Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.

Association between serum folate levels and schizophrenia based on sex.

AIM: Sex differences in serum folate concentrations are well known, but no studies have investigated the association between serum folate levels and schizophrenia based on sex. With this study in a Japanese population, we examined the difference in serum folate levels between patients with schizophrenia and non-psychiatric controls stratified by sex. The relations among serum folate levels, plasma total homocysteine (tHcy), and serum vitamin B6 (pyridoxal) levels were also examined using data from our previous studies. METHODS: The serum folate concentrations of 482 patients diagnosed with schizophrenia and 1350 non-psychiatric control subjects were measured. We conducted an analysis of covariance to examine the differences in serum folate levels between the two groups based on sex. Spearman's rank correlation was used to evaluate the relations among folate, tHcy, and vitamin B6 levels. RESULTS: In the control group, serum folate concentrations were higher in women than in men. Lower levels of serum folate were observed in both male and female patients with schizophrenia. An inverse correlation between serum folate and plasma tHcy and a weak positive correlation between serum folate and vitamin B6 were observed in the combined cohort. CONCLUSION: Our findings suggest that: (i) a low serum folate level may be associated with schizophrenia regardless of sex; and (ii) folate administration may be beneficial for the treatment of schizophrenia. In schizophrenic patients with low serum folate levels, folate administration might result in improvements in high tHcy and an increase in low vitamin B6 levels.

Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis.

BACKGROUND: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. METHODS: We first conducted a case-control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. RESULTS: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference -0.48, 95% confidence interval [CI] -0.57 to -0.39, p = 9.8 × 10-24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65-1.51, p = 0.96). LIMITATIONS: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. CONCLUSION: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach.

Decreased serum pyridoxal levels in schizophrenia: meta-analysis and Mendelian randomization analysis.

BACKGROUND: Alterations in one-carbon metabolism have been associated with schizophrenia, and vitamin B6 is one of the key components in this pathway. METHODS: We first conducted a case-control study of serum pyridoxal levels and schizophrenia in a large Japanese cohort (n = 1276). Subsequently, we conducted a meta-analysis of association studies (n = 2125). Second, we investigated whether rs4654748, which was identified in a genome-wide association study as a vitamin B6-related single nucleotide polymorphism, was genetically implicated in patients with schizophrenia in the Japanese population (n = 10 689). Finally, we assessed the effect of serum pyridoxal levels on schizophrenia risk using a Mendelian randomization (MR) approach. RESULTS: Serum pyridoxal levels were significantly lower in patients with schizophrenia than in controls, not only in our cohort, but also in the pooled data set of the meta-analysis of association studies (standardized mean difference -0.48, 95% confidence interval [CI] -0.57 to -0.39, p = 9.8 × 10-24). We failed to find a significant association between rs4654748 and schizophrenia. Furthermore, an MR analysis failed to find a causal relationship between pyridoxal levels and schizophrenia risk (odds ratio 0.99, 95% CI 0.65-1.51, p = 0.96). LIMITATIONS: Food consumption and medications may have affected serum pyridoxal levels in our cross-sectional study. Sample size, number of instrumental variables and substantial heterogeneity among patients with schizophrenia are limitations of an MR analysis. CONCLUSION: We found decreased serum pyridoxal levels in patients with schizophrenia in this observational study. However, we failed to obtain data supporting a causal relationship between pyridoxal levels and schizophrenia risk using the MR approach.

Glucocorticoid administration restores salience network activity in patients with spider phobia.

BACKGROUND: Glucocorticoids reduce phobic fear in patients with anxiety disorders. Although the neurobiology of anxiety disorders is not fully understood, convergent structural and functional neuroimaging studies have identified abnormalities in various brain regions, including those in the salience network (SN) and default mode network (DMN). Here, we examine the effects of glucocorticoid administration on SN and DMN activity during the processing of phobic stimuli. METHODS: We use functional magnetic resonance imaging to record brain activity in 24 female patients with spider phobia who were administered either 20 mg of cortisol or placebo while viewing pictures of spiders. Fourteen healthy female participants were tested with the same task but without substance administration. Independent component analysis (ICA) performed during stimulus encoding identified the SN and DMN as exhibiting synchronized activation in diverse brain regions; thus, we examined the effects of cortisol on these networks. Furthermore, participants had to rate their level of fear at various time points. RESULTS: Glucocorticoids reduced phobic fear in patients with spider phobia. The ICA performed during stimulus encoding revealed that activity in the SN and DMN was reduced in placebo-treated patients versus healthy controls. Brain activity in the SN, but not the DMN, was altered in cortisol- versus placebo-treated patients to a level that was similar to that observed in healthy controls. CONCLUSIONS: Activity in both the SN and DMN was reduced in patients with spider phobia. Cortisol administration altered the SN activity to a level that was comparable to that found in healthy controls. This alteration in SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.

Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

Prestimulus default mode activity influences depth of processing and recognition in an emotional memory task.

Low self-referential thoughts are associated with better concentration, which leads to deeper encoding and increases learning and subsequent retrieval. There is evidence that being engaged in externally rather than internally focused tasks is related to low neural activity in the default mode network (DMN) promoting open mind and the deep elaboration of new information. Thus, reduced DMN activity should lead to enhanced concentration, comprehensive stimulus evaluation including emotional categorization, deeper stimulus processing, and better long-term retention over one whole week. In this fMRI study, we investigated brain activation preceding and during incidental encoding of emotional pictures and on subsequent recognition performance. During fMRI, 24 subjects were exposed to 80 pictures of different emotional valence and subsequently asked to complete an online recognition task one week later. Results indicate that neural activity within the medial temporal lobes during encoding predicts subsequent memory performance. Moreover, a low activity of the default mode network preceding incidental encoding leads to slightly better recognition performance independent of the emotional perception of a picture. The findings indicate that the suppression of internally-oriented thoughts leads to a more comprehensive and thorough evaluation of a stimulus and its emotional valence. Reduced activation of the DMN prior to stimulus onset is associated with deeper encoding and enhanced consolidation and retrieval performance even one week later. Even small prestimulus lapses of attention influence consolidation and subsequent recognition performance.

Microarray analysis of global gene expression in leukocytes following lithium treatment.

OBJECTIVES: To elucidate the molecular effects of lithium, we studied global gene expression changes induced by lithium in leukocytes from healthy subjects. METHODS: Eight healthy male subjects participated in this study. Lithium was prescribed for weeks to reach a therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 and 2 weeks of medication and at 2 weeks after stopping medication. Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays (The Agilent Technologies, Santa Clara, CA, USA). Expression of some candidate genes was also assessed by real-time polymerase chain reaction (PCR). RESULTS: Gene ontology analysis revealed that the cellular and immune responses to stimulus and stress indeed played a major role in the cellular response to lithium treatment. Pathway analysis revealed that the interleukin 6 pathway, the inhibitor of differentiation pathway, and the methane metabolism pathway were regulated by lithium. Using real-time PCR, we also confirmed that five candidate genes in these pathways were significantly changed, including suppressor of cytokine signaling 3 and myeloperoxidase. CONCLUSIONS: Our investigation suggests that the molecular action of lithium is mediated in part by its effects on the cellular and immune response to stimulus and stress followed by the interleukin 6, inhibitor of differentiation, and methane metabolism pathways.

Associations between negative and positive automatic thoughts and clinical variables in patients with schizophrenia.

This study investigated the relationships between negative and positive automatic thoughts and clinical variables in patients with schizophrenia. The participants included 36 patients with schizophrenia (male = 16; female = 20; age = 42.86 ± 9.40) who were outpatients in the Department of Psychiatry at Tokushima University Hospital. We used the Automatic Thoughts Questionnaire-Revised (ATQ-R), Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), and Brief Assessment of Cognition in Schizophrenia (BACS) to assess negative and positive automatic thoughts, positive and negative symptoms, depressive symptoms, and neurocognition, respectively. Spearman rank correlation coefficients were calculated to determine the relationships between negative and positive automatic thoughts and clinical variables. No relationship was observed between negative and positive automatic thoughts. Negative automatic thoughts were related to depressive symptoms. Positive automatic thoughts were related to neurocognition. We therefore surmise that each automatic thought might have different clinical features and outcomes, and should therefore be treated accordingly.

An Exploratory Study of the Potential of Online Counseling for University Students by a Human-Operated Avatar Counselor.

Recently, the use of digital technologies, such as avatars and virtual reality, has been increasingly explored to address university students' mental health issues. However, there is limited research on the advantages and disadvantages of counselors using avatars in online video counseling. Herein, 25 university students were enrolled in a pilot online counseling session with a human counselor-controlled avatar, and asked about their emotional experiences and impressions of the avatar and to provide qualitative feedback on their communication experience. Positive emotions during the session were associated with impressions of the avatar's intelligence and likeability. The anthropomorphism, animacy, likeability, and intelligent impressions of the avatar were interrelated, indicating that the avatar's smile and the counselor's expertise in empathy and approval may have contributed to these impressions. However, no associations were observed between participant experiences and their prior communication with avatars, or between participant experiences and their gender or the perceived gender of the avatar. Accordingly, recommendations for future practice and research are provided. Accumulating practical and empirical findings on the effectiveness of human-operated avatar counselors is crucial for addressing university students' mental health issues.

Clinical correlates associated with cognitive dysfunction in people with schizophrenia.

AIMS: The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia. METHODS: The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = -0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = -0.51, P < 0.01), verbal fluency score (r = -0.39, P < 0.01), and composite score (r = -0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = -0.45, P < 0.01), and composite score (r = -0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores. CONCLUSIONS: These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction.

Phase-Synchronized Transcranial Alternating Current Stimulation-Induced Neural Oscillations Modulate Cortico-Cortical Signaling Efficacy.

Introduction: Synchronized oscillatory brain activity is considered a basis for flexible neuronal network communication. However, the causal role of inter-regional oscillatory phase relations in modulating signaling efficacy in cortical networks has not been directly demonstrated in humans so far. Aim: The current study addresses the causal role of transcranial alternating current stimulation (tACS)-induced oscillatory cross-network phase relations in modulating signaling efficacy across human cortical networks. Methods: To this end, concurrent tACS, transcranial magnetic stimulation (TMS), and electroencephalography (EEG) were employed to measure the modulation of excitability and signaling efficacy across cortical networks during externally induced neural oscillations. Theta oscillatory activity was introduced through tACS in two nodes of the human frontoparietal network: the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Six Hertz tACS was applied to the DLPFC and PPC simultaneously in an in-phase or antiphase manner. In addition, single-pulse TMS was administered over the DLPFC at four different phases of tACS and the propagation of TMS-evoked neuronal activity was measured with EEG. Results: We show that tACS-induced theta oscillations modulate TMS-evoked potentials (TEPs) in a phase-dependent manner, and that the induced oscillatory phase relation across the frontoparietal network affects the propagation of phase-dependent TEPs within as well as beyond the frontoparietal network. Conclusion: We show that the effect of tACS-induced phase relation across the frontoparietal network on signal transmission extends beyond the frontoparietal network. The results support a causal role of inter-nodal oscillatory phase synchrony in routing cortico-cortical information flow. Impact statement Theoretical models have proposed that phase relations of cross-network neural oscillations control communication efficacy across human cortical networks. The current study introduced concurrent transcranial alternating current stimulation-transcranial magnetic stimulation-electroencephalography (tACS-TMS-EEG) to experimentally study the theoretical framework. Dual-site in-phase or antiphase 6 Hz tACS was applied to the frontoparietal network. Synchronized tACS was shown to affect signaling within as well as beyond the targeted network. The study demonstrates how inter-regional oscillatory coherence supports the control of brain network signaling.

Obsessive-compulsive symptoms are negatively correlated with motor severity in patients with generalized dystonia.

We aimed to clarify the correlations between motor symptoms and obsessive-compulsive symptoms and between the volumes of basal ganglia components and obsessive-compulsive symptoms. We retrospectively included 14 patients with medically intractable, moderate and severe generalized dystonia. The Burke-Fahn-Marsden Dystonia Rating Scale and Maudsley Obsessional Compulsive Inventory were used to evaluate the severity of dystonia and obsessive-compulsive symptoms, respectively. Patients with generalized dystonia were divided into two groups; patients whose Maudsley Obsessional Compulsive Inventory score was lower than 13 (Group 1) and 13 or more (Group 2). Additionally, the total Maudsley Obsessional Compulsive Inventory scores in patients with dystonia were significantly higher than normal volunteers' scores (p = 0.025). Unexpectedly, Group 2 (high Maudsley Obsessional Compulsive Inventory scores) showed milder motor symptoms than Group 1 (low Maudsley Obsessional Compulsive Inventory scores) (p = 0.016). "Checking" rituals had a strong and significant negative correlation with the Burke-Fahn-Marsden Dystonia Rating Scale (ρ = - 0.71, p = 0.024) and a strong positive correlation with the volumes of both sides of the nucleus accumbens (right: ρ = 0.72, p = 0.023; left: ρ = 0.70, p = 0.034). Our results may provide insights into the pathogenesis of obsessive-compulsive disorder and dystonia.

Transdiagnostic comparisons of intellectual abilities and work outcome in patients with mental disorders: multicentre study.

BACKGROUND: Cognitive impairment is common in people with mental disorders, leading to transdiagnostic classification based on cognitive characteristics. However, few studies have used this approach for intellectual abilities and functional outcomes. AIMS: The present study aimed to classify people with mental disorders based on intellectual abilities and functional outcomes in a data-driven manner. METHOD: Seven hundred and forty-nine patients diagnosed with schizophrenia, bipolar disorder, major depression disorder or autism spectrum disorder and 1030 healthy control subjects were recruited from facilities in various regions of Japan. Two independent k-means cluster analyses were performed. First, intelligence variables (current estimated IQ, premorbid IQ, and IQ discrepancy) were included. Second, number of work hours per week was included instead of premorbid IQ. RESULTS: Four clusters were identified in the two analyses. These clusters were specifically characterised in terms of IQ discrepancy in the first cluster analysis, whereas the work variable was the most salient feature in the second cluster analysis. Distributions of clinical diagnoses in the two cluster analyses showed that all diagnoses were unevenly represented across the clusters. CONCLUSIONS: Intellectual abilities and work outcomes are effective classifiers in transdiagnostic approaches. The results of our study also suggest the importance of diagnosis-specific strategies to support functional recovery in people with mental disorders.

Subjective assessment of participants in education programs on clinical practice guidelines in the field of psychiatry.

The Effectiveness of Guidelines for Dissemination and Education in psychiatric treatment (EGUIDE) project, which is a nationwide dissemination and implementation program for clinical practice guidelines (CPGs) in the field of psychiatry, is currently ongoing. In the current study, a subjective assessment of the participants in the EGUIDE programs was assessed using a questionnaire. Then, the relationships between the subjective assessment, the characteristics of the participants, and the clinical knowledge of the CPGs were evaluated. More than 90% of the participants gave a high rating for the components of content, recommendation, knowledge, skill, and adherence, but not for the component of confidence. A positive correlation was found between years of professional experience and the score of confidence. These results suggest that it may be necessary to apply the knowledge and skills of CPGs obtained in the education programs into practice to increase confidence in the proper use of psychiatric therapies based on CPGs.

Lithium decreases VEGF mRNA expression in leukocytes of healthy subjects and patients with bipolar disorder.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is thought to be involved in the pathophysiology of mood disorders and the target of antidepressants. The aim of this study was to elucidate molecular effects of lithium on VEGF expression by using leukocytes of healthy subjects and patients with bipolar disorder. METHODS: Eight healthy male subjects participated in the first study. Lithium was prescribed for 2 weeks, enough to reach therapeutic serum concentration. Leukocyte counts and serum lithium concentrations were determined at baseline, at 1- and 2-week medication, and at 2 weeks after stopping medication. VEGF mRNA levels were also examined in nine lithium-treated bipolar patients and healthy controls in the second study. RESULTS: In the first study, leukocyte counts were significantly increased at 2 weeks compared with those at baseline and were normalized after 2 weeks. VEGF mRNA levels were significantly decreased at 2 weeks and after 2 weeks compared with those at baseline. Consistent with the first study, VEGF mRNA levels were significantly decreased in the lithium-treated bipolar patients compared with healthy controls. CONCLUSIONS: Our investigation suggests that VEGF mRNA expression may be useful as a peripheral marker of the effects of lithium.

Peritraumatic reactions, PTSD symptoms, and pain†: A study of train disasters in Japan.

Objective : The purpose of this study was to examine the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, and pain in people injured in train disasters. Methods : The participants were injured in a train crash in Japan that left more than 100 dead. There were 218 participants in the analysis, with a mean age of 37.50 ±â€…14.67 years. Peritraumatic reactions were assessed using the Peritraumatic Distress Inventory. PTSD symptoms were evaluated using the Impact of Event Scale-Revised Japanese-language version. Pain was measured using the Visual Analog Scale. Results : Peritraumatic reactions did not directly affect PTSD symptoms but were found to be associated via latent variables. Regarding pain and PTSD symptoms, intrusive memories were more associated with pain than other symptoms were. There was an associative path from intrusion to pain, but no such path from pain to intrusion. Conclusions : Our results suggest that a therapeutic approach to intrusion may be effective in ameliorating the pain caused by injury. Future research should examine integrated treatment approaches for both PTSD and pain, rather than just for aspects of PTSD. J. Med. Invest. 68 : 85-89, February, 2021.

An attempt to analyze the longitudinal psychological state of cancer patients in the active treatment stage.

The psychological state and changes over time of cancer patients in the active treatment stage were classified into emotions by the speech and behavior of the patient described in the medical record article of the cancer psychological interview record, and the analysis of the "emotional state map" was attempted. In all cases, positive / negative emotions were mixed and appeared with variation, but a relatively large number of positive emotions, including , , and , were manifested, and the same was true in patients who experienced stressful treatment events. In the background, the existence of appropriate support from medical professionals and psychological characteristics peculiar to the stage of active treatment was inferred, such as the active treatment of the target patient, the hospitalization environment in which mental and physical pain promptly appealed to medical professionals, and the influence of psychological interviews. Cancer patients during active treatment perceived and expressed changes in the body and pain caused by the disease, and after responses from medical professionals and family members, they were conscious of their physical condition and emotions. It is suggested that this analysis method helps to objectively understand and explain the invisible and ever-changing psychological state of cancer patients in the active treatment stage. J. Med. Invest. 68 : 148-153, February, 2021.