Showing papers in "Psychiatry and Clinical Neurosciences in 2010"

Brain-derived neurotrophic factor as a biomarker for mood disorders: an historical overview and future directions.

Abstract: Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), are the most prevalent psychiatric conditions, and are also among the most severe and debilitating. However, the precise neurobiology underlying these disorders is currently unknown. One way to combat these disorders is to discover novel biomarkers for them. The development of such biomarkers will aid both in the diagnosis of mood disorders and in the development of effective psychiatric medications to treat them. A number of preclinical studies have suggested that the brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of MDD. In 2003, we reported that serum levels of BDNF in antidepressant-naive patients with MDD were significantly lower than those of patients medicated with antidepressants and normal controls, and that serum BDNF levels were negatively correlated with the severity of depression. Additionally, we found that decreased serum levels of BDNF in antidepressant-naive patients recovered to normal levels associated with the recovery of depression after treatment with antidepressant medication. This review article will provide an historical overview of the role played by BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Particular focus will be given to the potential use of BDNF as a biomarker for mood disorders. BDNF is initially synthesized as a precursor protein proBDNF, and then proBDNF is proteolytically cleaved to the mature BDNF. Finally, future perspectives on the use of proBDNF as a novel biomarker for mood disorders will be discussed.

Psychometric properties of the 10-item Connor-Davidson Resilience Scale in Chinese earthquake victims.

Abstract: Aim Resilience refers to positive adaption in the face of stress or trauma. Assessing resilience is crucial in trauma-related research and practice. The 10-item Connor-Davidson Resilience Scale (CD-RISC) has been demonstrated to be a valid and reliable tool to achieve this goal. This study was designed to examine the psychometric properties of the 10-item CD-RISC in a sample of Chinese earthquake victims. Methods A total of 341 participants (185 women, 156 men) aged 20-63 years were recruited from a psychological relief program supported by the Institute of Psychology, Chinese Academy of Sciences following the 'Wenchuan' earthquake. The participants were given the 10-item CD-RISC and the 17-item post-traumatic stress disorder (PTSD) subscale of the Los Angeles Symptom Checklist (LASC) 4 months after the earthquake. Results The results of exploratory factor analysis indicated that a single-factor model consistent with the original design of the 10-item CD-RISC was support. The scale was also demonstrated to have good internal consistency (Cronbach's alpha = 0.91) and test-retest reliability (r = 0.90 for a two-week interval). Scores on the scale could reflect different levels of resilience in populations that are thought to be differentiated (probable PTSD vs healthy controls, t(339) = -7.60, P Conclusion The Chinese version of the 10-item CD-RISC has excellent psychometric properties, and is applicable for Chinese people.

Cytokine hypothesis of schizophrenia pathogenesis: Evidence from human studies and animal models

Abstract: The pathogenesis of schizophrenia has yet to be fully characterized. Gene–environment interactions have been found to play a crucial role in the vulnerability to this disease. Among various environmental factors, inflammatory immune processes have been most clearly implicated in the etiology and pathology of schizophrenia. Cytokines, regulators of immune/inflammatory reactions and brain development, emerge as part of a common pathway of genetic and environmental components of schizophrenia. Maternal infection, obstetric complications, neonatal hypoxia and brain injury all recruit cytokines to mediate inflammatory processes. Abnormal expression levels of specific cytokines such as epidermal growth factor, interleukins (IL) and neuregulin-1 are found both in the brain and peripheral blood of patients with schizophrenia. Accordingly, cytokines have been proposed to transmit peripheral immune/inflammatory signals to immature brain tissue through the developing blood–brain barrier, perturbing structural and phenotypic development of the brain. This cytokine hypothesis of schizophrenia is also supported by modeling experiments in animals. Animals treated with specific cytokines of epidermal growth factor, IL-1, IL-6, and neuregulin-1 as embryos or neonates exhibit schizophrenia-like behavioral abnormalities after puberty, some of which are ameliorated by treatment with antipsychotics. In this review, we discuss the neurobiological mechanisms underlying schizophrenia and novel antipsychotic candidates based on the cytokine hypothesis.

Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression

Abstract: Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated.

Behavioral problems and parenting style among Taiwanese children with autism and their siblings.

Abstract: Aims: The purpose of the present study was to investigate the behavioral problems and parenting style among children with autism and their siblings in an ethnic Chinese population. Methods: A total of 151 children with DSM-IV autistic disorder, aged 3–12, 134 siblings without autism, and 113 normally developing controls were recruited. Both parents reported their parenting styles and psychological status and mothers also reported children's behavioral problems. Results: Children with autism had significantly more severe behavioral problems and obtained less affection and more overprotection and authoritarian controlling from their parents than the other two groups. Compared to the controls, unaffected siblings showed some behavioral problems, and obtained less maternal care. Withdrawal and attention, social, and thought problems were the most associated behavioral syndromes to distinguish children with autism from those without. Conclusions: In addition to children with autism, who have a wide range of behavioral problems and impaired parent–child interactions, their siblings may be at risk for such problems.

Psychiatric comorbidity among patients with gender identity disorder

Abstract: Aims: Psychiatric comorbidity and mental instability seem to be important unfavorable prognostic factors for long-term psychosocial adjustment in gender identity disorder (GID). However, psychiatric comorbidity in patients with GID has rarely been assessed. In this study, we investigated the psychiatric comorbidity and life events of patients with GID in Japan. Methods: A total of 603 consecutive patients were evaluated independently by at least two senior psychiatrists at the GID clinic using clinical information and results of examinations. Results: Using DSM-IV criteria, 579 patients (96.0%) were diagnosed with GID. Among the GID patients, 349 (60.3%) were the female-to-male (FTM) type, and 230 (39.7%) were the male-to-female (MTF) type. Current psychiatric comorbidity was 19.1% (44/230) among MTF patients and 12.0% (42/349) among FTM patients. The lifetime positive history of suicidal ideation and self mutilation was 76.1% and 31.7% among MTF patients, and 71.9% and 32.7% among FTM patients. Among current psychiatric diagnoses, adjustment disorder (6.7%, 38/579) and anxiety disorder (3.6%, 21/579) were relatively frequent. Mood disorder was the third most frequent (1.4%, 8/579). Conclusions: Comparison with previous reports on the psychiatric comorbidity among GID patients revealed that the majority of GID patients had no psychiatric comorbidity. GID is a diagnostic entity in its own right, not necessarily associated with severe comorbid psychological findings.

Peritraumatic Distress Inventory as a predictor of post-traumatic stress disorder after a severe motor vehicle accident.

Abstract: AIM: The aim of this study was to examine the utility of the Peritraumatic Distress Inventory (PDI) as a predictor of subsequent post-traumatic stress disorder (PTSD) in severe motor vehicle accident survivors. METHODS: Patients consecutively admitted to the intensive care unit were assessed immediately and 1 month after accidents in this prospective study. The predictive value for post-traumatic stress symptoms at 1 month of the PDI at initial assessment was examined by using multivariate regression analysis. Moreover, the accuracy of the PDI as a predictor of PTSD was determined using receiver operator characteristic curve analysis. Post-traumatic stress symptoms were assessed using the Impact of Event Scale - Revised questionnaire, and PTSD was assessed using the Clinician-Administered PTSD Scale. RESULTS: Seventy-nine patients completed the Impact of Event Scale - Revised questionnaire, and 64 patients participated in a structured interview. Of 64 patients, 13 met the diagnostic criteria of full or partial PTSD. The PDI was an independent predictor of post-traumatic stress symptoms (P = 0.003). The data indicated that a cut-off score of 23 maximized the balance between sensitivity (77%) and specificity (82%) in this study. Compared with negative predictive value (93%), positive predictive value was not high (53%). CONCLUSION: The study suggests the predictive usefulness of the PDI for subsequent PTSD in accident survivors. Its adequate usage should be further elaborated. Language: en

The prevalence of restless legs syndrome in Taiwanese adults.

Abstract: Aim: Few studies have examined the prevalence of restless legs syndrome (RLS) in Asian populations, with existing data suggesting substantially lower rates of RLS in Asian populations compared with Caucasians. However, varying definitions of RLS as well as problematic methodology make conclusions about RLS prevalence in Asian populations difficult to interpret. The current study therefore examines the prevalence of RLS in Taiwanese adults. Methods: Subjects were 4011 Taiwanese residents over the age of 15 years. Data was collected using a computer-assisted telephone interviewing (CATI) system between 25 October 2006 and 6 November 2006. Results: The prevalence of RLS in Taiwanese adults was found to be 1.57%. In addition, individuals with RLS had a higher body mass index (BMI) and incidence of chronic conditions and comorbidities including insomnia, hypertension, cardiovascular disease, respiratory disease, arthritis, backache and mental illness. Women with RLS also had a higher incidence of post-menopausal syndrome. Conclusion: Findings from the current study suggest that the prevalence of RLS in Taiwan is 1.57% by telephone interview. Individuals with RLS had a higher incidence of chronic insomnia and many other chronic disorders. The association and long-term consequences of RLS with these chronic disorders warrants further longitudinal observation and study.

Neuroanatomical correlates of attention-deficit-hyperactivity disorder accounting for comorbid oppositional defiant disorder and conduct disorder.

Abstract: Aim: An increasing number of neuroimaging studies have been conducted to uncover the pathophysiology of attention-deficit–hyperactivity disorder (ADHD). The findings are inconsistent, however, at least partially due to methodological differences. In the present study voxel-based morphometry (VBM) was used to evaluate brain morphology in ADHD subjects after taking into account the confounding effect of oppositional defiant disorder (ODD) and conduct disorder (CD) comorbidity. Methods: Eighteen children with ADHD and 17 age- and gender-matched typically developing subjects underwent high-spatial resolution magnetic resonance imaging. The regional gray matter volume differences between the children with ADHD and controls were examined with and without accounting for comorbid ODD and CD in a voxel-by-voxel manner throughout the entire brain. Results: The VBM indicated significantly smaller regional gray matter volume in regions including the bilateral temporal polar and occipital cortices and the left amygdala in subjects with ADHD compared with controls. Significantly smaller regional gray matter volumes were demonstrated in more extensive regions including the bilateral temporal polar cortices, bilateral amygdala, right occipital cortex, right superior temporal sulcus, and left middle frontal gyrus after controlling for the confounding effect of comorbid ODD and CD. Conclusion: Morphological abnormalities in ADHD were seen not only in the regions associated with executive functioning but also in the regions associated with social cognition. When the effect of comorbid CD and ODD was taken into account, there were more extensive regions with significantly smaller volume in ADHD compared to controls.

Lipid peroxidation in patients with schizophrenia.

Abstract: Aims: There is evidence that dysregulation of free radicals metabolism associated with abnormal activities of antioxidative enzymes in schizophrenia can lead to lipid peroxidation in plasma, erythrocytes, blood platelets and cerebrospinal fluid. Injury to neurons in schizophrenia may affect their function, i.e. membrane transport, impairment of energy production in mitochondria, changes in membrane phospholipid composition, alteration of receptors and transporters as well as neurotransmission. The purpose of the present study was to assess the total antioxidant capacity (TAC) and lipid peroxidation (expressed as the level of thiobarbituric acid reactive substances [TBARS]) in plasma from schizophrenic patients taking olanzapine or risperidone. The level of TBARS estimated according to the Rice–Evans method and TAC ([ABTS; 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assay]) in plasma from schizophrenic patients (DSM-IV criteria for schizophrenia, n = 30, age 18–36) taking olanzapine or risperidone and from healthy volunteers (n = 30) were measured. Methods: The level of TBARS in plasma from healthy volunteers after incubation with olanzapine or risperidone was also estimated. Results: Significantly lower plasma TAC (P 0.05). The obtained results indicate that the pro-oxidant disturbances occur in schizophrenic patients (acute episode) taking stable doses of olanzapine or risperidone. Conclusion: It seems that second-generation antipsychotics (olanzapine and risperidone) are not responsible for increase of plasma lipid peroxidation.

Serum ghrelin is inversely associated with cognitive function in a sample of non-demented elderly

Abstract: Aim: The orexigenic hormone, ghrelin, is linked to learning and memory in animal studies. No previous study has investigated whether cognition is related to ghrelin in the non-demented elderly. Methods: Thirty-five older adults underwent neuropsychological testing and fasting blood draw with subsequent serum ghrelin quantification. Results: Ghrelin was negatively correlated with several cognitive domains, including verbal memory, working memory, and naming. Conclusion: Areas of cognition associated with ghrelin level were similar to the pattern of deficits observed in early Alzheimer's disease. Findings suggest a potential moderational role of ghrelin in pathological cognitive decline. Further work investigating mechanisms is needed.

Apolipoprotein E and central nervous system disorders: reviews of clinical findings.

Abstract: Dementia is a major health problem in developed countries with over 25 million people affected worldwide and probably over 75 million people at risk during the next 20 years. Alzheimer's disease (AD) is the most frequent cause of dementia (50-70%), followed by vascular dementia (30-40%), and mixed dementia (15-20%). AD pathogenesis is still to be elucidated but it is believed to be the complex interaction between genetic and environmental factors in later life. Three causative genes for familial AD have been identified: amyloid precursor protein, presenilin-1, and presenilin-2. There are 150 genes involved with increased neuronal vulnerability to premature death in the AD brain. Among these susceptibility genes, the apolipoprotein E (ApoE) gene is the most prevalent as a risk for AD pathogenic process in which complex interactions between genetic and environmental factors are involved, leading to a cascade of pathogenic events converging in final pathways to premature neuronal death. Some of these mechanisms are common to several neurodegenerative disorders that differ depending upon the genes affected and the involvement of environmental conditions. ApoE is a key lipoprotein in lipid and cholesterol metabolism and it is also the major risk gene for AD and many other central nervous system disorders. The pathogenic role of ApoE-4 is still to be clarified; however, diverse evidence suggests that ApoE may play pleiotropic functions in dementia and central nervous system disorders.

Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder.

Abstract: Aims: The posterior region of the orbitofrontal cortex (OFC), which forms its sulcogyral pattern during neurodevelopment, receives multisensory inputs. The purpose of the present study was to assess the relationship between posterior OFC sulcogyral pattern and OFC volume difference in patients with panic disorder. Methods: The anatomical pattern of the posterior orbital sulcus (POS) was classified into three subtypes (absent POS, single POS, double POS) using 3-D high-spatial resolution magnetic resonance images obtained from 28 patients with panic disorder and 28 age- and gender-matched healthy controls. Optimized voxel-based morphometry (VBM) was performed to assess OFC volume differences between the two groups by subtype. Categorical regression analysis was applied to examine the association of POS subtypes with State–Trait Anxiety Inventory and Revised Neuroticism-Extraversion-Openness Personality Inventory scores. Results: No significant difference was found in POS subtype distribution between control subjects and patients with panic disorder. VBM, however, indicated volume reduction in the right posterior–medial OFC region in panic disorder patients with absent POS and single POS. Single POS was positively associated with Trait-Anxiety (β = 0.446, F = 6.409, P = 0.020), and absent POS was negatively associated with Trait-Anxiety (β = −0.394, F = 5.341, P = 0.032) and Neuroticism trait (β = −0.492, F = 6.989, P = 0.017). Conclusions: POS subtypes may be relevant to volume reduction in OFC and the anxiety trait in patients with panic disorder. These findings suggest that volume reduction in OFC in panic disorder may be associated with neurodevelopment.

Relationship between late-life depression and life stressors: large-scale cross-sectional study of a representative sample of the Japanese general population.

Abstract: Aim: The purpose of the present study was to clarify the relationship between late-life depression and daily life stress in a representative sample of 10 969 Japanese subjects. Methods: Data on 10 969 adults aged ≥50 who participated in the Active Survey of Health and Welfare in 2000, were analyzed. The self-administered questionnaire included items on 21 reasons for life stressors and the magnitude of stress, as well as the Japanese version of the Center for Epidemiologic Studies Depression Scale (CES-D). The relationship between the incidence of life stressors and mild–moderate (D16) and severe (D26) depressive symptoms was examined using logistic regression analysis. Results: A total of 21.9% of subjects had D16 symptoms, and 9.3% had D26 symptoms. Further, increased age and being female were associated with more severe depressive state. Logistic regression analysis indicated that the strongest relationship between both the incidence of D16 and D26 symptoms and life stressors stemmed from ‘having no one to talk to’ (odds ratio = 3.3 and 5.0, respectively). Late-life depression was also associated with ‘loss of purpose in life’, ‘separation/divorce’, ‘having nothing to do’, ‘health/illness/care of self’, and ‘debt’. Conclusion: There is a relationship between late-life depression and diminished social relationships, experiences involving loss of purpose in life or human relationships, and health problems in the Japanese general population.

Development of 2-hour suicide intervention program among medical residents: first pilot trial.

Abstract: Aim: Suicide is associated not only with primary psychiatric disorders but also with physical disorders Physicians' education on suicide prevention contributes to reducing suicide Therefore, medical residents, who contact patients daily and who eventually become primary physicians in each specialty, might be the most appropriate candidates for intervention In this article, we introduce our newly developed suicide intervention program among medical residents Methods: We developed a 2-hour suicide intervention program among medical residents, based on the Mental Health First Aid (MHFA), which had originally been developed for the public The program contains a 1-hour lecture and a 1-hour role-play session As the first pilot trial, we conducted the program among 44 first-year medical residents at a university hospital and evaluated its effectiveness Changes in confidence, attitudes and behavior toward suicidal people were evaluated using self-reported questionnaires before, immediately after, and 6 months after the program Results: Participants' confidence and attitudes significantly improved after the program The total mean score (standard deviation) of the Suicide Intervention Response Inventory improved from 184 (20) before the intervention to 194 (20) immediately after the intervention However, the effectiveness was limited after 6 months In the course of 6 months, the participants learned to apply the MHFA principles in their daily clinical practice Conclusion: Our newly developed brief suicide intervention program demonstrating its effectiveness among medical residents should be modified in order to be more effective in the long term The next trial with a control group ought to be conducted to evaluate our developed program

Clinical utility of the Chinese version of the Pediatric Daytime Sleepiness Scale in children with obstructive sleep apnea syndrome and narcolepsy

Abstract: Aim: The present study examined the psychometric properties of the Chinese version of the Pediatric Daytime Sleepiness Scale (PDSS) and the utility of the PDSS as a screening tool for pathological daytime sleepiness in teenagers with obstructive sleep apnea (OSA) and narcolepsy. Methods: The PDSS was first administered to 238 middle and high school students to assess the reliability of the scale, and then administered to 28 teenagers with OSA, 31 teenagers with narcolepsy, and 34 normal controls to evaluate its clinical utility. Results: Test–retest reliability and internal consistency were acceptable. The PDSS scores were significantly higher in narcoleptic subjects than in subjects with OSA, and higher in OSA syndrome (OSAS) subjects than normal controls. Furthermore, the scores decreased in narcoleptic subjects after medical treatment. Both reliability and validity were proven to be good. As a screening tool for narcolepsy, receiver operator characteristic (ROC) curve analysis showed that the PDSS, with a cut-off score of 16/17, had good sensitivity (87.1%) and fair specificity (74.3%) for identifying individuals with narcolepsy. When used for screening OSA, however, the differentiating power was not as good. Conclusion: The PDSS is a reliable and valid tool for the measurement of sleepiness in clinical youth populations. When used as a screening tool, it is useful for sleep disorders involving more severe pathological sleepiness, as in narcolepsy.

Low serum HDL-cholesterol levels are associated with long symptom duration in patients with major depressive disorder

Abstract: Aims: The purpose of the present study was to examine whether the association between depression and the serum high-density lipoprotein cholesterol (HDL-C) is modified by symptom duration. Methods: Depressed patients (n = 88) and an age- and sex-matched group of healthy general population controls (n = 88) underwent a Structured Clinical Interview for DSM-IV (SCID), and depressed participants reported the duration of their symptoms. The serum levels of total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and non-HDL, and the ratios of LDL-C/HDL and TC/HDL-C were assessed. Results: Major depressive disorder (MDD) subjects with a long symptom duration (≥3 years) had lower levels of HDL-C compared with healthy controls or MDD subjects with a symptom duration <3 years. The likelihood for long symptom duration doubled for each 0.5-mmol/L decrease in HDL-C levels in regression models adjusted for age, gender, marital status, overweight, symptom severity, alcohol consumption, smoking, physical exercise, medication use, and non-HDL-C (P < 0.05). Conclusions: These findings suggest that a low serum HDL-C level, a risk factor for coronary heart disease, is specifically associated with long-term depressive symptomatology.

Duration of untreated illness and antidepressant fluvoxamine response in major depressive disorder

Abstract: Aims: The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode. Methods: A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables. Results: Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI. Conclusion: Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.

Relationship of psychopathological symptoms and cognitive function to subjective quality of life in patients with chronic schizophrenia

Abstract: Aims: The purpose of the present study was to examine the extent of the effects of psychopathological symptoms and cognitive function on quality of life (QOL) in patients with chronic schizophrenia. Methods: Data were obtained using the Japanese Schizophrenia Quality of Life Scale (JSQLS), Positive and Negative Syndrome Scale (PANSS), Wisconsin Card-Sorting Test (WCST) Keio version, and Continuous Performance Test (CPT) for 52 schizophrenia patients. Results: Stepwise regression analysis showed that PANSS depression/anxiety factors predicted JSQLS psychosocial conditions and motivation/energy, and that WCST Categories Achieved predicted JSQLS symptoms/side-effects. Conclusions: Psychopathological symptoms and cognitive function affect subjective QOL in patients with schizophrenia. If the final goal is treatment that improves QOL in a manner that patients themselves are aware of, clinicians probably need to consider a treatment strategy that improves depression/anxiety symptom.

Dorsal hippocampal opioidergic system modulates anxiety‐like behaviors in adult male Wistar rats

Abstract: Aims: In the present study, we investigated the possible influence of the opioidergic system of the dorsal hippocampus on anxiety-like behaviors. Methods: Elevated plus-maze, which is one of the methods used for testing anxiety, was used in the present study. Rats were anesthetized with ketamine and xylazine and special cannulas were inserted stereotaxically into the CA1 region of the dorsal hippocampus. After 1 week of recovery, the effects of intra-CA1 administration of morphine (0.25, 0.5, 1 and 2 µg/rat; 1 µl/rat; 0.5 µl/in each side), naloxone (2, 4, 6 and 8 µg/rat), enkephalin (1, 2, 5 and 10 µg/rat) and naltrindole (0.25, 0.5, 1 and 2 µg/rat) on percentage open arm time (%OAT) and percentage open arm entries (%OAE) were determined. Results: Bilateral administration of morphine into CA1 decreases %OAT and %OAE, indicating an anxiogenic-like effect. Intra-CA1 injection of naloxone, an opioid receptor antagonist, increased both %OAT and %OAE, parameters of anxiolytic-like behavior. Bilateral administration of δ-opioid receptor agonist, [D-Pen2,5]-enkephalin acetate hydrate into the CA1, induced an anxiolytic-like effect. Furthermore, intra-CA1 injection of δ-opioid receptor antagonist, naltrindole hydrochloride, increased anxiety-related behaviors. Conclusions: The results of the present study demonstrate that activation of μ-opioid receptors in this area produce an anxiogenic response while activation of δ-opioid receptors produces an anxiolytic response.

Relationship of alexithymia and temperament and character dimensions with lifetime post-traumatic stress disorder in male alcohol-dependent inpatients

Abstract: Aims: The purpose of the present study was to evaluate the prevalence of lifetime post-traumatic stress disorder (PTSD) in male alcohol-dependent inpatients and to investigate the relationship of PTSD with alexithymia and temperament and character dimensions. Methods: Participants were 156 consecutively admitted male alcohol-dependent subjects. Patients were investigated using the Clinician-Administered PTSD Scale (CAPS), the Toronto Alexithymia Scale (TAS-20) and the Temperament and Character Inventory (TCI). Results: Among alcohol-dependent inpatients 32.1% were considered as having lifetime PTSD. Mean scores of alexithymia, novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) were higher in the PTSD group, whereas age and self-directedness (S) were lower. Among age and other factors of TAS-20, ‘difficulty in identifying feelings (DIF)’ predicted PTSD in a logistic regression model. When age and personality dimensions of TCI were taken as independent variables, S predicted PTSD in the logistic regression model. Finally, among subscales of TCI, ‘impulsiveness versus reflection’ (NS2) and ‘congruent second nature versus bad habits’ (S5) predicted PTSD. Conclusions: Alexithymia and personality traits, particularly high DIF and S scores are related with lifetime PTSD diagnosis, even when controlling for age among alcohol-dependent inpatients. Causal relationships between alexithymia, personality dimensions and PTSD, and their implications on treatment are not clear and should be evaluated in longitudinal studies.

Diurnal cortisol patterns of young male patients with schizophrenia

Abstract: Aims: It has been suggested that schizophrenic patients are more vulnerable to stress than healthy persons, and that stressors can trigger a psychotic episode or worsen symptoms. The biological system often studied in relation to stress is the hypothalamic–pituitary–adrenal (HPA) axis, which controls the release of cortisol. We investigated whether the diurnal basal activity of the HPA axis differed between young male patients with schizophrenia and healthy controls. Methods: Twenty-seven male patients (mean age 22 ± 5 years) and 38 healthy male control subjects (mean age 22 ± 3 years) were included in the present study. Saliva was sampled at five time points during the day: directly after awakening, 30 min thereafter, and at 12.00 hours, 16.00 hours and 22.00 hours. Results: The cortisol concentration decreased significantly more during the day in the patient group thanin the control group. Patients also showed a significantly decreased area under the curve with respect to the increase, again indicating that the cortisol concentrations decreased more during the day in patients than in controls. Both the morning increase and the area under the curve with respect to the increase were significantly negatively correlated with negative symptom severity. Conclusions: Patients with schizophrenia showed a different daytime sensitivity of the HPA axis. Our findings further suggest that an increase in negative symptom severity is related to a decreased HPA axis sensitivity.

Plasma BDNF and tPA are associated with late-onset geriatric depression

Abstract: Aims: Studies in the recent decade have shown that brain-derived neurotrophic factor (BDNF) may play an important role in the pathogenesis of major depressive disorder (MDD). Tissue-type plasminogen activator (tPA) has been implicated in the control of the direction of BDNF action. The aim of the study was therefore to investigate the changes of BDNF/tPA levels and their clinical meanings in geriatric depression. Methods: Plasma BDNF and tPA levels were measured in late-onset geriatric depression (LGD) before treatment (n = 24) and after 6 weeks of antidepressant treatment (n = 24) compared with control subjects (n = 30) using enzyme-linked immunosorbent assay. The severity of depression was assessed with the Hamilton Depression Rating Scale. Results: Baseline plasma BDNF and tPA levels were significantly lower in LGD patients compared to controls (P = 0.037 and P = 0.000, respectively). There was a heightening tendency of plasma BDNF level after treatment. Conclusions: Plasma BDNF and tPA levels are associated with LGD. The complex mechanism of BDNF and tPA in LGD should be further explored in future studies.

Polysomnography in patients with post-traumatic stress disorder.

Abstract: Aims: The purpose of the present study was to investigate sleep structure in post-traumatic stress disorder (PTSD) patients with and without any psychiatric comorbidities. The relationship between sleep variables and measurements of clinical symptom severity were also investigated. Methods: Sleep patterns of 24 non-medicated male PTSD patients and 16 age- and sex-matched normal controls were investigated on polysomnography on two consecutive nights. Six PTSD-only patients and 15 PTSD patients with major depressive disorder (MDD) were also compared to normal controls. Sleep variables were correlated with PTSD symptoms. Results: Compared to the normal controls, the PTSD patients with MDD had difficulty initiating sleep, poor sleep efficiency, decreased total sleep time, decreased slow wave sleep (SWS), and a reduced rapid eye movement (REM) sleep latency. The PTSD patients without any comorbid psychiatric disorders had moderately significant disturbances of sleep continuity, and decreased SWS, but no abnormalities of REM sleep. REM sleep latency was inversely proportional to the severity of startle response. SWS was found to be inversely correlated with the severity of psychogenic amnesia. Conclusions: PTSD patients have disturbance of sleep continuity, and SWS deficit, without the impact of comorbid depression on sleep. The relationship between SWS and the inability to recall an important aspect of trauma may indicate the role of sleep in the consolidation of traumatic memories. The relationship between the severity of the startle response and REM latency may suggest that REM sleep physiology shares common substrates with the symptoms of PTSD.

Correlations between alexithymia and pain severity, depression, and anxiety among patients with chronic and episodic migraine.

Abstract: Aims: Some studies have found elevated alexithymia among patients with chronic pain, but the correlations between alexithymia and the severity of pain, depression, and anxiety among migraine patients are unclear. The aims of the present study were to investigate whether individuals suffering from episodic migraine (EM) differ from those with chronic migraine (CM) in regards to depression, anxiety, and alexithymia measures and to investigate the association of alexithymia with the results of depression and anxiety test inventories and illness characteristics. Methods: A total of 165 subjects with EM and 135 subjects with CM were studied. The Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), and Toronto Alexithymia Scale (TAS) were administered to all subjects. The correlation between alexithymia and sociodemographic variables, family history of migraine and illness characteristics (pain severity, frequency of episode, duration of illness) were evaluated. Results: Compared with EM patients, the CM patients had significantly higher scores on measures of depression but not alexithymia and anxiety. There was a positive correlation between TAS scores and age and education in both migraine groups, but there was no correlation between TAS scores and other demographic variables. Depression and anxiety were significantly correlated with alexithymia in both migraine groups. Conclusion: Our results indicate that CM patients are considerably more depressive than EM patients. In this study, depression and anxiety were significantly correlated with alexithymia in both migraine groups. Our results demonstrate a positive association between depression, anxiety, and alexithymia in migraine patients.

Clinical and pharmacologic risk factors for neuroleptic malignant syndrome and their association with death

Abstract: Aim: The aim of the present study was to evaluate demographics, clinical features, psychiatric diagnoses and prognosis of neuroleptic malignant syndrome (NMS) reported in Turkey, and to assess their association with mortality. Methods: Data on all reported cases of NMS in the Turkish Psychiatric Index between 1985 and 2005 were collected. The type, dosage and administration period of neuroleptics, the clinical and laboratory findings; and prognosis were compared in terms of mortality. Results: Thirty-six patients with a mean age of 33.67 ± 16.98 years were identified. Fifteen (41.7%) were diagnosed as having schizophrenia or other psychotic disorders and the same number were diagnosed as having affective disorder. Remaining five (13.9%) were diagnosed with other psychiatric disorders and 1 (2.7%) had no psychiatric diagnosis. Twenty-two (61.1%) of the NMS cases were associated with high potency typical neuroleptics. Association between an atypical antipsychotic and NMS has been reported in one case. NMS appeared within 7 days after initiation of the antipsychotic medication in the majority of samples (n = 19, 52.8%). Several combinations of rescue treatments were used in the majority of cases (n = 19, 52.8%), although bromocriptine (n = 22, 61.1%) was the most frequently preferred rescue treatment for NMS. Benzodiazepines were significantly better than the other treatment options in preventing mortality. Five out of the 36 patients (13.9%) with NMS had died. Age was the only significant independent factor that was associated with mortality. Conclusions: Benzodiazepines may be included in the treatment of NMS. The mortality rate due to NMS in Turkey was lower than the previously reported rates from other developing countries.

Caregiver burden and coping strategies for patients with schizophrenia: comparison between Japan and Korea.

Abstract: Aim: With the current shift to community-centered mental health services, considerable research on the family burden of caring for patients with schizophrenia has been conducted in developed countries. However, there has been no investigation of families with Japanese or Korean sociocultural backgrounds. Therefore, the present study compared the caregiver burden and coping strategies of families of patients with schizophrenia in Japan and Korea in order to elucidate similarities and differences in the sociocultural factors that affect the care experience of families in Northeast Asia. Methods: A total of 99 Japanese (Nagasaki) and 92 Korean (Seoul, Daegu) family members of patients with schizophrenia were surveyed in regards to caregiver burden, coping strategies, and nursing awareness of the caregiver role regarding the patient with schizophrenia. Results: Analysis revealed the following: (i) although no difference in caregiver burden and coping strategy was observed between the countries, the nursing awareness of families' caregiver role was significantly higher in Japan than in Korea; (ii) caregiver burden was significantly associated with the patient's social functioning and care needs in both countries; and (iii) caregiver burden was significantly associated with reduction of social interests, coercion, avoidance, resignation, and nursing awareness of caregiver role in both countries. Conclusion: Although the nursing awareness of families' roles in caring for patients with schizophrenia differed between Japan and Korea, similar trends were observed for the causes of caregiver burden. These findings suggest that in order to provide effective support for reducing caregiver burden, the necessity of such support must be emphasized in both countries.

A three-year follow-up study of the psychosocial predictors of delayed and unresolved post-traumatic stress disorder in Taiwan Chi-Chi earthquake survivors

Abstract: Aims: To predict the longitudinal course of post-traumatic stress disorder (PTSD) in survivors three years following a catastrophic earthquake using multivariate data presented six months after the earthquake. Methods: Trained assistants and psychiatrists used the Disaster-related Psychological Screening Test (DRPST) to interview earthquake survivors 16 years and older and to assess current and incidental psychopathology. A total of 1756 respondents were surveyed over the three-year follow-up period. Results: A total of 38 (9.1%) of the original 418 PTSD subjects and 40 of the original 1338 (3.0%) non-PTSD subjects were identified as having PTSD at the 3-year post-earthquake follow up. Younger age, significant financial loss, and memory/attention impairment were predictive factors of unresolved PTSD and delayed PTSD. Conclusions: The longitudinal course of PTSD three years after the earthquake could be predicted as early as six months after the earthquake on the basis of demographic data, PTSD-related factors, and putative factors for PTSD.

Reduced gray matter volume of dorsal cingulate cortex in patients with obsessive-compulsive disorder: a voxel-based morphometric study.

Abstract: Aims: Previous morphometric studies using magnetic resonance imaging (MRI) have revealed structural brain abnormalities in obsessive–compulsive disorder (OCD). The aim of the present study was to investigate the alterations in brain structure of patients with OCD using a voxel-based morphometry (VBM) method. Methods: Sixteen patients with OCD free of comorbid major depression, and 32 sex- and age-matched healthy subjects underwent MRI using a 1.5-T MR scanner. OCD severity was assessed with the Yale–Brown Obsessive–Compulsive Scale (mean ± SD: 22 ± 7.6; range: 7–32). MR images were spatially normalized and segmented using the VBM5 package (http://dbm.neuro.uni-jena.de/vbm/). Statistical analysis was performed using statistical parametric mapping software. Results: Significant reductions in regional gray matter volume were detected in the left caudal anterior cingulate cortex and right dorsal posterior cingulate cortex in the patients with OCD as compared to healthy controls (uncorrected, P < 0.001). No significant differences in white matter volumes were observed in any brain regions of the patients. No significant correlation between Yale–Brown Obsessive–Compulsive Scale score and regional gray matter or white matter volume was observed. Conclusions: Regional gray matter alteration in the dorsal cingulate cortex, which is suggested to play a role in non-emotional cognitive processes, may be related to the pathophysiology in OCD.

Effect of bromocriptine on antipsychotic drug-induced hyperprolactinemia: eight-week randomized, single-blind, placebo-controlled, multicenter study.

Abstract: Aim: The objective of the present study was to assess the efficacy and safety of bromocriptine treatment for patients with antipsychotic-drug-induced hyperprolactinemia in clinical practice. Methods: This was an 8-week randomized, single-blind, placebo-controlled, multicenter study. Sixty female schizophrenia patients were enrolled and were randomly assigned to one of four treatment groups: bromocriptine 2.5 mg/day, 5 mg/day, 10 mg/day, and placebo. Serum levels of prolactin, estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were evaluated on three occasions (baseline, and 4 and 8 weeks after commencement of the treatment paradigm). Extrapyramidal symptoms (EPS) and clinical symptoms were assessed using the Simpson–Angus scale and the Positive and Negative Syndrome Scale (PANSS), respectively. Results: Of the 60 subjects who were enrolled, 48 completed the study (n = 14, 13, 11, and 10 in the bromocriptine 2.5 mg/day, 5 mg/day, and 10 mg/day, and placebo groups, respectively). Four patients in the 10-mg/day group, two in the 5-mg/day group, and one in the placebo group resumed menses during the study. The mean level of prolactin significantly decreased from baseline to week 4, and then plateaued, showing no significant change for the remaining 4 weeks of the study. No significant changes in LH, FSH, or E2 levels were observed throughout the 8-week study period, either within or between groups. Conclusion: Administration of bromocriptine is a safe method for treating antipsychotic-drug-induced hyperprolactinemia without exacerbating either psychotic symptoms or EPS.