Practitioner Review: The effects of atypical antipsychotics and mood stabilisers in the treatment of depressive symptoms in paediatric bipolar disorder

Atkin, Tobias; Núñez, Nicolás A.; Gobbi, Gabriella

doi:10.1111/jcpp.12735

Cited by 12 publications

(9 citation statements)

References 108 publications

(177 reference statements)

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“…3B), which was distinct from the outcome of higher doses. Although the reason is unknown, it might be consistent with clinical reports that olanzapine could have antidepressant effects during the treatment of bipolar depression (31). We then tested the efficacy of the high-dose olanzapine treatment (1.0 mg/kg) on the behavioral abnormalities of the Syt7 KO mice using the LH/SPT/LDB paradigms.…”

Section: Identification Of Syt7 As a Candidate Risk Factor For Neuropsupporting

confidence: 56%

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice

Shen

Wang

Yaonan

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The pathogenesis of bipolar disorder (BD) has remained enigmatic, largely because genetic animal models based on identified susceptible genes have often failed to show core symptoms of spontaneous mood cycling. However, pedigree and induced pluripotent stem cell (iPSC)-based analyses have implicated that dysfunction in some key signaling cascades might be crucial for the disease pathogenesis in a subpopulation of BD patients. We hypothesized that the behavioral abnormalities of patients and the comorbid metabolic abnormalities might share some identical molecular mechanism. Hence, we investigated the expression of insulin/synapse dually functioning genes in neurons derived from the iPSCs of BD patients and the behavioral phenotype of mice with these genes silenced in the hippocampus. By these means, we identified synaptotagmin-7 (Syt7) as a candidate risk factor for behavioral abnormalities. We then investigated Syt7 knockout (KO) mice and observed nocturnal manic-like and diurnal depressive-like behavioral fluctuations in a majority of these animals, analogous to the mood cycling symptoms of BD. We treated the Syt7 KO mice with clinical BD drugs including olanzapine and lithium, and found that the drug treatments could efficiently regulate the behavioral abnormalities of the Syt7 KO mice. To further verify whether Syt7 deficits existed in BD patients, we investigated the plasma samples of 20 BD patients and found that the Syt7 mRNA level was significantly attenuated in the patient plasma compared to the healthy controls. We therefore concluded that Syt7 is likely a key factor for the bipolar-like behavioral abnormalities.

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Section: Identification Of Syt7 As a Candidate Risk Factor For Neuropsupporting

confidence: 56%

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice

Shen

Wang

Yaonan

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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“…As polypharmacy is a common clinical practice, investigation of whether psychiatric drugs with anti-inflammatory properties may attenuate metabolic side effects of pro-inflammatory drugs when administered simultaneously [18]. This is the Lithium (Li) case, that is an efficient mood modulator molecule concomitantly used in management of acute mania or manic episodes associated with bipolar disorder [19] and to treat some mixed episodes of major depressive and bipolar disorders [20]. Moreover, the combination of Li plus OLZ has been indicated to treat some mixed episodes of major depressive and bipolar disorders [2,20].…”

Section: Introductionmentioning

confidence: 99%

“…This is the Lithium (Li) case, that is an efficient mood modulator molecule concomitantly used in management of acute mania or manic episodes associated with bipolar disorder [19] and to treat some mixed episodes of major depressive and bipolar disorders [20]. Moreover, the combination of Li plus OLZ has been indicated to treat some mixed episodes of major depressive and bipolar disorders [2,20]. Previous in vitro study also suggested that Li could modulate in vitro proinflammatory macrophage response exposed to some antidepressant drugs [21].…”

Section: Introductionmentioning

confidence: 99%

Lithium is able to minimize olanzapine oxidative-inflammatory induction on macrophage cells

et al. 2019

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BackgroundOlanzapine (OLZ) is a second-generation antipsychotic drug used for treatment of schizophrenia, bipolar disorder, and other neuropsychiatric conditions. Undesirable side effects of OLZ include metabolic alterations associated with chronic oxidative-inflammation events. It is possible that lithium (Li), a mood modulator that exhibits anti-inflammatory properties may attenuate OLZ-induced oxi-inflammatory effects.MethodologyTo test this hypothesis we activated RAW 264.7 immortalized macrophages with OLZ and evaluated oxidation and inflammation at the gene and protein levels. Li and OLZ concentrations were determined using estimated plasma therapeutic concentrations.ResultsOLZ triggered a significant increase in macrophage proliferation at 72 h. Higher levels of oxidative markers and proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, with a concomitant reduction in IL-10, were observed in OLZ-exposed macrophages. Lithium (Li) exposure triggered a short and attenuated inflammatory response demonstrated by elevation of superoxide anion (SA), reactive oxygen species (ROS), IL-1β, and cellular proliferation followed by elevation of anti-inflammatory IL-10 levels. Li treatment of OLZ-supplemented macrophages was able to reverse elevation of oxidative and inflammatory markers and increase IL-10 levels.ConclusionsDespite methodological limitations related to in vitro protocols, results suggested that Li may attenuate OLZ-induced oxidative and inflammatory responses that result from metabolic side effects associated with OLZ.

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“…Analysis using repeated-measures mixed models showed that those on AT monotherapy (the reference group) had a gradually diminished, but statistically significant, monthly increase in BMI during all durations of drug exposure (3 When compared to AT monotherapy, the magnitude of increase in BMI associated with MS, AD monotherapy, and no treatment was significantly less at all time points; data indicated less steep slopes of BMI change over time compared with AT monotherapy, especially during the short-term exposure. The combinations of AT with other psychotropic medications (AT+MS, AT+AD) were associated with a similar BMI increase as AT monotherapy.…”

Section: Psychopharmacotherapy In Children and Adolescentsmentioning

confidence: 99%

“…When the risks of ADT use in this age group is matched with the benefits, it appears best that ADT use be limited to moderate-to-severe depression, where psychosocial interventions are either ineffective or not feasible. Practitioner review: The effects of atypical antipsychotics and mood stabilisers in the treatment of depressive symptoms in paediatric bipolar disorder (3) The management of depressive and mixed symptoms in children and adolescents with bipolar disorder (BD) remains a matter of debate. This review systematically examines the impact of atypical antipsychotics (AAPs) and mood stabilisers in the treatment of bipolar depression and/or mixed states.…”

Section: Ariyasinghe Ss Williamsmentioning

confidence: 99%

Psychopharmacotherapy in children and adolescents

Ariyasinghe

Williams

2017

Sri Lanka J. Psyc.

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Practitioner Review: The effects of atypical antipsychotics and mood stabilisers in the treatment of depressive symptoms in paediatric bipolar disorder

Abstract: These results mostly overlap with the approved treatments for bipolar depression in adults.

Cited by 12 publications

References 108 publications

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice

Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice

Lithium is able to minimize olanzapine oxidative-inflammatory induction on macrophage cells

Psychopharmacotherapy in children and adolescents

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