The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Leonardo Tondo - One of the best experts on this subject based on the ideXlab platform.

  • clinical response and metabolic effects of Lithium in 323 mood disorder patients
    Journal of Affective Disorders, 2020
    Co-Authors: Marco Pinna, C Visioli, Mirko Manchia, Leonardo Tondo
    Abstract:

    Abstract Background Lithium is the mainstay for the maintenance Treatment of mood disorders (MD), but its efficacy needs to be weighed against its side effects profile. Here, we assessed retrospectively the clinical response to long-term Lithium Treatment, as well as the rate of associated metabolic side effects. Methods Clinical data were collected from patients treated with Lithium for at least 12 months at the Lucio Bini Center for Mood Disorders in Cagliari, Italy. Clinical response was determined as the difference in number of mood episodes and percent of illness time before and during Lithium Treatment. Symptomatic values of metabolic parameters (plasma levels of glucose, cholesterol, urea nitrogen [BUN], creatinine, TSH, white blood cells [WBC]), and Body Mass Index (BMI) were determined. Results We studied 323 MD patients (60.2% women). The percent of illness time was significantly reduced for both depressive (F = 4.94, p Conclusions Long-term Lithium Treatment was clinically effective, but the rates of metabolic effects were substantial although some of them were also associated with older age. Lithium-treated patients should receive accurate clinical monitoring to decrease the impact of long-term side effects.

  • Lithium Treatment for unipolar major depressive disorder systematic review
    Journal of Psychopharmacology, 2019
    Co-Authors: Juan Undurraga, Leonardo Tondo, Kang Sim, Ariel Gorodischer, Emilio Azua, Kai Hong Tay, David Tan, Ross J Baldessarini
    Abstract:

    Background:The potential value of Lithium Treatment in particular aspects of unipolar major depressive disorder remains uncertain.Methods:With reports of controlled trials identified by systematic ...

  • long term Lithium Treatment in bipolar disorder effects on glomerular filtration rate and other metabolic parameters
    International Journal of Bipolar Disorders, 2017
    Co-Authors: Leonardo Tondo, Martin Alda, Alberto Bocchetta, Maria Abramowicz, Michael Bauer, Lorenza Bolzani, Cynthia V Calkin, Caterina Chillotti, Diego Hidalgomazzei
    Abstract:

    Concerns about potential adverse effects of long-term exposure to Lithium as a mood-stabilizing Treatment notably include altered renal function. However, the incidence of severe renal dysfunction; rate of decline over time; effects of Lithium dose, serum concentration, and duration of Treatment; relative effects of Lithium exposure vs. aging; and contributions of sex and other factors all remain unclear. Accordingly, we acquired data from 12 collaborating international sites and 312 bipolar disorder patients (6142 person-years, 2669 assays) treated with Lithium carbonate for 8–48 (mean 18) years and aged 20–89 (mean 56) years. We evaluated changes of estimated glomerular filtration rate (eGFR) as well as serum creatinine, urea–nitrogen, and glucose concentrations, white blood cell count, and body-mass index, and tested associations of eGFR with selected factors, using standard bivariate contrasts and regression modeling. Overall, 29.5% of subjects experienced at least one low value of eGFR (  55; risk of ≥2 low values was 18.1%; none experienced end-stage renal failure. eGFR declined by 0.71%/year of age and 0.92%/year of Treatment, both by 19% more among women than men. Mean serum creatinine increased from 0.87 to 1.17 mg/dL, BUN from 23.7 to 33.1 mg/dL, glucose from 88 to 122 mg/dL, and BMI from 25.9 to 26.6 kg/m2. By multivariate regression, risk factors for declining eGFR ranked: longer Lithium Treatment, lower Lithium dose, higher serum Lithium concentration, older age, and medical comorbidity. Later low eGFR was also predicted by lower initial eGFR, and starting Lithium at age ≥ 40 years. Control data for age-matched subjects not exposed to Lithium were lacking. Long-term Lithium Treatment was associated with gradual decline of renal functioning (eGFR) by about 30% more than that was associated with aging alone. Risk of subnormal eGFR was from 18.1% (≥2 low values) to 29.5% (≥1 low value), requiring about 30 years of exposure. Additional risk factors for low eGFR were higher serum Lithium level, longer Lithium Treatment, lower initial eGFR, and medical comorbidity, as well as older age.

  • cutaneous adverse reaction during Lithium Treatment a case report and updated systematic review with meta analysis
    International Journal of Bipolar Disorders, 2017
    Co-Authors: Martina Pinna, Leonardo Tondo, Mirko Manchia, Sergio Puddu, Giampaolo Minnai, Piergiorgio Salis
    Abstract:

    Objectives To present a new case of adverse cutaneous reaction during Lithium Treatment and to update the systematic review and meta-analysis of the incidence of this adverse reaction.

  • cutaneous adverse reaction during Lithium Treatment a case report and updated systematic review with meta analysis
    International Journal of Bipolar Disorders, 2017
    Co-Authors: Martina Pinna, Leonardo Tondo, Mirko Manchia, Sergio Puddu, Giampaolo Minnai, Piergiorgio Salis
    Abstract:

    To present a new case of adverse cutaneous reaction during Lithium Treatment and to update the systematic review and meta-analysis of the incidence of this adverse reaction. We conducted a systematic search (performed in September 2016) for peer-reviewed articles in English indexed in Medline (2011-present). Meta-analytical estimates were obtained using the “Metafor” package. Ms. H., a 31-year-old Caucasian woman with BD1, was admitted to the inpatient unit for a full-blown psychotic episode and treated with carbamazepine 400 mg q.d., Lithium carbonate 450 mg q.d., and risperidone 4 mg q.d. with clinical improvement. After 12 days from the start of psychopharmacological Treatment, she manifested a cutaneous reaction that motivated the stop of carbamazepine Treatment, as well as the increase in Lithium carbonate dose (750 mg q.d.). Risperidone dose remained unvaried. Since the skin lesion persisted after 8 days from withdrawal of carbamazepine, the private practitioner stopped also Lithium carbonate Treatment (de-challenge), maintaining risperidone Treatment. The cutaneous reaction resolved spontaneously after six days from withdrawal of Lithium carbonate. Subsequently, the worsening of psychopathological conditions motivated a new admission during which Lithium carbonate was reintroduced (16 days after its suspension) (re-challenge). On the following day, we observed an itching erythematous maculopapular rash involving the trunk, the four limbs, and the oral mucosa. Our case of an erythematous maculopapular rash during Lithium Treatment was the first to present a challenge–de-challenge–re-challenge sequence that suggests causality. Although meta-analysis does not point to an increased rate of adverse skin reaction during Lithium Treatment, clinicians should not neglect to monitor cutaneous symptoms during Lithium Treatment.

Ross J Baldessarini - One of the best experts on this subject based on the ideXlab platform.

  • Lithium Treatment for unipolar major depressive disorder systematic review
    Journal of Psychopharmacology, 2019
    Co-Authors: Juan Undurraga, Leonardo Tondo, Kang Sim, Ariel Gorodischer, Emilio Azua, Kai Hong Tay, David Tan, Ross J Baldessarini
    Abstract:

    Background:The potential value of Lithium Treatment in particular aspects of unipolar major depressive disorder remains uncertain.Methods:With reports of controlled trials identified by systematic ...

  • long term Lithium Treatment in the prevention of suicidal behavior in bipolar disorder patients
    Epidemiologia E Psichiatria Sociale-an International Journal for Epidemiology and Psychiatric Sciences, 2009
    Co-Authors: Leonardo Tondo, Ross J Baldessarini
    Abstract:

    We reviewed available research findings, including meta-analyses on effects of Lithium-Treatment associated with rates of suicidal behavior in bipolar disorder or unipolar major depressive disorder patients, and for comparisons of Lithium to mood-stabilizing anticonvulsants. Data from meta-analyses consistently indicate marked reductions of suicidal behavior and mortality during long-term Treatment with Lithium salts in bipolar disorder patients, and possibly also in unipolar, recurrent major depressive, perhaps even more effectively than with anticonvulsants proposed as mood-stabilizers. Suicidal risk is frequently associated with dysphoric-agitated symptoms, anger, aggression, and impulsivity-all of which may respond better to Treatment with Lithium or other mood-stabilizing medicines than to antidepressants. In these conditions, antidepressant Treatment may not provide a beneficial effect on risk of suicidal thoughts and perhaps attempts, particularly in juveniles, whereas, Lithium, perhaps even more than anticonvulsants, seems to be remarkably effective in the preventing suicidal behavior. The mechanism of action is not well defined and may be associated with either a prevention of mood recurrences or a more specific "antisuicidal" activity.

  • Lithium Treatment reduces suicide risk in recurrent major depressive disorder
    The Journal of Clinical Psychiatry, 2007
    Co-Authors: Francesca Guzzetta, Leonardo Tondo, Franca Centorrino, Ross J Baldessarini
    Abstract:

    OBJECTIVE: Evidence that clinical Treatment reduces suicide risk in major depressive disorder (MDD) is limited and inconsistent. Since Lithium shows major antisuicidal effects in bipolar disorders and in heterogeneous mood disorder samples, we evaluated evidence of antisuicidal effects of Lithium in patients with recurrent MDD. DATA SOURCES: We searched MEDLINE (January 1966 to April 2006; search terms: Lithium, suicide, affective disorder, depression, major depression, and mood disorder) for studies reporting suicides or suicide attempts during Treatment with and without Lithium in recurrent MDD patients, and we added data for 78 new subjects, provided from the Lucio Bini Mood Disorders Research Center in Sardinia, Italy. Suicide rates were pooled and analyzed by use of incidence-rate ratios (IRRs) and meta-analytic methods. DATA SYNTHESIS: Eight studies involved 329 MDD patients and exposure for 4.56 years (1149 person-years) with, and 6.27 years (1285 person-years) without, Lithium. Overall risk of suicides and suicide attempts was 88.5% lower with vs. without Lithium: 0.17%/y versus 1.48%/y (IRR = 8.71; 95% CI: 2.10 to 77.2, p = .0005); for completed suicides (85% risk reduction), IRR = 6.77 (95% CI: 1.29 to 66.8, p = .01). Meta-analysis by risk difference and risk ratio supported these findings, and sensitivity analysis yielded similar results with studies omitted serially. CONCLUSIONS: This is the first meta-analysis suggesting antisuicidal effects of Lithium in recurrent MDD, similar in magnitude to that found in bipolar disorders. Language: en

  • decreased risk of suicides and attempts during long term Lithium Treatment a meta analytic review
    Bipolar Disorders, 2006
    Co-Authors: Ross J Baldessarini, Leonardo Tondo, Paula Davis, Maurizio Pompili, Frederick K Goodwin, John Hennen
    Abstract:

    Objectives:  To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term Lithium Treatment. Methods:  Broad searching yielded 45 studies providing rates of suicidal acts during Lithium Treatment, including 34 also providing rates without Lithium Treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off Lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). Results:  In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among Lithium-treated subjects than among those not treated with Lithium (RR = 4.91, 95% CI 3.82–6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser Lithium superiority. Omitting one very large study or those involving Lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with Lithium-Treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. Conclusions:  Risks of completed and attempted suicide were consistently lower, by approximately 80%, during Treatment of bipolar and other major affective disorder patients with Lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.

  • Lithium Treatment and suicide risk in major affective disorders update and new findings
    The Journal of Clinical Psychiatry, 2003
    Co-Authors: Ross J Baldessarini, Leonardo Tondo, John Hennen
    Abstract:

    BACKGROUND: Evidence that therapeutic benefits of psychiatric Treatments include reduction of suicide risk is remarkably limited and poorly studied. An exception is growing evidence for such suicidal risk reduction with long-term Lithium maintenance. This report updates and extends analyses of Lithium Treatment and suicides and attempts. METHOD: We pooled data from studies providing data on suicidal acts, patients at risk, and average exposure times with or without Lithium maintenance therapy, and considered effects of Lithium on selected subgroups. RESULTS: Data from 34 reported studies involved 42 groups with Lithium maintenance averaging 3.36 years, and 25 groups without Lithium followed for 5.88 years, representing 16,221 patients in a total experience of 64,233 person-years. Risks for all suicidal acts/100 person-years averaged 3.10 without Lithium versus 0.210 during Treatment (93% difference) versus approximately 0.315 for the general population. For attempts, corresponding rates were 4.65 versus 0.312 (93% difference), and for completed suicides, 0.942 versus 0.174 (82% difference). Subjects with bipolar versus various recurrent major affective disorders showed similar benefits (95% vs. 91% sparing of all suicidal acts). Risk reductions for unipolar depressive, bipolar II, and bipolar I cases ranked 100%, 82%, and 67%. Suicide risk without Lithium tended to increase from 1970 to 2002, with no loss of effectiveness of Lithium Treatment. CONCLUSION: The findings indicate major reductions of suicidal risks (attempts > suicides) with Lithium maintenance therapy in unipolar >/= bipolar II >/= bipolar I disorder, to overall levels close to general population rates. These major benefits in syndromes mainly involving depression encourage evaluation of other Treatments aimed at reducing mortality in the depressive and mixed phases of bipolar disorder and in unipolar major depression. Language: en

Wagner F Gattaz - One of the best experts on this subject based on the ideXlab platform.

  • clinical and biological effects of long term Lithium Treatment in older adults with amnestic mild cognitive impairment randomised clinical trial
    British Journal of Psychiatry, 2019
    Co-Authors: Orestes Vicente Forlenza, Marcia Radanovic, Leda Leme Talib, Wagner F Gattaz
    Abstract:

    BackgroundExperimental studies indicate that Lithium may facilitate neurotrophic/protective responses in the brain. Epidemiological and imaging studies in bipolar disorder, in addition to a few trials in Alzheimer's disease support the clinical translation of these findings. Nonetheless, there is limited controlled data about potential use of Lithium to treat or prevent dementia.AimsTo determine the benefits of Lithium Treatment in patients with amnestic mild cognitive impairment (MCI), a clinical condition associated with high risk for Alzheimer's disease.MethodA total of 61 community-dwelling, physically healthy, older adults with MCI were randomised to receive Lithium or placebo (1:1) for 2 years (double-blind phase), and followed-up for an additional 24 months (single-blinded phase) (trial registration at clinicaltrials.gov: NCT01055392). Lithium carbonate was prescribed to yield subtherapeutic concentrations (0.25–0.5 mEq/L). Primary outcome variables were the cognitive (Alzheimer's Disease Assessment Scale – cognitive subscale) and functional (Clinical Dementia Rating – Sum of Boxes) parameters obtained at baseline and after 12 and 24 months. Secondary outcomes were neuropsychological test scores; cerebrospinal fluid (CSF) concentrations of Alzheimer's disease-related biomarkers determined at 0, 12 and 36 months; conversion rate from MCI to dementia (0–48 months).ResultsParticipants in the placebo group displayed cognitive and functional decline, whereas Lithium-treated patients remained stable over 2 years. Lithium Treatment was associated with better performance on memory and attention tests after 24 months, and with a significant increase in CSF amyloid-beta peptide (Aβ1−42) after 36 months.ConclusionsLong-term Lithium attenuates cognitive and functional decline in amnestic MCI, and modifies Alzheimer's disease-related CSF biomarkers. The present data reinforces the disease-modifying properties of Lithium in the MCI–Alzheimer's disease continuum.Declaration of interestNone.

  • leukocyte mitochondrial dna copy number in bipolar disorder
    Progress in Neuro-psychopharmacology & Biological Psychiatry, 2014
    Co-Authors: Rafael T De Sousa, Wagner F Gattaz, Miyuki Uno, Marcus V Zanetti, Sueli Mieko Oba Shinjo, Geraldo F Busatto, Sueli K N Marie, Rodrigo Machadovieira
    Abstract:

    Abstract Background Evidence supports the role for mitochondrial impairment in the pathophysiology of bipolar disorder (BD). BD has been associated with decreased mitochondrial electron transport chain activity and increased oxidative stress. Also, mitochondrial DNA (mtDNA) encodes mitochondrial electron transport chain proteins and has been associated with altered oxidative stress. Preclinical studies showed that Lithium Treatment increased mtDNA content, but no study has directly assessed mtDNA content in subjects with BD in vivo. Also, the effects of Lithium Treatment on mtDNA content have never been evaluated in humans. Methods Leukocyte mtDNA content using real time-PCR was evaluated in subjects with BD (n = 23) in a depressive episode (≥ 18 in the 21-item Hamilton Depression Rating Scale) before and after 6-week Lithium Treatment versus healthy controls (n = 24). Results mtDNA content showed no significant difference between subjects with BD at baseline and controls (p = 0.46); also no difference was observed when comparing before and after Lithium Treatment. A trend for decreased mtDNA content was specifically observed in BD type I compared to controls and BD type II (p = 0.05). Importantly, endpoint mtDNA copy number was significantly correlated with age. Conclusion In BD subjects who were younger, unmedicated and had a shorter duration of illness, no change was observed in mtDNA copy number. More studies with larger samples are warranted to evaluate mtDNA content changes in BD and its potential role as a Treatment target, especially in BD type I and its association with aging.

  • disease modifying properties of long term Lithium Treatment for amnestic mild cognitive impairment randomised controlled trial
    British Journal of Psychiatry, 2011
    Co-Authors: Orestes Vicente Forlenza, Breno S Diniz, Marcia Radanovic, Franklin Santana Santos, Leda Leme Talib, Wagner F Gattaz
    Abstract:

    Background Two recent clinical studies support the feasibility of trials to evaluate the disease-modifying properties of Lithium in Alzheimer’s disease, although no benefits were obtained from short-term Treatment. Aims To evaluate the effect of long-term Lithium Treatment on cognitive and biological outcomes in people with amnestic mild cognitive impairment (aMCI). Method Forty-five participants with aMCI were randomised to receive Lithium (0.25–0.5 mmol/l) (n = 24) or placebo (n = 21) in a 12-month, double-blind trial. Primary outcome measures were the modification of cognitive and functional test scores, and concentrations of cerebrospinal fluid (CSF) biomarkers (amyloid-beta peptide (Aβ42), total tau (T-tau), phosphorylated-tau) (P-tau). Trial registration: [NCT01055392][1]. Results Lithium Treatment was associated with a significant decrease in CSF concentrations of P-tau (P = 0.03) and better perform-ance on the cognitive subscale of the Alzheimer’s Disease Assessment Scale and in attention tasks. Overall tolerability of Lithium was good and the adherence rate was 91%. Conclusions The present data support the notion that Lithium has disease-modifying properties with potential clinical implications in the prevention of Alzheimer’s disease. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01055392&atom=%2Fbjprcpsych%2F198%2F5%2F351.atom

John Hennen - One of the best experts on this subject based on the ideXlab platform.

  • decreased risk of suicides and attempts during long term Lithium Treatment a meta analytic review
    Bipolar Disorders, 2006
    Co-Authors: Ross J Baldessarini, Leonardo Tondo, Paula Davis, Maurizio Pompili, Frederick K Goodwin, John Hennen
    Abstract:

    Objectives:  To update and extend comparisons of rates of suicides and suicide attempts among patients with major affective disorders with versus without long-term Lithium Treatment. Methods:  Broad searching yielded 45 studies providing rates of suicidal acts during Lithium Treatment, including 34 also providing rates without Lithium Treatment. We scored study quality, tested between-study variance, and examined suicidal rates on versus off Lithium by meta-analytic methods to determine risk ratios (RRs) and 95% confidence intervals (CI). Results:  In 31 studies suitable for meta-analysis, involving a total of 85,229 person-years of risk-exposure, the overall risk of suicides and attempts was five times less among Lithium-treated subjects than among those not treated with Lithium (RR = 4.91, 95% CI 3.82–6.31, p < 0.0001). Similar effects were found with other meta-analytic methods, as well as for completed versus attempted suicide, and for bipolar versus major mood disorder patients. Studies with higher quality ratings, including randomized, controlled trials, involved shorter exposures with somewhat lesser Lithium superiority. Omitting one very large study or those involving Lithium-discontinuation had little effect on the results. The incidence-ratio of attempts-to-suicides increased 2.5 times with Lithium-Treatment, indicating reduced lethality of suicidal acts. There was no indication of bias toward reporting positive findings, nor were outcomes significantly influenced by publication-year or study size. Conclusions:  Risks of completed and attempted suicide were consistently lower, by approximately 80%, during Treatment of bipolar and other major affective disorder patients with Lithium for an average of 18 months. These benefits were sustained in randomized as well as open clinical trials.

  • Lithium Treatment and suicide risk in major affective disorders update and new findings
    The Journal of Clinical Psychiatry, 2003
    Co-Authors: Ross J Baldessarini, Leonardo Tondo, John Hennen
    Abstract:

    BACKGROUND: Evidence that therapeutic benefits of psychiatric Treatments include reduction of suicide risk is remarkably limited and poorly studied. An exception is growing evidence for such suicidal risk reduction with long-term Lithium maintenance. This report updates and extends analyses of Lithium Treatment and suicides and attempts. METHOD: We pooled data from studies providing data on suicidal acts, patients at risk, and average exposure times with or without Lithium maintenance therapy, and considered effects of Lithium on selected subgroups. RESULTS: Data from 34 reported studies involved 42 groups with Lithium maintenance averaging 3.36 years, and 25 groups without Lithium followed for 5.88 years, representing 16,221 patients in a total experience of 64,233 person-years. Risks for all suicidal acts/100 person-years averaged 3.10 without Lithium versus 0.210 during Treatment (93% difference) versus approximately 0.315 for the general population. For attempts, corresponding rates were 4.65 versus 0.312 (93% difference), and for completed suicides, 0.942 versus 0.174 (82% difference). Subjects with bipolar versus various recurrent major affective disorders showed similar benefits (95% vs. 91% sparing of all suicidal acts). Risk reductions for unipolar depressive, bipolar II, and bipolar I cases ranked 100%, 82%, and 67%. Suicide risk without Lithium tended to increase from 1970 to 2002, with no loss of effectiveness of Lithium Treatment. CONCLUSION: The findings indicate major reductions of suicidal risks (attempts > suicides) with Lithium maintenance therapy in unipolar >/= bipolar II >/= bipolar I disorder, to overall levels close to general population rates. These major benefits in syndromes mainly involving depression encourage evaluation of other Treatments aimed at reducing mortality in the depressive and mixed phases of bipolar disorder and in unipolar major depression. Language: en

  • lower suicide risk with long term Lithium Treatment in major affective illness a meta analysis
    Acta Psychiatrica Scandinavica, 2001
    Co-Authors: Leonardo Tondo, John Hennen, Ross J Baldessarini
    Abstract:

    Objective: To compare suicide rates with vs. without long-term Lithium Treatment in major affective disorders. Method: Broad searching yielded 22 studies providing suicide rates during Lithium maintenance; 13 also provide rates without such Treatment. Study quality was scored, between-study variance tested, and suicide rates on vs. off Lithium examined by meta-analyses using random-effects regression methods to model risk ratios. Results: Among 5647 patients (33 473 patient-years of risk) in 22 studies, suicide was 82% less frequent during Lithium-Treatment (0.159 vs. 0.875 deaths/100 patient-years). The computed risk-ratio in studies with rates on/off Lithium was 8.85 (95% CI, 4.12–19.1; P<0.0001). Higher rates off-Lithium were not accounted for by Treatment-discontinuation. Conclusion: Suicide risk was consistently lower during long-term Treatment of major affective illnesses with Lithium in all studies in the meta-analysis, including the few involving Treatment-randomization.

  • effects of Lithium Treatment and its discontinuation on suicidal behavior in bipolar manic depressive disorders
    The Journal of Clinical Psychiatry, 1999
    Co-Authors: Ross J Baldessarini, Leonardo Tondo, John Hennen
    Abstract:

    Background: Whether mood-altering Treatments reduce risk of suicidal behavior remains largely unproved. Method: We compared suicidal rates in published studies of patients treated with Lithium with those who were not, and in a mood disorders clinic before, during, and after discontinuing Lithium. Results: Published reports indicate a 7.0-fold lower rate of suicidal acts with Lithium Treatment of manic-depressive patients. In new findings in over 300 bipolar patients, latency from illness onset to Lithium maintenance averaged 8.3 years (from 11.0 years in women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states and were associated with previous severe depression, prior attempts, and lower age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold during Lithium Treatment, with 8.3-fold cumulative sparing of risk by 15 years on Lithium. In the first year off Lithium, affective illness recurred in 67% of patients, and suicidal rates rose 20-fold but were much lower thereafter; fatalities were 14 times more frequent after discontinuation of Lithium. Early morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow versus rapid discontinuation. Conclusion: Lithium maintenance is associated with sustained reduction of suicidal acts in manic-depressive disorders. Treatment discontinuation, particularly abruptly, led to early affective morbidity and suicidal behavior. Improved diagnosis and Treatment as well as earlier intervention for potentially lethal bipolar depression are urgently needed, as are studies of all mood-altering agents for effects on suicidal behavior.

Demaw Chuang - One of the best experts on this subject based on the ideXlab platform.

  • the mood stabilizers valproic acid and Lithium enhance mesenchymal stem cell migration via distinct mechanisms
    Neuropsychopharmacology, 2010
    Co-Authors: Likai Tsai, Yan Leng, Zhifei Wang, Peter Leeds, Demaw Chuang
    Abstract:

    Mesenchymal stem cells (MSCs) show high potential for the therapy of several human diseases; however, the effectiveness of MSC transplantation has been hampered by the relatively poor migratory capacity of these cells toward disease target sites. This study investigated whether Treatment of MSCs with two mood stabilizers—valproic acid (VPA) and Lithium—would enhance cell migration and, if so, to explore the mechanisms underlying their effects. Short-term (3 h) exposure of MSCs to a relatively high concentration (2.5 mM) of VPA markedly increased the transcript and protein levels of CXC chemokine receptor 4 (CXCR4). VPA-induced CXCR4 expression required inhibition of histone deacetylases (HDACs), including the HDAC1 isoform, and involved histone hyperacetylation at the promoter region of the CXCR4 gene. Notably, VPA Treatment enhanced stromal cell-derived factor-1α (SDF-1α)-mediated MSC migration, which was completely blocked by AMD3100, a CXCR4 antagonist. Treatment of MSCs with Lithium (2.5 mM for 1 day) selectively elevated the transcript and protein levels of matrix metalloproteinase-9 (MMP-9) and its enzymatic activity; these effects were mimicked by inhibition or gene silencing of glycogen synthase kinase-3β (GSK-3β). Lithium Treatment also potentiated SDF-1α-dependent MSC migration across the extracellular matrix, which was suppressed by two MMP-9 inhibitors, doxycycline and GM6001. Combining VPA and Lithium Treatment further increased MSC migration. Overall, VPA and Lithium stimulated MSC migration through distinct targets and mediators: HDAC-CXCR4 and GSK-3β-MMP-9, respectively.

  • postinsult Treatment with Lithium reduces brain damage and facilitates neurological recovery in a rat ischemia reperfusion model
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: Ming Ren, Renwu Chen, Vladimir V Senatorov, Demaw Chuang
    Abstract:

    Lithium has long been a primary drug used to treat bipolar mood disorder, even though the drug's therapeutic mechanisms remain obscure. Recent studies demonstrate that Lithium has neuroprotective effects against glutamate-induced excitotoxicity in cultured neurons and in vivo. The present study was undertaken to examine whether postinsult Treatment with Lithium reduces brain damage induced by cerebral ischemia. We found that s.c. injection of Lithium dose dependently (0.5–3 mEq/kg) reduced infarct volume in the rat model of middle cerebral artery occlusion/reperfusion. Infarct volume was reduced at a therapeutic dose of 1 mEq/kg even when administered up to 3 h after the onset of ischemia. Neurological deficits induced by ischemia were also reduced by daily administration of Lithium over 1 week. Moreover, Lithium Treatment decreased the number of neurons showing DNA damage in the ischemic brain. These neuroprotective effects were associated with an up-regulation of cytoprotective heat shock protein 70 (HSP70) in the ischemic brain hemisphere as determined by immunohistochemistry and Western blotting analysis. Lithium-induced HSP70 up-regulation in the ischemic hemisphere was preceded by an increase in the DNA binding activity of heat shock factor 1, which regulates the transcription of HSP70. Physical variables and cerebral blood flow were unchanged by Lithium Treatment. Our results suggest that postinsult Lithium Treatment reduces both ischemia-induced brain damage and associated neurological deficits. Moreover, the heat shock response is likely to be involved in Lithium's neuroprotective actions. Additionally, our studies indicate that Lithium may have clinical utility for the Treatment of patients with acute stroke.

  • postinsult Treatment with Lithium reduces brain damage and facilitates neurological recovery in a rat ischemia reperfusion model
    Proceedings of the National Academy of Sciences of the United States of America, 2003
    Co-Authors: Ming Ren, Renwu Chen, Vladimir V Senatorov, Demaw Chuang
    Abstract:

    Lithium has long been a primary drug used to treat bipolar mood disorder, even though the drug's therapeutic mechanisms remain obscure. Recent studies demonstrate that Lithium has neuroprotective effects against glutamate-induced excitotoxicity in cultured neurons and in vivo. The present study was undertaken to examine whether postinsult Treatment with Lithium reduces brain damage induced by cerebral ischemia. We found that s.c. injection of Lithium dose dependently (0.5–3 mEq/kg) reduced infarct volume in the rat model of middle cerebral artery occlusion/reperfusion. Infarct volume was reduced at a therapeutic dose of 1 mEq/kg even when administered up to 3 h after the onset of ischemia. Neurological deficits induced by ischemia were also reduced by daily administration of Lithium over 1 week. Moreover, Lithium Treatment decreased the number of neurons showing DNA damage in the ischemic brain. These neuroprotective effects were associated with an up-regulation of cytoprotective heat shock protein 70 (HSP70) in the ischemic brain hemisphere as determined by immunohistochemistry and Western blotting analysis. Lithium-induced HSP70 up-regulation in the ischemic hemisphere was preceded by an increase in the DNA binding activity of heat shock factor 1, which regulates the transcription of HSP70. Physical variables and cerebral blood flow were unchanged by Lithium Treatment. Our results suggest that postinsult Lithium Treatment reduces both ischemia-induced brain damage and associated neurological deficits. Moreover, the heat shock response is likely to be involved in Lithium's neuroprotective actions. Additionally, our studies indicate that Lithium may have clinical utility for the Treatment of patients with acute stroke.

  • Lithium induced inhibition of src tyrosine kinase in rat cerebral cortical neurons a role in neuroprotection against n methyl d aspartate receptor mediated excitotoxicity
    FEBS Letters, 2003
    Co-Authors: Ryota Hashimoto, Koichiro Fujimaki, Mira Jeong, Lori Christ, Demaw Chuang
    Abstract:

    The neuroprotective effects of Lithium, a mood stabilizer, against glutamate-induced excitotoxicity in rat cortical neurons were associated with a decrease in Tyr1472 phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR2B subunit and a loss of receptor activity. Since this receptor tyrosine phosphorylation is mediated by the Src-family tyrosine kinases, we investigated the effects of Lithium on the Src kinase activity. Levels of phosphorylated Src kinase at Tyr416, an index of Src activation, were reduced after Treatment with LiCl (1 mM) for more than 3 days. Protein levels of Src-family kinases such as Src, Fyn, and Yes were unchanged by Lithium Treatment. The activities of cytosolic protein tyrosine kinase and protein phosphatase were also unchanged by Lithium Treatment, indicating the selectivity and the modulation. Moreover, the levels of postsynaptic densities (PSD) and SynGAP, the scaffolding proteins of the NMDA receptor complex, were unaltered by Lithium. A Src kinase inhibitor, SU6656, and an NR2B antagonist, ifenprodil, partially blocked glutamate excitotoxicity. Our results suggest that Lithium-induced inactivation of Src kinase contributes to this drug-induced NMDA receptor inhibition and neuroprotection against excitotoxicity.

  • long term Lithium Treatment suppresses p53 and bax expression but increases bcl 2 expression a prominent role in neuroprotection against excitotoxicity
    Journal of Biological Chemistry, 1999
    Co-Authors: Renwu Chen, Demaw Chuang
    Abstract:

    Abstract This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of Lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, Treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after Lithium Treatment for 5–7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. PreTreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium preTreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that Lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that Lithium, in addition to its use in the Treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration.