Abnormal fatty acid pattern in the superior temporal gyrus distinguishes bipolar disorder from major depression and schizophrenia and resembles multiple sclerosis

This study investigated the fatty acid composition of the postmortem superior temporal gyrus (STG), a cortical region implicated in emotional processing, from normal controls (n=15) and patients with bipolar disorder (BD, n=15), major depressive disorder (MDD, n=15), and schizophrenia (SZ, n=15). For comparative purposes, STG fatty acid composition was determined in a separate cohort of multiple sclerosis patients (MS, n=15) and normal controls (n=15). Compared with controls, patients with BD, but not MDD or SZ, exhibited abnormal elevations in the saturated fatty acids (SFA) palmitic acid (16:0), stearic acid (18:0), the polyunsaturated fatty acids (PUFA) linoleic acid (18:2n-6), arachidonic acid (20:4n-6), and docosahexaenoic acid (22:6n-3), and reductions in the monounsaturated fatty acid (MUFA) oleic acid (18:1n-9). The total MUFA/SFA and 18:1/18:0 ratios were lower in the STG of BD patients and were inversely correlated with total PUFA composition. MS patients exhibited a pattern of fatty acid abnormalities similar to that observed in BD patients including elevated PUFA and a lower 18:1/18:0 ratio. Collectively, these data demonstrate that BD patients exhibit a pattern of fatty acid abnormalities in the STG that is not observed in MDD and SZ patients and closely resembles MS patients.     

Lithium and valproic acid treatment effects on brain chemistry in bipolar disorder.

BACKGROUND: Prior work reported elevated gray matter (GM) lactate and Glx (glutamate + glutamine + GABA) concentrations in unmedicated patients with bipolar disorder (BP) compared with healthy controls (HC). This study examined whether lithium (Li) and valproic acid (VPA) treatment modulated these chemicals. METHODS: A subset of previously reported BP patients were treated with Li (n = 12, 3.6 +/- 1.9 months) or VPA (n = 9, 1.4 +/- 1.7 months) and compared untreated HC subjects (n = 12, 2.9 +/- 2.4 months) using proton echo-planar spectroscopic imaging. Regression analyses (voxel gray/white composition by chemistry) were performed at each time point, and change scores computed. Metabolite relaxation and regions of interest (ROI) were also examined. RESULTS: Across treatment, Li-treated BP subjects demonstrated GM Glx decreases (Li-HC, p =.08; Li-VPA p =.04) and GM myo-inositol increases (Li-HC p =.07; Li-VPA p =.12). Other measures were not significant. Serum Li levels were positively correlated with Glx decreases at the trend level. CONCLUSIONS: Li treatment of BP was associated with specific GM Glx decreases and myo-inositol increases. Findings are discussed in the context of cellular mechanisms postulated to underlie Li and VPA therapeutic efficacy.     

Initial symptoms of manic relapse in manic or mixed-manic bipolar disorder: post hoc analysis of patients treated with olanzapine or lithium

A post hoc analysis of Young Mania Rating Scale (YMRS) item scores was conducted to identify symptoms that may predict impending relapse using prospectively collected data from a double-blind, randomized relapse prevention study of patients treated with olanzapine (N=200, 5-20 mg/d) versus lithium (N=201, 300-1800 mg/d). METHODS: Relapses (YMRS > or = 15, or hospitalization) included in this analysis occurred 3-52 weeks after randomization. Repeated measures logistic regression of increases (> or = 1) in YMRS item scores prior to the visit that preceded relapse was used to estimate the odds of relapse. RESULTS: A total of 31 patients relapsed during the first 3-16 weeks of the study (olanzapine, n=12; lithium, n=19). YMRS items that increased most frequently within a 2-week period preceding relapse were (olanzapine vs. lithium, respectively): increased motor activity/energy (58.3%, 21.1%), irritability (33.3%, 31.6%), decreased need for sleep (25.0%, 10.5%), increased speech (25.0%, 10.5%), and elevated mood (25.0%, 15.8%). YMRS items with significant odds ratios (OR) that predicted relapse in patients treated with olanzapine or lithium, respectively, were: increased motor activity/energy (OR, 35.7; OR, 7.8), irritability (OR, 9.5; OR, 7.8), elevated mood (OR, 8.1; OR, 4.2), and increased sexual interest (OR, 13.7; OR, 7.7). CONCLUSIONS: Early recognition of symptom exacerbation in bipolar mania, particularly increased motor activity-energy may permit clinical interventions to help avert relapse.     

Lithium inhibitable enzymes in postmortem brain of bipolar patients

Despite considerable ongoing efforts at the epidemiological, genetic and molecular level, the etiology of bipolar disorder had not yet been elucidated. To study possible contributing components to the pathophysiology of this disorder, we have hypothesized that levels of enzymes inhibited by therapeutically relevant lithium ion concentrations in the brain of patients may differ from those in normal controls and may be involved in the etiology of the disorder. Three Li-inhibitable enzymes were studied in postmortem brain samples of bipolar patients and normal controls. The expression and function of the two enzymes that are obviously involved in signaling cascades, IMPase, involved in the second messenger system of the phosphatidylinositol cycle, and GSK-3, a mediator of an array of signaling cascades, were not found to be different in postmortem frontal and occipital cortex of bipolar patients and normal controls. Only PAP phosphatase protein levels, but not its mRNA levels or enzymatic activity, were found to be significantly decreased in frontal cortex of bipolar patients compared with normal controls.     

齐拉西酮合并碳酸锂治疗双相情感障碍躁狂发作的疗效及安全性

目的 评价齐拉西酮合并碳酸锂治疗双相情感障碍躁狂发作的疗效及安全性.方法 将2018年2月～2019年3月期间我院收治的70例双相情感障碍躁狂发作患者分成对照组和研究组,每组35例.对照组单用碳酸锂治疗;研究组联合碳酸锂与齐拉西酮治疗.对比观察两组患者的临床疗效.结果 研究组总有效率97.1％(34/35)高于对照组8...     

Lithium: still a major option in the management of bipolar disorder

Still after more than 50 years, lithium is a major treatment of bipolar disorder, even though it has not been promoted by the pharmaceutical industry over the last decades. In recent years the evidence base on lithium for bipolar disorder has substantially increased due to results from a number of trials. Therefore, a review of this evidence is timely. The efficacy of lithium as an acute treatment and as a maintenance treatment of bipolar disorder was evaluated through a review of the evidence, focusing on modern, randomized, parallel-group designed trials. Additionally, the evidence was sought translated into the proper use of lithium in clinical practice. Lithium's antimanic efficacy has been convincingly demonstrated. However, as blood monitoring due to the risk of toxicity is required and due to an insufficient response in highly agitated patients, lithium monotherapy has a limited place in the acute treatment of severe manic states. For acute bipolar depression, results are conflicting. Recent maintenance trials have added substantially to the documentation of lithium's long-term stabilizing properties in bipolar disorder, and these properties have been demonstrated independently of any acute response to lithium. Finally, it is now beyond doubt that not only does lithium prevent mania, but also depression in bipolar disorder. Lithium is still to be considered a major if not the most important mood- stabilizer, at least for maintaining long-term stability in patients with bipolar disorder. The potential risks of lithium should be weighed up against its benefits and the fact that serious adverse effects are usually avoidable.     

Pharmacokinetics of total and free valproic acid during monotherapy in infants

Summary The pharmacokinetics of free and total valproic acid (VPA) in plasma and whole blood after oral administration during steady state was investigated in seven infants (mean age 10.7 months) receiving monotherapy. The VPA concentrations in whole blood closely followed those in plasma but at a reduced level. A positive correlation was found between dose and mean plasma concentration (r=0.71). Mean terminal half-lives were similar in plasma and whole blood (12.5 and 15.5 h, respectively), but were considerably longer than for free VPA (6.4 and 6.5 h, respectively; P<0.01). There was a significant decrease in half-lives with increasing age (P<0.05). Plasma and whole blood clearance for total VPA was higher than reported in older infants and adults (17.8 and 28.9 ml/kg per hour) and was considerably higher for free VPA (127.6 and 188.8 ml/kg per hour, respectively). The increase in clearance compared with that in older subjects is well in concordance with a lower protein binding of VPA (mean 85.3%). Of special importance is that the percentage of unbound VPA increased with increasing concentrations of total VPA. The fraction of unbound VPA in plasma increased even more in subjects with low albumin concentrations (P<0.01).     

精神分裂症患者与躁狂发作患者父母教养方式对照研究

目的 探讨精神分裂症与双相情感障碍躁狂发作患者的父母教养方式特点.方法 采用父母教养方式评价量表(EMBU)对43例精神分裂症患者及38例双相情感障碍躁狂发作患者父母教养方式(研究组)进行评定,并与38例正常受试者(对照组)比较.结果 与双相情感障碍躁狂发作及正常被试比较,精神分裂症患者组在教养方式上,父母均表现为高惩罚与严厉、高过分干涉和高拒绝与否认(P＜0.05);双相情感障碍躁狂发作患者组教养方式各因子得分虽低于正常对照组,但差异无统计学意义(P＞0.05).结论 精神分裂症患者父母教养方式均存在多方面问题,可能对精神分裂症发病有一定影响.双相情感障碍躁狂发作患者的父母教养方式可能存在一定问题,需要进一步研究.     

丙戊酸钠合并碳酸锂治疗反复躁狂发作的长期疗效及安全性

目的 探讨丙戊酸钠合并碳酸锂治疗反复躁狂发作的长期疗效及安全性.方法 收集各类双相躁狂发作患者105例,分为碳酸锂组、丙戊酸钠组和碳酸锂+丙戊酸钠组(以下简称合并治疗组),每组各35例.急性期治疗6周后随访5年以上.随访者不干预患者治疗.基线及疗效采用倍克-拉范森躁狂量表(BRMS)评定.随访内容包括复发次数、药物剂量、长期疗效及安全性.结果 完成随访105例.急性期治疗后BRMS减分率:碳酸锂组(43±29)%;丙戊酸钠组(42±27)%;合并治疗组(58±25)%,三组间的差异有统计学意义(F=3.579,P=0.031).5年内躁狂复发次数:碳酸锂组(3.5±1.8)次,丙戊酸钠组(3.5±2.2)次,合并治疗组(2.0±1.5)次,三组间的差异有统计学意义(F=7.387,P=0.001);抑郁复发次数:碳酸锂组(2.1±2.4)次,丙戊酸钠组(2.1±2.6)次,合并治疗组(1.4±1.7)次,三组间的差异无统计学意义(F=1.313,P=0.273).合并治疗组与其他两组疗效的差异主要在快速循环型(F=4.120,P=0.033).合并治疗组的碳酸锂及丙戊酸钠剂量均分别明显低于其他两组(P＜0.01;P＜0.001).三组总体不良反应的差异无统计学意义.结论 丙戊酸钠合并碳酸锂用于双相情感障碍的维持治疗能减少躁狂的复发率,安全性较高.     

A role for protein kinase C and its substrates in the action of valproic acid in the brain: implications for neural plasticity

Valproic acid (VPA) is a broad-spectrum anticonvulsant with well-documented teratogenic effects, but whose mechanism of action is largely unknown. In the present study we have examined the effects of VPA on the expression of two prominent substrates for protein kinase C (PKC) in the brain, MARCKS and GAP-43, which have been implicated in actin-membrane plasticity and neurite outgrowth during neuronal differentiation, respectively, and are essential to normal brain development. Immortalized hippocampal HN33 cells exposed to VPA exhibited reduced MARCKS protein expression and demonstrated increased GAP-43 protein expression, with concomitant alterations in cellular morphology, including an increase in the number and length of neurites and accompanied by a reduction in cell growth rate. The effects of VPA were observed at clinically relevant concentrations following chronic (>1 day) VPA exposure. We also present evidence for a VPA-induced alteration in PKC activity, as well as temporal changes in individual PKC isozyme expression. Inhibition of PKC with the PKC-selective inhibitor, LY333531, prevented the VPA-induced down-regulation of membrane-associated MARCKS, but had no effect on the cytosolic MARCKS reduction or the GAP-43 up-regulation. Inhibition of PKC by LY333531 enhanced the differentiating effects of VPA; additionally, LY333531 alone induced greater neurite outgrowth in this cell line. Collectively, these data indicate that VPA induces neuronal differentiation, associated with a reduction in MARCKS expression and an increase in GAP-43 expression, consistent with the hypothesis that a reduction in MARCKS at the membrane may be permissive for cytoskeletal plasticity during neurite outgrowth.     

Altered glucocorticoid receptor signaling cascade in lymphocytes of bipolar disorder patients

Bipolar disorder (BD) is characterized by hypothalamic pituitary adrenal (HPA) axis hyperactivity, glucocorticoid insensitivity and alterations in serotonin and inflammatory mediators. The glucocorticoid receptor (GR), activator protein-1 (AP-1), nuclear factor-kappa B (NF-kappaB) and c-jun N-terminal kinase (JNK) regulate the above mentioned processes; we therefore assessed their role in BD. Fifteen bipolar depressed patients under multiple anti-depressant therapy, 15 bipolar euthymics under lithium monotherapy and 25 matched controls were studied. Whole cell and nuclear extracts from lymphocytes were immunoblotted for GR, c-fos, JNK and NF-kappaB and nuclear aliquots were submitted to electrophoretic mobility shift assay for GR, AP-1 and NF-kappaB. Associations with the anti-depressant therapy and the state of the disease were also sought. Results, expressed as percentage of pooled protein standard sample intergraded optical density (IOD) (mean +/- SD), revealed: (a) depressed patients had significantly higher GR levels than controls in whole cell (82.63 +/- 6.18 versus 76.27 +/- 4.21%, P < 0.01) and nuclear extracts (86.66 +/- 3.81 versus 81.72 +/- 2.71%, P < 0.001) but lower GR-DNA binding (68.75 +/- 7.91 versus 81.84 +/- 4.25%, P < 0.05). Euthymics had normalized whole cell GR content (73.64 +/- 5.95%) and GR-DNA binding activity (76.82 +/- 7.29%) but higher nuclear GR content (86.89+/-3.96%, P<0.01) than controls; (b) nuclear c-fos content and AP-1-DNA-binding were significantly lower in depressed patients than controls (80.49 +/- 2.03 versus 84.82 +/- 3.48%, P < 0.05 and 78.46 +/- 4.17 versus 84.80 +/- 5.79%, P < 0.05, respectively). Euthymics however, showed similar nuclear c-fos and AP-1-DNA-binding to controls (85.48 +/- 2.71 and 87.78 +/- 3.54%, respectively) but lower whole cell c-fos than in controls (81.18 +/- 3.87 versus 87.01 +/- 4.22%, P < 0.001); (c) depressed patients had significantly lower whole cell and nuclear JNK than controls (67.01 +/- 4.29 versus 72.00 +/- 3.68%, P < 0.05 and 80.10 +/- 2.53 versus 86.96 +/- 2.49%, P < 0.001) whereas euthymics showed lower nuclear JNK (83.27 +/- 1.93%, P < 0.01); (d) whole cell NF-kB was higher in the depressed patients than in controls (67.30 +/- 5.00 versus 63.63 +/- 3.3%, P < 0.05). Concluding, intracellular signaling of GR, AP-1 and JNK are altered in BD and may underly disease aetiopathogenesis and/or reflect the effect of the anti-depressants.     

抑郁症患者血小板蛋白激酶C水平的变化

目的：探讨抑郁症患者血小板细胞浆和细胞膜蛋白激酶C(PKC)的变化及其意义。方法：采用[^3H]12，13-二丁酰佛波醇酯(PDBu)结合法，测定23例抑郁症患者和10名正常对照者的血小板细胞浆和细胞膜PKC水平。结果：与正常对照组比较，抑郁症组血小板胞膜PKC水平显著降低，血小板胞浆PKC水平差异无显著性。结论：蛋白激酶C的改变在抑郁症发病机制中可能起一定作用。     

Expression of cellular prion protein (PrP<Superscript>c</Superscript>) in schizophrenia,bipolar disorder,and depression

Cellular prion protein (PrP(c)) is a copper-binding, membrane-attached GPI-anchored glycoprotein characterized by a high degree of amino acid sequence conservation among mammals. PrP(c) expression has been demonstrated in neurons, microglia, lymphocytes, and keratinocytes. Recently, the concept that PrP(c) may be involved in the defense against oxidative stress was advanced. In the present study, we used immunohistochemistry for PrP(c) to investigate 60 brains from the Stanley Neuropathology Consortium (15 controls, 15 patients with schizophrenia, 15 with bipolar disorder, and 15 with major depression). Rating scores as well as the numerical density of PrP(c)-positive and -negative neurons and glial cells were determined in the cingulate gyrus. All four groups showed a very high interindividual variation. PrP(c)-positive glial cells were significantly reduced in the white matter of patients with schizophrenia, bipolar disorder, and major depression. A similar result was obtained for the white matter in bipolar patients using rating scales. From the confounding variables, use of medication (i.e. antipsychotics, antidepressants, and mood stabilizers) had a significant effect on the expression of PrP(c) by neurons and glial cells. PrP(c)-immunoreactivities were significantly reduced for white matter glial cells in all examined groups. However, the results are not indicative for the occurrence of oxidative stress in the brains of schizophrenic and bipolar patients. Since the effect of antipsychotic and antidepressant medication as well as of mood stabilizers on the expression of PrP(c) was significant, it needs further clarification in experimental models.     

双相情感障碍血清尿酸水平研究

目的探讨双相情感障碍患者血清尿酸(uric acid,UA)水平变化及其临床意义。方法纳入双相情感障碍患者126例(躁狂发作77例,抑郁发作49例)、首发精神分裂症患者69例和正常对照126名,测定其血清UA水平,并采用杨氏躁狂量表(Young mania rating scale,YMRS)和汉密尔顿抑郁量表(Hamilton depressionscale,HAMD)评定双相情感障碍患者症状。结果双相情感障碍组血清UA水平[(349.34±107.21)μmol/L]高于精神分裂症组[(319.71±84.48)μmol/L]和对照组[(280.94±71.90)μmol/L],差异有统计学意义(P0.01);躁狂发作患者UA水平高于抑郁发作患者[(366.45±104.01)μmol/L vs.(322.45±107.69)μmol/L],且二者均高于对照组(P0.01);双相情感障碍患者中是否使用精神科药物的亚组间UA水平无统计学差异(P0.05)。双相情感障碍患者血清UA水平与YMRS、HAMD分数线性相关均无统计学意义(P0.05)。结论双相情感障碍患者血清UA水平升高,血清UA水平升高可能是双相情感障碍的一个生物标记物。     

Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder

Protein kinase C (PKC) is a group of calcium and phospholipid-dependent enzymes, which plays a pivotal role in cell signaling systems. Recently accumulated evidence indicates that alterations in PKC activity play a significant role in the pathophysiology of bipolar disorder. A number of laboratories investigated the effect of mood stabilizers on the regulation of PKC activity in bipolar patients, in animals, and in cultured cells. Following chronic lithium treatment, PKC activation was significantly reduced in rat brains, as measured by the translocation of cytoplasmic PKC to the membrane compartment, or by quantitative binding of the PKC ligand, PDBu. The effect of the therapeutic concentration of lithium in attenuating PKC-dependent intracellular parameters was also demonstrated in cultured cells. More importantly, alterations in platelet PKC was shown in bipolar patients during the manic state of the illness. In comparison to patients with major depressive disorder, schizophrenia, or healthy controls, PKC activity was significantly increased in manic patients, suggesting that changes in PKC may be an illness-specific marker. Interestingly, enhanced PKC activity during mania was suppressed following mood-stabilizer treatment as manic symptoms improved. In parallel to the findings in platelets, postmortem studies demonstrate that membrane-associated PKC and stimulation-induced translocation of cytosolic enzyme to the membrane were also increased in frontal cortex of bipolar patients. Other studies suggest alterations in other signal transduction mechanisms in bipolar disorder. These include alterations in G protein activation, phosphatidylinositol (PI) signaling, cyclic AMP formation, and intracellular calcium homeostasis. The alterations of PKC activity in bipolar disorder may be related to changes in these other intracellular signaling mechanisms. Alternatively, the changes of PKC activity may be the core pathology of the illness. More studies are required to further characterize the association of PKC changes with bipolar disorder, using a proper neuronal model.     

The effects of DISC1 risk variants on brain activation in controls, patients with bipolar disorder and patients with schizophrenia

Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n = 33), patients with schizophrenia (n = 20) and patients with bipolar disorder (n = 36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus. Moreover, there was an effect of SNP rs1538979 in the pre/postcentral gyrus with decreased activation in healthy controls and increased activation in patients with schizophrenia. In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. Clusters in the precentral gyrus, left middle temporal gyrus and left cerebellum were found to be significant on examining the group × genotype interactions. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of schizophrenia and bipolar disorder.     

Concentration of metabolites of valproic acid in plasma of epileptic patients

With the help of synthetic reference substances, five metabolites of valproic acid (VPA) could be quantitated by gas chromatography in the plasma of 26 epileptic patients undergoing chronic therapy with sodium valproate. The products of beta-oxidation, i.e., 2-en-VPA, 3-hydroxy-VPA, and 3-keto-VPA were found to be the major metabolites of VPA in plasma, whereas the intermediates of omega-oxidation, 4-hydroxy-VPA and 5-hydroxy-VPA, were present only in markedly lower concentrations. It was thus confirmed that in addition to the excretion of VPA as the glucuronide, beta-oxidation is the preferred metabolic pathway of VPA in man. However, taking the anticonvulsant activity of the metabolites as derived from animal experiments into consideration, none of the metabolites found in human plasma seems to contribute markedly to the therapeutic effect of VPA. Thus, in most patients, VPA seems responsible for more than 90% of the antiepileptic activity during continued medication in man.     

Bizarreness in dream reports and waking fantasies of psychotic schizophrenic and manic patients: empirical evidences and theoretical consequences

Several overlapping features have frequently been described between psychosis and the subjective experience of dreaming from the neurobiological to the phenomenological level, but whether this similarity reflects the cognitive organization of schizophrenic thought or rather that of psychotic mentation independent of diagnostic categories is still unclear. In this study, 40 actively psychotic inpatients were equally divided in two age- and education-matched groups according to their diagnosis (Schizophrenia and Bipolar Disorder). Participants were asked to report their dreams upon awakening and the Thematic Apperception Test (TAT) was administered to elicit waking fantasies; the same procedure was used in a control group of 20 non-psychiatric subjects. Two highly trained judges scored the collected material according to a Dream Bizarreness scale. The same level of cognitive bizarreness was found in TAT and dream reports of schizophrenic and manic subjects but was almost completely absent in the TAT stories of the control group. Two-way analysis of variance for repeated measures assessed the effect of diagnosis and experimental conditions (TAT stories and dream reports) on bizarreness yielding a significant interaction. Cognitive bizarreness seems to be a shared feature of dreaming and psychotic mentation, beyond diagnostic categorizations. Although these findings must be considered preliminary, this experimental measure of the cognitive architecture of thought processes seems to support the view that dreaming could be a useful model for the psychoses.     

Lithium and suicide prevention in bipolar disorder

IntroductionBipolar disorder (BD) is a severe and recurrent psychiatric disorder. The severity of prognosis in BD is mainly linked to the high rate of suicide in this population. Indeed, patients with BD commit suicide 20 to 30 times more frequently than the general population, and half of the BD population with an early age of onset have a history of suicide attempt. International therapeutic guidelines recommend lithium (Li) as the first-line treatment in BD for its prophylactic action on depressive or manic episodes. In addition, Li is the only mood stabilizer that has demonstrated efficacy in suicide prevention. This effect of Li is unfortunately often unknown to psychiatrists. Thus, this review aims to highlight evidence about the preventive action of Li on suicide in BD populations.MethodsWe conducted a literature search between April 1968 and August 2014 in PubMed database using the following terms: “lithium” AND “suicide” OR “suicidality” OR “suicide attempt”.ResultsAs confirmed by a recent meta-analysis, many studies show that Li has a significant effect on the reduction of suicide attempts and deaths by suicide in comparison to antidepressants or other mood-stabilisers in BD populations. Studies have demonstrated that long-term treatment with Li reduces suicide attempts by about 10% and deaths by suicide by about 20%. The combination of Li and an antidepressant could reduce suicidal behaviours by reducing suicidal ideation prior to depressive symptoms. It appears crucial for Li efficacy in suicide prevention to maintain the Li blood concentrations in the efficient therapeutic zone and to instate long-term Li treatment. The “impulsive-aggressive” endophenotype is associated with suicide in BD. The specific action of Li on the 5-HT serotoninergic system could explain the specific anti-suicidal effects of Li via the modulation of impulsiveness and aggressiveness. Furthermore, genetic variants of the glycogen synthase kinase 3α/β (GSK3α and β; proteins inhibited by Li) seem to be associated with more impulsiveness in BD populations.ConclusionThe anti-suicidal effect of Li has been very well demonstrated. By its specific action on the serotoninergic system, treatment with Li significantly reduces “impulsive-aggressive” behaviour which is a vulnerability factor common to suicide and BD. Long-term appropriately modulated treatment with Li seems to have considerable impact on the reduction of suicidal behaviours, suicidal ideation and death by suicide in the BD population.     

High-sensitivity C-reactive protein levels in patients with major depressive disorder and bipolar mania

The serum high-sensitivity C-reactive protein (hsCRP) levels in patients with major depressive disorder and bipolar I disorder in acute phases were investigated. During a 1-year period, a total of 67 participants including 23 patients with major depressive disorder, 13 patients with bipolar I disorder (manic episode) and 31 healthy controls were recruited in this study. The diagnoses of mental disorders in participants were made by one psychiatrist according to the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID). Both patient groups with major depression and bipolar disorder had higher mean serum hsCRP levels than the healthy control group. Using analysis of covariance with age adjustment, patients with bipolar I disorders still had significantly higher hsCRP levels than healthy controls (P=0.043). However, patients with major depression did not have significantly higher hsCRP levels than healthy controls (P=0.172). These results suggest that patients with bipolar I disorder might have a more severe inflammation reaction than patients without major depression. However, larger samples and adequate statistical methods are needed to prove these results.