Mood disorders are highly prevalent across the world, affecting 5-10% of the adult population in a given year1, 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 stimuli5, 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 disorders8, 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 CBT10. 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 ameliorate 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.
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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.
- Waraich P, Goldner EM, Somers JM, Hsu L. Prevalence and incidence studies of mood disorders: a systematic review of the literature. Can J Psychiatry. 2004 Feb;49(2):124-38. Review.
- Steel Z, Marnane C, Iranpour C, Chey T, Jackson JW, Patel V, Silove D. The global prevalence of common mental disorders: a systematic review and meta-analysis 1980-2013. Int J Epidemiol. 2014 Apr;43(2):476-93.
- Murray CJL, Lopez AD, editors. The global burden of disease. Geneva: World Health Organization;1996
- Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, Corey-Lisle PK. The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry. 2003 Dec;64(12):1465-75.
- Ressler KJ, Mayberg HS. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci. 2007 Sep;10(9):1116-24.
- Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME. Subgenual prefrontal cortex abnormalities in mood disorders. Nature. 1997 Apr 24;386(6627):824-7.
- Morrissette DA, Stahl SM. Modulating the serotonin system in the treatment of major depressive disorder. CNS Spectr. 2014 Dec;19 Suppl 1:57-67; quiz 54-7, 68.
- Rock PL, Roiser JP, Riedel WJ, Blackwell AD. Cognitive impairment in depression: a systematic review and meta-analysis. Psychol Med. 2014 Jul;44(10):2029-40.
- Sweeney JA, Kmiec JA, Kupfer DJ. Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery. Biol Psychiatry. 2000 Oct 1;48(7):674-84.
- Linde K, Rücker G, Sigterman K, Jamil S, Meissner K, Schneider A, Kriston L. Comparative effectiveness of psychological treatments for depressive disorders in primary care: network meta-analysis. BMC Fam Pract. 2015 Aug 19;16:103. doi: 10.1186/s12875-015-0314-x.
- 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.
- Connolly KR, Thase ME. The clinical management of bipolar disorder: a review of evidence-based guidelines. Prim Care Companion CNS Disord. 2011;13(4).
- Szentagotai A, David D. The efficacy of cognitive-behavioral therapy in bipolar disorder: a quantitative meta-analysis. J Clin Psychiatry. 2010 Jan;71(1):66-72.