Effects of sodium butyrate on oxidative stress and behavioral changes induced by administration of d-AMPH

Several evidences have demonstrated that oxidative stress has a central role in bipolar disorder (BD). Recently, studies have been suggested histone deacetylases (HDAC) as a possible target for new medications in treatment of mood disorders. In this study, we investigated the effects of sodium butyrate (SB, a histone deacetilase inhibitor) on oxidative stress in rats submitted to an animal model of mania induced by d-amphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. Locomotor activity and risk-taking behavior were assessed by open-field test and oxidative stress was measured in prefrontal cortex, amygdala, hippocampus and striatum. The results showed that SB reversed and prevented d-AMPH-induced behavioral effects. The d-AMPH administration induced oxidative damage in all brain structures analyzed. Depending on the cerebral area and technique, SB was able to reverse this impairment. The present study reinforces the need for more studies of HDAC inhibitors as possible target for new medications in treatment for BD.     

Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania

There is an emerging body of data suggesting that mood disorders are associated with decreased brain-derived neurotrophic factor (BDNF). The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder. In the first experiment (acute treatment), rats were administered D-amphetamine (AMPH) or saline for 14 days, and then between day 8 and 14, rats were treated with either Li, VPT or saline. In the second experiment (maintenance treatment), rats were pretreated with Li, VPT or saline, and then between day 8 and 14, rats were administered AMPH or saline. In both experiments, locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus by sandwich-ELISA. Li and VPT reversed AMPH-induced behavioral effects in the open-field test in both experiments. In the first experiment, Li increased BDNF levels in rat hippocampus. In the second experiment, AMPH decreased BDNF levels and Li and VPT increased BDNF levels in rat hippocampus. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.     

Differences in hypothyroidism between lithium-free and -treated patients with bipolar disorders

The majority of the previous studies of thyroid abnormalities in bipolar patients was conducted in populations containing various proportions of lithium-treated subjects. In the present study, we sought to determine whether there exist differences in hypothyroid profile between lithium-free and -treated bipolar patients. Bipolar patients never treated with lithium and carbamazepine (n=78) and those currently in lithium therapy (n=53) were included in this study. Serum concentrations of total thyroxine (T(4)), total triiodothyronine (T(3)), and thyroid-stimulating hormone (TSH) were compared between lithium-free and -treated patients. The rate of hypothyroidism in lithium-free patients was significantly lower than those treated with lithium (6.3%-10.8% vs. 28.0%-32.1%). Significant changes in the three thyroid indices indicative of hypothyroidism were consistently associated with longer illness duration in lithium-free manic patients, but with greater severity of mania and more mood episodes in their lithium-treated counterparts. In lithium-free depressed patients, more episodes were associated with lower T(4) levels; whereas in their lithium-treated counterparts, longer illness duration was associated with higher TSH levels and females with lower T(3) levels. These results suggest that bipolar patients with and without lithium exposure differ in prevalence and association of hypothyroidism and may have different response to thyroid hormone therapy.     

Increased cerebrospinal fluid levels of S100B protein in rat model of mania induced by ouabain

Bipolar disorder is a chronic and severe mental disorder. Recently, new animal models have emerged to further investigate underlying mechanisms of bipolar disorder such as ouabain-induced hyperactivity in rats. In this study, we investigated the cerebrospinal fluid levels of S100B protein as a putative marker of astrocytic activity in bipolar mania induced by intracerebroventricular administration of ouabain in rats. Ouabain induced a two-fold increase in crossing responses in the open field test and increased 30% the cerebrospinal fluid concentration of S100B, as compared to vehicle group. Our findings reinforce the role of astroglial cells in the pathogenesis of bipolar disorder and S100B protein as a marker of bipolar mania.     

TULIP study: Trail of Lurasidone in bipolar disorder in Pakistan

BackgroundThis study examined usefulness and efficiency of Lurasidone in appraisal with the placebo as for the treatment of Bipolar Disorders.MethodsSeven treatment centers in Pakistan were selected for the purpose of starting a six week-long control trial (randomized and double-blind placebo). 76 subjects, already diagnosed with Bipolar I or II based on DSM 5 diagnosis, were selected after randomization. Patients were allocated in one of the two groups. Primary efficacy of the drug was measured using Young Mania Rating Scale. Positive response of the drug was defined as 50% reduction in symptoms from the baseline/13 point less than the baseline score on Young Mania Rating Scale. Efficacy and safety of the drug was assessed using variety of markers such as administering extra-pyramidal symptoms rating scale, adverse side effects reported, electrocardiograms, body weight, vital signs changes, and laboratory investigations.ResultsPatients treated with Lurasidone showed enhanced improvement in their overall health and symptoms manifestation in comparison to patients who were given placebo. Lurasidone treated patients showed a better response to the drug (66%), in comparison with the placebo treated patients (42%).LimitationsStudy was conducted on small scale due to complexity.ConclusionPatients treated with Lurasidone showed reduction in bipolar symptoms and tolerate the drug well.     

Personality correlates with sleep-wake variables

A mail-in questionnaire study and two confirmatory archival analyses are described. Variables related to personality and measures of sleep timing, sleep quality, and sleep duration were initially assessed by self-report in a sample of 54 working adults (31.5% male, 23-48 yrs). Extraversion and neuroticism were measured by the Eysenck Personality Inventory (EPI), and the level of sub-clinical manic-type symptoms by the Attitude to Life Questionnaire (ATLQ). The quality of sleep was measured by the Pittsburgh Sleep Quality Index (PSQI) and by questions relating to habitual sleep latency and minutes awake after sleep onset from the Sleep Timing Questionnaire (STQ). The duration and timing of sleep was assessed using the STQ separately for work-week nights (Sunday-Thursday) and for weekend nights (Friday and Saturday). Morningness-eveningness was assessed using the Composite Scale of Morningness (CSM). Two confirmatory analyses using separate archival samples (Study A: n=201, 55.7% male, 20-57 yrs; Study B: n=101, 47.5% male, 18-59 yrs) were then used to confirm specific correlations of interest. In both initial and confirmatory studies, increased sub-clinical manic-type symptoms were found to be significantly associated with later bedtimes and wake-times during the work-week and lower (more evening-type) CSM scores, and higher neuroticism was associated with poorer sleep as indicated by higher PSQI scores. In contrast, no significant correlations emerged between any of the personality variables and any of the sleep duration variables. Personality appears to affect certain aspects of the timing and subjective quality of sleep, but not necessarily its duration.     

Endogenous opiates: 1981

This paper is the fourth of an annual series reviewing the research concerning the endogenous opiate peptides. This installment covers only work published during 1981 and attempts to provide a comprehensive, but not exhaustive, survey of the area. Previous papers in the series have dealt with research done before 1981. Topics concerning endogenous opiates reviewed here include a delineation of their receptors, their distribution, their precursors and degradation, behavioral effects resulting from their administration, their possible involvement in physiological responses, and their interactions with other peptides and hormones. Due to the burgeoning literature in this field, the comprehensive nature of this review in the future will be limited to considerations of behavioral phenomena related to the endogenous opiates.     

Mood stabilizers target cellular plasticity and resilience cascades

Bipolar disorder is a devastating disease with a lifetime incidence of about 1% in the general population. Suicide is the cause of death in 10 to 15% of patients and in addition to suicide, mood disorders are associated with many other harmful health effects. Mood stabilizers are medications used to treat bipolar disorder. In addition to their therapeutic effects for the treatment of acute manic episodes, mood stabilizers are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. The most established and investigated mood-stabilizing drugs are lithium and valproate but other anticonvulsants (such as carbamazepine and lamotrigine) and antipsychotics are also considered as mood stabilizers. Despite the efficacy of these diverse medications, their mechanisms of action remain, to a great extent, unknown. Lithium’s inhibition of some enzymes, such as inositol monophosphatase and gycogen synthase kinase-3, probably results in its mood-stabilizing effects. Valproate may share its anticonvulsant target with its mood-stabilizing target or may act through other mechanisms. It has been shown that lithium, valproate, and/or carbamazepine regulate numerous factors involved in cell survival pathways, including cyclic adenine monophospate response element-binding protein, brain-derived neurotrophic factor, bcl-2, and mitogen-activated protein kinases. These drugs have been suggested to have neurotrophic and neuroprotective properties that ameliorate impairments of cellular plasticity and resilience underlying the pathophysiology of mood disorders. This article also discusses approaches to develop novel treatments specifically for bipolar disorder.     

瑞芬太尼联合丙泊酚对躁狂症患者电休克治疗后的再定向时间和认知功能的影响

摘要 目的：探究瑞芬太尼联合丙泊酚对躁狂症患者电休克治疗后的再定向时间和认知功能的影响。方法：招募2018年2月至2019年9月在本院就诊的150例躁狂症患者,将患者分为对照组和观察组,各75例。通过简易精神状态检查（MMSE）评分系统比较电休克疗法（ECT）后的认知障碍。通过杨氏躁狂量表（YMRS）评分系统比较躁狂症患者的狂躁严重程度。通过MMSE评分系统比较躁狂症患者ECT后的时间定向能力。通过无创血压和心电图监测患者ECT前后的平均动脉压和心率。结果：两组患者一般资料统计无差异（P>0.05）。观察组术后5小时无障碍率较对照组升高（P<0.05）,观察组术后5小时出现严重认知障碍率较对照组降低（P<0.05）,中度认知障碍率两组比较无差异（P>0.05）。ECT后5小时和24小时观察组与对照组的YMRS评分比较无差异（P>0.05）。ECT前,观察组时间定向评分与对照组比较无差异（P>0.05）,ECT后,观察组时间定向评分较对照组升高（P<0.05）。ECT前和ECT后,观察组的平均动脉压和心率比较无差异（P>0.05）。结论：在接受ECT的躁狂患者中,瑞芬太尼补充丙泊酚诱导麻醉不影响ECT的疗效,并且能减少ECT后认知障碍的发生,缩短重定向时间。