Annotated Bibliography

American Psychiatric Association, American Psychiatric Association DSM-5 Task Force. Diagnostic and statistical manual of mental disorders: DSM-5. (American Psychiatric Association, 2013).

The up to date text used by most practicing clinicians to diagnose mental disorders, the DSM V is a useful reference resource for diagnostic information about bipolar.

Botros, H. G. et al. Crystal structure and functional mapping of human ASMT, the last enzyme of the melatonin synthesis pathway. J. Pineal Res. 54, 46–57 (2013).

This paper reports on relevant ASMT crystal structures for use in studying mutations linked to bipolar disorder.

Cade, J. F. Lithium salts in the treatment of psychotic excitement. 1949. Bull World Health Organ 78, 518–520 (2000).
This is a republication of the paper that introduced lithium as a treatment for mania, and establishes the historical basis of the disease.

Can, A., Piantadosi, S. C. & Gould, T. D. Differential antidepressant-like response to lithium treatment between mouse strains: effects of sex, maternal care, and mixed genetic background. Psychopharmacology (Berl.) 228, 411–418 (2013).

Original research done by the same group from the lithium pharmacogenetics review. This study looks at lithium treatment in mouse models and takes into account a number of factors, like sex and genetic background, when evaluating the efficacy of lithium.

Can, A., Schulze, T. G. & Gould, T. D. Molecular actions and clinical pharmacogenetics of lithium therapy. Pharmacology Biochemistry and Behavior doi:10.1016/j.pbb.2014.02.004 (review)

A review looking at important literature pertaining to the use of lithium as a therapeutic for bipolar disorder. This work is being used as a reference point for lithium treatment throughout this project.

Chen, H. M. et al. Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 4, e375 (2014).

The creation of induced pluripotent stem cell lines from BD patients in this paper represents a significant advance in the methods used to study bipolar, and these authors studied the changes in channel protein expression, as well as the effects of lithium treatment on the cells, in particular calcium signaling. Break through paper in terms of introducing a new model system for the disease

Chen, G., Huang, L. D., Jiang, Y. M. & Manji, H. K. The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J. Neurochem. 72, 1327–1330 (1999).

After establishing that lithium inhibits GSK-3, this paper takes the next logic step and determines that valproate, the most common substitute for lithium as a mood stabilizer, also inhibits GSK-3. Does not propose a biochemical mechanism, however.

Corena-McLeod, M. et al. New Model of Action for Mood Stabilizers: Phosphoproteome from Rat Pre-Frontal Cortex Synaptoneurosomal Preparations. PLoS One 8, (2013).
This more recent paper takes a look at the cellular energetics behind  bipolar disorder in the form of mitochondrial movement in neurons, a process regulated by phosphorylation of cytoskeletal and motor proteins. The study establishes the effects of mood stabilizers (lithium, valproate and paliperidone) on the movement of mitochondria in neurons.
 Corena-McLeod, M. del P. et al. Paliperidone as a mood stabilizer: a pre-frontal cortex synaptoneurosomal proteomics comparison with lithium and valproic acid after chronic treatment reveals similarities in protein expression. Brain Res. 1233, 8–19 (2008).

 An earlier study by Corena-McLeod et al. that will be useful for discussing the current treatment methods used to combat bipolar disorder. Also provides background for the developments that lead to her teams 2013 paper in PLoS One

 Etain, B. et al. Genetic and functional abnormalities of the melatonin biosynthesis pathway in patients with bipolar disorder. Hum. Mol. Genet. 21, 4030–4037 (2012).

This article provides biochemical information on the involvement of the melatonin biosynthesis pathway in patients with bipolar disorder. The authors connect several mutations in the promoter region of ASMT (acetylserotonin O-methyltransferase) to increased risk of Bipolar Disorder by finding said mutations in higher levels in patients diagnosed with the disorder. The sample size was sizable (several hundred individuals in both the experimental and control groups, with a replicate study done in another country).

 Feier, G. et al. Lithium and valproate modulate energy metabolism in an animal model of mania induced by methamphetamine. Pharmacol. Biochem. Behav. 103, 589–596 (2013).

This is another study looking at the effects of mood stabilizers on the mitochondria and metabolism. The authors use a meth-induced mania model in rats to measure levels of various krebs cycle proteins before and after treatment with mood stabilizers in an attempt to learn more about the causes of bipolar. The authors conclude that changes in krebs cylce enzymes may be involved.
Freland, L. & Beaulieu, J.-M. Inhibition of GSK3 by lithium, from single molecules to signaling networks. Front Mol Neurosci 5, (2012).
provides a background on lithium and GSK-3, this paper was used primarily to arrive at other pieces of literature used in the project.
Hirschowitz, J., Kolevzon, A. & Garakani, A. The Pharmacological Treatment of Bipolar Disorder: The Question of Modern Advances. Harvard Review of Psychiatry (Taylor & Francis Ltd) 18, 266–278 (2010).
This provides an excellent overview of the different types of drugs used to treat bipolar disorder.

Kakiuchi, C. et al. Impaired feedback regulation of XBP1 as a genetic risk factor for bipolar disorder. Nat. Genet. 35, 171–175 (2003).

Important paper for understanding the effects of valproate, one of several mood stabilizers used to treat bipolar disorder. The protein XBP1 has impaired expression from a mutation found in bipolar patients, and valproate activates an up stream transcription factor that rescues the impaired expression of XBP1 in response to ER stress.

Kao, C.-Y. et al. The mood stabilizer valproate activates human FGF1 gene promoter through inhibiting HDAC and GSK-3 activities. J. Neurochem. 126, 4–18 (2013).
This paper establishes some of the downstream effects of lithium and valproate after they inhibit GSK-3, and HDAC.
Klein, P. S. & Melton, D. A. A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93, 8455–8459 (1996).
This paper, in the process of determining the effects of lithium on development, shows that lithium inhibits the activity of GSK-3

Kripke, D. F. et al. Polymorphisms in melatonin synthesis pathways: possible influences on depression. J Circadian Rhythms 9, 8 (2011).

This is another article on the relationship of melatonin and circadian rhythms to bipolar disorder. The study evaluated the effects of mutations in the gene for ASMT. The paper does however present evidence that ASMT may not be as important as some earlier studies suggested. This will be an important piece of information to look at when outlining the possible modes of action for the disease (since as far as can be seen there is, as of yet, no generally agreed upon mechanism).

Yang, S., Van Dongen, H. P. A., Wang, K., Berrettini, W. & Bućan, M. Assessment of circadian function in fibroblasts of patients with bipolar disorder. Mol Psychiatry 14, 143–155 (2009).

This article looks at the genetic and protein expression related causes of changes in the circadian rhythm of patients with bipolar disorder. The finds they present show that for some proteins, (namely the kinases GSK3α and β) the level of phosphorylation is affected. This is particularly interesting in light of the fact that GSK3β is a direct target of lithium, one of the oldest and most widely used treatments for bipolar disorder.

Zarate, C. A. & Manji, H. K. Putative Drugs and Targets for Bipolar Disorder. Mt Sinai J Med 75, 226–247 (2008).

This is a review of all of the treatment methods for bipolar disorder. It is being used to provide background on the different treatment options as well as the variety of pathways being targeted by those treatments.

Zhang, K. et al. Continuous GSK-3β overexpression in the hippocampal dentate gyrus induces prodepressant-like effects and increases sensitivity to chronic mild stress in mice. Journal of Affective Disorders 146, 45–52 (2013).
This paper establishes the effects of GSK-3 beta over expression in a model system for depression. Turns out that copious amounts of GSK-3 cause depressive symptoms.