Depression and Bipolar Disorder

Overview of Depression and Bipolar Disorder

Depressive disorders include a heterogeneous spectrum of clinical conditions which are characterized by several common features such as the presence of sad, empty, or irritable mood, accompanied by somatic and cognitive changes that significantly affect the individual’s capacity to function. Especially when depressive episodes are long-lasting and with moderate or severe intensity, the disorder becomes a serious health condition, that can possibly lead to suicide. Indeed, according to an estimation by the World Health Organization that about 788.000 people died due to suicide, denoting the need for urgent actions.

Bipolar disorder, previously known as manic depressive illness, is a severe chronic mood disorder characterized by episodes of mania, hypomania, and alternating or intertwining episodes of depression. Bipolar disorder is a lifelong episodic illness with a variable course that can often result in functional and cognitive impairment and a reduction in quality of life. Because bipolar disorder is mainly diagnosed in young adulthood, it affects the economically active population and, therefore, connotes high costs to society. Because of the recurrence and chronicity of the bipolar disorder, not only is acute treatment for the management of mood episodes fundamental but also pharmacological and psychological approaches for prevention of further episodes are important.

Fig.1 Life chart showing progression of bipolar disorder. (Grande, 2016)

Pathology of Depression and Bipolar Disorder

The current understanding of depression has expanded well beyond the scope of the monoamine hypothesis. Due to its varied and complex features, no one theory has proven sufficient to explain both the polymorphic nature of the disorder and the identification of biomarkers that can be reliably used for diagnosis are lacking. As a result, modern behavioral accounts of depression must look at both interoceptive and environmental components. Advances in genetic research and neuroimaging will continue to transpire new findings based on the complex circuitry and brain architecture associated with depression.

Knowledge of the pathogenesis and pathophysiology of bipolar disorder has progressed rapidly over the past few decades. Although bipolar disorder is one of the most heritable psychiatric disorders, a multifactorial model in which genes and environments interact is currently thought to best fit this disorder. Modulation of synaptic and neural plasticity seems to be important in the circuitry regulating affective and cognitive functions. Other pathways that can affect neuronal interconnectivity are also under study, including mitochondrial dysfunction and endoplasmic reticulum stress, neuroinflammation, oxidation, apoptosis, and epigenetic changes, particularly histone and DNA methylation.

Fig.2: Major depressive disorder specifiers. (Malhi, 2018)

Regulating Factors of Depression and Bipolar Disorder

The monoamine theory of major depressive disorder was supported by findings that tricyclic antidepressants and monoamine oxidase inhibitors (MAOIs) enhanced monoamine neurotransmission by different mechanisms. In addition, one of the most consistent biological findings in more severe depression with melancholic features, and associated with changes in the hypothalamic-pituitary adrenal (HPA) axis, is the increased amount of plasma cortisol. Inflammation also plays role in depression: individuals with autoimmune diseases and severe infections are more likely to have depression, and cytokines administered therapeutically, such as interferon-gamma and interleukin 2, trigger depression. Furthermore, the process of neurogenesis is controlled by regulatory proteins, such as brain-derived neurotrophic factor (BDNF), which is diminished in patients with major depressive disorder.

Mood disorders were thought to result from an imbalance in monoaminergic neurotransmitter systems such as the serotonergic, noradrenergic, and in bipolar disorder the dopaminergic neurotransmitter system. Neurotrophic molecules, such as BDNF, have a vital role in signaling pathways of dendritic sprouting and neural plasticity. In addition, dendritic spine loss has been noted in post-mortem brain tissue of patients with bipolar disorder.

Treatment of Depression and Bipolar Disorder

Psychotherapies are effective in the treatment of depression in primary care patients. The effects are comparable with those of antidepressant medication in the short term and probably more effective in the longer term. Combined treatment is more effective than either psychotherapy or pharmacotherapy alone. Many patients prefer psychotherapy over pharmacotherapy, and it is also more acceptable.

Diverse factors can affect pharmacological and psychological strategies; these include medical and psychiatric comorbidities, previous or current treatments, response to treatment or adverse effects in patients and relatives, and the patient’s willingness to be treated. Clinicians should consider these factors, particularly in the initial treatment of an acute episode, to optimize efficacy, minimize the risk of adverse events and lack of adherence, and avoid switching of drugs. In acute management, the primary goals are to ensure the safety of the patient and people nearby and to achieve clinical and functional stabilization with minimum adverse effects. Moreover, engagement and development of a therapeutic alliance are important in any lifelong disorder that needs long-term adherence, and this collaboration is especially true during the first episode. In long-term management, the main aims are to prevent the recurrence of episodes and ensure functionality while optimizing treatment.

Fig.3 Pharmacotherapy of major depressive disorder: antidepressant actions at the synapse. (Malhi, 2018)