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This study examined the validity and reliability of the Korean version of the Generalized Anxiety Disorder‐7 (GAD‐7) scale. The GAD‐7 was standardized with data from 112 patients at a psychiatric outpatient clinic. The GAD‐7 revealed high internal consistency, good test‐retest reliability, and convergent validity. The ROC analysis resulted in poor sensitivity and specificity for detecting anxiety disorders in a psychiatric setting. The GAD‐7 may not be useful in diagnosing anxiety disorders in a psychiatric setting, even though it appears to be a reliable, efficient, and valid measurement tool for evaluating anxiety symptoms. [ABSTRACT FROM AUTHOR]

Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (pFDR = 1.95 × 10–6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients. [ABSTRACT FROM AUTHOR]

ABSTRACTBackground:Complement factor H (CFH) plays a key role in regulating the cascade of the alternative pathway of the complement system. Dysregulation of CFH may be involved in the pathophysiology of various inflammation-mediated diseases including neuropsychiatric illnesses. This study aimed to investigate this relationship by examining determining CFH levels in elderly individuals with and without depression.Methods: A total of 152 elderly individuals (major depressive disorder (MDD) group, n = 76; comparison sample, n = 76) were selected from the Ansan Geriatric study. The plasma level of CFH was measured. MDD was diagnosed with the Mini-International Neuropsychiatric Interview as per DSM-IV criteria. The severity of depression was evaluated with the geriatric depression scale (GDS). Mean CFH levels were compared using the Mann-Whitney U test. After adjusting for possible confounding factors including age, sex, marital status, education, alcohol use, hemoglobin levels, and the Korean version of the Mini-Mental State Examination (MMSE-KC), a multiple regression analysis was conducted. The GDS score and plasma level of CFH were analyzed using Spearman's correlation.Results: Plasma CFH level was significantly higher in individuals with MDD than in the comparison sample (289.51 ± 21.16 vs. 339.67 ± 66.23, p < 0.001). In a regression model adjusted for possible confounders, CFH was significantly associated with geriatric depression (p < 0.001). CFH levels were not significantly related to GDS scores in the depressed group.Conclusion: This study revealed an association between high plasma levels of CFH and geriatric depression, thereby suggesting the alternative pathway of the complement system contributing to the development of geriatric depression. [ABSTRACT FROM AUTHOR]

Introduction: Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment.Methods: Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6-8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested.Results: None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p < 0.01) was observed for HTR2A, BDNF, CHL1, RORA and HOMER1 SNPs. In secondary analyses, HTR2A (rs643627, p = 0.002) and CHL1 (rs4003413, p = 0.002) were found associated with risk for BD, HOMER1 (rs6872497, p = 0.002) with lifetime history of suicide attempt in patients, and RORA with early onset and presence of psychotic features in BD. Marginal results were also observed for ST8SIA2 and COMT.Discussion: Despite limitations linked to multiple testing on small samples, methodological shortcomings and small significance of the findings, this study may support the involvement of some candidate genes in the outcomes of treatments for mood disorders, as well as in BD risk and other disease features. [ABSTRACT FROM AUTHOR]

Introduction: Countless antidepressant randomized trials were conducted and showed statistically significant benefits of selective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) over placebo. Meanwhile, critics are increasing regarding the efficacy of antidepressants in the treatment of MDD because at least a proportion of clinical trials could be hampered by various biases. In contrast, number of failed trials is increasing in the recent years which have made developing psychiatric medications progressively more time-consuming and expensive. Areas covered: Biases and related issues in clinical trials for antidepressants can be identified as an important common contributing factor to the two paradoxical phenomenon. This review identifies possible biases that can occur before, during, and after clinical trials of antidepressant. Expert commentary: Recent studies not only may over-estimate efficacy of antidepressants, but also may exaggerate placebo response because of various biases. Sponsorship and publication biases have been one of the targets of the criticism and ethical debate. Thus, initiating new trend of research by re-organizing academic-industry partnership will be the most important task in the next five years. [ABSTRACT FROM PUBLISHER]

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response. [ABSTRACT FROM AUTHOR]

Purpose: This study developed formulas to predict obstructive sleep apnea (OSA) and the Apnea-Hypopnea Index (AHI) in Korean patients with suspected OSA using clinical, anthropometric, and cephalometric variables. Methods: We evaluated relevant variables in 285 subjects with suspected OSA. These included demographic characteristics, sleep-related symptoms, medical history, clinical scales, anthropometric measurements including facial surface measurements, and cephalometric measurements. All participants underwent full-night laboratory polysomnography. The prediction formula for the probability of OSA was created by logistic regression analysis and confirmed by the bootstrap resampling technique. The formula for predicting the AHI was developed using multiple linear regression analysis. Results: The probability of having OSA was as follows: p = 1 / (1 + exponential (exp)), where f = −16.508 + 1.445 × loudness of snoring 4 + 0.485 × loudness of snoring 3 + 0.078 × waist circumference + 0.209 × subnasale-to-stomion distance + 0.183 × thickness of the uvula (UTH) supine + 0.041 × age. The AHI prediction formula was as follows: −112.606 + 3.516 × body mass index + 0.683 × mandibular plane-hyoid supine + 10.915 × loudness of snoring 4 + 6.933 × loudness of snoring 3 + 1.297 × UTH supine + 0.272 × age. Conclusion: This is the first study to establish formulas to predict OSA and the AHI in Koreans with suspected OSA using cephalometric and other variables. These results will contribute to prioritizing the order in which patients with suspected OSA are referred for polysomnography. [ABSTRACT FROM AUTHOR]

Introduction: There are numerous antidepressants for the treatment of major depressive disorder (MDD) on the market. However, inadequate treatment response, therapeutic lag between drug administration and the onset of clinical improvement, and safety/tolerability issues with the use of contemporary antidepressants have accelerated the search for newer antidepressants with novel mechanisms of action. Areas covered: The authors review novel antidepressants with rapid efficacy for diverse MDD symptoms and have fewer adverse effects (AEs). Mechanisms of action for novel therapeutic molecules are through glutamatergic, opiate, cholinergic receptors and neuroplasticity. We enumerate results from human trials with novel agents in all phases, highlighting proximity to approval and therapeutic potential based on quality of evidence. Expert commentary: There is a huge unmet need to diversify conventional antidepressant targets. Glutamatergic and opiate agents may be most promising among newer therapeutic agents. It is also important to develop advanced but flexible synergistic treatment strategies with newer therapeutic agents that are usable in routine clinical practice. This would include combining newer molecules with existing antidepressants and using molecules that target specific symptom dimensions of MDD. These strategies would lead to a systematic approach to tackle treatment resistant depression (TRD) and treatment of residual symptoms in partially remitted MDD. [ABSTRACT FROM PUBLISHER]

Background: This study aimed to evaluate the psychometric properties of the Korean version of the Clinically Useful Anxiety Outcome Scale (CUXOS) and to examine the current diagnostic comorbidity and differential severity of anxiety symptoms between major depressive disorder (MDD) and anxiety disorders. Methodology: In total, 838 psychiatric outpatients were analyzed at their intake appointment. Diagnostic characteristics were examined using the structured clinical interview from the DSM-IV because the DSM5 was not available at the start of the study. The CUXOS score was measured and compared with that of 3 clinician rating scales and 4 self-report scales. Principal findings: The CUXOS showed excellent results for internal consistency (Cronbach’s α = 0.90), test–retest reliability (r = 0.74), and discriminant and convergent validity. The CUXOS significantly discriminated between different levels of anxiety severity, and the measure was sensitive to change after treatment. Approximately 45% of patients with MDD were additionally diagnosed with anxiety disorders while 55% of patients with anxiety disorders additionally reported an MDD. There was a significant difference in CUXOS scores between diagnostic categories (MDD only, anxiety only, both disorders, and no MDD or anxiety disorder). The CUXOS scores differed significantly between all categories of depression (major, minor, and non-depression) except for the comparison between minor depression and non-depression groups. Conclusions: The Korean version of the CUXOS is a reliable and valid measure of the severity of anxiety symptoms. The use of the CUXOS could broaden the understanding of coexisting and differentiating characteristics of anxiety and depression. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. Methods: One hundred and thirtytwo subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. Results: Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. Limitations: Limited sample size and risk of false-positive findings. Discussion: Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results. [ABSTRACT FROM AUTHOR]

Introduction: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action.Methods: Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated.Results: Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C-rs12668837 C-rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G-rs2657375 T-rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)-rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters.Conclusion: Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies. [ABSTRACT FROM AUTHOR]

Introduction: Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers.Methods: A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively.Results: In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode.Conclusion: The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders. [ABSTRACT FROM AUTHOR]

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did. [ABSTRACT FROM AUTHOR]

Introduction: Precision medicine is an emerging medical model that can provide accurate diagnoses and tailored therapeutic strategies for patients based on data pertaining to genes, microbiomes, environment, family history and lifestyle. Areas covered: Here, we provide basic information about precision medicine and newly introduced concepts, such as the precision medicine ecosystem and big data processing, and omics technologies including pharmacogenomics, pharamacometabolomics, pharmacoproteomics, pharmacoepigenomics, connectomics and exposomics. The authors review the current state of omics in psychiatry and the future direction of psychopharmacology as it moves towards precision medicine. Expert commentary: Advances in precision medicine have been facilitated by achievements in multiple fields, including large-scale biological databases, powerful methods for characterizing patients (such as genomics, proteomics, metabolomics, diverse cellular assays, and even social networks and mobile health technologies), and computer-based tools for analyzing large amounts of data. [ABSTRACT FROM PUBLISHER]

Background: Previous studies suggest that there is a strong association between depression and cognitive decline, and that concurrent depressive symptoms in MCI patients could contribute to a difference in neurocognitive characteristics compared to MCI patients without depression. The authors tried to compare neurocognitive functions between MCI patients with and without depression by analyzing the results of neuropsychological tests.Methods: Participants included 153 MCI patients. Based on the diagnosis of major depressive disorder, the participants were divided into two groups: depressed MCI (MCI/D+) versus non-depressed MCI (MCI/D-). The general cognitive and functional statuses of participants were evaluated. And a subset of various neuropsychological tests was presented to participants. Demographic and clinical data were analyzed using Student t-test or χ 2 test.Results: A total of 153 participants were divided into two groups: 94 MCI/D+ patients and 59 MCI/D- patients. Age, sex, and years of education were not significantly different between the two groups. There were no significant differences in general cognitive status between MCI/D+ and MCI/D- patients, but MCI/D+ participants showed significantly reduced performance in the six subtests (Contrasting Program, Go-no-go task, Fist-edge-palm task, Constructional Praxis, Memory Recall, TMT-A) compared with MCI/D- patients.Conclusions: There were significantly greater deficits in neurocognitive functions including verbal memory, executive function, attention/processing speed, and visual memory in MCI/D+ participants compared to MCI/D-. Once the biological mechanism is identified, distinct approaches in treatment or prevention will be determined. [ABSTRACT FROM AUTHOR]

Background: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. Methods: Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the 2 statistics. Repeatedmeasure ANOVA was used to test possible influences of single- nucleotide polymorphisms on treatment efficacy. In case of positive findings, clinical and demographic variables were added as covariates, in order to investigate possible stratification bias. Results: The rs2717 and rs6926279 within the NMBR gene and rs702304 and rs2235481 within the EPM2A gene were associated with SCZ liability. rs1415744 was also associated with Positive and Negative Symptom Scale negative clinical improvement. The results remained the same after inclusion of the covariates and were partially confirmed in the allelic and haplotype analyses. Conclusion: Our preliminary findings suggest a possible role of NMBR and EPM2A genes in SCZ susceptibility and, for the second one, also in antipsychotic pharmacogenetics. Nonetheless, further research is needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Despite the availability of numerous antidepressants, many patients with depression do not show adequate response. The therapeutic lag between drug administration and onset of clinical improvement observed with conventional antidepressants has led to a need for antidepressants with a novel mechanism of action. Recently, five such agents, including acetyl-L-carnitine, scopolamine, ω-3 polyunsaturated fatty acids, ketamine, and selective 5-HT7serotonin receptor antagonists, have gained interest as potential antidepressants with enhanced symptom control, improved tolerability, and faster onset of action compared to conventional antidepressants. This review provides an update and critical examination of these five novel therapeutic agents as potential antidepressants. [ABSTRACT FROM PUBLISHER]

Diagnosis of fibromyalgia (FM) remains controversial even though diverse diagnostic criteria have been developed. This review looks at the history, evolution of diagnostic criteria, endless controversy, recent trends and future perspectives regarding FM diagnosis. Some have criticized that diagnosis of FM could lead to medicalization, whereas others have raised concerns of under-diagnosing FM. With the evolution of diagnosis criteria from American College of Rheumatology 1990 to modified American College of Rheumatology 2010, diagnosis of FM has become simpler. The recent trend of applying patient-reported questionnaires has also increased a simpler FM diagnosis. Reliable biomarkers will not be available for the foreseeable future, so diverse assessment tools will have to be used more pro-actively. After initial diagnosis, multiple and comprehensive assessment measures are needed during the course of treatment in order to better understand type and severity of FM symptoms. These, in turn, could help classify FM based on symptom domain, symptom severity, and comorbidity which would enable more personalized treatment. [ABSTRACT FROM AUTHOR]

Due to inadequate efficacy of antidepressants, various new chemical entities and agents of natural origin have been tested for therapeutic efficacy both alone and to augment existing antidepressants, producing varied clinical results. This article summarizes the basic properties of curcumin and its mechanisms of action, with specific emphasis on the etiopathogenesis of depression, preclinical and current clinical evidence, and future research directions, to better understand the possible role of curcumin in treating depression. Curcumin may have antidepressant activities with diverse mechanisms of action involving primarily neurotransmitters, transcription pathways, neurogenesis, the hypothalamic-pituitary-adrenal axis and inflammatory and immune pathways, as demonstrated in various animal and human studies. Current published randomized clinical trials suggest a small, non-significant benefit of curcumin for major depression. More adequately-powered and methodologically improved studies are mandatory. [ABSTRACT FROM AUTHOR]

Introduction Older adults commonly experience somatic symptoms, and those who do are more likely to have depressive disorders as well. Our goal in this study is to examine the influence of the number and severity of somatic symptoms on the severity of depressive symptoms, including suicidality, in elderly adults. Methods This study was conducted as part of the Ansan Geriatric ( AGE) Study, a community-based cohort study in Ansan City, South Korea. A total of 3,210 elderly adults aged 60 years or over (1,388 males and 1,770 females) participated in this study. The Korean version of the Beck Depression Inventory ( BDI) was used to measure depressive symptoms and suicidality. Somatic symptoms were assessed by the Patient Health Questionnaire-15 ( PHQ-15). Results Both mild and severe somatic symptoms significantly increased the risk for severe depression and high suicidality. Severe somatic symptoms doubled the risk for severe depression and suicidal intent. Discussion Somatic symptoms not fully explained as medical illnesses are closely associated with late-life depression, even after adjustments for comorbid physical illnesses and other confounding factors. The presence of somatic symptoms concurrent with, but not fully explained by comorbid physical illness or disability, seems to be an independent marker for predicting the severity of late-life depression and suicidality. [ABSTRACT FROM AUTHOR]

Introduction The objective of the current study was to assess, in a naturalistic treatment setting, the clinical benefits of lamotrigine add-on therapy for patients with bipolar disorder. Methods This was an open-label, prospective, naturalistic, 12-week, observational study that included 98 bipolar patients treated with lamotrigine add-on therapy, in addition to mood stabilizers or atypical antipsychotics for 1-4 weeks. The clinical benefits of lamotrigine augmentation were evaluated using the Clinical Global Impression- Clinical Benefit ( CGI-CB) Scale, and the Clinical Global Impression of Bipolar Disorder- Severity scale was used to evaluate the severity of the patients' conditions. Results According to paired t-test analyses, the mean CGI-CB score significantly decreased from 7.2 ± 2.7 at baseline to 3.8 ± 2.5 at Week 12. Likewise, the mean score for Clinical Global Impression of Bipolar Disorder- Severity scale significantly decreased from 4.7 ± 0.9 at baseline to 3.1 ± 1.2 at Week 12. Analysis of covariance showed that the extent to which CGI-CB scores changed from baseline to Week 12 did not significantly differ between patients with bipolar I and II disorder. However, the change in CGI-CB scores between Weeks 4 and 12 was significantly smaller in bipolar II patients than bipolar I patients. A total of 21 (21.4%) patients dropped out during the course of the study, and 30 patients (30.6%) reported 82 adverse events. Discussion The results of this study demonstrated that the use of lamotrigine in patients with bipolar disorder, especially those whom conventional mood stabilizers or antipsychotics are insufficiently effective or intolerable, can be beneficial regardless of the type of bipolar disorder. [ABSTRACT FROM AUTHOR]

Objective. The gene coding for the catechol-O-methyltransferase ( COMT) and the one coding for the dopamine receptor 2 ( DRD2) have been linked with major depression (MD) and with the response to antidepressants in several studies. However, contrasting findings have been reported as well. The aim of the present study is, therefore, to investigate possible influences of rs4680 within COMT and rs6276 within DRD2, analyzed both individually and in combination, on the diagnosis and clinical outcomes in a sample of Korean MD patients treated with antidepressants. Methods. Totally, 184 Korean in-patients suffering from MD treated with either paroxetine or venlafaxine and 220 healthy control subjects were included in the present study. Depression severity was assessed by means of the Hamilton Rating Scale for Depression. Results. We were not able to find any association between the two variants under investigation and diagnosis of MD, as well as with antidepressant response. Conclusions. Although limited by several factors, including the small sample size and the impossibility to extend our findings to patients treated with different antidepressants, the results of our study provide support to the notion that these variants might not play a major role in the etiology and clinical outcomes of MD. [ABSTRACT FROM AUTHOR]

Evaluation of: Cusin C, Iovieno N, Iosifescu DV et al. A randomized, double-blind, placebo-controlled trial of pramipexole augmentation in treatment-resistant major depressive disorder. J. Clin. Psychiatry 74(7), e636-e641 (2013). To overcome limited efficacy in antidepressants, clinicians may choose augmentation, switching to a different antidepressant, or a combination of different antidepressant drugs based on the individual patient's clinical circumstances. Among such options for difficult-to-treat major depressive disorder (MDD) patients, augmentation therapy with atypical antipsychotics, psychostimulants, dopamine agonists, serotonin 1A partial agonists, lithium, and thyroid hormones are commonly used in clinical practice. In fact, augmentation therapy has some clinical merits and is more convenient than switching medications and combination approaches for treating MDD. One such augmentation agent, pramipexole has been proposed, and has been implicated in the development and treatment of MDD. Recently, randomized controlled trials with pramipexole augmentation have been conducted and have demonstrated that pramipexole is a safe and potentially efficacious augmentation strategy. This article will discuss currently available clinical trial data and the potential role of pramipexole in MDD treatment, including clinical significance, limitations, and future research directions. [ABSTRACT FROM AUTHOR]

Objectives. This review is to inform clinicians of currently available data on vilazodone for treating patients with major depressive disorder (MDD), focusing on its differential action mechanism and extended clinical utility. Methods. A data search was conducted in June 2012 using the PubMed/MEDLINE/relevant clinical trial databases with the key terms "vilazodone" or "Viibryd." Results. The efficacy, safety, and tolerability of vilazodone have been demonstrated in two pivotal 8-week, randomized, double-blinded, placebo-controlled studies. Certain pharmacological characteristics of vilazodone were observed, including early onset of action, fewer sexual side effects, the absence of known cardiac toxicity, and minimal effect on weight gain, that may provide potential clinical advantages compared with currently available antidepressants. However, such possibilities should be replicated and confirmed in more well-designed and adequately powered clinical trials. Vilazodone requires dose titration up to 2 weeks to reach a target dose of 40 mg/d due to high rate of gastrointestinal side effects. No direct comparative studies with other antidepressants are currently available to confirm the aforementioned potential clinical utility. Conclusion. Vilazodone is a newer antidepressant possessing different action mechanisms compared to currently available antidepressants but whether it has superiority to other class of antidepressants in terms of efficacy and safety should still warrant further evaluation through more well-controlled and direct comparison clinical trials. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a chronic, recurrent mental disease that causes serious disability. Because currently available antidepressants have limited efficacy with respect to response and remission in patients with MDD, clinicians must choose the best available treatment interventions for patients who do not respond to initial antidepressant treatment. The existing literature demonstrates that augmentation with atypical antipsychotics (AAs) shows higher response and remission rates compared with antidepressant monotherapy, but is associated with more withdrawals due to adverse events. In this paper, specific clinical issues in the use of AA augmentation for patients with MDD are briefly discussed. Given the limited information and clinical knowledge on the proper and effective use of AAs for MDD, future research should focus on practical clinical issues that can be commonly seen in routine practice but have not been addressed yet. This is because the use of AAs is likely to expand as there is good evidence for their effectiveness and tolerability as augmentation therapy for patients with MDD. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence that supports the use of atypical antipsychotics as augmentation agents for nonpsychotic unipolar major depressive disorder (MDD) in adults. Unfortunately, varying definitions of treatment-resistant depression, the limited evidence available for interventions after two or more treatment failures, and when and whether to use medications from nonantidepressant classes, remain a key gap in the knowledge base for clinicians. We identified and reviewed the following guidelines to discuss the status of augmentation therapy with atypical antipsychotic agents in MDD: American Psychiatric Association practice guidelines for treatment of patients with MDD; Canadian Network for Mood and Anxiety Treatments clinical guidelines for the management of MDD in adults; National Institute for Health and Clinical Excellence guidelines for treatment and management of depression in adults; British Association of Psychopharmacology guidelines for treatment of depressive disorders; Institute for Clinical Systems Improvement healthcare guideline for MDD in adults in primary care; clinical practice recommendations for depression; international consensus statement on MDD; German Society of Psychiatry, Psychotherapy and Neurology guidelines for unipolar depression; and World Federation of Societies of Biological Psychiatry guidelines for biological treatment of unipolar depressive disorders in primary care. Reflecting the cumulative evidence in the past decade, augmentation strategies including atypical antipsychotic augmentation are recommended in most guidelines for partial or nonresponders, at the same stage as switching or combination strategies. However, there are few direct comparisons of different augmentation strategies and little information about the optimal duration of augmentation strategies or use in special populations. Clinicians should note that guidelines are derived from an evolving database of evidence and cannot take into account the myriad of clinical variables that differ between individual patients. Therefore, they are intended to provide a useful framework for the management of depression and should be used in conjunction with other recognized sources of patient information and the application of clinical wisdom. [ABSTRACT FROM AUTHOR]

Various clinical issues are involved in the appropriate diagnosis and proper treatment interventions for patients with major depressive disorder (MDD). Despite a number of diverse antidepressants for treating MDD now, response and remission rates following adequate trials of antidepressant intervention are still not satisfactory. Furthermore, a significant proportion of MDD patients have residual symptoms, which are associated with increased relapse and recurrence of MDD, leading to negative impacts on the clinical course and outcomes of MDD. Timely and appropriate decision-making regarding the proper management of such cases is required in our routine daily practice. These issues are illustrated and also framed by one MDD case with a complicated clinical course. This review paper may give physicians clinical insight into how we can effectively and properly evaluate and manage such patients in clinical practice. [ABSTRACT FROM AUTHOR]

Asian and western countries differ in the prevalence, symptom manifestation, diagnostic procedures, patient recognition and treatments of major depressive disorder (MDD), according to a number of studies. Ethnic differences in pharmacological profiles are also important in the prescription of certain antipsychotic medications because they may impact treatment outcomes and adverse events. Differential pharmacokinetic and pharmacodynamic properties of antipsychotics may be practically useful in the control of specific depressive symptoms. Furthermore, patient compliance with prescribed medications has been found to be different across races and ethnicities. Therefore, this article explores practical clinical issues for the use of atypical antipsychotics in patients with MDD, focusing on ethno-cultural differences. [ABSTRACT FROM AUTHOR]

Aims The goal of this study was to assess the efficacy and tolerability of tianeptine in combination with selective serotonin re-uptake inhibitor ( SSRI) in partial responders or non-responders to SSRI monotherapy. Methods In this prospective, open-label, 6-week study, 150 patients with major depressive disorder who had previously not responded or partially responded to SSRI monotherapy were recruited. Tianeptine was given in combination with an SSRI for 6 weeks. Results Significant improvements were observed in the mean scores of the Hamilton Depression Rating Scale ( HDRS), Montgomery- Åsberg Depression Rating Scale ( MADRS), and Clinical Global Impression- Severity ( CGI-S). The change in the mean HDRS, MADRS, and CGI- S scores was significant from week 1. The response rates were 64.7% ( HDRS) and 68.7% ( MADRS), and the remission rates were 34.0% ( HDRS) and 42.0% ( MADRS) at week 6. Thirty-six patients (24.0%) reported adverse events that were determined by the investigator to be related to one of the study drugs. The tianeptine and SSRI combination was generally well-tolerated. Conclusions A combination strategy with tianeptine may be an effective and well-tolerated tool for patients who have failed to adequately respond to SSRI monotherapy. [ABSTRACT FROM AUTHOR]

Background and Objective: A number of operational definitions have been proposed to describe outcomes in bipolar disorders; the criteria used to define terms such as recurrence, relapse, response, remission and recovery have varied both in observational studies and in clinical trials. We carried out a post hoc analysis of rates of symptomatic point remission and sustained remission using four different remission criteria that had been evaluated in a previously published 24-week, double-blind, placebo-controlled study. Methods: After stabilization for 8 consecutive weeks on open-label ziprasidone plus lithium or valproate, stabilized subjects were randomized to two groups, ziprasidone with lithium or valproate (ziprasidone group), or placebo with lithium or valproate (placebo group) for 16 weeks. Four remission criteria included (i) Mania Rating Scale (MRS) score ≤7, (ii) MRS ≤7 + Montgomery-Åsberg Depression Rating Scale (MADRS) score ≤10, (iii) MRS ≤7 + Clinical Global Impression-Improvement (CGI-I) = 1, (iv) MRS score ≤7 + MADRS score ≤10 + CGI-I score = 1. We examined the percentages of subjects in each treatment group achieving symptomatic point (i.e. at each visit) and sustained (i.e. for ≥8 weeks) remission during the double-blind phase. Results: At week 24, symptomatic point remission based on the above two more stringent criteria was achieved by 48.0 and 24.4% of the ziprasidone group versus 36.9 and 18.0% of placebo recipients, respectively (p = 0.04 and 0.14). Sustained remission rates at 24 weeks were 42.5 and 18.1% for ziprasidone, respectively (vs 33.3 and 14.4% for placebo, p = 0.04 and 0.21, respectively). Conclusion: This analysis indicates that ziprasidone plus lithium or valproate treatment showed modest to moderate remission rates at week 24 based on four different remission criteria in terms of symptomatic and sustained remission, despite the stringent criteria. Our findings indicate that ziprasidone may be effective in achieving sustained remission in bipolar I disorder and propose that a better understanding regarding the definition of remission in bipolar disorders should be required in clinical practice since our results showed different remission rates with different remission criteria. [ABSTRACT FROM AUTHOR]

Introduction The development of medical knowledge has involved increasing numbers of clinical studies, including trials of treatment modalities among elderly individuals. We evaluated knowledge about and attitudes on participation in various clinical trials among elderly individuals. Methods A semi-structured survey was developed and distributed to community-living elders who agreed to participate in the Ansan Geriatric Study. Survey items addressed (i) the process of acquiring consent, (ii) the advantages of participation in clinical trials, (iii) worries about participation, (iv) clinical field trials in which they would like to participate, and (v) reasons behind participation. Results A total of 361 individuals (158 women and 203 men, mean age 71.1 years) agreed to answer the survey about clinical trials. The reported advantages of participation in clinical trials were access to cost-free medication or interventions (44.9%), prevention or early diagnosis of possible future diseases (23.8%), diagnostic and laboratory tests at no charge (14.7%), and contribution to human wellbeing (13.3) The reported disadvantages were the possibility of side-effects from the new treatments (32.1%), giving blood for frequent laboratory tests (28.5%), concerns about intrusions on human dignity (9.9%), and possible leakage of personal identifying data (8.6%). An additional 10.8% saw no disadvantages. Subjects were interested in participating in clinical field trials for interventions or medication to treat metabolic syndrome and medical diseases (43.5%), Alzheimer's and Parkinson's diseases (11.1%), late-life depression (2.5%). Although more than two-thirds (77.3%) of the subjects believed that they should provide consent for themselves, some believed that their spouses (14.4%) or other family members (8.3%) should be able to receive the explanation of the clinical trial and sign the informed consent forms. Discussion We should consider the attitudes of elderly participants during the processes of explaining clinical trials and acquiring consent. [ABSTRACT FROM AUTHOR]

The present study is aimed to exploring whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with major depressive disorder (MDD) and whether they could predict clinical outcomes in Korean in-patients, respectively, treated with antidepressants. One hundred forty-five (145) patients with MDD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures, including the Montgomery-Asberg Depression Rating Scale (MADRS) for patients with MDD, were recorded. No association was observed between alleles, genotypes and haplotypes under investigation and clinical and demographical variables. As a secondary finding, a marginal association was observed between rs4302506 and rs4403097 alleles within GRIA2 and age of onset in patients with MDD. Our findings provide evidence for a possible association between rs4302506 and rs4403097 SNPs and age of onset in patients with MDD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate possible associations between a set of single-nucleotide polymorphisms (SNPs) within 10 genes with Schizophrenia (SCZ) and response to antipsychotics in Korean in-patients treated with antipsychotics. Two hundred and twenty-one SCZ in-patients and 170 psychiatrically healthy controls were genotyped for 42 SNPs within ABCB1, ABCB4, TAP2, CLOCK, CPLX1, CPLX2, SYN2, NRG1, 5HTR1A and GPRIN2. Baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), were recorded. Rs10042486 within 5HTR1A was associated with both SCZ and clinical improvement on PANSS total scores as well as on PANSS positive and PANSS negative scores. The haplotype analyses focusing on the four, three and two blocks' haplotypes within 5HTR1A confirmed such findings as well. We did not observe any significant association between the remaining genetic variants under investigation in this study and clinical outcomes. Our preliminary findings suggest that rs10042486 within 5HTR1A promoter region could be associated with SCZ and with clinical improvement on PANSS total, positive and negative scores in Korean patients with SCZ. However, taking into account the several limitations of our study, further research is needed to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Objective. The present study aimed to investigate whether some single nucleotide polymorphisms (SNPs) within GRIA1, GRIA2 and GRIA4 could be associated with bipolar disorder (BD) and they could predict clinical outcomes in in-patients with BD treated with mood stabilizers. Methods. One hundred and thirty-two (132) patients with BD and 170 healthy controls were genotyped for 17 SNPs within GRIA1, GRIA2 and GRIA4. Baseline and final clinical measures including Young Mania Rating Scale for patients with BD were recorded. Statistical significance was set at the 0.005 level in order to reduce the likelihood of false positive results. Results. We failed to show an evidence for a possible association of GRIA1, GRIA2 and GRIA4 with BD patients, in terms of influences on diagnosis and treatment outcomes, although this was the first study to explore the influence of such genes for bipolar disorder. Conclusion. Our results suggest that 17 SNPs within GRIA1, GRIA2 and GRIA4 may not be associated with the development and treatment outcomes in BD. However, taking into account that the several limitations of our study including the moderately small sample size of our study, our findings should be considered with caution and further research is needed to draw more definitive conclusions. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to explore whether some single nucleotide polymorphisms (SNPs) within the BDNF gene could be associated with major depression (MD), bipolar disorder (BD) and schizophrenia, and whether they could predict clinical outcomes in Korean inpatients treated with antidepressants, mood stabilizers and antipsychotics, respectively. Methods: One hundred and forty-five patients with MD, 132 patients with BD, 221 patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for 5 BDNF SNPs (rs2030324, rs7103873, rs10835210, rs11030101 and rs6265). Baseline and final clinical measures - including the Montgomery-Asberg Depression Rating Scale, Young Mania Rating Scale and Positive and Negative Symptoms Scale for patients with MD, BD and schizophrenia, respectively - were recorded. Results: rs10835210 CA and rs11030101 AT genotype frequencies were higher in BD and schizophrenia patients than in healthy and MD subjects. No significant association was found with clinical improvement. Discussion: Our findings provide evidence of an association between BDNF and BD and schizophrenia. However, taking into account the several limitations of our study, including the moderately small sample size, further research is needed to draw more definitive conclusions. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective. The present study explored whether d-amino acid oxidase activator ( DAOA) variants were associated with schizophrenia and whether they could predict the clinical outcomes of patients treated with various antipsychotics. Methods. Two hundred and twenty-one (221) patients with schizophrenia and 170 psychiatrically healthy controls were genotyped for seven DAOA single-nucleotide polymorphisms (SNPs) (rs3916966, rs3916967, rs2391191, rs3916968, rs7139958, rs9558571 and rs778293). We also administered baseline and final clinical measures, including the Positive and Negative Symptoms Scale (PANSS), to patients with schizophrenia. Results. None of the SNPs under investigation was associated with the development of schizophrenia. However, the rs7139958 AA and rs9558571 TT as well as the rs7139958 A and rs9558571 T genotypes were associated with higher scores on the PANSS positive subscale among patients with schizophrenia, possibly reflecting their greater susceptibility to the development of more severe positive symptoms. No other allele, genotype, or haplotype under investigation was significantly associated with any of the clinical parameters, including clinical improvement, in patients with schizophrenia. Conclusion. Our results suggested that rs7139958 and rs9558571 SNPs may be associated with more severe baseline positive symptoms in patients with schizophrenia. However, further research is needed to draw more definitive conclusions given the limitations of our study. [ABSTRACT FROM AUTHOR]

Multiple measurements of depression symptoms over time were more predictive of cardiovascular mortality than a single time measurement performed at baseline. The aim of this study is to evaluate the association of the course of depression symptoms, based on repeated assessments of depression symptoms over time, with left ventricular mass index (LVMI) and left ventricular filling pressure (LVFP) in patients on haemodialysis (HD). The level of depression symptoms in 61 patients on HD were prospectively assessed using the Beck Depression Inventory (BDI) at baseline and at three intervals (5, 10, 15 months). Doppler echocardiographic examinations were performed at the end of follow up. At the end of follow up, the patients were divided into three groups according to their course of depression symptoms: non-depression ( n = 21), intermittent depression ( n = 23) and persistent depression ( n = 17). LVMI and LVFP were significantly increased in the persistent depression symptoms group compared to those of the non-depression symptoms group and the intermittent depression symptoms group. Persistent depression symptoms were independently associated with LVMI (β-coefficient = 0.347, P = 0.017) and LVFP (β-coefficient = 0.274, P = 0.048) after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, diabetes and interdialytic weight gain. In our study, persistent depression symptoms were associated with left ventricular hypertrophy and diastolic dysfunction. Our data may provide a more complete understanding of cardiovascular risk associated with depression symptoms in patients on HD. Depression has previously been linked to left ventricular hypertrophy (LVH) in dialysis patients. This study demonstrates that only persistent depression correlates with LVH and diastolic dysfunction. [ABSTRACT FROM AUTHOR]

Objectives. The SLC6A3 40 base variable number of tandem repeats (VNTR) polymorphism has been associated with several clinical phenotypes associated with dysregulation of dopamine transmission. However, there is only little evidence about a possible influence of such genetic variant on the response to antipsychotics. The aim of the present study is to investigate whether SLC6A3 40 base VNTR polymorphism could modulate response to risperidone in a sample of Korean schizophrenia subjects. Methods. One hundred and forty-two schizophrenia inpatients were treated with a flexible dose of risperidone. Efficacy was assessed at baseline and at discharge using the scores of the Clinical Global Impression-severity (CGI-S), Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Symptom Score (PANSS). Multivariate analysis of covariance was used to test possible influences of SLC6A3 VNTR variants on clinical scores. Results. None of the genotypes and of the alleles under investigation was associated with clinical scores at discharge or with changes of clinical scores over time. In addition, we also failed to find any association between genotypes and allele frequency distribution in accordance with treatment response defined as a 20% (or 30%) or more reduction in the total PANSS scores from the baseline to the end of treatment. Conclusion. Our findings do not suggest a possible association between SLC6A3 40 base VNTR polymorphism and response to risperidone. However, because of several limitations including the investigation of a single drug, the flexible design of the present study and the absence of a complete coverage of features which could influence the response, further investigations could be required. [ABSTRACT FROM AUTHOR]

Lithium efficacy is, at least partially, under genetic control. We investigated the association between markers in BDNF and lithium prophylactic efficacy. A set of 10 SNPs within BDNF were genotyped in a sample of 83 bipolar patients. Response to lithium was assessed by presence or absence of any illness phases during a period of 3 years of longitudinal observation. No significant association was detected between the genetic variants tested in BDNF and lithium prophylaxis. Despite the negative association, limitations including small sample size suggest that larger scale genetic associations studies of these genes and lithium prophylaxis are nonetheless indicated. [ABSTRACT FROM AUTHOR]

Aims: The goal of the present study was to evaluate the efficacy of risperidone combined with mood stabilizers for treating bipolar mixed state. Methods: The present study was a 24-week, open-label, combination, prospective investigation of the efficacy of risperidone in combination with mood stabilizers. Risperidone (1–6 mg/day) was given in combination with mood stabilizers in flexible doses according to clinical response and tolerability for 114 patients in mixed or manic episode. Results: Forty-four patients met our criteria for mixed state bipolar disorder and 70 met the criteria for pure mania. Mean age for the subjects was 39.0 ± 11.0 years and 55.3% were female. The combination of risperidone with mood stabilizers significantly improved the scores on the Young Mania Rating Scale (YMRS), 17-item Hamilton Rating Scale for Depression (HAMD), 18-item Brief Psychiatric Rating Scale (BPRS), Global Assessment Scale (GAS), and Clinical Global Impression Scale for use in bipolar illness Severity (CGI-BP) at 24 weeks ( P < 0.0001). Analysis of the YMRS, BPRS, GAS, and CGI-BP scores showed significant improvement in both the manic and mixed groups. The rate of response in YMRS scores was 84.2% ( n = 96) and the rate of YMRS remission was 77.2% ( n = 88) at week 24 in the total population. Seventy-four patients met both YMRS ≤ 12 and HAMD ≤ 7 at week 24 (64.9%). Risperidone was well tolerated, and adverse events were mostly mild. Conclusion: The combination of risperidone with mood stabilizers was an effective and safe treatment for manic symptoms and coexisting depressive symptoms of bipolar disorder. [ABSTRACT FROM AUTHOR]

Despite several decades of research, the characteristics distinguishing atypical depression from other depressive subtypes remain ambiguous. Multiple lines of evidence support the designation of atypical depression as a scientifically and clinically relevant subtype, including differences in hormonal responses, brain laterality, psychological profile and psychiatric co-morbidity and differential treatment response. The evolution of the diagnostic criteria for atypical depression has led to the designation of mood reactivity as the cardinal feature, and the research supporting this conclusion is reviewed. This paper also reviews the evidence for the drug treatment of atypical depression, with a particular focus on research related to the superior efficacy of monoamine oxidase inhibitors (MAOIs) compared with tricyclic antidepressants (TCAs). Data relevant to the efficacy of newer antidepressants, including selective serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline (norepinephrine) reuptake inhibitors, transdermal selegiline and other new agents for atypical depression, are discussed. In summary, the diagnostic reliability and validity of atypical depression still remain elusive and open to further evolution. Currently available findings suggest that atypical depression has preferential response to MAOIs over TCAs. More data are required to determine the efficacy of newer agents relative to MAOIs and TCAs, although limited studies have shown a non-inferior efficacy and better tolerability of newer agents such as SSRIs compared with those of MAOIs and TCAs. Finally, future directions for research include further refinement of the diagnostic criteria for atypical depression, and clarification of the role of newer antidepressants in the treatment of this subtype with evidence from randomized, controlled trials. [ABSTRACT FROM AUTHOR]

Objectives. We conducted a post-hoc analysis to determine whether a history of physical or sexual abuse was associated with response to treatment in a double-blind, randomized, placebo-controlled trial of paroxetine controlled release (CR) in fibromyalgia. Methods. A randomized, double-blind, placebo-controlled trial of paroxetine controlled release (CR) (dose 12.5-62.5 mg/day) was conducted in patients with fibromyalgia for 12 weeks. A total of 112 subjects provided complete information on childhood history of abuse that was recorded using the Sexual and Physical Abuse Questionnaire and randomized to treatments. Outcome evaluations in the abuse subgroup were identical to those in the entire sample. Health Status was determined using the 36-Item Short Form Health Survey (SF-36), the Sheehan Disability Scale (SDS), and the Perceived Stress Scale (PSS). Fibromylagia symptom severity was determined using the Fibromyalgia Impact Questionnaire (FIQ) and the Visual Analogue Scale for Pain (VAS). The primary outcome was treatment response defined as ≥25% reduction in the FIQ-total score. Secondary outcomes include changes in scores on the Clinical Global Impression-Severity and Improvement (CGI-S and CGI-I respectively) and SF-36. Results. The rate of childhood physical and/or sexual abuse was 52.7% ( n=59). The baseline characteristics (health status, perceived stress, symptom severity) were not associated with abuse history. In logistic regression, the history of abuse did not predict treatment response as measured by ≥25% reduction in FIQ-total score (OR = 1.16, 95% CI = 1.18-1.60, P = 0.35), while the drug status (paroxetine CR) was significantly associated with treatment response (OR = 2.51, 95% CI = 1.12-5.64, P = 0.02). Abuse history did not predict CGI-I ( P = 0.32) or CGI-S ( P = 0.74) improvements during treatment. After 12 weeks of treatment, subjects with sexual abuse history showed significantly lower mean change in health status (SF-36) than those without sexual abuse history ( P = 0.04). Conclusions. Although, a significant proportion of patients with fibromyalgia reported a history of abuse, it does not appear to have any significant clinical correlates at baseline. History of abuse did not predict response to treatment in patients with fibromyalgia participating in a controlled trial of paroxetine controlled release. Prospective, well-designed studies are needed to confirm whether selective serotonin uptake inhibitors are effective in patients with fibromyalgia irrespective of their abuse history. [ABSTRACT FROM AUTHOR]

We previously investigated a group of single-nucleotide polymorphisms of a set of genes coding for heat shock proteins (HSPA1A, HSPA1B and HSPA1L) and found a significant association between one HSPA1B variation and schizophrenia (SZ). We now report an association between a set of variations (rs2227956, rs2075799, rs1043618, rs562047 and rs539689) within the same genes and a larger sample of schizophrenic inpatients. A single variation, rs539689 (HSPA1B), was found to be marginally associated with Positive and Negative Syndrome Scale (PANSS) positive scores at discharge, and haplotype analysis revealed a significant association between improvement in PANSS scores with both A-C-G-G and A-C-G-G haplotypes. These findings further support a role of heat shock proteins in the pathophysiology of SZ. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]