Open-label study comparing the efficacy and tolerability of aripiprazole and haloperidol in the treatment of pediatric tic disorders.

Due to its unique pharmacodynamic properties of dopamine partial agonist activity, and its association with few and mild side effects, aripiprazole is a candidate atypical antipsychotic for patients with tic disorders. This open-label study compared the efficacy and tolerability of aripiprazole with haloperidol, a typical antipsychotic widely used to treat patients with tic disorders. Forty-eight children and adolescents with tic disorders were recruited from the outpatient clinic at South Korea and treated with aripiprazole (initial dose, 5.0 mg/d; maximum dose 20 mg/d) or haloperidol (initial dose, 0.75 mg/d; maximum dose, 4.5 mg/d) for 8 weeks. Treatment efficacy was measured using the yale global tic severity scale (YGTSS), and tolerability was measured using the extrapyramidal symptom rating scale (ESRS) and an adverse effects checklist. Total tic scores as measured by the YGTSS decreased over time in both groups (p < 0.001) without any significant differences between groups. ESRS scores were significantly higher in the haloperidol group during the 4 weeks after commencement of medication (p < 0.05). These results indicate that aripiprazole may be a promising drug in the treatment of children and adolescents with tic disorders. Further controlled studies are needed to determine the efficacy and tolerability of aripiprazole in these patients.

Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats.

BACKGROUND: Cholesterol may have a role in the pathophysiology of depression. Lowering cholesterol levels with statins reduces risks for cardiovascular events, and there is clinical evidence that statins exert neuroprotective properties not fully explained by their effects on serum cholesterol levels. Altered cholesterol levels can affect serotonergic neurotransmission, which might be involved in the clinical efficacy of standard antidepressants. METHODS: We examined interactions between a statin (lovastatin) and a selective serotonin reuptake inhibitor (fluoxetine) using the forced swim test (FST) in rats, a behavioral assay that identifies treatments with antidepressant effects in humans. Specifically, we determined if the addition of lovastatin to the diet would increase the efficacy of a subeffective dose of fluoxetine. RESULTS: Rats maintained on a lovastatin-enriched diet for 30 days were more sensitive to the antidepressant-like effects of a low (subthreshold) dose of fluoxetine. The behavior of rats treated with this combination resembled that normally seen with higher doses of fluoxetine. No effects were observed in rats maintained on a lovastatin-enriched diet for 3 days. CONCLUSIONS: Lovastatin can augment the antidepressant-like effects of a low dose of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.

Patterns of temperament and character in patients with posttraumatic stress disorder and their association with symptom severity.

OBJECTIVES: The aim of this study was to identify the patterns of temperament and character of patients with posttraumatic stress disorder (PTSD) and to explore the relationship between the patterns of temperament and character and PTSD symptoms severity. METHODS: Temperament and character features of 130 patients with PTSD (n = 65) and age and sex-matched healthy controls (n = 65) were evaluated using the Temperament and Character Inventory. Severity of PTSD symptoms and general anxiety symptoms was measured with the Impact of Events Scale-Revised (IES-R) and the Hamilton Anxiety Rating Scale (HARS). RESULTS: Patients with PTSD showed significantly higher scores on subscales of harm avoidance and self-transcendence and lower scores on self-directedness and cooperativeness compared to controls. Harm avoidance and self-transcendence scores were significantly associated with PTSD symptom severity as measured by IES-R but not with general anxiety symptom severity as measured by HARS. CONCLUSIONS: Patterns of temperament and character of patients with PTSD were significantly different from those of healthy controls. In addition, these patterns are specifically associated with the PTSD symptom severity.

Diminished rostral anterior cingulate activity in response to threat-related events in posttraumatic stress disorder.

BACKGROUND: Previous brain imaging studies have reported hyperactivation of the amygdala and hypoactivation of the anterior cingulate in posttraumatic stress disorder (PTSD) patients, which is believed to be an underlying neural mechanism of the PTSD symptoms. The current study specifically focuses on the abnormal activity of the rostral anterior cingulate, using a paradigm which elicits an unexpected processing conflict caused by salient emotional stimuli. METHODS: Twelve survivors (seven men and five women) of the Taegu subway fire in 2003, who later developed PTSD, agreed to participate in this study. Twelve healthy volunteers (seven men and five women) were recruited for comparison. Functional brain images of all participants were acquired using functional magnetic resonance imaging while performing a same-different judgment task, which was modified to elicit an unexpected emotional processing conflict. RESULTS: PTSD patients, compared to comparison subjects, showed a decreased rostral anterior cingulate functioning when exposed to situations which induce an unexpected emotional processing conflict. Moreover, PTSD symptom severity was negatively correlated to the level of decrease in the rostral anterior cingulate activity. CONCLUSIONS: The results of this study provide evidence that the rostral anterior cingulate functioning is impaired in PTSD patients during response-conflict situations that involve emotional stimuli.

A preliminary study: novelty seeking, frontal executive function, and dopamine receptor (D2) TaqI A gene polymorphism in patients with methamphetamine dependence.

INTRODUCTION: Dopamine receptor polymorphisms have been associated with specific patterns of novelty seeking (NS) temperamental nature and frontal executive function. In addition, carriers of dopamine receptor type 2 (DRD2)-TaqI A1 have been hypothesized to be potentially vulnerable to addictive behaviors. In the present study, the association between dopamine D2 polymorphisms, NS, and frontal executive function was studied. METHODS: Thirty-seven methamphetamine (MA)-dependent subjects and 40 healthy comparison subjects participated in the current study. The severity of addiction, NS temperament, and frontal executive functions were measured using the Addiction Severity Index, the NS subscale in the Temperament and Character Inventory, and the Wisconsin Card Sorting Test, respectively. All subjects were genotyped with regard to DRD2-TaqI polymorphisms. RESULTS: The prevalence of DRD2-TaqI A1 allele polymorphisms was greater in the MA-abuser group than in the comparison group. Patients with MA dependence also had higher NS characteristics and high scores in total trials, errors, and perseverative errors of the Wisconsin Card Sorting Test than comparison subjects. Within patients with MA dependence, the subgroup of DRD2-TaqI A1 carrier had greater NS scores relative to those without, whereas there was only a trend level of lower frontal executive function in the first subgroup. CONCLUSION: In the present study, the MA-dependent patients with DRD2-TaqI A1 allele had significantly greater NS scores and lower frontal executive function with a trend level than those without. These preliminary results suggest that MA-dependent patients may have the possibility of genetic and biogenic vulnerability to MA.

Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients.

Eleven patients with bipolar depression were given doses of up to 18 g per day of triacetyluridine (TAU) over 6 weeks to test the effect of uridine on symptoms of depression via Montgomery-Asberg Depression Rating Scale (MADRS; Asberg, Montgomery, Perris, Schalling, & Sedvall, 1978) scores and on cellular bioenergetics using phosphorus magnetic resonance spectroscopic imaging (31P-MRSI). All patients and comparison participants (n = 9) completed baseline 31P-MRSI scans, and 9 patients completed posttherapy scans. The percentage changes for MADRS scores (Week 2, -23.8; Week 3, -34.9; Week 4, -42.5) and the time effects of TAU on MADRS scores (Week 2, z = -2.07, p = .039; Week 3, z = -4.28, p < .001; Week 4, z = -4.54, p < .001) may reflect TAU effects on early symptom improvement. TAU responders (patients who had a 50% or greater reduction in MADRS scores from baseline at any time) demonstrated a significant difference from nonresponders in pH changes from baseline (effect size = 150). These results suggest that TAU treatment may decrease symptoms of depression and improve mitochondrial functioning.

Clinical response of quetiapine in rapid cycling manic bipolar patients and lactate level changes in proton magnetic resonance spectroscopy.

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.

Decreased GABA levels in anterior cingulate and basal ganglia in medicated subjects with panic disorder: a proton magnetic resonance spectroscopy (1H-MRS) study.

The purpose of this study was to investigate the brain gamma-aminobutyric acid (GABA) concentration and its relationship with clinical variables in patients with panic disorder (PD). Single voxel proton magnetic resonance spectroscopy ((1)H-MRS) scan was performed on 22 medicated subjects with PD and 25 age and sex-matched healthy comparison subjects. GABA and other metabolite levels were measured in the anterior cingulate cortex (ACC) and basal ganglia. GABA levels were significantly lower in the ACC and basal ganglia of PD patients relative to comparison subjects. Lactate and choline concentrations in the ACC in PD patients were also higher than in the comparison subjects. Our data suggested in part that alterations of the GABA function and the energy metabolism in ACC and basal ganglia may play an important role in the pathophysiology of panic disorder.

The neurobiological role of the dorsolateral prefrontal cortex in recovery from trauma. Longitudinal brain imaging study among survivors of the South Korean subway disaster.

CONTEXT: A multiwave longitudinal neuroimaging study in a cohort of direct survivors of a South Korean subway disaster, most of whom recovered from posttraumatic stress disorder 5 years after trauma, provided a unique opportunity to investigate the brain correlates of recovery from a severe psychological trauma. OBJECTIVES: To investigate region-specific brain mobilization during successful recovery from posttraumatic stress disorder by assessing cortical thickness multiple times from early after trauma to recovery, and to examine whether a brain-derived neurotrophic factor gene polymorphism was associated with this brain mobilization. DESIGN: Five-year follow-up case-control study conducted from 2003-2007. SETTING: Seoul National University and Hospital. PARTICIPANTS: Thirty psychologically traumatized disaster survivors and 36 age- and sex-matched control group members recruited from the disaster registry and local community, respectively, who contributed 156 high-resolution brain magnetic resonance images during 3 waves of assessments. MAIN OUTCOME MEASURES: Cerebral cortical thickness measured in high-resolution anatomic magnetic resonance images using a validated cortical thickness analysis tool and its prospective changes from early after trauma to recovery in trauma-exposed individuals and controls. RESULTS: Trauma-exposed individuals had greater dorsolateral prefrontal cortical (DLPFC) thickness 1.42 years after trauma (right DLPFC, 5.4%; left superior frontal cortex, 5.8%; and left inferior frontal cortex, 5.3% [all clusters, P ≤ .01]) relative to controls. Thicknesses gradually normalized over time during recovery. We found a positive linear trend, with trauma-exposed individuals with a valine/valine genotype having the greatest DLPFC cortical thickness, followed by those with a methionine genotype and controls (P < .001 for trend). Greater DLPFC thickness was associated with greater posttraumatic stress disorder symptom reductions and better recovery. CONCLUSION: The DLPFC region might play an important role in psychological recovery from a severely traumatic event in humans.

Amygdalar shape analysis method using surface contour aligning, spherical mapping, and probabilistic subregional segmentation.

The objective of this study was to develop a reliable method for the shape analysis of the amygdala, a structure that is important in gaining a better understanding of the limbic system in the human brain. The goal of this study was threefold; to develop (1) a robust method for aligning the contour of the amygdala; (2) a reproducible method for extracting surface parameters of the amygdala using a spherical mapping technique; and (3) a standardized approach for statistical assessment and visualization of shape alterations by applying the probabilistic maps of amygdalar subregions. This technique was validated by conducting an artificial phantom study and by assessing sex-related amygdalar shape differences using T1-weighted images from healthy volunteers. In the phantom study, the region with atrophy was detected successfully through the shape analysis process. In the human study, the average radii of the centromedial (CM) subregion in the left amygdala and laterobasal (LB), superficial (SF) and CM subregions in the right amygdala were different between sexes (t-tests, p=0.02, 0.04, 0.04, and 0.002, respectively). In addition, focal regions with larger radii in amygdalae of men than those of women were found predominantly on the surfaces of bilateral SF and bilateral CM subregions, after the volumes of the amygdala had been scaled to the unit volume (1000mm(3)) (Mann-Whitney U-test, false discovery rate corrected p<0.05, clustered vertex points>25). Regions with smaller radii in amygdalae of men were found predominantly on the anterior surfaces of the right LB and SF subregions (Mann-Whitney U-test, false discovery rate corrected p<0.05, clustered vertex points>25). This is generally in agreement with previous findings from animal studies. The current method may be used for measuring subtle local shape changes of the amygdala in various psychiatric or neurologic disorders.

In vivo evidence for long-term CNS toxicity, associated with chronic binge use of methamphetamine.

OBJECTIVE: The aim of this study was to examine disturbances in regional cerebral blood flow (rCBF) associated with methamphetamine abuse. METHODS: Using Single Photon Emission Computed Tomography (SPECT), rCBF was measured in 20 men who had previously injected methamphetamine intravenously for over 30 months and who were now abstinent for a minimum of 9 months and for an average of 2 years. Values were compared with those in 12 healthy men who had never injected methamphetamine. RESULTS: While rCBF was significantly and disproportionately reduced in subcortical and dorsal cortical brain regions, including the striatum, thalamus, cingulum, mesiodorsal prefrontal cortex, and pons (all t's>8.3 after global normalization, corrected p's<0.001), whole brain CBF was also significantly reduced in the former methamphetamine users. Binge use of methamphetamine is associated with long-term changes in both global and regional blood flows, likely representing severe and enduring neural toxicity of monoaminergic neurotransmitter systems in the brain, producing a pattern of hypoperfusion that resembles patterns reported previously for persons with atypical Parkinson's disease. CONCLUSIONS: These findings suggest that methamphetamine abusers may be possibly at increased risk for neurodegenerative diseases later in life.

Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study.

Cytidine-5'-diphosphate choline (CDP-choline), as an important intermediate for major membrane phospholipids, may exert neuroprotective effects in various neurodegenerative disorders. This longitudinal proton magnetic resonance spectroscopy ((1)H-MRS) study aimed to examine whether a 4-week CDP-choline treatment could alter neurometabolite levels in patients with methamphetamine (MA) dependence and to investigate whether changes in neurometabolite levels would be associated with MA use. We hypothesized that the prefrontal levels of N-acetyl-aspartate (NAA), a neuronal marker, and choline-containing compound (Cho), which are related to membrane turnover, would increase with CDP-choline treatment in MA-dependent patients. We further hypothesized that this increase would correlate with the total number of negative urine results. Thirty-one treatment seekers with MA dependence were randomly assigned to receive CDP-choline (n=16) or placebo (n=15) for 4 weeks. Prefrontal NAA and Cho levels were examined using (1)H-MRS before medication, and at 2 and 4 weeks after treatment. Generalized estimating equation regression analyses showed that the rate of change in prefrontal NAA (p=0.005) and Cho (p=0.03) levels were greater with CDP-choline treatment than with placebo. In the CDP-choline-treated patients, changes in prefrontal NAA levels were positively associated with the total number of negative urine results (p=0.03). Changes in the prefrontal Cho levels, however, were not associated with the total number of negative urine results. These preliminary findings suggest that CDP-choline treatment may exert potential neuroprotective effects directly or indirectly because of reductions in drug use by the MA-dependent patients. Further studies with a larger sample size of MA-dependent patients are warranted to confirm a long-term efficacy of CDP-choline in neuroprotection and abstinence.

Lithium-induced gray matter volume increase as a neural correlate of treatment response in bipolar disorder: a longitudinal brain imaging study.

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.

Laterobasal amygdalar enlargement in 6- to 7-year-old children with autism spectrum disorder.

CONTEXT: There is substantial imaging evidence for volumetric abnormalities of the amygdala in younger children with autism spectrum disorder (ASD). The amygdala can be divided into functionally distinct laterobasal, superficial, and centromedial subregions. To date, we are not aware of any in vivo reports specifically assessing subregional amygdalar abnormalities in individuals with ASD. OBJECTIVES: To evaluate alterations in subregional amygdalar morphology in children with ASD compared with typically developing (TD) children and to examine the relationships with ASD symptom severity. DESIGN: A cross-sectional study encompassing a narrow age range of children with ASD and age-matched TD children that evaluated magnetic resonance imaging-defined subregional morphology of the amygdala using a novel subregional analytic method. SETTING: Participants were recruited and clinically evaluated through the University of Washington Autism Center and imaged at the Diagnostic Imaging Sciences Center at the University of Washington. Imaging data were analyzed through the Brain Imaging Laboratory at the Seoul National University. PARTICIPANTS: Fifty-one children 6 to 7 years of age (ASD, n = 31 and TD, n = 20) were assessed using magnetic resonance imaging and behavioral measures. MAIN OUTCOME MEASURES: Volume and subregional measures of the amygdala and measures of social and communication functioning. RESULTS: The ASD group exhibited larger right and left amygdalae, by 12.7% and 11.0%, respectively, relative to the TD group. Subregional analysis revealed that the ASD group had enlarged laterobasal amygdalar subregions, relative to the TD group, after adjusting for age, sex, and hemispheric cerebral volume (P < .05, false discovery rate corrected and with clustered surface points >15). Exploratory analyses revealed that there were linear trends comparing a strictly defined subgroup of children with autistic disorder, who exhibited the greatest extent of laterobasal enlargement, followed by a subgroup of children with pervasive developmental disorder not otherwise specified and then the group of TD children (P for linear trend <.001). There were linear trends between enlargement of laterobasal subregions and lower levels of social and communication functioning (P < .001, P < .001, and P = .001 for 3 areas in the right laterobasal subregion; P < .001 for 1 area in the left laterobasal subregion). CONCLUSION: The current study demonstrates bilateral enlargement of laterobasal subregions of the amygdala in 6- to 7-year-old children with ASD and that subregional alterations are associated with deficits in social and communicative behavior.

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.

Brain structural abnormalities and mental health sequelae in South Vietnamese ex-political detainees who survived traumatic head injury and torture.

CONTEXT: A pilot study of South Vietnamese ex-political detainees who had been incarcerated in Vietnamese reeducation camps and resettled in the United States disclosed significant mental health problems associated with torture and traumatic head injury (THI). OBJECTIVES: To identify structural brain alterations associated with THI and to investigate whether these deficits are associated with posttraumatic stress disorder and depression. DESIGN: Cross-sectional neuroimaging study. SETTING: Massachusetts General Hospital and McLean Hospital. PARTICIPANTS: A subsample of Vietnamese ex-political detainees (n = 42) and comparison subjects (n = 16) selected from a community study of 337 ex-political detainees and 82 comparison subjects. MAIN OUTCOME MEASURES: Scores on the Vietnamese versions of the Hopkins Symptom Checklist-25 (HSCL) and Harvard Trauma Questionnaire for depression and posttraumatic stress disorder, respectively; cerebral regional cortical thickness; and manual volumetric morphometry of the amygdala, hippocampus, and thalamus. RESULTS: Ex-political detainees exposed to THI (n = 16) showed a higher rate of depression (odds ratio, 10.2; 95% confidence interval, 1.2-90.0) than those without THI exposure (n = 26). Ex-political detainees with THI had thinner prefrontotemporal cortices than those without THI exposure (P < .001 by the statistical difference brain map) in the left dorsolateral prefrontal and bilateral superior temporal cortices, controlling for age, handedness, and number of trauma/torture events (left superior frontal cortex [SFC], P = .006; left middle frontal cortex, P = .01; left superior temporal cortex [STC], P = .007; right STC, P = .01). Trauma/torture events were associated with bilateral amygdala volume loss (left, P = .045; right, P = .003). Cortical thinning associated with THI in the left SFC and bilateral STC was related to HSCL depression scores in THI-exposed (vs non-THI-exposed) ex-political detainees (left SFC, P for interaction = .007; left STC, P for interaction = .03; right STC, P for interaction = .02). CONCLUSIONS: Structural deficits in prefrontotemporal brain regions are linked to THI exposures. These brain lesions are associated with the symptom severity of depression in Vietnamese ex-political detainees.

Associations between anterior cingulate cortex glutamate and gamma-aminobutyric acid concentrations and the harm avoidance temperament.

Converging lines of evidence have suggested that the personality traits might have neurobiological underpinnings. The anterior cingulate cortex (ACC) has been implicated to play an important role in the human fear and anxiety. Functional and structural characteristics of ACC have been suggested to be associated with the harm avoidance (HA) temperament, one of the important temperament dimensions. Therefore, we aimed to investigate correlations between neurometabolite concentrations in ACC, specifically glutamate and gamma-aminobutyric acid (GABA), which are major excitatory and inhibitory neurotransmitters, respectively, and HA scores. Neurometabolite concentrations were measured using high resolution single voxel proton magnetic resonance spectroscopy ((1)H-MRS), and the HA temperament was evaluated using the Temperament and Character Inventory (TCI). Correlations between HA scores from 37 participants (21 men/16 women, age of 30.3+/-7.0) and glutamate and GABA concentrations in the mid-ACC region were evaluated. HA scores correlated negatively with glutamate concentrations in ACC (partial correlation, R=-0.54, df=33, P=0.001) and positively with GABA concentrations in ACC (partial correlation, R=0.48, df=30, P=0.005). These findings suggest that glutamate and GABA concentrations in ACC are closely related to levels of the HA temperament in healthy subjects.

Altered prefrontal glutamate-glutamine-gamma-aminobutyric acid levels and relation to low cognitive performance and depressive symptoms in type 1 diabetes mellitus.

CONTEXT: Neural substrates for low cognitive performance and depression, common long-term central nervous system-related changes in patients with type 1 diabetes mellitus, have not yet been studied. OBJECTIVE: To investigate whether prefrontal glutamate levels are higher in patients with type 1 diabetes and whether an elevation is related to lower cognitive performance and depression. DESIGN: Cross-sectional study. SETTING: General clinical research center. PARTICIPANTS: One hundred twenty-three patients with adult type 1 diabetes with varying degrees of lifetime glycemic control and 38 healthy participants. MAIN OUTCOME MEASURES: With the use of proton magnetic resonance spectroscopy, prefrontal glutamate-glutamine-gamma-aminobutyric acid (Glx) levels were compared between patients and control subjects. Relationships between prefrontal Glx levels and cognitive function and between Glx levels and mild depressive symptoms were assessed in patients with type 1 diabetes. RESULTS: Prefrontal Glx concentrations were 9.0% (0.742 mmol/L; P = .005) higher in adult patients with type 1 diabetes than in healthy control subjects. There were positive linear trends for the effects of lifetime glycemic control on prefrontal Glx levels (P for trend = .002). Cognitive performances in memory, executive function, and psychomotor speed were lower in patients (P = .003, .01, and <.001, respectively) than in control subjects. Higher prefrontal Glx concentrations in patients were associated with lower performance in assessment of global cognitive function (0.11 change in z score per 1-mmol/L increase in Glx) as well as with mild depression. CONCLUSIONS: The high prefrontal glutamate levels documented in this study may play an important role in the genesis of the low cognitive performance and mild depression frequently observed in patients with type 1 diabetes. Therapeutic options that alter glutamatergic neurotransmission may be of benefit in treating central nervous system-related changes in patients with adult type 1 diabetes.

Decreased N-acetyl-aspartate levels in anterior cingulate and hippocampus in subjects with post-traumatic stress disorder: a proton magnetic resonance spectroscopy study.

The purpose of this study was to investigate the concentration of N-acetyl-aspartate (NAA) in the brain and its relationship with clinical characteristics in patients with post-traumatic stress disorder (PTSD). Proton magnetic resonance spectroscopy was performed in order to measure NAA concentrations in the anterior cingulate cortex (ACC) and bilateral hippocampus in 26 subjects with fire-related PTSD, who were survivors of a subway fire in South Korea, and 25 age- and sex-matched healthy comparison subjects. There were decreased NAA levels in the ACC (t = -3.88, d.f. = 49, P < 0.001) and bilateral hippocampus (right, t = -3.88, d.f. = 49, P < 0.001; left, t = -3.62, d.f. = 49, P < 0.001) in the PTSD group relative to the healthy comparison group. Also, NAA levels of the ACC (r = -0.43, n = 26, P = 0.027) and bilateral hippocampus (right, r = -0.48, n = 26, P = 0.013; left, r = -0.40, n = 26, P = 0.04) were negatively correlated with re-experience symptom scores in subjects with PTSD. In conclusion, our findings suggest that subjects with PTSD had decreased neuronal viabilities in the ACC and bilateral hippocampus, and that these deficits may play an important role in the pathophysiology of PTSD, especially regarding the re-experiencing of traumatic events.