Alterations in structural rich-club connectivity of the precuneus are associated with depressive symptoms among individuals with subjective memory complaints.

The association between subjective memory complaints (SMCs) and depressive symptoms has been widely reported and both have been regarded as risk factors for dementia, such as Alzheimer's disease (AD). Although SMCs arise as early as in middle age, the exact neural correlates of comorbid depressive symptoms among individuals who are middle-aged and with SMCs have not yet been well investigated. Because rich-club organization of the brain plays a key role in the pathophysiology of various neuropsychiatric disorders, the investigation of rich club organization may provide insight regarding the neurobiological mechanisms of depressive symptoms in SMCs. In the current study, we compared the rich-club organization in the structural brain connectivity between individuals who have SMCs along with depressive symptoms (SMCD) and individuals with SMCs but without depressive symptoms (SMCO). A total of 53 individuals with SMCD and 91 individuals with SMCO participated in the study. For all participants, high-resolution, T1-weighted images and diffusion tensor images were obtained, and the network analysis was performed. Individuals with SMCD had lower connectivity strength between the precuneus and other rich-club nodes than those with SMCO, which was significant after adjusting for potential confounders. Our findings suggest that disruptions of rich-club connectivity strength of the precuenus are associated with depressive symptoms in middle-aged individuals with SMCs. Given that the precuneus is one of the commonly affected regions in the early stages of AD, our findings may imply that the concomitant depressive symptoms in middle-aged individuals with SMCs could reflect structural alterations related to AD.

Altered functional connectivity in the fear network of firefighters with repeated traumatic stress.

BACKGROUND: Firefighters are routinely exposed to various traumatic events and often experience a range of trauma-related symptoms. Although these repeated traumatic exposures rarely progress to the development of post-traumatic stress disorder, firefighters are still considered to be a vulnerable population with regard to trauma.AimsTo investigate how the human brain responds to or compensates for the repeated experience of traumatic stress. METHOD: We included 98 healthy firefighters with repeated traumatic experiences but without any diagnosis of mental illness and 98 non-firefighter healthy individuals without any history of trauma. Functional connectivity within the fear circuitry, which consists of the dorsal anterior cingulate cortex, insula, amygdala, hippocampus and ventromedial prefrontal cortex (vmPFC), was examined using resting-state functional magnetic resonance imaging. Trauma-related symptoms were evaluated using the Impact of Event Scale - Revised. RESULTS: The firefighter group had greater functional connectivity between the insula and several regions of the fear circuitry including the bilateral amygdalae, bilateral hippocampi and vmPFC as compared with healthy individuals. In the firefighter group, stronger insula-amygdala connectivity was associated with greater severity of trauma-related symptoms (ß = 0.36, P = 0.005), whereas higher insula-vmPFC connectivity was related to milder symptoms in response to repeated trauma (ß = -0.28, P = 0.01). CONCLUSIONS: The current findings suggest an active involvement of insular functional connectivity in response to repeated traumatic stress. Functional connectivity of the insula in relation to the amygdala and vmPFC may be potential pathways that underlie the risk for and resilience to repeated traumatic stress, respectively.Declaration of interestNone.

Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells.

We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess.

Prefronto-temporal white matter microstructural alterations 20 years after the diagnosis of type 1 diabetes mellitus.

OBJECTIVE: Microvascular pathophysiology that uniquely manifests as white matter (WM) abnormalities is often implicated in type 1 diabetes mellitus (T1DM)-related central nervous system (CNS) complications. This study sought to identify regional WM abnormalities in young adults diagnosed with T1DM and further examine their association with cognitive and emotional dysfunction. RESEARCH DESIGN AND METHODS: Diffusion tensor images (DTI) obtained from 34 young adults with T1DM for ≥15 years (mean duration, 20.9 years), and 16 age- and sex-matched healthy control subjects were analyzed using tract-based spatial statistics. Fractional anisotropy (FA) values of the whole brain were analyzed, and their associations with memory function and depressive symptoms were assessed. RESULTS: Whole brain voxel-wise analyses showed that T1DM-related FA reductions were most prominent within the fronto-temporo-parietal regions of the brain. Reduced FA values in the bilateral superior longitudinal fasciculi, at which group differences were most prominent, correlated with lower working memory performance in young adults with T1DM (left, P < .001; right, P = .009). Subsyndromal depressive symptoms were also associated with lower FA values in the right inferior fronto-occipital fasciculus (P = .004). CONCLUSION: Widespread WM microstructural abnormalities in the fronto-temporo-parietal brain regions, which are associated with emotional and cognitive dysfunction, may be a contributing factor to the neural mechanisms underlying T1DM-related CNS complications, thus affecting the quality of life in young adults with T1DM.

Metabolic alterations in the anterior cingulate cortex and related cognitive deficits in late adolescent methamphetamine users.

The adolescent brain, with ongoing prefrontal maturation, may be more vulnerable to drug use-related neurotoxic changes as compared to the adult brain. We investigated whether the use of methamphetamine (MA), a highly addictive psychostimulant, during adolescence affect metabolic and cognitive functions of the anterior cingulate cortex (ACC). In adolescent MA users (n = 44) and healthy adolescents (n = 53), the levels of N-acetyl aspartate (NAA), a neuronal marker, were examined in the ACC using proton magnetic resonance spectroscopy. The Stroop color-word task was used to assess Stroop interference, which may reflect cognitive functions of behavior monitoring and response selection that are mediated by the ACC. Adolescent MA users had lower NAA levels in the ACC (t = -2.88, P = 0.005) and relatively higher interference scores (t = 2.03, P = 0.045) than healthy adolescents. Moreover, there were significant relationships between lower NAA levels in the ACC and worse interference scores in adolescent MA users (r = -0.61, P < 0.001). Interestingly, early onset of MA use, as compared to late onset, was related to both lower NAA levels in the ACC (t = -2.24, P = 0.03) as well as lower performance on interference measure of the Stroop color-word task (t = 2.25, P = 0.03). The current findings suggest that metabolic dysfunction in the ACC and its related cognitive impairment may play an important role in adolescent-onset addiction, particularly during early adolescence.

A performance comparison between the two language versions of the Affective Go/No-Go test: A randomised crossover study.

The purpose of this randomised crossover study is to validate the Korean version of the Affective Go/No-go (AGN) test. The Korean words for the AGN test were selected after careful evaluation of emotional valences, word length and frequency. Fifteen Korean advanced learners of English were administered both Korean and English versions, yielding 30 data points. The performance of both language versions was compared for each of the AGN test parameters (response latency, commission error and omission error) using two-way analysis of variance (ANOVA). Intraclass correlation coefficients (ICCs) were estimated to evaluate associations between the two versions. The ICCs were high for response latencies of all valences and commission errors of positive and neutral words, but not for that of negative words and omission errors of all valences. A similar pattern of test results, as revealed by the high ICCs and non-significant interaction effects between language and word valence, suggests that the psychometric properties of the AGN test may be comparable over different language versions.

Psychometric Properties of the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) in Public First Responders.

Problematic alcohol consumption is prevalent among first responders because alcohol is commonly used to cope with occupational stress and frequent exposure to traumatic incidents, making them an at-risk population for alcohol use disorders (AUD). This study investigated the psychometric properties of the Korean version of the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) among public first responders. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-IV-Text Revision (SCID), AUDIT-C, AUDIT, and CAGE were administered to 222 public first responders, who were recruited by convenience sampling. One-week test-retest reliability was evaluated in a subsample (n = 24). Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the diagnostic accuracy and estimate the optimal cut-off scores for any AUD and alcohol dependence. Three different analytic criteria were utilized to calculate the cut-off scores. The AUDIT-C demonstrated good test-retest reliability (intraclass correlation coefficient for test-retest reliability = 0.91) and satisfactory convergent validity. The areas under the ROC curves for any AUD and alcohol dependence of the AUDIT-C were 0.87 and 0.93, respectively. For any AUD, all three criteria suggested a cut-off score of 7.5 (sensitivity = 81.8%, specificity = 79.8%), whereas for alcohol dependence, a cut-off score of 8.5 (sensitivity = 85.7%, specificity = 86.1%) was derived from two criteria. In conclusion, the AUDIT-C demonstrated good reliability and validity and proved to be a brief and effective screening test for AUD among first responders.

Validation of the Athens Insomnia Scale for screening insomnia in South Korean firefighters and rescue workers.

PURPOSE: Sleep problems are a major cause of occupational stress in firefighters and rescue workers. We evaluated the psychometric properties of the Athens Insomnia Scale (AIS) among South Korean firefighters and rescue workers. METHODS: Structured clinical interviews and self-report questionnaires were administered to 221 firefighters and rescue workers. The Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Short-Form 36-item Health Survey (SF36), and Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) were used to examine convergent and divergent validity. Test-retest reliability was calculated from a subsample (n = 24). Analysis of internal consistency, factor analysis, and receiver operator characteristic curve analysis were conducted. RESULTS: Cronbach's alpha was 0.88. The mean item-total correlation coefficient was 0.73. The test-retest reliability was excellent (ICC = 0.94). Significant correlations of the AIS with the PSQI, ISI, ESS, and SF36 confirmed convergent validity. Nonsignificant associations of the AIS with the AUDIT-C and socioeconomic status showed divergent validity. Factor analysis revealed a one-factor structure. For groups with different symptom severity, group-specific cutoff scores which may improve positive predictive values were suggested. CONCLUSIONS: The AIS may be a useful tool with good reliability and validity for screening insomnia symptoms in firefighters and rescue workers.

Validation of the Korean version of the Connor-Davidson Resilience Scale-2 in firefighters and rescue workers.

OBJECTIVE: Resilience has been considered as a protective factor against stress. Evaluating resilience in firefighters and rescue workers, who are frequently exposed to traumatic events, is important and relevant. This study examined the psychometric properties of the Korean version of the Connor-Davidson Resilience Scale-2 (CD-RISC2). METHODS: Two-hundred twenty-two current professional firefighters and rescue workers were assessed by standardized, semi-structured clinical interviews and self-report questionnaires. Internal consistency, correlation with the CD-RISC, convergent validity, divergent validity, and predictive validity of posttraumatic stress disorder (PTSD) symptom severity were analyzed. RESULTS: The CD-RISC2 demonstrated good internal consistency (α=0.75), item-total correlation (r=0.89-0.90), and convergent and divergent validity. The total score of the CD-RISC2 showed significant correlations with the subtotal of the remaining 23 CD-RISC items (r=0.77, p<0.001) and with the score of each CD-RISC item (r=0.15-0.66, all p<0.05). The magnitude of the relationship between the number of traumatic experiences and PTSD symptom severity was greater in the low resilience group than in the high resilience group (p for interaction=0.002). The likelihood-ratio test confirmed that the model predicting PTSD symptom severity based on the CD-RISC2 total score was not improved by the inclusion of subtotal scores of the remaining 23 CD-RISC items (χ(2)=0.31, p=0.58). CONCLUSIONS: These results suggest that the CD-RISC2 would be a valuable tool in evaluating resilience quickly and efficiently in firefighters and rescue workers.

The patient health questionnaire-15 and its abbreviated version as screening tools for depression in Korean college and graduate students.

OBJECTIVE: Over half of all suicides worldwide occur in Asia. Given the close association between suicide and depression, it is quite unexpected that depression is least frequently diagnosed in Asia. This is, in part, due to the fact that Asians somatize depression. Young adults including college and graduate students are no exceptions. Therefore, a somatic symptom-focused screening tool would be useful in detecting depression in Asian college and graduate students. The purpose of this study was to evaluate the psychometric properties of the Patient Health Questionnaire-15 (PHQ-15) in screening for depression among Korean college and graduate students. In addition, we developed an abbreviated version of the PHQ-15 (aPHQ-15) and studied validity measures. METHODS: Three-hundred and fifty Korean college and graduate students were screened with the PHQ-15. Of all participants, 176 were interviewed using the Structured Clinical Interview for DSM-IV to diagnose major depressive episode, while the other 174 were evaluated with the Beck Depression Inventory-II (BDI-II) and the Inventory of Depressive Symptomatology-Self-Report (IDS-SR). Reliability and validity measures including the internal consistency, test-retest reliability, and criterion, convergent, and divergent validity were tested. Principal component analysis was used in developing the abbreviated version of the PHQ-15. RESULTS: The PHQ-15 showed good internal consistency and test-retest reliability (Cronbach's alpha 0.82, intra-class correlation coefficient 0.87). The optimal cut-off point for detecting depression was estimated to be 8. There were strong correlations between the PHQ-15 total scores and self-report measures of depressive symptom severity (BDI-II: r=0.69 and p<0.001, IDS-SR: r=0.77 and p<0.001). The 5-item aPHQ-15 had comparable validity with the PHQ-15. CONCLUSIONS: The somatic symptom-focused PHQ-15 and aPHQ-15 can work as effective screening tools for depression.

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.

Modelling information flow along the human connectome using maximum flow.

The human connectome is a complex network that transmits information between interlinked brain regions. Using graph theory, previously well-known network measures of integration between brain regions have been constructed under the key assumption that information flows strictly along the shortest paths possible between two nodes. However, it is now apparent that information does flow through non-shortest paths in many real-world networks such as cellular networks, social networks, and the internet. In the current hypothesis, we present a novel framework using the maximum flow to quantify information flow along all possible paths within the brain, so as to implement an analogy to network traffic. We hypothesize that the connection strengths of brain networks represent a limit on the amount of information that can flow through the connections per unit of time. This allows us to compute the maximum amount of information flow between two brain regions along all possible paths. Using this novel framework of maximum flow, previous network topological measures are expanded to account for information flow through non-shortest paths. The most important advantage of the current approach using maximum flow is that it can integrate the weighted connectivity data in a way that better reflects the real information flow of the brain network. The current framework and its concept regarding maximum flow provides insight on how network structure shapes information flow in contrast to graph theory, and suggests future applications such as investigating structural and functional connectomes at a neuronal level.

Efficacy and Safety of Tremella fuciformis in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

The efficacy and safety of Tremella fuciformis (TF) as a nutritional supplement were assessed in individuals with subjective cognitive impairment (SCI). Seventy-five individuals with SCI were enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of TF (600 mg/day, n = 30 or 1200 mg/day, n = 30) or placebo (n = 15). The primary outcome measure was changes in total scores of the subjective memory complaint questionnaire. The secondary outcome measures were changes in performance on short-term memory and executive functions, which were assessed using standardized cognitive tests. In addition, voxel-based morphometry was performed to examine the effects of TF on changes in gray matter volume. The individuals in the TF group showed greater improvements in the total scores on the subjective memory complaint questionnaire compared with those in the placebo group. There were also significantly greater improvements in short-term memory and executive functions in the TF group relative to the placebo group. Exploratory analysis demonstrated that there were significant group-by-visit interactions on the left precuneus, right supramarginal gyrus, right middle frontal gyrus, and right postcentral gyrus at corrected P < .05. Overall frequency of adverse events did not differ among high-dose TF (40.4%), low-dose TF (35.1%), and placebo groups (41.4%). The current findings suggest that TF could be safely administered to relieve subjective memory complaints and enhance cognition in individuals with SCI.

Natural Products from Single Plants as Sleep Aids: A Systematic Review.

Insufficient sleep, insomnia, and sleep-related problems are important health issues, as their overall prevalence accounts for about 30% of the general population. The aim of this study was to systematically review previous studies investigating the effects of orally administered single plant-derived extracts on sleep-related outcomes in humans. Data sources were PubMed, Google Scholar, and Cochrane Library. The data search was conducted in two steps: step 1, names of plants which have been studied as sleep aids in humans were searched and retrieved; and step 2, each ingredient listed in step 1 was then added into the search term. Only original articles or reviews were applicable to the scope of this review. Studies on human subjects, with or without sleep-related disorders, were included. Sleep-related disorders refer to not only insomnia or sleep behavior disorders but also diseases with sleep-related symptoms. Studies were considered eligible for this review when the plant extracts were administered orally. Outcome measures relevant to sleep quality, duration, or other sleep-related problems were included. Twenty-one plants were listed in the first step of the search as potential candidates for natural sleep aids. Seventy-nine articles using these single plant-derived natural products were included in the final review. Although valerian was most frequently studied, conflicting results were reported, possibly due to the various outcome measures of each study. Other plants were not as rigorously tested in human studies. There was limited evidence with inconclusive results regarding the effects of single plant-derived natural products on sleep, warranting further studies.

Brain structural changes in cynomolgus monkeys administered with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A longitudinal voxel-based morphometry and diffusion tensor imaging study.

In animal models of Parkinson's disease (PD), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is one of the most widely used agents that damages the nigrostriatal dopaminergic pathway. However, brain structural changes in response to MPTP remain unclear. This study aimed to investigate in vivo longitudinal changes in gray matter (GM) volume and white matter (WM) microstructure in primate models administered with MPTP. In six cynomolgus monkeys, high-resolution magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) scans were acquired 7 times over 32 weeks, and assessments of motor symptoms were conducted over 15 months, before and after the MPTP injection. Changes in GM volume and WM microstructure were estimated on a voxel-by-voxel basis. Mixed-effects regression models were used to examine the trajectories of these structural changes. GM volume initially increased after the MPTP injection and gradually decreased in the striatum, midbrain, and other dopaminergic areas. The cerebellar volume temporarily decreased and returned to its baseline level. The rate of midbrain volume increase was positively correlated with the increase rate of motor symptom severity (Spearman rho = 0.93, p = 0.008). Mean, axial, and radial diffusivity in the striatum and frontal areas demonstrated initial increases and subsequent decreases. The current multi-modal imaging study of MPTP-administered monkeys revealed widespread and dynamic structural changes not only in the nigrostriatal pathway but also in other cortical, subcortical, and cerebellar areas. Our findings may suggest the need to further investigate the roles of inflammatory reactions and glial activation as potential underlying mechanisms of these structural changes.

Firefighters, posttraumatic stress disorder, and barriers to treatment: Results from a nationwide total population survey.

Repeated exposure to traumatic experiences may put professional firefighters at increased risk of developing posttraumatic stress disorder (PTSD). To date, however, the rate of PTSD symptoms, unmet need for mental health treatment, and barriers to treatment have only been investigated in subsamples rather than the total population of firefighters. We conducted a nationwide, total population-based survey of all currently employed South Korean firefighters (n = 39,562). The overall response rate was 93.8% (n = 37,093), with 68.0% (n = 26,887) complete responses for all variables. The rate of current probable PTSD was estimated as 5.4%. Among those with current probable PTSD (n = 1,995), only a small proportion (9.7%) had received mental health treatment during the past month. For those who had not received treatment, perceived barriers of accessibility to treatment (29.3%) and concerns about potential stigma (33.8%) were reasons for not receiving treatment. Although those with higher PTSD symptom severity and functional impairment were more likely to seek treatment, greater symptom severity and functional impairment were most strongly associated with increased concerns about potential stigma. This nationwide study points to the need for new approaches to promote access to mental health treatment in professional firefighters.

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.

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.

Diagnostic potential of multimodal neuroimaging in posttraumatic stress disorder.

Despite accumulating evidence of physiological abnormalities related to posttraumatic stress disorder (PTSD), the current diagnostic criteria for PTSD still rely on clinical interviews. In this study, we investigated the diagnostic potential of multimodal neuroimaging for identifying posttraumatic symptom trajectory after trauma exposure. Thirty trauma-exposed individuals and 29 trauma-unexposed healthy individuals were followed up over a 5-year period. Three waves of assessments using multimodal neuroimaging, including structural magnetic resonance imaging (MRI) and diffusion-weighted MRI, were performed. Based on previous findings that the structural features of the fear circuitry-related brain regions may dynamically change during recovery from the trauma, we employed a machine learning approach to determine whether local, connectivity, and network features of brain regions of the fear circuitry including the amygdala, orbitofrontal and ventromedial prefrontal cortex (OMPFC), hippocampus, insula, and thalamus could distinguish trauma-exposed individuals from trauma-unexposed individuals at each recovery stage. Significant improvement in PTSD symptoms was observed in 23%, 52%, and 88% of trauma-exposed individuals at 1.43, 2.68, and 3.91 years after the trauma, respectively. The structural features of the amygdala were found as major classifiers for discriminating trauma-exposed individuals from trauma-unexposed individuals at 1.43 years after the trauma, but these features were nearly normalized at later phases when most of the trauma-exposed individuals showed clinical improvement in PTSD symptoms. Additionally, the structural features of the OMPFC showed consistent predictive values throughout the recovery period. In conclusion, the current study provides a promising step forward in the development of a clinically applicable predictive model for diagnosing PTSD and predicting recovery from PTSD.

Recovery from Posttraumatic Stress Requires Dynamic and Sequential Shifts in Amygdalar Connectivities.

The neural mechanisms underlying the development and maintenance of posttraumatic stress disorder (PTSD) have long been studied. However, little is known about the neural correlates of the recovery process from PTSD. A 5-year longitudinal study was conducted to investigate the trajectory of structural connectivities of the amygdala in disaster survivors with PTSD. Thirty disaster survivors, who were diagnosed with PTSD, and 29 healthy individuals, who were not exposed to trauma, underwent three waves of assessments including neuroimaging scanning over a 5-year period from the time of the disaster at approximately 1.3-year intervals. All disaster survivors showed significant improvements in PTSD symptoms over time. Using diffusion tensor imaging analysis, a 5-year trajectory of amygdalar structural connectivities with key brain regions was assessed. The amygdala-insula connection was initially strengthened and then normalized during recovery, while the amygdala-prefrontal cortex (PFC) connection was at first unaffected, then strengthened, and eventually normalized. The lower tract strength of the amygdala-thalamus connection normalized during recovery, while that of amygdala-hippocampus connection remained low. The greater amygdala-PFC connectivity was associated with less PTSD symptom severity. The present longitudinal study revealed that recovery from PTSD parallels dynamic and sequential shifts in amygdalar connectivities with multiple brain regions, suggesting the expanded view of fear circuitry including the insula and thalamus, beyond the traditional model which primarily involves the amygdala, PFC, and hippocampus.