Role of Dopamine Transporter in the Relationship Between Plasma Cortisol and Cognition.

OBJECTIVE: Cortisol is associated with cognition in both healthy individuals and patients with neuropsychiatric disorders. Regarding the effects of cortisol on the dopamine system and the association between dopamine transporter (DAT) and cognition, DAT might be a central target linking cortisol and cognition. This study explored the role of striatal DAT in the cortisol-cognition relationship. METHODS: We recruited 33 patients with carbon monoxide poisoning and 33 age- and sex-matched healthy controls. All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT was used to determine striatal DAT availability. Plasma cortisol, tumor necrosis factor α, and interleukin-10 levels were measured using enzyme-linked immunosorbent assays. RESULTS: Compared with healthy controls, patients with carbon monoxide poisoning had lower cognitive performance, bilateral striatal DAT availability, and plasma tumor necrosis factor-α levels and higher cortisol and interleukin-10 levels. In all participants, plasma cortisol level and bilateral striatal DAT availability were negatively and positively related to cognition, respectively, including memory and executive function with ß from -0.361 (95% confidence interval [CI] = -0.633 to -0.090) to 0.588 (95% CI = 0.319 to 0.858). Moreover, bilateral striatal DAT mediated the cortisol-cognition relationship with indirect effects from -0.067 (95% CI = -0.179 to -0.001) to -0.135 (95% CI = -0.295 to -0.024). The cytokine levels did not influence the mediation effects. CONCLUSIONS: This is the first study to demonstrate that striatal DAT mediates the cortisol-cognition relationship. Future studies are needed to comprehensively evaluate the role of the dopamine system in cortisol-cognition associations and treatment implications.

International Society for Bipolar Disorders Task Force on Suicide: meta-analyses and meta-regression of correlates of suicide attempts and suicide deaths in bipolar disorder.

OBJECTIVES: Bipolar disorder is associated with a high risk of suicide attempts and suicide death. The main objective of the present study was to identify and quantify the demographic and clinical correlates of attempted and completed suicide in people with bipolar disorder. METHODS: Within the framework of the International Society for Bipolar Disorders Task Force on Suicide, a systematic review of articles published since 1980, characterized by the key terms bipolar disorder and 'suicide attempts' or 'suicide', was conducted, and data extracted for analysis from all eligible articles. Demographic and clinical variables for which ≥ 3 studies with usable data were available were meta-analyzed using fixed or random-effects models for association with suicide attempts and suicide deaths. There was considerable heterogeneity in the methods employed by the included studies. RESULTS: Variables significantly associated with suicide attempts were: female gender, younger age at illness onset, depressive polarity of first illness episode, depressive polarity of current or most recent episode, comorbid anxiety disorder, any comorbid substance use disorder, alcohol use disorder, any illicit substance use, comorbid cluster B/borderline personality disorder, and first-degree family history of suicide. Suicide deaths were significantly associated with male gender and first-degree family history of suicide. CONCLUSIONS: This paper reports on the presence and magnitude of the correlates of suicide attempts and suicide deaths in bipolar disorder. These findings do not address causation, and the heterogeneity of data sources should limit the direct clinical ranking of correlates. Our results nonetheless support the notion of incorporating diagnosis-specific data in the development of models of understanding suicide in bipolar disorder.

Epidemiology, neurobiology and pharmacological interventions related to suicide deaths and suicide attempts in bipolar disorder: Part I of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder.

OBJECTIVES: Bipolar disorder is associated with elevated risk of suicide attempts and deaths. Key aims of the International Society for Bipolar Disorders Task Force on Suicide included examining the extant literature on epidemiology, neurobiology and pharmacotherapy related to suicide attempts and deaths in bipolar disorder. METHODS: Systematic review of studies from 1 January 1980 to 30 May 2014 examining suicide attempts or deaths in bipolar disorder, with a specific focus on the incidence and characterization of suicide attempts and deaths, genetic and non-genetic biological studies and pharmacotherapy studies specific to bipolar disorder. We conducted pooled, weighted analyses of suicide rates. RESULTS: The pooled suicide rate in bipolar disorder is 164 per 100,000 person-years (95% confidence interval = [5, 324]). Sex-specific data on suicide rates identified a 1.7:1 ratio in men compared to women. People with bipolar disorder account for 3.4-14% of all suicide deaths, with self-poisoning and hanging being the most common methods. Epidemiological studies report that 23-26% of people with bipolar disorder attempt suicide, with higher rates in clinical samples. There are numerous genetic associations with suicide attempts and deaths in bipolar disorder, but few replication studies. Data on treatment with lithium or anticonvulsants are strongly suggestive for prevention of suicide attempts and deaths, but additional data are required before relative anti-suicide effects can be confirmed. There were limited data on potential anti-suicide effects of treatment with antipsychotics or antidepressants. CONCLUSION: This analysis identified a lower estimated suicide rate in bipolar disorder than what was previously published. Understanding the overall risk of suicide deaths and attempts, and the most common methods, are important building blocks to greater awareness and improved interventions for suicide prevention in bipolar disorder. Replication of genetic findings and stronger prospective data on treatment options are required before more decisive conclusions can be made regarding the neurobiology and specific treatment of suicide risk in bipolar disorder.

A review of factors associated with greater likelihood of suicide attempts and suicide deaths in bipolar disorder: Part II of a report of the International Society for Bipolar Disorders Task Force on Suicide in Bipolar Disorder.

OBJECTIVES: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors. METHODS: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords 'bipolar disorder' and 'suicide attempts or suicide'. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables. RESULTS: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants. CONCLUSION: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.

Association of thalamic serotonin transporter and interleukin-10 in bipolar I disorder: a SPECT study.

OBJECTIVES: The serotonin hypothesis plays a critical role in the etiology of bipolar disorder (BD). Although many studies have demonstrated reciprocal relationships between serotonin metabolism and immune-inflammatory pathways that occur in depression, studies linking serotonergic function and cytokines are still limited concerning BD. The aim of this study was to investigate the interaction of brain serotonin transporter (SERT) and cytokines in BD. METHODS: Twenty patients with euthymic BD and 20 age- and sex-matched healthy controls (HC) were recruited. Single photon emission computed tomography with the radiotracer (123) I-ADAM was used for the SERT imaging. The specific uptake ratio, which represents SERT availability, was the primary measured outcome. Cytokines included the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory cytokine interleukin-10 (IL-10). Cytokine concentration was measured using an enzyme-linked immunosorbent assay. RESULTS: SERT availability was significantly lower in the midbrain and caudate of patients with BD compared with HC, but not in the thalamus and putamen. IL-10 was significantly higher, whereas TNF-α was not different in euthymic patients with BD compared with HC. There was a significant association of SERT availability and IL-10 in the thalamus, but not in the midbrain, caudate, or putamen. CONCLUSIONS: Our results demonstrate the interaction of SERT availability and IL-10 in euthymic BD. This result may further explain the role of SERT and cytokines in the etiology of BD.

Cognitive impairment in schizophrenia is associated with prefrontal-striatal functional hypoconnectivity and striatal dopaminergic abnormalities.

BACKGROUND: A better understanding of the mechanisms underlying cognitive impairment in schizophrenia is imperative, as it causes poor functional outcomes and a lack of effective treatments. AIMS: This study aimed to investigate the relationships of two proposed main pathophysiology of schizophrenia, altered prefrontal-striatal connectivity and the dopamine system, with cognitive impairment and their interactions. METHODS: Thirty-three patients with schizophrenia and 27 healthy controls (HCs) who are right-handed and matched for age and sex were recruited. We evaluated their cognition, functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC)/middle frontal gyrus (MiFG) and striatum, and the availability of striatal dopamine transporter (DAT) using a cognitive battery investigating attention, memory, and executive function, resting-state functional magnetic resonance imaging with group independent component analysis and single-photon emission computed tomography with 99mTc-TRODAT. RESULTS: Patients with schizophrenia exhibited poorer cognitive performance, reduced FC between DLPFC/MiFG and the caudate nucleus (CN) or putamen, decreased DAT availability in the left CN, and decreased right-left DAT asymmetry in the CN compared to HCs. In patients with schizophrenia, altered imaging markers are associated with cognitive impairments, especially the relationship between DLPFC/MiFG-putamen FC and attention and between DAT asymmetry in the CN and executive function. CONCLUSIONS: This study is the first to demonstrate how prefrontal-striatal hypoconnectivity and altered striatal DAT markers are associated with different domains of cognitive impairment in schizophrenia. More research is needed to evaluate their complex relationships and potential therapeutic implications.

Hippocampal subfields in remitted schizophrenia.

BACKGROUND: Current evidence of volume changes in hippocampal subdivisions in schizophrenia remains inconsistent, and few studies have investigated the relationship between regional hippocampal volumes and symptom remission. METHODS: In this cross-sectional study, we recruited 31 patients with schizophrenia and 31 healthy controls (HCs). Symptomatic remission in schizophrenia was determined according to Remission in Schizophrenia Working Group criteria. The volumes of hippocampal longitudinal subregions and transverse subfields were measured using manual and automatic techniques, respectively. Between-group regional hippocampal volume differences were analyzed using multivariate analysis of covariance followed by univariate analysis of covariance. RESULTS: Compared with the HCs, the patients with schizophrenia had smaller bilateral heads and tails along the longitudinal axis; they also had reduced volumes of the bilateral CA1, CA3, CA4, GC-ML-DG, molecular layer, tail, left subiculum, left HATA, and right parasubiculum along the transverse axis in the hippocampus (all corrected p < 0.05). Furthermore, compared with the HCs and patients with remitted schizophrenia, the patients with nonremitted schizophrenia had smaller bilateral hippocampal tail subfields (corrected p < 0.05). CONCLUSION: Our results indicated that the pathophysiology and symptomatic remission of schizophrenia are related to changes in the volumes of hippocampal subdivisions. These volume changes might be clinically relevant as biomarkers for schizophrenia identification and treatment.

Association of brain serotonin transporter availability and brain-derived neurotrophic factor in models of serotonin transporter genotypes in healthy subjects.

The S-allele of functional polymorphisms of the serotonin transporter (SERT) gene has been demonstrated to have lower transcriptional activity compared with the L-allele, which shows low expression of SERT in the brain. However, this finding cannot be consistently replicated in vivo. The aim of this study was to determine the availability of SERT based on SERT genotype. We also examined the relationship between brain-derived neurotrophic factor (BDNF) and the availability of SERT. Sixty-two healthy subjects were recruited. Each subject underwent single-photon emission computed tomography with I-ADAM (I-labeled 2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) for imaging SERT in the brain. The specific uptake ratio was measured, and venous blood was drawn when the subject underwent single-photon emission computed tomography to evaluate BDNF levels and SERT genotype. All subjects expressed SERT genotypes that were consistent with a biallelic model, and 26 subjects had SERT genotypes that were consistent with a triallelic model. No differences in specific uptake ratio were detected in the midbrain, putamen, caudate, and thalamus based on the SERT genotype using the biallelic and triallelic models. Interestingly, The Pearson correlation coefficient revealed a positive correlation between BDNF and SERT availability. In particular, this relationship was observed in homozygous S-allele expression and a genotype with low functional expression (SaSa/SaLg) in the biallelic and triallelic models of SERT genotypes, respectively. This finding might explain why the SS genotype of SERT did not increase the risk of major depressive disorder in Asian populations and implicate an important role of BDNF in the patients, who has the SS genotype of the SERT gene.

Molecular imaging findings for treatment resistant depression.

Approximately 40% of patients with major depressive disorder (MDD) had limited response to conventional antidepressant treatments, resulting in treatment-resistant depression (TRD), a debilitating subtype that yielded a significant disease burden worldwide. Molecular imaging techniques, such as positron emission tomography (PET) and single photon emission tomography (SPECT), can measure targeted macromolecules or biological processes in vivo. These imaging tools provide a unique possibility to explore the pathophysiology and treatment mechanisms underlying TRD. This work reviewed and summarized prior PET and SPECT studies to examine the neurobiology and treatment-induced changes of TRD. A total of 51 articles were included with supplementary information from studies for MDD and healthy controls (HC). We found that there were altered regional blood flow or metabolic activity in several brain regions, such as the anterior cingulate cortex, prefrontal cortex, insula, hippocampus, amygdala, parahippocampus, and striatum. These regions have been suggested to engage in the pathophysiology or treatment resistance of depression. There was also limited data to demonstrate the changes in the markers of serotonin, dopamine, amyloid, and microglia over some regions in TRD. Moreover, several observed abnormal imaging indices were linked to treatment outcomes, supporting their specificity and clinical relevance. To address the limitations of the included studies, we proposed that future studies needed longitudinal designs, multimodal approaches, and radioligands targeting specific neural substrates for TRD to evaluate their baseline and treatment-related alterations in TRD. Adequate data sharing and reproducible data analysis can facilitate advances in this field.

Amygdala substructure volumes and serotonin transporter in first-episode, drug- naïve major depressive disorder: A pilot study.

INTRODUCTION: Amygdala and serotonergic system abnormalities have been documented in major depressive disorder (MDD). However, most studies have been conducted on recurrent MDD, and only a few have assessed their interaction. This study aimed to concurrently examine both the amygdala and serotonergic systems and their clinical relevance in first-episode, drug-naïve MDD. METHODS: This study included 27 patients with first-episode, drug-naïve MDD and 27 age- and gender-matched healthy controls (HCs). The amygdala substructure volumes were performed with Freesurfer from a 1.5 T magnetic resonance image. Serotonin transporter (SERT) availability was detected by single-photon emission computed tomography with 123I-ADAM. The Benjamini-Hochberg method was applied to adjust for multiple comparisons. RESULTS: No significant difference was found in the amygdala substructure volume and SERT availability between the two groups, respectively. Within MDD patients, the right medial, cortical nucleus, and centromedial volumes were positively associated with caudate SERT availability, respectively. Moreover, the right lateral nucleus volume in the amygdala was positively correlated with depression severity. However, these significances did not survive correction for multiple testing. CONCLUSIONS: There were no significant abnormalities in the amygdala substructure volumes and SERT availability in patients with first-episode, drug-naïve MDD. We did not observe an association between amygdala substructure volume and serotonergic dysregulation and their correlations with depression severity in patients with MDD. A larger sample size is warranted to elucidate the actual correlation.

Abnormalities of Hippocampal Subfield and Amygdalar Nuclei Volumes and Clinical Correlates in Behavioral Variant Frontotemporal Dementia with Obsessive-Compulsive Behavior-A Pilot Study.

(1) Background: The hippocampus (HP) and amygdala are essential structures in obsessive-compulsive behavior (OCB); however, the specific role of the HP in patients with behavioral variant frontotemporal dementia (bvFTD) and OCB remains unclear. (2) Objective: We investigated the alterations of hippocampal and amygdalar volumes in patients with bvFTD and OCB and assessed the correlations of clinical severity with hippocampal subfield and amygdalar nuclei volumes in bvFTD patients with OCB. (3) Materials and methods: Eight bvFTD patients with OCB were recruited and compared with eight age- and sex-matched healthy controls (HCs). Hippocampal subfield and amygdalar nuclei volumes were analyzed automatically using a 3T magnetic resonance image and FreeSurfer v7.1.1. All participants completed the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Neuropsychiatric Inventory (NPI), and Frontal Behavioral Inventory (FBI). (4) Results: We observed remarkable reductions in bilateral total hippocampal volumes. Compared with the HCs, reductions in the left hippocampal subfield volume over the cornu ammonis (CA)1 body, CA2/3 body, CA4 body, granule cell layer, and molecular layer of the dentate gyrus (GC-ML-DG) body, molecular layer of the HP body, and hippocampal tail were more obvious in patients with bvFTD and OCB. Right subfield volumes over the CA1 body and molecular layer of the HP body were more significantly reduced in bvFTD patients with OCB than in those in HCs. We observed no significant difference in amygdalar nuclei volume between the groups. Among patients with bvFTD and OCB, Y-BOCS score was negatively correlated with left CA2/3 body volume (τb = -0.729, p < 0.001); total NPI score was negatively correlated with left GC-ML-DG body (τb = -0.648, p = 0.001) and total bilateral hippocampal volumes (left, τb = -0.629, p = 0.002; right, τb = -0.455, p = 0.023); and FBI score was negatively correlated with the left molecular layer of the HP body (τb = -0.668, p = 0.001), CA4 body (τb = -0.610, p = 0.002), and hippocampal tail volumes (τb = -0.552, p < 0.006). Mediation analysis confirmed these subfield volumes as direct biomarkers for clinical severity, independent of medial and lateral orbitofrontal volumes. (5) Conclusions: Alterations in hippocampal subfield volumes appear to be crucial in the pathophysiology of OCB development in patients with bvFTD.

Reproducibility of brain dopamine transporter binding with Tc-99m TRODAT-1 SPECT in healthy young men.

Single photon emission computed tomography (SPECT) with Tc-99m TRODAT-1 as ligand can be used to evaluate striatal dopamine transporters (DAT) in young subjects. The purpose of this study was to evaluate the reproducibility of (99m)Tc-TRODAT-1 SPECT in DAT binding in healthy young men. Fourteen healthy young men were recruited. The test-retest studies were performed 1week apart. Specific uptake ratios (SUR) of the striatum (ST) and its subregions, the caudate (CA) and the putamen (PU), were measured using the occipital cortex as the reference tissue. The reliability of the two measurements between test and retest, showed significant correlations for the ST, CA and PU, was demonstrated by calculating the intraclass correlation coefficient (ICC). Thus, (99m)Tc-TRODAT-1 SPECT might provide a reproducible and reliable tool in clinical management of young patients with DAT-related disorders.

The effect of cognitive behavioral group therapy for depression: a meta-analysis 2000-2010.

OBJECTIVE: The goals of the meta-analysis were to investigate the overall effectiveness of cognitive behavioral group therapy (CBGT) for depression and relapse prevention in depression from 2000 to 2010, and to investigate how the variables (episode, residual symptoms, group size, control group, group manual, therapist experience, therapy frequency, session length, and take-home assignment) of a CBGT study could affect the effect size. METHOD: This study collected actual study designs sought of CBGT for depression published from 2000 to 2010. These studies were then cross-referenced using Medical Subject Headings (MeSH) with the following keywords: group therapy, cognitive therapy, cognitive behavioral therapy, cognitive behavioral group therapy, psychotherapy, depression, relapse, and recurrence. The quality of the studies was evaluated using Cochrane Collaboration Guidelines. The effect size of CBGT on depression and relapse prevention in depression used the formula devised by Hedges and Olkin (1985). RESULTS: The study investigated the results of 32 studies on the effect of CBGT for depression. The CBGT had an immediate (g=-0.40) and continuous effect over 6 months (g=-0.38), but no continuous effect after 6 months (g=-0.06). The CBGT lowered the relapse rate of depression (RD = 0.16). Variables significantly different from each other in terms of immediate effect were: CBGT versus usual care, therapy sessions lasting longer than 1 hour, and take-home assignments. Preintervention severity of depression and patient turnover rate were found to be significantly related to the size of the immediate effect. The relapse rate after 6 months was significantly related only to "participants have no residual symptoms/participants did not mention residual symptoms." CONCLUSIONS: Researchers and clinicians should take note that CBGT had a moderate effect on the level of depression and a small effect on the relapse rate of depression. The results of this study suggest that the patient should receive a course of therapy at least every 6 months.

Cognitive factor structure and measurement invariance between healthy controls and patients with major depressive disorder.

Cognitive impairments are crucial in functional outcomes of major depressive disorder (MDD). The effectiveness of currently available treatment methods for cognitive deficits is suboptimal. A cognitive test battery is often applied to evaluate cognition with multiple interrelated and difficult-to-interpret outcomes. Generating cognitive factor scores after the confirmation of a common cognitive structure and measurement invariance between healthy controls (HCs) and patients may aid in understanding cognition further. This methodology has been applied for several neuropsychiatric disorders, but not for MDD. Therefore, we conducted a series of exploratory factor analyses (EFA), confirmatory factor analyses (CFA), and multiple groups CFA (MGCFA) for a cognitive test battery in HCs and patients with MDD. The initial EFA of 106 HCs yielded a three-factor model-comprising attention, memory, and executive function. The CFA confirmed the initial model in other 94 HCs with revisions, which reasonably fit the cognitive data of 54 patients with MDD. MGCFA supported the measurement invariance of the determined model between HCs and patients with MDD. The associations of cognitive factor scores with age or education and the effect sizes of group differences in cognitive factor scores externally validated the determined model. In conclusion, this is the first study to demonstrate the measurement invariance of a cognitive model between HCs and patients with MDD using MGCFA. The measurement invariance substantiated valid group comparisons of factor scores and their relationships with other markers. The current results may be applicable for the development of improved treatment strategies for cognitive impairments in MDD.

Interactions between dopamine transporter and N-methyl-d-aspartate receptor-related amino acids on cognitive impairments in schizophrenia.

BACKGROUND: Cognitive impairments, the main determinants of functional outcomes in schizophrenia, had limited treatment responses and need a better understanding of the mechanisms. Dysfunctions of the dopamine system and N-methyl-d-aspartate receptor (NMDAR), the primary pathophysiologies of schizophrenia, may impair cognition. This study explored the effects and interactions of striatal dopamine transporter (DAT) and plasma NMDAR-related amino acids on cognitive impairments in schizophrenia. METHODS: We recruited 36 schizophrenia patients and 36 age- and sex-matched healthy controls (HC). All participants underwent cognitive assessments of attention, memory, and executive function. Single-photon emission computed tomography with 99mTc-TRODAT and ultra-performance liquid chromatography were applied to determine DAT availability and plasma concentrations of eight amino acids, respectively. RESULTS: Compared with HC, schizophrenia patients had lower cognitive performance, higher methionine concentrations, decreased concentrations of glutamic acid, cysteine, aspartic acid, arginine, the ratio of glutamic acid to gamma-aminobutyric acid (Glu/GABA), and DAT availability in the left caudate nucleus (CN) and putamen. Regarding memory scores, Glu/GABA and the DAT availability in left CN and putamen exhibited positive relationships, while methionine concentrations showed negative associations in all participants. The DAT availability in left CN mediated the methionine-memory relationship. An exploratory backward stepwise regression analysis for the four biological markers associated with memory indicated that DAT availability in left CN and Glu/GABA remained in the final model. CONCLUSIONS: This study demonstrated the interactions of striatal DAT and NMDAR-related amino acids on cognitive impairments in schizophrenia. Future studies to comprehensively evaluate their complex interactions and treatment implications are warranted.

Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers--a SPECT study.

Striatal dopaminergic activity is significantly correlated with various cognitive activities, mood regulation, and even metabolic homeostasis, and is modulated by the dopamine transporter (DAT). The availability of DAT could be regulated by presynaptic autoreceptors, which are G-protein coupled receptors; however, whether functional variations in the common downstream signaling molecule, G-protein, could cause individual differences in presynaptic transporter availability remains unclear. To investigate this relationship, the DAT availability in seventy-eight healthy subjects was approximated using single photon emission computed tomography (SPECT) with [(99m)Tc] TRODAT-1, a radio-labeled form of tropan derivative for the selective labeling of DAT. The C825T single nucleotide polymorphism (SNP) (rs5443) of the beta subunit of the G-protein second messenger (GNß3) gene was genotyped, and analysis of variance showed a significant difference in striatal DAT when referenced to the entire occipital lobe among the three genotypes. Post hoc independent t tests were also performed, and showed that the striatal DAT availability of the CC genotype was higher than that of the other two genotypes. These results indicated that genetic variation in the common downstream signaling molecule of the dopamine autoreceptor could affect the functional status of the striatal dopamine system. These results together with the known role of the GNß3 gene might provide further evidence to support the common effect of the striatal dopamine system on mood and metabolic regulation.

Faster onset of antidepressant effects of citalopram compared with sertraline in drug-naïve first-episode major depressive disorder in a Chinese population: a 6-week double-blind, randomized comparative study.

Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.

Striatal dopamine transporter binding for predicting the development of delayed neuropsychological sequelae in suicide attempters by carbon monoxide poisoning: A SPECT study.

Carbon monoxide poisoning (COP) after charcoal burning results in delayed neuropsychological sequelae (DNS), which show clinical resemblance to Parkinson's disease, without adequate predictors at present. This study examined the role of dopamine transporter (DAT) binding for the prediction of DNS. Twenty-seven suicide attempters with COP were recruited. Seven of them developed DNS, while the remainder did not. The striatal DAT binding was measured by single photon emission computed tomography with (99m)Tc-TRODAT. The specific uptake ratio was derived based on a ratio equilibrium model. Using a logistic regression model, multiple clinical variables were examined as potential predictors for DNS. COP patients with DNS had a lower binding on left striatal DAT binding than patients without DNS. Logistic regression analysis showed that a combination of initial loss of consciousness and lower left striatal DAT binding predicted the development of DNS. Our data indicate that the left striatal DAT binding could help to predict the development of DNS. This finding not only demonstrates the feasibility of brain imaging techniques for predicting the development of DNS but will also help clinicians to improve the quality of care for COP patients.

Short term vs. long term test-retest reproducibility of ¹²³I-ADAM for the binding of serotonin transporters in the human brain.

Previous brain imaging studies have demonstrated a seasonal difference of serotonin transporter (SERT) binding in the human brain. However, the results were somewhat contradictory. We conducted test-retest study with single photon emission computed tomography (SPECT) with ¹²³I-ADAM as ligand in 28 healthy subjects. Ten of the subjects were studied within 1 month, whereas 18 were randomly assigned to be studied over a period of up to 1 year. The primary measure was the specific uptake ratio (SUR). Regions of interest included the midbrain, thalamus, putamen and caudate. The intra-class correlation coefficient (ICC) was 0.52-0.94 across different brain regions over 1 month, whereas the ICC was -0.24-0.63 over a 1-year period. The 1-month variability ranged from 6.5 ± 5.1% to 12.5 ± 10.6% across different brain regions, and the 1-year variability ranged from 16.5 ± 9.6% to 41.9 ± 35.5%. The Kruskal-Wallis test revealed a significant difference of variability across months. The Wilcoxon Signed Ranks Test showed the SUR between test-retest scans was of borderline significance. Curve fitting, using a 4th degree polynomial model, revealed a significant circadian correlation between the variability and interval of test-retest measurements. Our findings demonstrate the test-retest reproducibility of ¹²³I-ADAM in different time periods and suggest that circadian variation of SERT levels in the human brain might exist.

Sub-regional hippocampal volumes in first-episode drug-naïve major depression disorder.

Hippocampal volume reduction was reported to underlie depressive symptomatology, however, the evidence to date remains inconsistent. For the complex intrinsic organization of hippocampus, the hippocampal volumes can be further divided into subfields or axial parts. The current study aimed to explore the alterations of hippocampal sub-regional volumes in first episode drug-naïve major depressive disorder (MDD) by two segmentation methods. Thirty-five first-episode drug-naïve MDD and 35 age- and gender-matched healthy controls (HC) were recruited. Volumes of three sub-regions of hippocampus along the longitudinal axis (head, body and tail) were analyzed manually and eight transverse subfields were automatically determined using FreeSurfer. An asymmetric index (AI) of volumes was defined as (∣Left - Right∣/∣Left + Right∣) * 100. There were significant reductions in the volumes of bilateral hippocampal head in MDD compared to HC. The volumes of eight subfields were not different between groups. MDD patients had higher AI values in the subfield of cornu ammonis 4/dentate gyrus than HC. The change in hippocampal sub-regional volumes might be an imaging biomarker in the first-episode, drug-naïve patients with MDD. Current findings may contribute to developing new diagnostic and therapeutic strategies for major depression.