I-Hui Lee

PSYCHIATRIC MORBIDITY AND POST-TRAUMATIC SYMPTOMS AMONG SURVIVORS IN THE EARLY STAGE FOLLOWING THE 1999 EARTHQUAKE IN TAIWAN

This study reports the clinical psychiatric presentations and post-traumatic symptoms among 525 survivors at Yu-Chyr District in Nantou County who sought psychiatric service in the first month following the devastating earthquake that struck the central area of Taiwan. All subjects received psychiatric interviews and assessments using the 12-item Chinese Health Questionnaire (CHQ-12) and a checklist for post-traumatic symptoms. The most common psychiatric symptoms reported were insomnia, palpitations, nervousness, and dizziness with headache. Eleven percent of the subjects reported having thought of death or having suicidal ideation. The mean score on the CHQ-12 was 6.43 (S.D.=2.89). The rate of probable psychiatric morbidity as defined by a CHQ-12 score > or =3 was 89.9%. Post-traumatic symptoms were very prevalent, particularly symptoms of re-experiencing the earthquake and hyper-arousal. Factors significantly associated with high psychiatric morbidity were being female, serious destruction of property and house, and personality characteristics of nervousness and obsessiveness. Findings of this study suggest that early psychiatric intervention, including pharmacological treatment for acute stress disorder, is indicated during the early stages following a disastrous earthquake.

Neuropsychological functions in patients with bipolar I and bipolar II disorder

UNLABELLED The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls. METHODS The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function. RESULTS The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory. CONCLUSIONS BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.

Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers--a SPECT study.

Recent lines of research suggest that, in addition to hypothalamic sites, the striatum dopaminergic system may be a target for regulating homeostasis that may be represented by the body mass index (BMI). Although it has been reported that the striatal dopamine receptor (DRD2) availability of very obese individuals was reduced in proportion to their BMI, the correlation between the striatal dopamine system and the BMI in healthy individuals remains unclear. To investigate this relationship, the striatal dopamine transporter (DAT) availability of 50 healthy volunteers was measured using single position emission computational topography (SPECT) and [99mTc]-TRODAT-1. The serum levels of sugar, C-peptide, insulin, glycosylated hemoglobin and leptin were measured. Our results showed that age and the BMI are significantly negatively associated with the striatal DAT availability. Moreover, BMI was the only significant predictor for striatal DAT availability. These results suggest that the striatal dopamine system may be involved in body mass index regulation. Thus, molecular imaging studies measuring the striatal DAT availability should consider the BMI, rather than age, as a covariant.

Increased Plasma Leptin in Antipsychotic-Naïve Females with Schizophrenia, but Not in Males

Background: Metabolic abnormalities, including insulin resistance and increased leptin levels, were noted in patients with schizophrenia who had received antipsychotics. In this study, we examined the leptin levels of antipsychotic-naïve schizophrenic patients. Method: Seventeen antipsychotic-naïve patients with schizophrenia and 16 sex-, age- and body mass index (BMI)-matched subjects were recruited from the psychiatric outpatient clinic and community, respectively. Serum leptin levels of the healthy controls and antipsychotic-naïve patients were compared. The relationships between leptin level and gender, Positive and Negative Syndrome Scale score, and duration of illness were analyzed by Spearman’s correlation. Results: Compared with sex-, age- and BMI-matched subjects, the female schizophrenic patients had elevated serum leptin levels. In the male patients, the results of this preliminary study also revealeda positive correlation between leptin levels andthe Aggression Risk Profile subscale of the PANSS. Conclusion: This preliminary study suggests possible gender-specific leptin dysregulation in antipsychotic-naïve schizophrenic patients.

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia.

OBJECTIVE Brain-derived neurotropic factor (BDNF) is widely distributed in the peripheral and central nervous systems. BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of several mental illnesses. To elucidate the role of BDNF, we compared the plasma BDNF levels and the BDNF Val66Met gene variants effect in several mental disorders. METHOD We enrolled 644 participants: 177 patients with bipolar I disorder (BP-I), 190 with bipolar II disorder (BP-II), 151 with schizophrenia, and 126 healthy controls. Their plasma BDNF levels and BDNF Val66Met single nucleotide polymorphisms (SNP) were checked before pharmacological treatment. RESULTS Plasma levels of BDNF were significantly lower in patients with schizophrenia than in healthy controls and patients with bipolar disorder (F = 37.667, p<0.001); the distribution of the BDNF Val66Met SNP was not different between groups (χ(2) = 5.289, p = 0.507). Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not influence plasma BDNF levels in our participants. Plasma BDNF levels were, however, significantly negatively correlated with depression scores in patients with bipolar disorder and with negative symptoms in patients with schizophrenia. CONCLUSION We conclude that plasma BDNF profiles in different mental disorders are not affected by BDNF Val66Met gene variants, but by the process and progression of the illness itself.

The effects of add-on low-dose memantine on cytokine levels in bipolar II depression: a 12-week double-blind, randomized controlled trial.

Abstract Memantine, a noncompetitive N-methyl-d-aspartate receptor antagonist with a mood-stabilizing effect, and an association between bipolar disorder and proinflammatory cytokine levels have been reported. Whether adding-on memantine would reduce cytokine levels and is more effective than valproic acid (VPA) alone in bipolar II disorder was investigated. A randomized, double-blind, controlled, 12-week study was conducted. Patients undergoing regular VPA treatments were randomly assigned to a group: VPA + memantine (5 mg/d) (n = 106) or VPA + placebo (n = 108). The Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS) were used to evaluate clinical response. Symptom severity, plasma tumor necrosis factor &agr; (TNF-&agr;), interleukin 6 (IL-6), IL-8, and IL-1 levels were examined during weeks 0, 1, 2, 4, 8, and 12. To adjust within-subject dependence over repeated assessments, multiple linear regressions with generalized estimating equation methods were used to examine the therapeutic effect. Tumor necrosis factor &agr; levels were significantly lower in the VPA + memantine group than in the VPA + placebo group (P = 0.013). Posttreatment HDRS and YMRS scores decreased significantly in both groups, but not significant, nor was the other between-group cytokine level difference pretreatment and posttreatment. The HDRS score changes were significantly associated with IL-6 (P = 0.012) and IL-1 (P = 0.005) level changes and changes in YMRS score changes with TNF-&agr; (P = 0.005) level changes. Treating bipolar II depression with VPA + memantine may improve the plasma TNF-&agr; level. However, adding-on memantine may not improve clinical symptoms or cytokine levels other than TNF-&agr;. Clinical symptoms may be correlated with certain cytokines.

Negative Symptoms and Regional Cerebral Blood Flow in Patients with Schizophrenia: A Single Photon Emission Computed Tomography Study

There have been few functional imaging studies of negative symptoms in schizophrenia during the resting state, particularly in Asian patients with schizophrenia. The aim of this study was to evaluate the relationship between regional cerebral flood flow (rCBF) and negative symptoms, and to discuss the association between severity and subgroups of negative symptoms and rCBF. Sixteen patients with chronic schizophrenia were evaluated for negative symptoms using the Scale for the Assessment of Negative Symptoms (SANS), and brain single photon emission computed tomography (SPECT) imaging to assess rCBF during the resting state. Results were assessed using Spearmans correlation analysis. Total SANS scores were significantly negatively correlated with bilateral hypofrontality, especially in the left orbital frontal and bilateral superior frontal areas. Subscores for attention were significantly negatively correlated with the left lower frontal‐temporal area and the right cerebellum. Subscores for anhedonia had a negative correlation with the right hemisphere. Subscores for affect were negatively correlated with rCBF in the bilateral prefrontal and bilateral superior frontal areas. There were no associations between rCBF and SANS in alogia and avolition. These results support the notion that frontal lobe dysfunction in schizophrenia is associated with negative symptoms. The left anterior hemisphere may play an important role in attention deficit. These relationships between negative symptoms and neuroanatomy require further clarification.

Therapeutic effects of add-on low-dose dextromethorphan plus valproic acid in bipolar disorder

UNLABELLED Changes in inflammatory cytokines and dysfunction of the neurotrophic system are thought to be involved in the pathology of bipolar disorder (BP). We investigated whether inflammatory and neurotrophic factors were changed in BP. We also investigated whether treating BP with valproic acid (VPA) plus low-dose (30 or 60 mg/day) dextromethorphan (DM) is more effective than treating it with VPA only, and whether DM affects plasma cytokines and brain derived neurotrophic factor (BDNF) levels. In a 12-week, randomized, double-blind study, patients were randomly assigned to the VPA+DM30, VPA+DM60, or VPA+Placebo groups. The Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HDRS) were used to evaluate symptom severity, and ELISA to analyze plasma cytokine and BDNF levels. We recruited 309 patients with BP and 123 healthy controls. Before treatment, patients with BP had significantly higher plasma cytokine and lower plasma BDNF levels than did healthy controls. After treatment, HDRS and YMRS scores in each group showed significant improvement. Plasma cytokine levels tended to decline in all groups. Changes in plasma BDNF levels were significantly greater in the VPA+DM60 group than in the VPA+Placebo group. CONCLUSION patients with BP have a certain degree of systemic inflammation and BDNF dysfunction. Treatment with VPA plus DM (60 mg/day) provided patients with BP significantly more neurotrophic benefit than did VPA treatment alone.

Correlation of plasma brain-derived neurotrophic factor and metabolic profiles in drug-naïve patients with bipolar II disorder after a twelve-week pharmacological intervention

Brain‐derived neurotrophic factor (BDNF) is thought to be involved in the pathophysiology of bipolar disorder (BD) and metabolic syndrome. We investigated the correlation between plasma BDNF with mood symptoms and metabolic indices in patients with BD‐II over a 12‐week pharmacological intervention.

Lower availability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder - a preliminary two-ligand SPECT study

PURPOSE Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD. METHODS Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [¹²³I] 2-((2-((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(⁹⁹m)Tc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment. RESULTS SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups. CONCLUSIONS The results with regard to the midbrain SERT level suggest the heritability of MDD.