Longitudinal Study on the Neuroprotective and Neurotrophic Effects of Lithium
Condition: Bipolar Disorder; Bipolar Depression
MeSH terms: Depression; Bipolar Disorder
Study type: Interventional
Phase: Phase 4

Summary: 
      Thirty subjects with a DSM-IV (Diagnostic and Statistical Manual, fourth version)diagnosis of
      BPD during a depressive or hypomanic episode will be divided in two groups according to age
      and time of illness. All patients will receive lithium (flexible therapeutic dose) for 6
      weeks and improvement will be evaluated weekly using depression and mania rating scales; this
      study also objectives to identify state/trait markers and predictors of response.
    

Detailed description: 
      Mood disorders are the most prevalent psychiatric, presenting chronic course and high
      morbidity, affecting 10-15% of population. Diverse structural, functional and biochemical
      cerebral changes described in the pathophysiology of mood disorders, in special Bipolar
      Disorder (BPD), have been associated with impairments in neuroprotective mechanisms and
      cellular resilience. However, the clinical relevance of these pathophysiological findings
      have been rarely addressed. Meanwhile, lithium has been considered the most used mood
      stabilizer worldwide, showing significant efficacy in the treatment of manic and depressive
      episodes, as well as in the prevention of suicide and maintenance. Several studies have
      demonstrated significant neuroprotective and neurotrophic effects induced by lithium
      treatment in diverse cellular and molecular targets, but again, few is known about the
      potential association between these cerebral effects and the its therapeutic clinical
      efficacy induced by this proof of concept agent. The present project aims to investigate
      brain levels of lithium using magnetic resonance spectroscopy (7Li-MRS) and its association
      with different markers of neuronal viability such as n-acetyl-aspartate (using
      1-hydrogen-MRS), as well as peripheral markers of mitochondrial, endoplasmic reticulum and
      neurotrophic factors activity, all highly implicated in the pathophysiology of BD. The
      investigator has been working in this area in the last ten years, in which the last three and
      a half in the Lab of Molecular Pathophysiology and Experimental Therapeutics, National
      Institute of Mental Health (NIMH), National Institutes of Health. The candidate is looking
      forward to establish appropriate structure to develop a "Research Center for the Study of
      Neuroplasticity and Neuroprotection in Psychiatric Disorders" in the Institute of Psychiatry,
      University of Sao Paulo, Brazil. Overall, the study on the neuroplasticity-mediated
      pathophysiological basis of BPD implicated in the clinical presentation and outcome may shed
      light on the development of new, improved therapeutics for this and other devastating
      psychiatric disorders.
    

Intervention name(s): Lithium
Intervention type(s): Drug
Intervention MeSH terms: Lithium Carbonate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: predictors of response; bipolar disorder; depression; lithium treatment; biomarkers