Mood Disorder

Introduction

Mood disorders are common psychiatric conditions within the general population. It has been estimated that up to 15% of the population will experience at least one mood disorder episode during their lifetime, leading to moderate-to-severe impairment in working and social activities. Mood disorders account for considerable psychiatric morbidity (such as pain and suffering), significant disability, and consequent loss of productivity. Patients affected by mood disorders are exposed to a high risk of suicidal behavior.

Classification of Mood Disorders

Primary mood disorders are classified according to the nature and severity of symptoms during each episode and the course of the illness. A basic distinction is drawn between unipolar (depressive) disorder and bipolar disorder (manic depression).

• Unipolar Disorder

Within the unipolar mood disorder category, major depression disorder (MDD) is the primary subtype. MDD refers to the experience of (single or reoccurring) major depressive episodes, with no history of manic or hypomanic episodes. It is characterized by episodes of low mood and/or anhedonia, together with a range of additional cognitive and somatic symptoms that are severe enough to cause clinically distress or impair functioning over at least two weeks.

• Bipolar Disorders

Bipolar disorders have been investigated and have a substantial range of clinical manifestations, including bipolar I disorder (BPI), bipolar II disorder (BPII), cyclothymia, and others. BPI is characterized by the experience of a manic episode with or without depressive and/or hypomanic episodes. BPII is characterized by the experience of at least one hypomanic episode and one major depressive episode, with no history of manic episodes. Cyclothymic disorder is clinically significant distress or impaired functioning caused by intermixed, intermittent, or alternating depressive and hypomanic symptoms. In bipolar disorder, depressed and euthymic periods are interspersed with manic episodes, when an abnormally elevated mood is accompanied by associated behaviors and cognitions (e.g., grandiosity, irritability, disinhibition). While bipolar disorder is associated with creativity, bipolar disorder can be quite disabling in its severe forms and bears the lifetime risk of suicide of 15% when untreated.

Neuropathological Study of Mood Disorders

The precise pathophysiology of mood disorders remains obscure, as does the neurobiology of normal mood regulation. However, recent advances in neuroscience, particularly in molecular neurobiology and functional brain imaging, are rapidly advancing our understanding of the biological substrates of normal and pathological mood states. A range of neuropathological abnormalities has been reported. They are mainly in the prefrontal cortex and are cytoarchitectural in nature. A loss of glia is the most notable finding, along with a reduced size and density of some neurons. There are also alterations described in the hippocampal formation and subcortical structures and concerning synaptic terminals and dendrites. Together, these changes suggest a difference in the cellular composition and circuitry of these regions in mood disorder.

Fig.1 Intracellular pathways affected by mood stabilizers and antidepressants. (Coyle, 2003)

Genetic Factors with Mood Disorders

Recent studies have uncovered several loci on the human genome associated with the risk for bipolar disorder, although there is no specific gene to be identified. It is reasonable to suggest that the development of mood disorders results from the effects of multiple environmental and genetic factors. The potential pathogenic mechanisms include dysregulation in serotonin (5-HT) neurotransmission, DA, GABA, and glutamate and abnormalities of common neuroanatomical structures in the limbic circuit.

In addition, genetic studies have identified several candidate genes involved in the dopaminergic and other neurotransmitter pathways. For example, COMT gene effects can be modulated by exposure to stress, particularly in the pathophysiology of depressed mood and related neurocognitive processes. Other commonly studied genes are the brain-derived neurotrophic factor (BDNF) gene, the transcription factor CREB1 (cyclic adenosine monophosphate response element-binding protein-1), and the mitogen-activated protein kinase 1 (MAPK1). There is a close association between CREB1 and MAPK1 as they are both involved in regulating neuronal plasticity and inflammatory pathways, which retain a fundamental role in the pathophysiology of MDD.

Mood Disorders Associated with Other Diseases

Mood disorders frequently co-occur with many medical illnesses that involve inflammatory pathophysiologic mechanisms, such as cancer and cardiovascular diseases. The development of mood disorders is linked to inflammation and experimental activation of inflammatory reactions, which is demonstrated to induce symptoms of mood disorders in some human and animal studies. Indeed, CNS inflammation and blood-CNS barrier dysfunction have been observed in subgroups of patients with severe depression. Consequently, it appears that infections and autoimmune diseases can affect the brain independently and synergistically, which may ultimately increase the risk of the subsequent development of mood disorders.

Products Provided by Creative Biolabs

Creative Biolabs is a leading service and product provider that focuses on the field of neuroscience. With the help of our highly experienced staff, we can provide the best products for your scientific research, such as animal models, vectors, cell lines, proteins & peptides, and antibodies.

To see more detailed information on our products, please directly send us your inquiry.

Reference

1. Coyle, J. T.; Duman, R. S. Finding the intracellular signaling pathways affected by mood disorder treatments. Neuron. 2003, 38(2), 157-160.