Stress, a risk factor of major depression induces cytokine mediated inflammation and decreased neurogenesis. In patients with major depression, significant increases of pro-inflammatory cytokines have been consistently reported. The pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal (HPA) axis to release glucocorticoids. In the brain, microglia and play a role of immune activation in response to stress. Increased pro-inflammatory cytokine play a role in restricting neurogenesis in the brain. Although neurogenesis may not be essential for the development of depression, it may be required for clinically effective antidepressant treatment. Hence, stimulation of neurogenesis is regarded as a promising strategy for new antidepressant targets. This review introduces changes in neurotransmitter, cytokine and neurogenesis in major depression and explores the possible relationship between pro-inflammatory cytokines and neurogenesis related to stress in major depression.

Depressive disorders have strong genetic components. However, conventional linkage and association studies have not yielded definitive results. These might be due to the absence of objective diagnostic tests, the complex nature of human behavior or the incomplete penetrance of psychiatric traits. Imaging genetics explores the influences of genetic variation on the brain function or structure. This technique could provide a more sensitive assessment than traditional behavioral measures in psychiatric studies. Imaging genetics is a relatively new field of psychiatric researches, and may improve our understanding on neurobiology of psychiatric disorders. In this review, current understanding in neurobiology of depressive disorders, especially imaging genetic studies on serotonin transporter will be discussed.

Major depression is a devastating disorder of which lifetime prevalence rate is as high as up to 25% in general population. Although the etiology of the disorder is still poorly understood, it is generally accepted that both genetic and environmental factors are involved in the precipitation of depression. Stressful lifetime events are potent precipitating environmental factors for major depression and early-life stress is in particular an important element that predisposes individuals to major depression later in life. How environmental factors such as stress can make our neural networks susceptible to depression and how those factors leave long-lasting influences have been among the major questions in the field of depression research. Epigenetic regulations can provide a bridging mechanism between environmental factors and genetic factors so that these two factors can additively determine individual predispositions to major depression. Here we introduce epigenetic regulations as candidate mechanisms that mediate the integration of environmental adversaries with genetic predispositions, which may lead to the development of major depression, and summarize basic molecular events that underlie epigenetic regulations as well as experimental evidences that support the active role of epigenetic regulation in major depression.

Major depressive disorder is characterized by cellular and molecular alterations resulting in the depressive behavioral phenotypes. Preclinical and clinical studies have demonstrated the deficits, including cell atrophy and loss, in limbic and cortical regions of patients with depression, which is restored with antidepressants by reestablishing proper molecular changes. These findings have implicated the involvement of relevant intracellular signaling pathways in the pathogenetic and therapeutic mechanisms of depressive disorders. This review summarizes the current knowledge of the signal transduction mechanisms related to depressive disorders, including cyclic-AMP, mitogen-activated protein kinase, Akt, and protein translation initiation signaling cascades. Understanding molecular components of signaling pathways regulating neurobiology of depressive disorders may provide the novel targets for the development of more efficacious treatment modalities.

Subsyndromal anxiety disorder indicates mental states of having anxiety symptoms not fulfilling criteria for anxiety disorders. Despite of the lack of previous objective findings of the subsyndromal anxiety disorder, its clinical importance has increased. It can cause many kinds of clinical anxiety symptoms and functional disabilities. But the early intervention and early treatment make it possible not only to attenuate the anxiety symptoms and functional disabilities but also to prevent disease progression to a full syndromal anxiety disorder. In this article, we will review the previous studies about the subsyndromal anxiety disorder and discuss its clinical characteristics and importance.

In medicine, general clinical practice moves in the direction of early detection and intervention for the prevention of progressive disease. In psychiatry, research in subjects with the risk syndrome for psychosis, has been conducted for the prevention of schizophrenia, known as a devastating chronic disease. The inclusion of 'attenuated psychosis syndrome', based on the results of early intervention studies, is one of the major issues in the upcoming DSM-V. Further investigations are needed to find biological markers and endophenotypes to supplement the diagnostic criteria. In the future, adoption of clinical staging is promising to overcome the shortcoming of current diagnosis of schizophrenia. In clinical practice, more concerns are needed about attenuated psychotic symptoms which might be risk signals for the transition to psychosis.

Subsyndromal depression (SSD) is found to be more prevalent than major depressive disorder (MDD) and minor depressive disorder (MnDD). SSD is also associated with adverse clinical outcomes, increased risk of suicide, increased social dysfunction and disability, increased risk for future mood disorders, and increased uses of medical and mental health services. DSM-IV diagnostic criteria are not suitable for capturing SSD. Although there is no agreement on gold standard to define SSD so far, three definitions of SSD are available. First, SSD is defined as having two or more current depressive symptoms without core depressive symptoms (depressive mood or loss of interest) and with time threshold (most of the day and nearly every day over at least two weeks). Second, SSD is defined as having two or more current depressive symptoms with core depressive symptoms and without time threshold. Third, SSD is defined by using cutoff points of depression rating scales. SSD may represent a prodromal, residual, or interepisode symptomatic state in the course of MDD and MnDD. More than a half of SSD patients became any type of depressive disorders (SSD, MnDD and MDD) at 1 year. SSD may represent a discrete category of its own, without prior or consequent episodes of MDD. Considering clinical significance of SSD such as its high prevalence, significant psychosocial impairment and chronicity and serious outcomes, researchers and clinicians should be more vigilant in capturing and caring for patients with SSD.

Subsyndromal bipolar symptoms are common during maintenance treatment and appear to be associated with relapse into an episode of the same polarity. This implies subsyndromal symptoms are an important problem in recurrent bipolar disorder and require more additive and infallible therapeutic intervention. Undetected, untreated subsyndromal states lead patients to have poor prognosis and quality of life. The combination of a long undetected illness and significant psychosocial impairment renders early identification and intervention vital for the treatment of bipolar disorders. Methods for early identification includes finding prodromes, using screening tools such as the HCL-32 (Hypomania Checklist-32) and the BSDS (bipolar spectrum diagnostic scale). Various augmentation treatment methods would be needed to reduce subsyndromal symptoms, especially, psychosocial treatment has the potential to help patients address the multiple psychosocial problems associated with this chronic illness. To overcome difficulties of diagnosing subsyndromal disorder and to treat it appropriately, a staging system was suggested by some researchers. It assumes that earlier stages have better prognosis and require simpler therapeutic regimens. Staging may assist in treatment planning and prognosis of bipolar disorder, and emphasize the importance of early intervention. Further research is required in this exciting and novel area.

Objectives Atypical antipsychotics show better treatment efficacy, safety and tolerability than typical antipsychotics. Among the adverse events observed during treatment with antipsychotics, extrapyramidal syndrome (EPS) and negative symptoms has been greatly reduced. But still, weight gain is receiving growing attention. The aim of this study was to investigate the association between therapeutic response to atypical antipsychotics and weight gain in admission status. Methods The study was conducted for Korean inpatients with schizophrenia in a university hospital in Seoul, between Jan 2006 and Dec 2010. Data was collected by reviewing the medical record of 39 consecutively hospitalized patients with Schizophrenia (DSM-IV) at a university hospital. Positive and Negative Symptom Scale (PANSS), Body Mass Index (BMI) and body weights were measured. Results No significant difference was observed for sex, age, illness onset age, family history of schizophrenia, numbers of hospitalization before treatment, educational years, marriage status, occupational status and subtype of schizophrenia between weight gainers and non-weight gainers. Regarding treatment response to atypical antipsychotics, weight gainers show significantly more PANSS decrease than non-weight gainers during admission period. Conclusions Our findings suggest that it appears to be more likely to respond to atypical antipsychotics in weight gainers than non-weight gainers (that weght gainers appear to be more likely to respond to atypical antipsychotics than non-weight gainers). These results show that the antipsychotic-induced body weight gain is associated with therapeutic response of antipsychotics in Korean inpatients with schizophrenia.

Objectives Optimized voxel based morphometry (VBM) has been increasingly applied to investigate differences in the brain morphology between a group of patients with mild cognitive impairment (MCI) and control subjects. Optimized VBM permits comparison of gray matter (GM) volume at voxel-level from the entire brain. The purpose of this study was to assess the regional GM volume change measured by optimized VBM in MCI subjects compared to controls. Methods Twenty patients with MCI and 20 control subjects with normal cognition were recruited for this study. We applied the optimized VBM protocol to the image data including study-specific template and the modulation of the data with the Jacobian determinants. GM volume differences between the MCI subjects and the control subjects and their correlations with the neuropsychological performances were investigated. Results Optimized VBM analysis revealed GM volume reduction in hippocampus, precentral gyrus, insula and parietal operculum in the MCI group compared to the control group (family wise error corrected p < 0.05). Korean version of the Consortium to Establish a Registry for Alzheimer's disease (CERAD-K) word list recall scores were significantly correlated with the GM volumes of hippocampus, precuneus and posterior cingulate in the MCI group (FWE corrected p < 0.05). Conclusions The results confirm previous findings of atrophic changes in medial temporal lobe and parietal lobe in the MCI group and suggest that these abnormalities may be related with cognitive decline and prognosis in patients with MCI.

Objectives Schizophrenic patients have been shown to be impaired in both emotional self-awareness and recognition of others' facial emotions. Alexithymia refers to the deficits in emotional self-awareness. The relationship between alexithymia and recognition of others' facial emotions needs to be explored to better understand the characteristics of emotional deficits in schizophrenic patients. Methods Thirty control subjects and 31 schizophrenic patients completed the Toronto Alexithymia Scale-20-Korean version (TAS-20K) and facial emotion recognition task. The stimuli in facial emotion recognition task consist of 6 emotions (happiness, sadness, anger, fear, disgust, and neutral). Recognition accuracy was calculated within each emotion category. Correlations between TAS-20K and recognition accuracy were analyzed. Results The schizophrenic patients showed higher TAS-20K scores and lower recognition accuracy compared with the control subjects. The schizophrenic patients did not demonstrate any significant correlations between TAS-20K and recognition accuracy, unlike the control subjects. Conclusions The data suggest that, although schizophrenia may impair both emotional self-awareness and recognition of others' facial emotions, the degrees of deficit can be different between emotional self-awareness and recognition of others' facial emotions. This indicates that the emotional deficits in schizophrenia may assume more complex features.

Objectives In the current study, we quantitatively estimated changes in appetite and eating behavior of bipolar disorder patients during the pharmacotherapy. We also investigated their contribution to the weight gain and their association with specific food-craving characteristics of the patients. Methods Subjects included forty-one bipolar disorder patients and fifty-six controls. Currently sustained natures of food craving were assessed using the General-Food Craving Questionnaire-Trait (G-FCQ-T) and changes in appetite and eating behavior were measured using the Drug-Related Eating Behavior Questionnaire (DR-EBQ). Results Compared to the control group, the patients' group showed significantly higher body mass index (t=2.028, p=0.045). The patients' group had significantly higher 'Preoccupation with food' factor score of G-FCQ-T (p=0.016) than that of the control group. Hierarchical multiple regression analysis showed that only 'preoccupation with food' factor independently predicted psychotropic medication-induced appetite change. Conclusions Appetite change while receiving psychotropic medication seems to be related to the weight-gain and associated with craving natures of 'preoccupation with food' in bipolar disorder. Appetite and/or eating behavioral changes measured by G-FCQ-T and DR-EBQ could be regarded as an important mediating factor in future studies exploring biological mechanisms of weight gain related with pharmacotherapy for bipolar disorder.

Objectives The aim of this study was to assess variations in caudate volume according to dopamin receptor D2/ankyin repeat and kinase domain containing 1 (DRD2/ANKK1) Taq 1a polymorphisms in young healthy adults and to evaluate the relationship between caudate volumes and psychiatric symptoms as measured by the Brief Psychiatric Rating Scale. Methods Genetic information regarding DRD2/ANKK1 Taq 1a and T1-weighted brain magnetic resonance images were acquired from 30 young healthy adults. Automatic segmentation of caudate was performed using the FreeSurfer program. Results Individuals with A2 homozygotes of DRD2/ANKK1 Taq 1a polymorphisms (n = 10) had greater right caudate volumes compared to those with A1 allele (s)(18.4% greater ; p = 0.019). Right caudate volumes were negatively associated with total scores of the Brief Psychiatric Rating Scale (${\beta}$=-0.50 ; p = 0.016). Conclusions Our findings suggest the possibility that DRD2/ANKK1 Taq 1a polymorphisms may underlie the psychiatric symptoms by influencing the structure of the right caudate.

Objectives The second to fourth digit ratio (2D : 4D) is known to reflect testosterone level during intrauterine period. Testosterone is essential for masculinization of brain. Cloninger's type II alcoholism is characterized by early age at onset and largely limited to males. Compared with type I alcoholism, type II alcoholism is thought to be masculine. There is a possibility that the digit ratio of type II alcoholism is low compared with type I. We examined digit length ratio in Cloninger's type I and II alcoholism to understand the effects of intrauterine testosterone on the development of alcoholism. Methods The participants were 87 alcohol dependent patients. We divided two subtypes of patients by Irwin's symptom list, based on Cloninger's concept. We captured the images of both palms by the scanner and measured the lengths of digits by the graphic program. Then we analyzed the digit ratios by independent-sample t-test. Results The mean 2D : 4D of type I was 0.942 (right), 0.952 (left). The mean 2D : 4D of type II was 0.927 (right), 0.940 (left). In both hands, 2D : 4D of type II was significantly lower than type I. Conclusions Type II alcoholism showed masculine type of digit length ratio compared with type I. It suggests the exposure of testosterone during intrauterine period might play an important role in determining the course and feature of alcoholism.