Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Use of topiramate, a new anti-epileptic as a mood stabilizer

Rationale: Because some anti-epileptic drugs (AEDs) are effective in bipolar affective disorders, the new AED topiramate (TPM) may be effective in psychiatric illnesses. TPM was evaluated in mood disorders refractory to previous therapies including newer AEDs. Methods: Charts of 58 consecutive patients, 39 outpatients (15 males, 24 females) and 19 inpatients (6 males, 13 females) were reviewed. TPM 25 mg. b.i.d. was added to existing therapy and titrated in 50 mg increments every 3–7 days. Improvement was rated on a Likert global assessment scale of marked, moderate, mild, or no improvement or worse, based on quality of sleep, appetite, mood, and concentration. Results: Of the 58 patients with psychiatric disorders, 44 patients had rapid cycling bipolar disorders characterized by manic, hypomanic, or mixed episodes. Eighteen patients had previously failed to respond to lamotrigine and/or gabapentin in addition to conventional mood stabilizers. Fourteen were Bipolar I, six Bipolar II, and seven mixed, ten patients had cyclothymic disorder, seven had bipolar disorder not otherwise specified. Of the remaining 14 patients, nine had schizoaffective disorder, three patients had dementia and two had psychosis. Mean duration of TPM treatment was 16.0 weeks; mean TPM dosage approximately 200 mg/day. Thirty-six of 58 (62%) patients exhibited marked or moderate improvement, usually within days or weeks. Twenty-three of 44 (52%) patients with bipolar affective disorders showed marked or moderate improvement. Minimal/no improvement was observed in 16; six were rated as worse. Adverse events included delirium in one patient with Bipolar Disorder Type I who overmedicated with TPM (800 mg) and tranylcypromine sulfate (170 mg) combined with alcohol. Other adverse effects were minor and included: paresthesias, somnolence, fatigue, impaired concentration and memory, nausea, and diarrhoea. Limitations: This study was performed in a nonrandom open and retrospective fashion. Therefore, any findings are limited by the design of this study. Conclusion: TPM may be useful in patients with mood disorders unresponsive to traditional therapy and warrants further clinical investigation.     

Coping strategies,hostility, and depressive symptoms: A path model

Previous studies of coping, hostility, and depressive symptoms have highlighted the significant relations between all possible pairs of these 3 variables. To more completely explore the nature of depressive symptoms, we link them all together in this study by testing a coping→hostility→depressive symptoms path model. One hundred forty participants completed psychological questionnaires measuring coping strategies, hostility, and depressive symptoms. While controlling age and social class as covariates, SPSS stepwise regression analyses were used to examine relations among these 3 constructs. Results suggest that coping has a direct relation with depressive symptoms as well as an indirect relation mediated by hostility. Passive coping may lead to increased hostility, resulting in depressive symptoms. Active coping may have the opposite effect. These findings suggest that the inclusion of measures of both coping strategies and hostility yields a more thorough understanding of concomitants of depressive symptoms. From a clinical perspective, knowing what coping strategies a person uses and how much anger they experience and express may be useful in guiding the management of depressive symptoms.     

Lithium effects on time estimation and mood in manic-melancholic patients. A study of diurnal variations

Behavioural measurements of time experience and phenomenological self-ratings of mood-variations (Beecher's Mood Scale) have been carried out at night and on the following morning in a group of lithium-treated patients, in a group of psychiatric patients not given lithium, and in an untreated group of healthy subjects. In all the groups investigated the internal "clock" was slower in the morning than in the night. The results indicated that the internal "clock" in lithium-treated patients was slower than in the two other groups, but only at night. Mood variations from night ot morning were observed in all three groups. The group of lithium-treated patients had fewer complaints as to self-report of mood-variations compared with the other groups.     

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies

Objectives: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment.

Methods: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants.

Results: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect.

Conclusions: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.     

Relationship of childhood physical and sexual abuse to adult bipolar disorder

Objectives: To characterize whether adult depressives with either bipolar or unipolar disorder differ in the prevalence of childhood sexual or physical abuse.

Method: The investigators reviewed data from patients who were evaluated over a 2-year period by a semi-structured clinical interview. In total, 333 cases with a bipolar or unipolar diagnosis were included in the present study.

Results: A childhood history of abuse, in particular sexual abuse, was significantly more frequent in bipolar subjects compared with unipolar subjects. Consistent with previous studies, women reported higher rates of sexual abuse than men, although no interaction by diagnosis was shown. Sexual abuse incidence in male samples was markedly dissimilar, with male bipolar subjects demonstrating a significantly increased rate of sexual abuse and combined sexual and physical abuse compared with unipolar male subjects.

Conclusion: The increased incidence of sexual abuse in women supports growing evidence of gender differences in sexual abuse among adult depressives. In contrast to literature reports, the finding that male bipolar patients have significantly increased rates of sexual abuse histories suggests differences in psychiatric depressive subgroups. This result may reflect the particular characteristics of our cohort (treatment resistant, privately insured, and educated). Further work will aid in characterizing sexual abuse prevalence in other male bipolar samples.     

Abnormalities of cAMP signaling in affective disorders: implication for pathophysiology and treatment

Objective: During the last decade, much attention has been given to the role of signal transduction pathways in affective disorders. This review describes the possible role of the cAMP signaling in such disorders.

Methods: Among the components of cAMP signaling, this review focuses on the cAMP-dependent phosphorylation system. We analyzed the basic components of the cAMP-dependent phosphorylation system and the preclinical evidence supporting their involvement in the biochemical action of antidepressants and mood stabilizers. The clinical data available until now, concerning the possible link between the cAMP-dependent phosphorylation system and the pathophysiology of affective disorders, are also reviewed.

Results: The studies herein presented demonstrated that the levels and the activity of cAMP-dependent protein kinase are altered by antidepressants and mood stabilizers. Furthermore, these medications are able to modify the phosphorylation state, as well as the levels of some of the cAMP-dependent protein kinase substrates. More recently, clinical studies have reported abnormalities in the cAMP-dependent phosphorylation system in both peripheral cells and the postmortem brain of patients with affective disorders.

Conclusions: Overall, these studies support an involvement of cAMP signaling in affective disorders. The precise knowledge of the findings has the potential to improve the understanding of pharmacotherapy and to provide directions for the development of novel biochemical and genetic research strategies on the pathogenesis of affective disorders.     

身心综合治疗对晚期肿瘤病人负性情绪影响

[目的]探讨身心综合治疗对晚期肿瘤病人负性情绪的影响。[方法]将63名晚期肿瘤患者随机分为对照组32例和治疗组31例。对照组病人给予最佳支持治疗,以达到减轻躯体症状的目的;治疗组除给予最佳支持治疗外,还给予系统的心理治疗,方法包括:一般心理治疗方法、暗示和催眠疗法、认知行为疗法等。于初诊及治疗1个月后用症状自评量表(SCL-90)评定患者的躯体化症状和心理状况(主要评定焦虑和抑郁情绪)。应用SPSS10.0做统计分析。[结果]两组病人治疗前均有较明显的抑郁和焦虑,躯体化症状明显,但程度比较无统计学差异(P>0.05);对照组病人治疗后抑郁、焦虑和躯体化症状程度无明显变化(P>0.05);治疗组病人经身心综合治疗后,抑郁、焦虑和躯体化症状程度较治疗前明显减轻(P<0.01);两组病人治疗后抑郁、焦虑和躯体化症状的变化程度有统计学差异(P<0.01)。[结论]身心综合治疗有助于晚期肿瘤患者减轻和消除负性情绪,从而改善其生活质量。     

心境障碍病人176例住院用药状况调查分析

目的:了解心境障碍病人住院用药情况,为临床合理用药提供参考。方法:对确诊的176例心境障碍病人应用各种精神药物的分布及频率进行调查统计。结果: 接受抗抑郁药治疗的107例病人中,使用第2代抗抑郁药占78. 5 % (84 /107 )。接受抗精神病药治疗占全部病人的57. 4 % ( 101 176),其中第2代抗精神病药占26. 1 % (46 /176)。合并用心境稳定剂占45. 5 % (80 /176 ),其中碳酸锂居首位。合并丁螺环酮和苯二氮艹卓类药分别占20. 5 % (36 /176)和39. 2 % (69 /176)。结论: 处方方式逐渐以第2代抗精神病药和抗抑郁药占主流,锂盐仍然为一线情感稳定剂。     

Chronic low-level mercury exposure, BDNF polymorphism, and associations with self-reported symptoms and mood.

Recent reports have described neurobehavioral impairments in human subjects carrying a V66M polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF). Inasmuch as ventral nervous system (CNS) deficits associated with this BDNF polymorphism are similar to those observed among subjects with chronic exposure to elemental mercury (Hg degrees ), we examined the potential effect of this BDNF polymorphism on symptoms and mood in an established cohort of dental practitioners with chronic low-level Hg degrees exposure. Self-reported symptoms and mood were obtained by computerized questionnaire from 193 male dentists (DTs) and 230 female dental assistants (DAs). Spot urine samples were analyzed for mercury concentrations to evaluate recent exposure. Detailed work histories were obtained to calculate chronic indices of Hg degrees exposure. Buccal cell samples were obtained to identify the V66M polymorphism of BDNF. Scores for 11 current and 12 recent and chronic symptom groups, along with six mood factors, were evaluated with respect to recent and chronic Hg degrees exposure and BDNF polymorphism. Multiple regression analysis controlled for age, race, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for DTs and DAs. Twenty-three associations between recent or chronic Hg degrees exposure and BDNF status and self-reported symptoms were observed with p < 0.10. All but three were in the expected direction (symptom scores increasing with Hg degrees exposure or BDNF polymorphism), and all but six were among DAs. All eight correlations between chronic exposure indices and recent and chronic symptoms among DAs were in the expected direction. All seven associations between BDNF and symptoms were in the expected direction and split between DTs and DAs. All three associations with mood factors were among DAs and in the expected direction. These results indicate that among DAs very low levels of occupational Hg degrees exposure are associated with increased symptoms. The BDNF polymorphism is also associated with increased symptom and mood scores. Notably, Hg degrees and BDNF polymorphism were additive with respect to their associations with the same symptom group.