Depression

Mood disorders are highly prevalent across the world, affecting 5-10% of the adult population in a given year^{1, 2}. The most common mood disorders are major depressive disorder, dysthymia, and bipolar disorder.

Major depressive disorder (also known as depression) is characterised by low mood and/or loss of interest in previously pleasurable activities; in addition to a combination of several other symptoms such as impaired attention, changes in body weight, sleep disturbance, fatigue, excessive feelings of guilt, and negative thoughts.

In bipolar disorder, individuals experience at least one episode of manic symptoms, but depressive episodes are also common. Mania refers to a distinct period of elevated, expansive, or irritable mood coupled with excess energy.

Collectively, mood disorders cause considerable distress to affected individuals and can have a devastating impact on quality of life and everyday functioning.

In the World Health Organization’s Global Burden of Disease study, depression was second only to ischaemic heart disease in terms of associated disability³. In addition to consequences for the individual, mood disorders are important at an economic level – for example, the total economic cost of depression in the USA was estimated at $83.1 billion in the year 2000⁴.

Pathology and functional impact of depression and affective disorders

Current biological models for mood disorders emphasise dysregulation of the prefrontal cortex and subgenual cingulate cortex, which play important roles in emotional regulation and executive processes; as well as dysfunction of the hippocampus and amygdala, which are involved in memory formation and detection of threatening stimuli^{5, 6}.

According to the ‘monoamine hypothesis’, depression is linked with dysregulation of the serotonin, dopamine, and norepinephrine systems⁷.

Given the centrality of these brain regions and neurochemical systems in cognition, it is not surprising that cognitive deficits are extremely common in people with mood disorders^{8, 9}.

Research and development in depression and affective disorders

Multiple evidence-based treatment options exist for mood disorders, but the precise choice of treatments should be determined on an individual basis following assessment by a healthcare professional, taking into consideration relevant local guidelines.

Psychotherapy, notably cognitive behavioural therapy (CBT), has a strong evidence base in the treatment of depressive disorders¹⁰. Traditionally, face-to-face CBT was used, but there is growing evidence to support remote therapist-led CBT and also guided self-help CBT. Other types of therapy, including mindfulness-based interventions, can be helpful¹¹.

In moderate to severe depressive disorder, first-line pharmacological treatments include the selective serotonin reuptake inhibitors (SSRIs), with other agents also being used as non-first line including monoamine oxidase inhibitors (MAO-Is), and tricyclics. Various pharmacological augmentation strategies can be utilised where needed, such as with an antipsychotic medication.

For bipolar disorder, current first-line treatments for acute mania include lithium, divalproex, or an atypical antipsychotic medication. Mixed episodes (involving both depressive and manic symptoms concurrently) can be treated with divalproex or an atypical antipsychotic, while depression in the context of bipolar disorder can be treated with an atypical antipsychotic (with or without an SSRI), or lamotrigine¹².

Adjunctive psychotherapy can be useful in bipolar disorder, but effect sizes may be smaller than those found in the treatment of primary depression¹³.

While treatments are available for mood disorders, in many cases individuals cannot tolerate particular medications due to side effects and/or the need for physical health monitoring, or symptoms do not improve adequately. Another limitation regarding existing treatments is that cognitive deficits can persist even into recovery, despite adequate courses of first-line pharmacotherapy/psychotherapy.

The search is on for treatments that can reduce cognitive impairment in mood disorders, in order to maximise long-term outcomes and quality of life. Another key area of ongoing research is the search for objective markers capable of identifying, for a given individual, treatment options that are most likely to be effective and well-tolerated.

You might also be interested in…

Clark., L., (2009). Neurocognitive mechanisms in depression: implications for treatment. Annu Rev Neurosci.

Ressler K.J., and Mayberg H.S., (2007). Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci.

Drevets W.C., et al (1997). Subgenual prefrontal cortex abnormalities in mood disorders. Nature.

Rock P.L., et al (2014). Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med.

Grady M.M., and Stahl S.M., (2013). Novel agents in development for the treatment of depression. CNS Spectr.

Pringle A., et al (2011). A cognitive neuropsychological model of antidepressant drug action. Prog Neuropsychopharmacol Biol Psychiatry.

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11. _{Strauss C, Cavanagh K, Oliver A, Pettman D. Mindfulness-based interventions for people diagnosed with a current episode of an anxiety or depressive disorder: a meta-analysis of randomised controlled trials. PLoS One. 2014 Apr 24;9(4):e96110. doi: 10.1371/journal.pone.0096110. eCollection 2014.}
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