A Fully Automated Visual Grading System for White Matter Hyperintensities of T2-Fluid Attenuated Inversion Recovery Magnetic Resonance Imaging.

BACKGROUND: The Fazekas scale is one of the most commonly used visual grading systems for white matter hyperintensity (WMH) for brain disorders like dementia from T2-fluid attenuated inversion recovery magnetic resonance (MR) images (T2-FLAIRs). However, the visual grading of the Fazekas scale suffers from low-intra and inter-rater reliability and high labor-intensive work. Therefore, we developed a fully automated visual grading system using quantifiable measurements. METHODS: Our approach involves four stages: (1) the deep learning-based segmentation of ventricles and WMH lesions, (2) the categorization into periventricular white matter hyperintensity (PWMH) and deep white matter hyperintensity (DWMH), (3) the WMH diameter measurement, and (4) automated scoring, following the quantifiable method modified for Fazekas grading. We compared the performances of our method and that of the modified Fazekas scale graded by three neuroradiologists for 404 subjects with T2-FLAIR utilized from a clinical site in Korea. RESULTS: The Krippendorff's alpha across our method and raters (A) versus those only between the radiologists (R) were comparable, showing substantial (0.694 vs. 0.732; 0.658 vs. 0.671) and moderate (0.579 vs. 0.586) level of agreements for the modified Fazekas, the DWMH, and the PWMH scales, respectively. Also, the average of areas under the receiver operating characteristic curve between the radiologists (0.80 ± 0.09) and the radiologists against our approach (0.80 ± 0.03) was comparable. CONCLUSIONS: Our fully automated visual grading system for WMH demonstrated comparable performance to the radiologists, which we believe has the potential to assist the radiologist in clinical findings with unbiased and consistent scoring.

Impact of Transcranial Direct Current Stimulation on Cognitive Function, Brain Functional Segregation, and Integration in Patients with Mild Cognitive Impairment According to Amyloid-Beta Deposition and APOE ε4-Allele: A Pilot Study.

Anodal transcranial direct current stimulation (anodal-tDCS) is known to improve cognition and normalize abnormal network configuration during resting-state functional magnetic resonance imaging (fMRI) in patients with mild cognitive impairment (MCI). We aimed to evaluate the impact of sequential anodal-tDCS on cognitive functions, functional segregation, and integration parameters in patients with MCI, according to high-risk factors for Alzheimer's disease (AD): amyloid-beta (Aß) deposition and APOE ε4-allele status. In 32 patients with MCI ([18 F] flutemetamol-: n = 10, [18 F] flutemetamol+: n = 22; APOE ε4-: n = 13, APOE ε4+: n = 19), we delivered anodal-tDCS (2 mA/day, five times/week, for 2 weeks) over the left dorsolateral prefrontal cortex and assessed the neuropsychological test battery and resting-state fMRI measurements before and after 2 weeks stimulation. We observed a non-significant impact of an anodal-tDCS on changes in neuropsychological battery scores between MCI patients with and without high-risk factors of AD, Aß retention and APOE ε4-allele. However, there was a significant difference in brain functional segregation and integration parameters between MCI patients with and without AD high-risk factors. We also found a significant effect of tDCS-by-APOE ε4-allele interaction on changes in the functional segregation parameter of the temporal pole. In addition, baseline Aß deposition significantly associated negatively with change in global functional integrity of hippocampal formation. Anodal-tDCS might help to enhance restorative and compensatory intrinsic functional changes in MCI patients, modulated by the presence of Aß retention and the APOE ε4-allele.

Regional cortical thickness and subcortical volume changes in patients with metabolic syndrome.

Although previous studies have demonstrated an association between metabolic syndrome (MS) and changes in the integrity of cerebral white matter, no study has evaluated cortical thickness or subcortical volumes in MS with MRI. The purpose of our study was to investigate changes in cortical thickness and subcortical volume in an asymptomatic MS population. A total of 86 asymptomatic subjects (40 patients with MS and 46 subjects without MS) underwent 3T brain MRI scanning, and cortical thickness was compared between the groups across multiple locations. The subcortical volumes were also compared on a structure-by-structure basis. ANCOVA adjusted for age, education, total intracranial volume (TIV), and gender revealed significant volume reductions in the right nucleus accumbens in the MS group compared with the control group. The MS group showed a significant reduction in mean cortical thickness and volume in both hemispheres compared with controls. A group comparison analysis of the regional cortical thickness between the two groups also revealed significant reductions in cortical thickness in the MS group in the left insular, superior parietal, postcentral, entorhinal, and right superior parietal cortices compared with those of the control group (all comparisons p < 0.05, FDR corrected). We demonstrated a significant reduction in cortical and subcortical areas in MS patients, especially in areas involved in body weight control and cognitive function. Our results suggest an initial neurodegenerative process according to metabolic syndrome even in the preclinical stage, and further prospective studies are required to evaluate this process.

Sub-regional volumes changes of the corpus callosum in the drug naive patients with late-onset depression.

Although sub-regional analysis methods of the corpus callosum (CC) have been developed, there has been no in vivo magnetic resonance imaging (MRI) study on a sub-regional volume analysis of the CC of late-onset depression (LOD). The aim of this study was to investigate the CC volume differences between LOD subjects and healthy elderly controls using a sub-regional analysis technique. Forty subjects with LOD and thirty nine group-matched healthy control subjects underwent 3T MRI scanning, and sub-regional volumes of the CC were measured and compared between the groups. The volumes of total (F=5.8, p=0.001), the anterior (F=5.2, p=0.001) and the posterior CC (F=5.1, p=0.001) were significantly reduced in the LOD group as compared to the control group. We measured cognitive functions in several different domains (language functions, verbal learning, visuospatial functions, delayed recall, memory consolidation, recognition memory, and executive functions) through the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease. The anterior CC volume in the LOD group showed significant positive correlation with the Verbal Fluency scores. The posterior CC volume in the LOD group was positively correlated significantly with the Word List Memory, the Word List Recall and the Constructional Praxis scores. This study is the first to elaborate the sub-regional volume differences of the CC between controls and LOD patients. These structural changes in the CC might be at the core of the underlying neurobiological mechanisms in LOD.

Sleep and cognitive problems in patients with attention-deficit hyperactivity disorder.

OBJECTIVES: Attention-deficit hyperactivity disorder (ADHD) is characterized by inattentive and impulsive behavior. Many ADHD patients reportedly have cognitive dysfunction and sleep problems, including longer sleep latency, lower sleep efficiency, and shorter total sleep time. The purpose of this study was to examine neurocognitive functions and nocturnal sleep parameters in patients with ADHD, using a cognitive function test and actigraphy. METHODS: Subjects included 37 male patients with ADHD and 32 controls (7-12 years of age). For each participant, we determined intelligence quotient (IQ) and administered the Matching Familiar Figures Test (MFFT) and 72-hour actigraphy. The relationships between sleep parameters and cognitive functions were assessed. RESULTS: ADHD patients significantly differed from controls in several cognitive functions and sleep variables. In the MFFT, response error rate (P<0.001) and error counts (P=0.003) were significantly increased in ADHD patients compared with control children. MFFT response latency was significantly shorter in ADHD patients than in controls (P<0.001). In addition, sleep latency (P=0.01), wake after sleep onset (WASO) (P<0.001), and fragmentation index (P<0.001) were evaluated by actigraphy and found to be significantly increased in patients with ADHD compared with controls. However, no significant differences in total sleep time or sleep efficiency were observed. WASO and response error rates were positively correlated in patients with ADHD (rho =0.52, P=0.012). Furthermore, fragmentation index sleep variables were significantly positively correlated with response error (rho =0.44, P=0.008) and response latency rates (rho =0.4, P=0.018) in the MFFT. Reaction error rate was significantly associated with the fragmentation index (beta =0.94, P=0.024). CONCLUSION: Patients with ADHD had more sleep problems, including significantly increased sleep latency, WASO, and fragmentation index, and poorer cognitive function, compared with controls. Some of these sleep problems, including WASO and the fragmentation index, were positively correlated with impulsivity, illustrated by the cognitive function tests in patients with ADHD. However, further studies with large sample sizes and the addition of polysomnography and determination of ADHD subtypes should be performed to confirm our results regarding sleep and cognitive problems in patients with ADHD.

Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics.

The aim of this study was to investigate the microstructural alterations of white matter (WM) in Alzheimer's disease (AD) patients with apathy and to observe the relationships with the severity of apathy. Sixty drug-naïve subjects took part in this study (30 apathetic and 30 nonapathetic subjects with AD). The loss of integrity in WM was compared in AD patients with and without apathy through measurement of fractional anisotropy (FA) using by tract-based spatial statistics (TBSS). In addition, we explored the correlation pattern between FA values and the severity of apathy in AD patients with apathy. The apathy group had significantly reduced FA values (p(corrected)<0.05) in the genu of the corpus callosum compared to the nonapathy group. The severity of apathy was negatively correlated with FA values of the left anterior and posterior cingulum, right superior longitudinal fasciculus, splenium, body and genu of the corpus callosum and bilateral uncinate fasciculusin the apathy group (p(corrected)<0.05). This study was the first to explore FA values in whole brain WM in AD patients with apathy. The findings of these microstructural alterations of WM may be the key to the understanding of underlying neurobiological mechanism and clinical significances of apathy in AD.

Hippocampal shape and cognitive performance in amnestic mild cognitive impairment.

Previous studies have carried out hippocampal shape analysis of amnestic mild cognitive impairment (aMCI) patients using automated segmentation techniques. However, the relationships between hippocampal deformations and various episodic memory impairments were not clear. The aim of this study was to investigate hippocampal shape changes and their relationships with various episodic memory impairments in aMCI. Hippocampal volumes and deformations were compared between the aMCI and the controls. In addition, we explored the correlation pattern between hippocampal deformations and cognitive dysfunctions in aMCI using a comprehensive neuropsychological battery. Patients with aMCI exhibited significant hippocampal deformations in the right cornu ammonis 1 (CA1) and subiculum areas compared with healthy individuals. Significant correlations were observed between constructional recall scores and the right CA1 and subiculum areas in aMCI. Verbal delayed recall scores were also significantly correlated with the left CA1 and subiculum areas in aMCI. This study was the first to explore the relationships between hippocampal deformations and various types of cognitive performances in aMCI. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction and their relevance to verbal and visuospatial delayed recall in aMCI.

A validation study of the Korean version of SPAN.

PURPOSE: The SPAN, which is acronym standing for its four components: Startle, Physiological arousal, Anger, and Numbness, is a short post-traumatic stress disorder (PTSD) screening scale. This study sought to develop and validate a Korean version of the SPAN (SPAN-K). MATERIALS AND METHODS: Ninety-three PTSD patients (PTSD group), 73 patients with non-psychotic psychiatric disorders (psychiatric control group), and 88 healthy participants (normal control group) were recruited for this study. Participants completed a variety of psychiatric assessments including the SPAN-K, the Davidson Trauma Scale (DTS), the Clinician-Administered PTSD Scale (CAPS), and the State-Trait Anxiety Inventory (STAI). RESULTS: Cronbach's α and test-retest reliability values for the SPAN-K were both 0.80. Mean SPAN-K scores were 10.06 for the PTSD group, 4.94 for the psychiatric control group, and 1.42 for the normal control group. With respect to concurrent validity, correlation coefficients were 0.87 for SPAN-K vs. CAPS total scores (p<0.001) and 0.86 for SPAN-K vs. DTS scores (p<0.001). Additionally, correlation coefficients were 0.31 and 0.42 for SPAN-K vs. STAI-S and STAI-T, respectively. Receiver operating characteristic analysis of SPAN-K showed good diagnostic accuracy with an area under the curve (AUC) of 0.87. The SPAN-K showed the highest efficiency at a cutoff score of 7, with a sensitivity of 0.83, a specificity of 0.81, positive predictive value (PPV) of 0.88, and negative predictive value (NPV) of 0.73. CONCLUSION: These results suggest that the SPAN-K had good psychometric properties and may be a useful instrument for rapid screening of PTSD patients.

Effect of dance exercise on cognitive function in elderly patients with metabolic syndrome: a pilot study.

Metabolic syndrome is associated with an increased risk of cognitive impairment. The purpose of this prospective pilot study was to examine the effects of dance exercise on cognitive function in elderly patients with metabolic syndrome. The participants included 38 elderly metabolic syndrome patients with normal cognitive function (26 exercise group and 12 control group). The exercise group performed dance exercise twice a week for 6 months. Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K). Repeated-measures ANCOVA was used to assess the effect of dance exercise on cognitive function and cardiometabolic risk factors. Compared with the control group, the exercise group significantly improved in verbal fluency (p = 0.048), word list delayed recall (p = 0.038), word list recognition (p = 0.007), and total CERAD-K score (p = 0.037). However, no significance difference was found in body mass index, blood pressure, waist circumference, fasting plasma glucose, triglyceride, and HDL cholesterol between groups over the 6-month period. In the present study, six months of dance exercise improved cognitive function in older adults with metabolic syndrome. Thus, dance exercise may reduce the risk for cognitive disorders in elderly people with metabolic syndrome. Key pointsMetabolic syndrome (MS) is associated with an increased risk of cognitive impairment.Aerobic exercise improves cognitive function in elderly people and contributes to the prevention of degenerative neurological disease and brain damage. Dance sport is a form of aerobic exercise that has the additional benefits of stimulating the emotions, promoting social interaction, and exposing subjects to acoustic stimulation and music.In the present study, dance exercise for a 6-month period improved cognitive function in older adults with MS. In particular, positive effects were observed in verbal fluency, word list delayed recall, word list recognition, and the total CERAD-K score.Our data suggest that the implementation of dance exercise programs may be an effective means of prevention and treatment of cognitive disorders.

Reliability and validity of the Korean version of the Impact of Event Scale-Revised.

OBJECTIVES: The aim of this study was to explore the reliability and validity of the Impact of Event Scale-Revised Korean version (IES-R-K), a self-report scale for assessment of posttraumatic stress disorder (PTSD). METHODS: The original Impact of Event Scale-Revised was translated into Korean, and the comparability of content was verified through back-translation procedures. This multicenter study included 93 patients with PTSD, 73 nonpsychotic psychiatric patients, and 88 healthy controls drawn from 18 hospitals across the country. The subjects were assessed using IES-R-K, Clinician-Administered PTSD Scale (CAPS), Beck Depression Inventory, and State Trait Anxiety Inventory (STAI; state anxiety subscale [STAI-S], trait anxiety subscale [STAI-T]) scales. RESULTS: In the reliability test, Cronbach alpha coefficient and test-retest reliability were .93 and 0.91, respectively, indicating that the IES-R-K has good internal consistency. One-way analysis of variance revealed significant differences in IES-R-K scores among the patients with PTSD, nonpsychotic psychiatric patients, and healthy controls (F = 139.1, P < .001). Duncan post hoc test showed the significant differences among the 3 groups. To assess the validity of the IES-R-K, correlation coefficient between the IES-R-K and CAPS, STAI-S, and STAI-T was calculated. We found that there was a relatively high degree of correlation between the IES-R-K and CAPS (r = 0.92, P < .001). However, there was a relatively less degree of correlation between STAI-S and STAI-T and IES-R-K (r = 0.30, P < .001). Taken these together, IES-R-K showed good discriminant validity. CONCLUSION: The IES-R-K showed good reliability and validity for the assessment of PTSD symptom severity. The IES-R-K is a useful instrument for assessing PTSD symptoms in Korea.

Psychometric validation of the Korean version of Structured Interview for Post-traumatic Stress Disorder (K-SIP).

For diagnosis and management of post-traumatic stress disorder (PTSD), the easily administered assessment tool is essential. Structured Interview for PTSD (SIP) is a validated, 17-item, simple measurement being used widely. We aimed to develop the Korean version of SIP (K-SIP) and investigated its psychometric properties. Ninety-three subjects with PTSD, 73 subjects with mood disorder or anxiety disorder as a psychiatric control group, and 88 subjects as a healthy control group were enrolled in this study. All subjects completed psychometric assessments that included the K-SIP, the Korean versions of the Clinician-Administered PTSD Scale (CAPS) and other assessment tools. The K-SIP presented good internal consistency (Cronbach's alpha=0.92) and test-retest reliability (r=0.87). K-SIP showed strong correlations with CAPS (r=0.72). Among three groups including PTSD patients, psychiatric controls, and normal controls, there were significant differences in the K-SIP total score. The potential cut-off total score of K-SIP was 20 with highest diagnostic efficiency (91.9%). At this point, the sensitivity and specificity were 95.5% and 88.4%, respectively. Our result showed that K-SIP had good reliability and validity. We expect that K-SIP will be used as a simple but structured instrument for assessment of PTSD.

Verbal working memory dysfunction in schizophrenia: an FMRI investigation.

Impaired processing of working memory information is one of the cognitive deficits seen in patients with schizophrenia. This study aims at corroborating the differences in the brain activities involved in the process of working memory between patients with schizophrenia and the controls. Twelve patients with schizophrenia and 11 controls participated in the study. Functional magnetic resonance imaging (fMRI) was used to assess cortical activities during the performance of a two-back verbal working memory paradigm using the Korean alphabet as mnemonic content. Group analysis revealed that inferior fontal, middle frontal, and superior temporal region showed decreased cortical activities in the patient group compared to those of the controls. This study showed a decreased activation in inferior fontal (BA 47), middle frontal (BA 6), and superior temporal (BA 22/38) neural networks from the patient group and confirmed the earlier findings on the impaired working memory of schizophrenic patients in the fMRI investigation.

Altered verbal working memory process in patients with Alzheimer's disease: an fMRI investigation.

Impaired working memory processing is one of the broad range of cognitive deficits in patients with Alzheimer's disease (AD). We aimed to elucidate the differences in brain activities involved in the process of working memory between AD patients and healthy comparison subjects. Twelve patients with AD were recruited along with 12 healthy volunteers as a comparison group. Functional magnetic resonance imaging was employed to assess cortical activities during the performance of a 1-back working memory paradigm using the Korean alphabet as mnemonic content. Subsequently, the difference in neural activities between the 2 groups was analyzed. The AD group performed the tasks with reduced accuracy. Group comparison analysis revealed that the AD group showed decreased brain activity in the left frontal pole (Brodmann area, BA, 10), the left ventrolateral prefrontal cortex (BA47), the left insula (BA13) and the right premotor cortex (BA6) compared to the control group. The AD group showed increased activation in the left precuneus (BA7) compared to the control group. A decreased level of activation in the prefrontal cortex and an increased level of activation in the parietal neural networks from the patient group may document an altered verbal working memory process in the patients with AD.

Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and Alzheimer's disease.

Soluble fractalkine plays a distinctive role in the inflammatory processes of the nervous system; however, the role of soluble fractalkine in Alzheimer's disease (AD) has not yet been investigated. In the present study, we evaluated the levels of plasma soluble fractalkine in patients with mild cognitive impairment (MCI), patients with AD and healthy controls. We also investigated the changes in the levels of plasma soluble fractalkine in patients with AD. A total of 102 patients with cognitive impairment, including 51 patients with MCI, 51 patients with AD, and 57 healthy control subjects, were enrolled in this study. The Mini-Mental Status Examination (MMSE) was used to evaluate the severity of cognitive impairment in patients with MCI and AD. The levels of plasma soluble fractalkine were measured using a specific enzyme-linked immunosorbent assay. There were significant group differences in the levels of plasma soluble fractalkine between the MCI, AD, and control groups. Post hoc analyses revealed significant differences between the MCI and control groups, the AD and control groups, and the MCI and AD groups. The level of plasma soluble fractalkine was significantly greater in the patients with mild to moderate AD than in the patients with severe AD. In addition, there was a positive correlation between MMSE score and plasma soluble fractalkine level in the patients with AD. This study provides preliminary evidence that soluble fractalkine is involved in the pathogenesis of AD.

Reliability and validity of the Korean version of the Davidson Trauma Scale.

The Davidson Trauma Scale (DTS) is a validated, 17-item, brief global assessment scale for posttraumatic stress disorder (PTSD). The purposes of this study were to develop a Korean version of the DTS (DTS-K) while maintaining its basic structure and to evaluate its reliability and validity for the Korean population. Participants of this study included 93 patients with PTSD (PTSD group), 73 patients with nonpsychotic mood or other anxiety disorders (psychiatric control group), and 88 healthy controls (normal control group). Subjects completed psychometric assessments, including the DTS-K and the Korean version of the Clinician-Administered PTSD Scale and the State Trait Anxiety Inventory. The DTS-K showed good internal consistency (Cronbach alpha = .97) and test-retest reliability (r = .93). The DTS-K showed a significantly positive correlation with Clinician-Administered PTSD Scale (r = .94). The highest diagnostic efficiency of DTS-K was at a total score of 47, with sensitivity and specificity of 0.87 and 0.84, respectively. Our findings suggest that the DTS-K is composed of good psychometric properties and is a valid and reliable tool for assessing the frequency and severity of PTSD symptoms regardless of ethnicity.

Psychometric properties of the Korean version of the Short Post-Traumatic Stress Disorder Rating Interview (K-SPRINT).

AIMS: The Short Post-traumatic Stress Disorder (PTSD) Rating Interview (SPRINT) is a validated, eight-item, brief global assessment scale for PTSD. This report investigated the psychometric properties of the Korean version of the SPRINT (K-SPRINT). METHODS: Eighty-seven PTSD patients, 47 other psychiatric patients, and 63 healthy control subjects were enrolled in the study. All subjects completed a psychometric assessment package that included the K-SPRINT and the Korean versions of the Clinician-Administered PTSD Scale (CAPS), the Beck Depression Inventory (BDI), and the State Trait Anxiety Inventory (STAI). RESULTS: The K-SPRINT showed good internal consistency (Cronbach's alpha = 0.86) and test-retest reliability (r = 0.82). K-SPRINT showed moderatecorrelations with CAPS (r = 0.71). An exploratory factor analysis produced one K-SPRINT factor. The optimal diagnostic efficiency (91.9%) of the K-SPRINT was found at a total score of 15, at which point the sensitivity and specificity were 90.8% and 92.7%, respectively. CONCLUSIONS: The present findings demonstrate that the K-SPRINT had good psychometric properties and can be used as a reliable and valid instrument for the assessment of PTSD.

Fatigue as a core symptom in major depressive disorder: overview and the role of bupropion.

Fatigue is one of the most common symptoms found in both community and medical care settings. Fatigue may imply a prodromal or residual symptom of major depressive disorder or an adverse reaction to antidepressant treatment. Fatigue may also compromise antidepressant treatment by delaying response to antidepressants. Despite the importance of fatigue as a core depressive symptom, data specific to the effects of fatigue on pharmacological treatment are still lacking. Bupropion is an atypical antidepressant, chemically unrelated to classical agents such as tricyclic antidepressants, selective serotonin reuptake inhibitors and other contemporary antidepressants. With a pharmacological profile that involves neurotransmitter reuptake inhibition, bupropion shares a broad range of biological properties with psychostimulants. The primary action mode of bupropion involves dopaminergic and noradrenergic neurotransmissions rather than serotonergic mechanisms, although its exact pharmacodynamic properties remain uncertain. Hence, it is possible that bupropion may play a role in the treatment of fatigue-related symptoms of major depressive disorder. This paper presents a brief overview of the clinical implications and neurobiology of major depressive disorder-related fatigue, as well as the pharmacological profile of bupropion and currently available clinical data related to its treatment of fatigue-related symptoms of major depressive disorder.

Selegiline transdermal system: current awareness and promise.

Many monoamine oxidase inhibitors (MAOIs) have been used to treat major depressive disorder (MDD). However, the prescription of MAOIs has decreased considerably as a result of side effects such as tyramine-induced hypertensive crisis, which is also known as the 'Cheese Effect'. The drug delivery system itself can affect the bioavailability of certain drugs, which might influence the efficacy and tolerability of medications, as well as improve the compliance and reduce the incidence of recurrence and relapse. Therefore, there is a need for advanced drug delivery techniques that can evade the potentially hazardous toxic effects of the parent compound, including extended-release oral, cutaneous, intravesical and intravaginal routes, etc. In this context, the selegiline transdermal system (STS, EMSAM) was introduced with improved side effect profiles and efficacy compared with the conventional form of the selegiline oral tablet. STS allows the targeted inhibition of the monoamine A (MAO-A) and MAO-B isoenzymes with minimal effects on the MAO-A in the gastrointestinal and hepatic systems. Hence, STS can reduce the risk of interactions with tyramine-rich foods. Many fundamental clinical and preclinical studies have reported that 6 mg/24 h of STS is effective against MDD without the need for dietary restrictions with an equal efficacy and improved safety profile. In addition, STS might benefit MDD patients with atypical features or who are resistant to other antidepressants. Overall, familiarity with the properties and indications of STS will have the clinicians another option of biological treatments for MDD patients but subsequent more data including actual post-market clinical experiences will be mandatory.

Extended-release formulation of venlafaxine in the treatment of post-traumatic stress disorder.

There is abundant evidence for abnormalities of both norepinephrine and serotonin neurotransmitter systems in post-traumatic stress disorder (PTSD). Venlafaxine extended-release formulation (venlafaxine XR) is a serotonin and norepinephrine re-uptake inhibitor with antidepressant and anxiolytic properties relevant to the pathophysiology of PTSD. Venlafaxine XR is currently approved for the treatment of panic disorder, generalized anxiety disorder and social anxiety disorder, as well as major depression in adults, based on a number of randomized, double blind, placebo-controlled clinical trials. Limited data also demonstrate that venlafaxine XR maintains a therapeutic response for more than 6 months in these anxiety disorders. Venlafaxine XR has demonstrated short- and long-term efficacy for the treatment of PTSD in two recent randomized, double-blind, placebo-controlled clinical trials, although it has not been extensively studied for PTSD, compared with other anxiety disorders. This review focuses on the potential role of venlafaxine XR in the treatment of PTSD, based on currently available evidence.