Mitochondria DNA change and oxidative damage in clinically stable patients with major depressive disorder.

BACKGROUND: To compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD). METHODS: Patients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups. RESULTS: 40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036). LIMITATIONS: The study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered. CONCLUSIONS: Our study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD.

Mitochondrial DNA variation and increased oxidative damage in euthymic patients with bipolar disorder.

AIM: The aim of this study was to compare alterations of mitochondrial DNA (mtDNA) copy number, single nucleotide polymorphisms, and oxidative damage of mtDNA in clinically stable patients with bipolar I disorder (BD). METHODS: Patients meeting DSM-IV diagnostic criteria for BD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding 2 months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any history of major psychiatric disorders and they were non-smokers. By analyzing peripheral blood leukocytes, copy number, single nucleotide polymorphisms and oxidative damage of mtDNA were compared between the two groups. RESULTS: The median age of the subjects was 38 years and 41.5 years in the comparison and BD groups, respectively. The leukocyte mtDNA copy number of the BD group was significantly lower than that of the comparison group (P < 0.001). BD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.1 vs 3.9, P < 0.001). After generalized linear model adjusting with age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the BD group (P < 0.001). MtDNA oxidative damage was positively correlated with age (P = 0.034), although mtDNA oxidative damage was similar between these two groups. CONCLUSION: Possible involvement of oxidative stress and mitochondria in the pathophysiology of BD needs more large-scale studies. It is important that psychiatrists retain a high level of suspicion for mitochondrial dysfunction in patients with bipolar disorder.

Electroencephalography when meditation advances: a case-based time-series analysis.

Increased alpha and theta activities in electroencephalography (EEG) have been found during various forms of meditation. However, advanced stage of meditation drew less attention to date. We aimed at exploring EEG characteristics during advanced meditation. Bilateral absolute alpha and theta EEG powers were recorded when a single meditator at rest, exercising breath meditation, and reaching the advanced meditative stage in 10 sessions of meditation. Averaged time-series data were analyzed using simulation modeling analysis to compare the powers during different meditative phases. During breath meditation, significantly higher activities compared with baseline were found only in bilateral theta (P = 0.0406, 0.0158 for left and right sides, respectively), but not in alpha (P = 0.1412, 0.0978 for left and right sides, respectively) bands. When meditation advanced, significantly increased activities were found both in bilateral alpha (P = 0.0218, 0.0258 for left and right sides, respectively) and theta (P = 0.0308, 0.0260 for left and right sides, respectively) bands compared against breath meditation. When advanced meditation compared against baseline, bilateral alpha (P = 0.0001, 0.0001 for left and right sides, respectively) and theta (P = 0.0001, 0.0001 for left and right sides, respectively) bands revealed significantly increased activities. Our findings support that internalized attention manifested as theta activity continuingly enhances significantly in sequential phases of meditation, while relaxation manifested as alpha activity is significant only after the advanced meditative phase is reached.

Mitochondrial dysfunction and psychiatric disorders.

Mitochondria are intracellular organelles crucial in the production of cellular energy. Mitochondrial diseases may result from malfunctions in this biochemical cascade. Several investigators have proposed that mitochondrial dysfunction is related to the pathophysiology of bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). The authors reviewed recent study findings and tried to delineate the current understanding of the correlation between mitochondrial dysfunction and psychiatric disorders. A growing body of evidence suggests that mitochondrial dysfunction is important in patients with psychiatric disorders. The evidence include impaired energy metabolism in the brain detected using results of magnetic resonance spectroscopy, electron microscopy, co-morbidity with mitochondrial diseases, the effects of psychotropics on mitochondria, increased mitochondrial DNA (mtDNA) deletion in the brain, and association with mtDNA mutations/polymorphisms or nuclear-encoded mitochondrial genes. It is possible that the new information will lead to a focus on psychiatric disorder as a metabolic disease. Treatment with psychotropics might ultimately enhance energy metabolism and reduce the damage of oxidative stress. The next step in the study of mitochondrial dysfunction in patients with psychiatric disorders should be clarification of how mitochondrial dysfunction, a nonspecific risk factor, causes specific symptoms. Further study of mitochondrial dysfunction in patients with psychiatric disorder is expected to be useful for the development of cellular disease markers and new psychotropics.

Randomized study of school-based intensive interpersonal psychotherapy for depressed adolescents with suicidal risk and parasuicide behaviors.

AIM: The aim of the present study was to examine the intervention effects of intensive interpersonal psychotherapy for depressed adolescents with suicidal risk (IPT-A-IN) by comparison with treatment as usual (TAU) at schools. METHODS: A total of 347 students from one-fifth of the classes of a high school in southern Taiwan completed the Beck Depression Inventory-II, the Beck Scale for Suicide Ideation, the Beck Anxiety Inventory and the Beck Hopelessness Scale for screening for suicidal risk. Of them, 73 depressed students who had suicidal risk on screening were randomly assigned to the IPT-A-IN or TAU group. Analysis of covariance (ANCOVA) was performed to examine the effect of IPT-A-IN on reducing the severity of depression, suicidal ideation, anxiety and hopelessness. RESULTS: Using the pre-intervention scores as covariates, the IPT-A-IN group had lower post-intervention severity of depression, suicidal ideation, anxiety and hopelessness than the TAU group. CONCLUSION: Intensive school-based IPT-A-IN is effective in reducing the severity of depression, suicidal ideation, anxiety and hopelessness in depressed adolescents with suicidal risk.

Effects of amisulpride on the cognitive function of patients with schizophrenia who switched from risperidone.

Objectives. The aims of this 13-week study were to examine the efficacy and safety of amisulpride, and effects on cognitive function in patients with schizophrenia after they switched from risperidone. Methods. Twenty-three patients with schizophrenia whose antipsychotic was switched from risperidone to amisulpride were recruited. The efficacy, safety, and cognitive function were assessed. Results. Significant improvements were noted in the PANSS, CGI-S, and MADRS. The prolactin level, but not any of the remaining laboratory variables, increased significantly. The cognitive function improved significantly, particularly in memory subtests. Conclusions. Switching antipsychotic from risperidone to amisulpride in schizophrenia might have significantly improved not only the efficacy, but also various domains of cognitive function. However, hyperprolactinemia existed and was sometimes even worse.

Catatonia associated with coadministration of tramadol and meperidine.

Tramadol and meperidine are frequently prescribed medications in the management of oncologic patients. The pharmacologic interaction of these two drugs may induce mental disturbance. This was demonstrated by our case of a 39-year-old woman with gastric mucosa associated lymphoid tissue lymphoma (MALToma), stage III after chemotherapy. She was admitted to our medical ward with the complaint of abdominal pain. Pantoprazole 40 mg and tramadol 150 mg daily were prescribed with intravenous route after hospitalization. Two days later, the patient developed transient visual hallucinations and disorientation after additional injection of meperidine (25 mg). Six hours later, catatonic features appeared. The duty doctor stopped all the medications. Two days later, the catatonic features disappeared. From the clinical course, we suggest that the catatonia was caused by drug interactions between tramadol and meperidine. The pharmacodynamic mechanism might be related to the dopamine and serotonin systems.