cerebral gray matter volume in patients with BD and that these changes are related to the therapeutic efficacy of lithium.

Decreased Glutamate/Glutamine Levels May Mediate Cytidine’s Efficacy in Treating Bipolar Depression: A Longitudinal Proton Magnetic Resonance Spectroscopy Study

Yoon, Sujung J,Lyoo, In Kyoon,Haws, Charlotte,Kim, Tae-Suk,Cohen, Bruce M,Renshaw, Perry F American College of Neuropsychopharmacology 2009 Neuropsychopharmacology Vol.34 No.7

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.Neuropsychopharmacology (2009) 34, 1810–1818; doi:10.1038/npp.2009.2; published online 4 February 2009

Decreased frontal white-matter integrity in abstinent methamphetamine abusers

Chung, Ain,Lyoo, In Kyoon,Kim, Seog Ju,Hwang, Jaeuk,Bae, Soojeong C.,Sung, Young Hoon,Sim, Minyoung E.,Song, In Chan,Kim, Jihyun,Chang, Kee Hyun,Renshaw, Perry F. CAMBRIDGE UNIVERSITY PRESS 2007 INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY Vol.10 No.6

Asymmetrically Altered Integrity of Cingulum Bundle in Posttraumatic Stress Disorder

Kim, Seog Ju,Jeong, Do-Un,Sim, Minyoung E.,Bae, Soojeong C.,Chung, Ain,Kim, Minue J.,Chang, Kee Hyun,Ryu, Jeong,Renshaw, Perry F.,Lyoo, In Kyoon S. Karger 2007 Neuropsychobiology Vol.54 No.2

<P>Previously, our group reported the altered white matter tract integrity of the left anterior cingulate in posttraumatic stress disorder (PTSD) in whole-brain exploration. Current study intended to explore whether the alteration was more prominent in any specific regions of the cingulum bundle. Diffusion tensor images of 21 PTSD subjects and 21 healthy comparison subjects were acquired. Eight isocubic regions of interest (ROIs), i.e. bilateral rostral, subgenual, dorsal, and upper cingulum bundle, were selected. Fractional anisotropy values in each ROI, which indicate the white matter tract integrity, were measured and compared between groups. Relative to comparison subjects, PTSD subjects had significantly smaller fractional anisotropy values in the left side of rostral, subgenual and dorsal cingulum bundle (26.7, 25.0, 22.2% decrease, respectively), but not in the right side ROIs. We report an asymmetrical alteration of the cingulum bundle in PTSD.</P><P>Copyright © 2006 S. Karger AG, Basel</P>