The mood is defined as a pervasive and sustained feeling tone that is endured internally, and that impacts nearly all aspects of a person’s behavior in the external world. Mood disorders or affective disorders are described by marked disruptions in emotions (severe lows called depression or highs called hypomania or mania). These are common psychiatric disorders leading to an increase in morbidity and mortality.
According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), mood disorders have been broadly categorized as bipolar disorders and depressive disorders. Bipolar disorders are further categorized as bipolar I, bipolar II, cyclothymic disorder, bipolar and related disorder to another medical condition, substance/medication-induced bipolar and related disorder, other specified bipolar and related disorder, and unspecified bipolar and related disorder.
Major depressive disorder is diagnosed by the presence of 5 out of the 9 symptoms of sad mood, insomnia, feelings of guilt, decreased energy levels, decreased concentration, decreased appetite, decrease in pleasurable activities (anhedonia), increased or decreased psychomotor activity and recurrent suicidal ideation/acts of self-harm/suicide attempt existing over a period of 2 weeks.
Three new depressive disorders have been incorporated under mood disorders in DSM-5:
Major depression episodes may precede or occur concurrently with persistent depressive disorder, and this is known as double depression.
Other depressive disorders include depressive disorder due to another medical condition, substance or medication-induced depressive disorder, other specified depressive disorder, and unspecified depressive disorder.
The brain areas responsible for controlling our feelings and emotions are the amygdala and orbitofrontal cortex. Patients with mood disorders have shown to have an enlarged amygdala on brain imaging, which substantiates the certainty that abnormalities in these areas lead to mood disorders. Ventricular expansion results from repeated episodes of mood disorders.
Neurotransmitters that play an important function in mood disorders are serotonin and norepinephrine, which are decreased in episodes of depression. Serotonin is the neurotransmitter most commonly associated with depression. Dopamine has also been implicated in mood disorders with research showing that it may be decreased in depression and increased in mania.
Medical conditions which lead to mood disorders include:
There are certain drugs and medications, consumption of which lead to symptoms simulating a mood disorder. These are amphetamines, cocaine, procarbazine, and steroids.
According to research based on twin studies, there are certain genes causing mood disorder. Family and adoption studies have also indicated the heritability of mood disorders. People who have a strong positive family history of a mood disorder are more likely to develop mood disorders themselves. The parental mood disorder is a vital and constant risk factor for developing mood disorder in their children.
Increased HPA activity is associated with stress and depression. Increased TSH has been shown to be associated with depression.
Stressful life changes (death of significant other, parents, siblings, etc.) traumatic events and childhood abuse have been found to be major risk factors for the development of mood disorder later on in life, especially depressive disorder. Personality traits or certain personality disorders like borderline and obsessive-compulsive disorder (OCD) are more frequently associated with depression. Attachment problems and early childhood adversity have been associated with depression.
Research shows that mood disorder leads to the altered release of neuroactive cytokines like IL-1beta, IL-6, and TNF-alpha.
Recent research has found a crucial role of nitric oxide (NO) involved in causing the inflammatory process that leads to signs and symptoms of mood disorder. Altered levels of NO have also been found in patients suffering from mood disorders.
Increased frequency of abnormal hyperintensities is seen in subcortical regions in depressive disorders and bipolar disorder.
Major depression has a lifetime prevalence of about 5% to 17%. Women have almost twice the prevalence rate vs. men. The annual prevalence rate of depression is 7.1% in U.S. adults, while the annual prevalence rate for bipolar disorder is 2.8%. The median age of onset of major depressive disorder is 32 years.
Mood disorders are commonly seen in children and adolescents with an estimated rate of 15% suffering from any mood disorder, and 12% have a mood disorder with severe impairment. Depression is prominent in children and adolescents, with rates as high as 18% to 22% in girls and 7% to 10% in boys by the age of 17. Research shows the prevalence of disruptive mood dysregulation disorder ranges from 0.8% to 4.3% in children. The lifetime prevalence of bipolar disorder subtypes is 0.6% for bipolar I, 0.4% for bipolar II, and 2.4% for bipolar spectrum disorder (BPS).
Depression is a complex neuropsychiatric disorder represented by severe anhedonia (a substantial incapacity to enjoy pleasurable activities), sad mood, feelings of guilt, suicidality, and cognitive impairment. One of the primary risk factors for the development of depressive disorders is chronic stress. The pathophysiology of constant stress results from overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, which results in glucocorticoid cortisol level increase. Neuronal plasticity also plays a significant role in the pathophysiology of mood disorder. Patients with poor social support show signs of impaired neuronal plasticity, predisposing them to mood disorders. Mild to moderate impairment of neuronal plasticity causes depression, while severe impairment results in mania.
Other symptoms of mood disturbances are decreased sleep and appetite. There could be increased (agitation) or decreased psychomotor activity. Increased agitation can be life-threatening as it can lead to muscle breakdown, followed by kidney failure (due to increased creatinine). In severe cases, the patient may develop psychotic symptoms of delusions and hallucinations. Neurocognitive changes with deficits in attention and concentration, recent and remote memory, and executive functions have been detected in cases of mood disorders. These signs and symptoms are due to an interplay of factors such as genetic vulnerability, positive family history, and social support systems.
The evaluation for mood disorders mandates a comprehensive and detailed history taking. Patients with bipolar disorder are easily diagnosed when they present with episodes of mania characterized by inflated self-esteem, grandiosity, impulsivity, irritability, increased psychomotor activity, delusions, or hallucinations. When the patients exhibit symptoms of depression such as sad mood, decreased concentration, guilt, decreased interest in pleasurable activities, ideas of self-harm, and suicide, it is crucial to differentiate unipolar from bipolar depression. Clinical features suggestive of bipolar depression are early age of onset, acute onset, recurrent episodes of depression (more than 5 episodes), positive family history of bipolar disorder, antidepressant-induced hypomania, depression with psychotic symptoms before the age of 25, postpartum depression and depressive mixed state. During history taking patients often ignore past hypomanic or manic episodes, so clinicians must explore periods with mood dysregulation associated with decreased need for sleep and increased energy in the past. A careful assessment of the risk of suicide and homicide is essential.
Once the patient is stabilized, a formal mental status examination is mandatory. Patients suffering from depression show poor/limited eye contact during the interview, have a flat or blunted affect with decreased speech and increased reaction time. They appear disheveled with unkempt hair and poor hygiene. Psychomotor activity is markedly decreased. On the other hand, patients with mania have increased psychomotor activity, are agitated, irritable, hyper talkative, have pressured speech, tangentiality, decreased reaction time, and are difficult to interrupt. Patients with mania can sometimes have hallucinations, delusions, and paranoia. Occasionally, major depression can have psychotic features.
A detailed longitudinal and in-depth family history, followed by a thorough mental status examination, is crucial for early diagnosis of mood disorders. Mood disorders secondary to substance abuse require a urine drug test. Specific rating scales are also available for the evaluation of mood disorders. Hamilton Rating Scale for Depression (HAM-D) and the Montgomery-Asberg Depression Rating Scale (MADRS) are for depression, and the Young Mania Rating Scale (YMRS) is for mania.
Timely diagnosis and treatment of mood disorders can decrease the associated morbidity and mortality. The first step towards choosing an optimal treatment is a thorough assessment of the patient's safety and level of functioning. Distinct objectives of psychiatric management include solidifying and preserving a therapeutic alliance, educating the patient about signs and symptoms of mood disorders, reinforcing medication compliance, emphasizing the importance of regular sleep and appetite, foreseeing stressors, recognizing recurrences, and lessening social and functional impairment.
Pharmacotherapy for Bipolar Disorder
Dosage recommendation— In adults, the starting dose is 300 milligrams of the regular release formulation two-three times a day. In elderly persons with renal impairment, the starting dose is 300 milligrams once or twice daily. At a dose of 900 to 1200 milligrams, the plasma concentration of the drug is 0.6 - 1.0 milliequivalents/liter, which is effective in treating bipolar disorder. At a dose of 1200 to 1800 milligrams, the plasma concentration is 0.8 - 1.2 milliequivalent/liter.
Adverse effects—Gastrointestinal upset, fine tremors, polyuria, and polydipsia-reduction in urinary concentrating capacity leading to nephrogenic diabetes insipidus, hypothyroidism, hyperthyroidism, increased risk of hyperparathyroidism and cognitive impairment. Check sodium, calcium, phosphorus, electrocardiogram, creatinine, urinalysis, complete blood count, thyroid function test, renal function test, and a pregnancy test. Lithium has a narrow therapeutic index; therefore, it requires monitoring of blood levels.
Dosage recommendation—For patients having acute mania, oral loading is 20 to 30 milligram/kilogram/day. Therapeutic plasma concentration is attained on a dosage between 1,200 and 1,500 milligram/day given in divided doses. Sodium valproate can also be given as intravenous (IV) infusion to stabilize a patient who comes with agitated behavior rapidly.
Adverse effects— Weight gain, gastric irritation, hair loss, thrombocytopenia, leucopenia, red cell hypoplasia, tremor, menstrual irregularities, polycystic ovaries, hyperandrogenism, hirsutism, obesity, insulin resistance, fatal hepatotoxicity, pancreatitis, hyperammonemia-induced encephalopathy.
Dosage recommendation—The target dose for antimanic activity is 1,200 mg a day.
Adverse effects are dizziness, diplopia, drowsiness, ataxia, nausea and headache, dry mouth, edema, hyponatremia, and sexual dysfunction. Preliminary workup should include a CBC, liver function tests (LFTs), electrolytes, and ECG.
Dosage recommendation— 50 to 200 milligrams per day is used for bipolar depression. It is usually started at 25 mg daily, and the dose is titrated upwards gradually to reduce the risk of Stevens-Johnson syndrome.
Adverse effects— Increased risk of rash (Stevens-Johnson syndrome /toxic epidermal necrolysis), which is associated with the speed of dose titration. The appearance of any kind of rash necessitates sudden discontinuation of Lamotrigine regime.
Other anticonvulsants which can be used as a mood stabilizer are riluzole, topiramate, zonisamide, gabapentin, pregabalin, and levetiracetam. Of these, topiramate is used most commonly and is associated with renal stones.
Pharmacotherapy for Unipolar depression or dysthymia:
SSRIs are the first-line treatment option for depressive disorder, as they are tolerated better with lesser side-effects. They normally take 4 to 5 weeks to display full effects. When on SSRI, it is important to monitor for suicidal thoughts, especially in young adults. The commonly seen adverse effects are nausea, vomiting, diarrhea, dizziness, loss of appetite, reduced sexual desire, anxiety, and insomnia.
These are next in line medication for the treatment of depression after SSRIs. This category of the medication has a dual-action and found to be beneficial in cases with comorbid pain. The common side effects include nausea, dry mouth, hypertension, fatigue, loss of appetite, insomnia, sweating, and anxiety.
Mirtazapine also acts as a second-line medication for depression. Side effects include somnolence, increased appetite, and weight gain. Bupropion lowers the seizure threshold and is contraindicated in cases with epilepsy, and in eating disorders.
This category of medications can be effective, but no longer used as primary agents for depression due to the various side effects and toxicity due to overdose. Common side effects include weight gain, somnolence, orthostatic hypotension, increased heart rate, constipation, giddiness, and urinary retention.
Serotonin modulators act as antagonists and agonists at postsynaptic serotonin receptors and inhibit the reuptake of postsynaptic serotonin. Nefazodone is contraindicated in liver disease. Priapism may be seen with trazodone.
These include tranylcypromine, phenelzine, and selegiline. These are scarcely used due to their particular dietary regulations to avoid the hypertensive crisis and serotonin syndrome. Commonly seen side effects include orthostatic hypotension and decreased sleep.
Phototherapy (bright light therapy) is used in the treatment of seasonal affective disorder (SAD).
Apart from pharmacotherapy, patients suffering from depression and other mood disorders benefit from several types of nonpharmacological therapies.
CBT, interpersonal therapy, and behavioral activation are considered important psychological treatments for depression. Behavioral activation involves encouraging depressed patients to be involved in activities that uplift mood like exercise, new skills, chores, etc.
Brain Stimulation Therapy
Differential diagnosis: According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) following are the differential diagnosis of mood disorders.
In the first year of follow-up, the patients who had a childhood-onset mood disorder, delay in the diagnosis, and longer duration of untreated illness exhibited quite considerable severity of the disorder, the larger number of episodes, additional days depressed, additional ultradian cycling, and limited days of euthymia. About one-third of mood disorders recur, one-third of the patients develop psychotic disorders, and another one third develops a lifetime anxiety disorder. Thoughts of dying (80.8%) and thoughts of suicide (69.5%) were continuous, and specific suicidal plans were more frequent in females during follow-up. There are higher chances of comorbid lifelong anxiety, substance abuse disorder, absenteeism from work, and family discord leading to poor quality of life. It is also associated with increased direct and indirect health care expenditures because of the longer duration of hospital stay.
Findings suggest a possible association between a longer duration of illness and a worse outcome in mood disorder, especially in terms of self-harm/suicide. Mood disorders, especially bipolar disorders might be undiagnosed or misdiagnosed for as long as 10 years. A late diagnosis of bipolar disorder has serious outcomes. It leads to several forms of substance abuse. Anxiety disorder was amongst the most frequent lifetime comorbidity associated with mood disorders. Attention deficit-hyperactivity disorder, oppositional defiant disorder, and conduct disorders were also frequently seen. Mood disorders can cause serious functional impairment, for example, inability to work and problems in sustaining emotional relationships with family and friends.
Mood disorders are common psychiatric disorders associated with high morbidity and mortality. Educating the patients regarding the symptoms and timely treatment is mandatory for recovery from mood disorders. Psychoeducation is important for treatment adherence to medications and psychotherapy and continued engagement in treatment and reduced risk of relapse. At the time of discharge from in-patient facilities, the patients and the caregivers should be taught about the early warning signs of mood disorder relapse. If the patients develop symptoms such as the decreased need for sleep, increased talkativeness, racing thoughts, and feeling more energetic, he/she should be immediately brought to the psychiatry office for treatment optimization. Recovery from mania and depression is very critical, and adherence to medication and therapy is important to recover fully. Regular follow-ups and compliance to treatment should be emphasized in every office visit.
The optimal treatment of patients with mood disorders requires the involvement of various health care professionals comprising of family physicians, nurses, psychiatrists, psychologists, and social workers with the strong cooperation of family and support groups. This formulates an integrated care team. Most of the time, the first contact of the patient is a family physician. Patients feel more comfortable discussing their personal matters with family physicians when confronted with a crisis and are unable to cope with the situation. Therefore, the family physician plays a key role in understanding the severity of the symptoms, formulating a diagnosis, and concluding whether a specialist psychiatry referral is required. Patients with moderate to severe mood symptoms with or without active suicidal ideation need a psychiatric referral.
A mental health case manager (mental health care nurse) appointed by the mental health care team often in community mental health settings is important in cases of severe mood disorders to coordinate patient care. All health care providers involved in the management of the patient need to be notified of the current treatment plan regularly while the patient is admitted to an in-patient psychiatric unit in the event of a crisis. Outpatient treatment records must be sought from psychiatrists and outpatient providers and completed discharge summaries with a detailed plan of care during psychiatric admission. Psychiatric medications should be sent to outpatient providers prior to discharge from in-patient units.
The psychiatrist plays an important role in the decision making and treatment plan of the patient, but an overall effective response is seen when the different professionals involved in the patient care work as a collective team. Positive treatment response requires regular communication between the psychiatrists, family physicians, social workers, nurses, case managers, and pharmacists in both in-patient and outpatient settings.
|||Spijker J,Claes S, [Mood disorders in the DSM-5]. Tijdschrift voor psychiatrie. 2014; [PubMed PMID: 24643826]|
|||Kurumaji A, [The trends of mood disorders in ICD-11: bipolar and depressive disorders]. Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica. 2013; [PubMed PMID: 23691796]|
|||Łojko D,Suwalska A,Rybakowski J, [Bipolar and related disorders and depressive disorders in DSM-5]. Psychiatria polska. 2014 Mar-Apr; [PubMed PMID: 25016763]|
|||Kloiber S,Rosenblat JD,Husain MI,Ortiz A,Berk M,Quevedo J,Vieta E,Maes M,Birmaher B,Soares JC,Carvalho AF, Neurodevelopmental pathways in bipolar disorder. Neuroscience and biobehavioral reviews. 2020 Feb 5; [PubMed PMID: 32035092]|
|||Bhangle SD,Kramer N,Rosenstein ED, Corticosteroid-induced neuropsychiatric disorders: review and contrast with neuropsychiatric lupus. Rheumatology international. 2013 Aug; [PubMed PMID: 23588411]|
|||Palma-Gudiel H,Córdova-Palomera A,Navarro V,Fañanás L, Twin study designs as a tool to identify new candidate genes for depression: A systematic review of DNA methylation studies. Neuroscience and biobehavioral reviews. 2020 Feb 14; [PubMed PMID: 32068032]|
|||Kolaitis G, [Mood disorders in childhood and adolescence: continuities and discontinuities to adulthood]. Psychiatrike = Psychiatriki. 2012 Jun; [PubMed PMID: 22796978]|
|||Juruena MF,Eror F,Cleare AJ,Young AH, The Role of Early Life Stress in HPA Axis and Anxiety. Advances in experimental medicine and biology. 2020; [PubMed PMID: 32002927]|
|||Bhattacharya A,Derecki NC,Lovenberg TW,Drevets WC, Role of neuro-immunological factors in the pathophysiology of mood disorders. Psychopharmacology. 2016 May; [PubMed PMID: 26803500]|
|||Ghasemi M,Claunch J,Niu K, Pathologic role of nitrergic neurotransmission in mood disorders. Progress in neurobiology. 2019 Feb; [PubMed PMID: 29890213]|
|||Rakofsky J,Rapaport M, Mood Disorders. Continuum (Minneapolis, Minn.). 2018 Jun; [PubMed PMID: 29851879]|
|||Kessler RC,Berglund P,Demler O,Jin R,Merikangas KR,Walters EE, Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of general psychiatry. 2005 Jun [PubMed PMID: 15939837]|
|||Merikangas KR,He JP,Burstein M,Swanson SA,Avenevoli S,Cui L,Benjet C,Georgiades K,Swendsen J, Lifetime prevalence of mental disorders in U.S. adolescents: results from the National Comorbidity Survey Replication--Adolescent Supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry. 2010 Oct; [PubMed PMID: 20855043]|
|||Tang MH,Pinsky EG, Mood and affect disorders. Pediatrics in review. 2015 Feb; [PubMed PMID: 25646309]|
|||Merikangas KR,Jin R,He JP,Kessler RC,Lee S,Sampson NA,Viana MC,Andrade LH,Hu C,Karam EG,Ladea M,Medina-Mora ME,Ono Y,Posada-Villa J,Sagar R,Wells JE,Zarkov Z, Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of general psychiatry. 2011 Mar; [PubMed PMID: 21383262]|
|||McGinn MA,Pahng AR, Pathophysiology of affective disorders: functional interaction of stress hormones and hippocampal excitation. Journal of neurophysiology. 2017 Feb 1; [PubMed PMID: 27169510]|
|||Omata N,Mizuno T,Mitsuya H,Wada Y, [Multiaxial evaluation of the pathophysiology of mood disorder and therapeutic mechanisms of clinical drugs by neuronal plasticity and neuronal load]. Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology. 2013 Nov; [PubMed PMID: 25069263]|
|||Jorge RE, Mood disorders. Handbook of clinical neurology. 2015; [PubMed PMID: 25701910]|
|||Galvão F,Sportiche S,Lambert J,Amiez M,Musa C,Nieto I,Dubertret C,Lepine JP, Clinical differences between unipolar and bipolar depression: interest of BDRS (Bipolar Depression Rating Scale). Comprehensive psychiatry. 2013 Aug; [PubMed PMID: 23375261]|
|||Furukawa TA, Assessment of mood: guides for clinicians. Journal of psychosomatic research. 2010 Jun; [PubMed PMID: 20488276]|
|||Phillips AL,Burr RL,Dunner DL, rTMS effects in patients with co-morbid somatic pain and depressive mood disorders. Journal of affective disorders. 2018 Dec 1; [PubMed PMID: 30145511]|
|||Kolar D, Current status of electroconvulsive therapy for mood disorders: a clinical review. Evidence-based mental health. 2017 Feb; [PubMed PMID: 28053184]|
|||Post RM,Leverich GS,Kupka RW,Keck PE Jr,McElroy SL,Altshuler LL,Frye MA,Luckenbaugh DA,Rowe M,Grunze H,Suppes T,Nolen WA, Early-onset bipolar disorder and treatment delay are risk factors for poor outcome in adulthood. The Journal of clinical psychiatry. 2010 Jul; [PubMed PMID: 20667291]|
|||Kiss E,Baji I,Kellner A,Mayer L,Kapornai K, [Long-term follow-up of childhood-onset depression - comorbidity, suicidal behavior and prognosis in adulthood]. Psychiatria Hungarica : A Magyar Pszichiatriai Tarsasag tudomanyos folyoirata. 2020; [PubMed PMID: 31854323]|
|||Cotrena C,Branco LD,Shansis FM,Fonseca RP, Predictors of quality of life in bipolar disorder: A path analytical study. Psychiatry research. 2020 Feb 4; [PubMed PMID: 32066003]|
|||Altamura AC,Dell'Osso B,Berlin HA,Buoli M,Bassetti R,Mundo E, Duration of untreated illness and suicide in bipolar disorder: a naturalistic study. European archives of psychiatry and clinical neuroscience. 2010 Aug; [PubMed PMID: 19911248]|
|||Lublóy Á,Keresztúri JL,Németh A,Mihalicza P, Exploring factors of diagnostic delay for patients with bipolar disorder: a population-based cohort study. BMC psychiatry. 2020 Feb 19; [PubMed PMID: 32075625]|