Mood Disorders

What Does “mood” Mean?

Mood is defined as a person’s internal emotional state that is sustained over time. Mood is subjective and experienced by the person. Terms used to describe mood:

  • Normal
  • Sad
  • Angry
  • Irritable
  • Anxious
  • Happy

What Does “affect” Mean?

Affect is a term used to describe the outward expression of a mood state. In other words, an individual’s affect is visible to others. Healthcare providers obtain important information about an individual’s internal emotional experience (mood) based on their emotional expression (affect). Terms used to describe an individual’s affect:

  • Dysphoric
  • Happy
  • Excited
  • Irritable
  • Angry
  • Tearful
  • Blunted
  • Euthymic
  • Flat

What are mood disorders?

Mood disorders are group of psychiatric disorders in which disturbances of mood or affect are severe and persistent enough to cause significant problems in an individual’s life. Moods by themselves are not pathological and many of us have experienced a wide range of mood states. When moods become severe and persistent enough to cause dysfunction and issues in an individual’s life, then we use the term “mood disorder.” 

Mood disorders can be better defined as syndromes consisting of a cluster of signs and symptoms that often “come and go” in “episodes” which persist for weeks, months, or even years. During these “episodes,” there is a significant change in the individual’s mood which may negatively impact work performance, relationships, or other important areas of functioning. 

The most common mood disorder is major depressive disorder (MDD), often referred to as “Unipolar depression.” Bipolar disorders are also mood disorders that differ from unipolar depression by the presence of elevated mood states called hypomania or mania.

Other mood disorders include Disruptive Mood Dysregulation Disorder, Persistent Depressive Disorder (Dysthymia) and Premenstrual Dysphoric Disorder (Premenstrual Dysphoria). 

Below we review Major Depressive Disorder (MDD) and Bipolar Disorder in detail and provide the DSM-5 criteria for a few other mood disorders commonly diagnosed.

Depression

What are common signs and symptoms of Depression, also called Major Depressive Disorder?

Depression, or clinical depression, or Major Depressive Disorder, are terms used to describe a combination of symptoms that occur for the majority of each day for at least a few consecutive weeks. Depression presents in many different ways and is not one clearly defined disorder. Symptoms of depression include a combination of the following:

  1. Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad, empty, hopeless) or observation made by others (e.g., appears tearful).
  2. Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation).
  3. Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day.
  4. Insomnia or hypersomnia nearly every day.
  5. Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down).
  6. Fatigue or loss of energy nearly every day.
  7. Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick).
  8. Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others).
  9. Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide.

Other signs and symptoms of Depression:

  • Tearfulness
  • Irritability
  • Brooding
  • Obsessive and/or anxious rumination or preoccupation (thinking repeatedly about the past, for example)
  • Excessive worry over physical health
  • Somatic complaints
  • Delusions
  • Hallucinations
  • Seasonal mood changes (more depressed during winter months, for example)

Who can be affected by depression?

  • Depression occurs in both males and females and is not bound by socioeconomic or cultural lines (however, stigma and access to mental health care must be recognized)
  • While the prevalence of depression is higher in females, it is unclear whether this is due to underreporting of males 
  • Prevalence is 3x higher in the 18-29 year old age group compared to over 60 year old age group

Individuals suffering from Depression may also suffer from other disorders such as

  • Addiction Disorders
  • Panic Disorder
  • Obsessive-Compulsive Disorder
  • Eating Disorders
  • Personality Disorders
  • Attention Deficit Hyperactivity Disorder
  • Anxiety Disorders
  • Psychotic Disorders
  • Trauma-related Disorders

What are some risk factors for suicide?

  • Male
  • Single/Living alone
  • Previous suicide attempts
  • Psychotic symptoms
  • Family history of suicide
  • Concurrent substance use
  • Feelings of hopelessness
  • Borderline Personality Disorder

What does the prognosis of depression look like?

  • 50-60% of those who have a depressed episode will have a second episode.
  • 70% of those experiencing two depressed episodes will have a third.
  • 90% of those having three will have a fourth depressed episode.
  • 5-10% of first depressed episode patients will have a subsequent manic episode.

What Causes Depression?

Based on current evidence, depression is likely caused by a combination of genetic and environmental factors

Genetic Factors

  • Depression is 1.5 – 3 times more common among first degree relatives of patients with depression than the general population.
  • Family and twin studies suggest that genetics explains about 40% of the cause of depression

Environmental Factors

  • Low socioeconomic status
  • Multiple medical problems
  • Lack of social support
  • Negative life events
  • Trauma (Adverse Childhood Events)

What do we know about the Neurobiology of Depression?

Although the pathophysiology of depression remains unclear, genetic studies, imaging studies, biochemical studies, and behavioral studies suggest depression is a multifactorial disorder and likely a common final pathway for a number of abnormalities including the following:

Biochemical: Dysregulation of monoamines (serotonin, norepinephrine, dopamine), monoamine receptors, acetylcholine, glutamate, and GABA neurotransmitters. Also, lower than normal levels of brain derived Neurotrophic factor (BDNF), an important protein involved in neuron growth and viability has been observed in depressed patients. 

Neuroendocrine abnormalities: Dysregulation of HPA (Hypothalamic-Pituitary-Adrenal) Axis (e.g., cortisol), Growth Hormone, Thyroid dysfunction

Structural/Functional/Anatomical Abnormalities: Decrease in hippocampal size, Areas of decreased metabolic activity or perfusion in left frontal region (PET), and Increased number of focal signal hyper intensities in white matter (MRI)

Treatment of Depression

Therapy

Cognitive Behavioral Therapy
Interpersonal Psychotherapy
Supportive Psychotherapy
Psychodynamic Psychotherapy

Medication

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Mirtazapine

Trazodone

Bupropion

Vortioxetine

Lithium (augmentation) 

Amphetamines (augmentation)

Methylphenidates (augmentation)

Thyroid hormone (augmentation)

Buspirone (augmentation)

Atypical antipsychotics (augmentation) 

Ketamine

Other Modalities

Electroconvulsive Therapy

Transcranial Magnetic Stimulation (TMS)

Vagal nerve stimulation

Phototherapy/”bright light” Therapy

Deep Brain Stimulation

Bipolar Disorder

What is Mania?

Mania is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy which lasts at least seven consecutive days for most of each day. During this period of elevated or irritable mood, an individual may experience any combination of the following which is a noticeable change from their usual behavior:

  1. Inflated self-esteem or grandiosity.
  2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).
  3. More talkative than usual or pressure to keep talking.
  4. Flight of ideas or subjective experience that thoughts are racing.
  5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
  6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation (i.e., puφoseless non-goal-directed activity).
  7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

It is important to note that a manic episode that emerges while taking an antidepressant or other treatment (e.g., electroconvulsive therapy, TMS) but persists despite treatment discontinuation is still considered a manic episode and, therefore, warrants a diagnosis of bipolar disorder (per DSM). At least one lifetime manic episode is required for the diagnosis of bipolar I disorder.

 

What is Hypomania?

Hypomania is essentially the same as mania but less severe and doesn’t last as long or impair functioning quite as much. More formally, hypomania is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased goal-directed activity or energy which lasts at least four consecutive days for most of each day. During this period of elevated or irritable mood, an individual may experience any combination of the following which is a noticeable change from their usual behavior:

  1. Inflated self-esteem or grandiosity.
  2. Decreased need for sleep (e.g., feels rested after only 3 hours of sleep).
  3. More talkative than usual or pressure to keep talking.
  4. Flight of ideas or subjective experience that thoughts are racing.
  5. Distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli), as reported or observed.
  6. Increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation.
  7. Excessive involvement in activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).

It is important to note that a hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists despite treatment discontinuation is still considered a hypomanic episode (per DSM). Hypomanic episodes are common in bipolar I disorder but are not required for the diagnosis of bipolar I disorder.

What is the difference between Bipolar I and Bipolar II Disorder?

Bipolar 1 Disorder means a patient has experienced at least one manic episode with or without depressed episodes. In other words, if an individual experiences a manic episode then that is sufficient, per DSM, to make a diagnosis of Bipolar I disorder (i.e., depression is not required but most individuals with bipolar disorder spend more time depressed than manic). 

Bipolar II Disorder means a patient has experienced both a hypomanic episode AND a depressed episode (both are required).

What is Rapid Cycling?

Rapid cycling Bipolar Disorder means an individual experiences four (4) or more mood episodes (either manic or depressive) in a 12 month period. 

What do we know about the Neurobiology of Bipolar Disorder?

The underlying biochemical abnormalities that cause or contribute to bipolar disorder remain unclear. However, studies have suggested neurobiological differences between unipolar and bipolar depression which is further supported by the relative lack of efficacy of classic antidepressant monotherapy in the treatment and prevention of bipolar depression. Human studies have found increased concentrations of noradrenaline (norepinephrine) and dopamine (DA) and decreased concentrations of serotonin (5-HT) in manic patients which suggests that norepinephrine and dopamine dysregulation may play a primary role in manic symptoms.

In patients with unipolar depression, both serotonin (5-HT) and norepinephrine concentrations are low. Perhaps the imbalance partially explains bipolarity? Lastly, glutamate and GABA dysregulation have been implicated in the pathophysiology of bipolar disorder. Animals studies suggest increased glutamatergic neurotransmission via NMDA receptors in manic patients. In addition, the efficacy of anticonvulsants and benzodiazepines in the treatment of bipolar disorder suggests the likelihood that glutamate and GABA systems are involved in uncertain ways. 

It is likely that the combination of vulnerable genetics and environmental stressors lead to intracellular changes in transcription, signal transduction, and synaptic functioning that ultimately give rise (via poorly understood mechanisms) to symptoms of bipolar disorder.

Functional Connectivity Studies have demonstrated or suggested decreased connectivity between the amygdala and anterior cingulate cortex and increased connectivity between the amygdala and the supplemental motor area.

Functional Neuroimaging Studies have demonstrated or suggested decreased size and activity in the prefrontal cortex (PFC) of patients with bipolar disorder—similar to that found in patients with unipolar depression, larger and more active amygdala in bipolar patients, and abnormal interactions between the PFC and subcortical regions such as the amygdala (an abnormality not usually seen with unipolar depression).

How is Bipolar Disorder Treated?

Bipolar Disorder is best managed with a combination of therapy, family support, and medication. See the table below for medications used to treat the various stages of bipolar disorder.

 

Pharmacotherapy For Bipolar ManiaMonotherapyCombination Therapy Options
First-LineLithiumLithium + Atypical Antipsychotic
Lithium + Benzodiazepine
Valproic AcidValproic Acid + Atypical Antipsychotic
Atypical Antipsychotic: Olanzapine, Quetiapine, Risperidone, Aripiprazole, Ziprasidone, Asenapine, Paliperidone
Second-LineCarbamazepine Lithium + Valproic Acid

 

Pharmacotherapy For Bipolar MaintenanceMonotherapyCombination Therapy
First-LineLithiumLamotrigine + Quetiapine
Valproic AcidValproic Acid + Quetiapine
Atypical Antipsychotic: Quetiapine, OlanzapineValproic Acid + Bupropion
Olanzapine + Fluoxetine
Second-LineCarbamazepine Lithium + Valproic Acid
Lithium + Olanzapine
Lithium + Carbamazepine
Valproic Acid + Olanzapine

 

Pharmacotherapy For Bipolar DepressionMonotherapyCombination Therapy
First-LineLithiumLithium + Bupropion
Lithium + Valproic Acid
Lamotrigine Lamotrigine + Lithium
Lamotrigine + Quetiapine
Atypical Antipsychotic: Quetiapine, LurasidoneValproic Acid + Bupropion
Olanzapine + Fluoxetine
Second-LineValproic AcidLithium + Valproic Acid
Carbamazepine

Persistent Depressive Disorder (Dysthymia) 

DSM-5 Criteria:

A. Depressed mood for most of the day, for more days than not, as indicated by either subjective account or observation by others, for at least 2 years. Note: In children and adolescents, mood can be irritable and duration must be at least 1 year.

B. Presence, while depressed, of two (or more) of the following:

  1. Poor appetite or overeating.
  2. Insomnia or hypersomnia.
  3. Low energy or fatigue.
  4. Low self-esteem.
  5. Poor concentration or difficulty making decisions.
  6. Feelings of hopelessness.

C. During the 2-year period (1 year for children or adolescents) of the disturbance, the individual has never been without the symptoms in Criteria A and B for more than 2 months at a time.

D. Criteria for a major depressive disorder may be continuously present for 2 years.

E. There has never been a manic episode or a hypomanie episode, and criteria have never been met for cyclothymic disorder.

F. The disturbance is not better explained by a persistent schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder.

G. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g. hypothyroidism).

H. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.

Treatment

Treatment of PDD is similar to depression. However, patients with PDD are more resistant to medication and usually don’t respond as robustly. 

Therapy

Cognitive Behavioral Therapy
Interpersonal Psychotherapy
Supportive Psychotherapy
Psychodynamic Psychotherapy

Medication

Selective Serotonin Reuptake Inhibitors (SSRIs)

Serotonin Norepinephrine Reuptake Inhibitors (SNRIs)

Mirtazapine

Trazodone

Bupropion

Vortioxetine

Lithium (augmentation) 

Amphetamines (augmentation)

Methylphenidates (augmentation)

Thyroid hormone (augmentation)

Buspirone (augmentation)

Atypical antipsychotics (augmentation) 

Ketamine

Other Modalities

Electroconvulsive Therapy

Transcranial Magnetic Stimulation (TMS)

Vagal nerve stimulation

Phototherapy/”bright light” Therapy

Deep Brain Stimulation

Premenstrual Dysphoria Disorder (PMDD)

DSM-5 Criteria:

A. In the majority of menstrual cycles, at least five symptoms must be present in the final week before the onset of menses, start to improve within a few days after the onset of menses, and become minimal or absent in the week post-menses.

B. One (or more) of the following symptoms must be present:

  1. Marked affective lability (e.g., mood swings: feeling suddenly sad or tearful, or increased sensitivity to rejection).
  2. Marked irritability or anger or increased interpersonal conflicts.
  3. Marked depressed mood, feelings of hopelessness, or self-deprecating thoughts.
  4. Marked anxiety, tension, and/or feelings of being keyed up or on edge.

C. One (or more) of the following symptoms must additionally be present, to reach a total of five symptoms when combined with symptoms from Criterion B above.

  1. Decreased interest in usual activities (e.g., work, school, friends, hobbies).
  2. Subjective difficulty in concentration.
  3. Lethargy, easy fatigability, or marked lack of energy.
  4. Marked change in appetite; overeating; or specific food cravings.
  5. Hypersomnia or insomnia.
  6. A sense of being ovenwhelmed or out of control.
  7. Physical symptoms such as breast tenderness or swelling, joint or muscle pain, a sensation of “bloating,” or weight gain.

Note: The symptoms in Criteria A-C must have been met for most menstrual cycles that occurred in the preceding year.

D. The symptoms are associated with clinically significant distress or interference with work, school, usual social activities, or relationships with others (e.g., avoidance of social activities; decreased productivity and efficiency at work, school, or home).

E. The disturbance is not merely an exacerbation of the symptoms of another disorder, such as major depressive disorder, panic disorder, persistent depressive disorder (dysthymia), or a personality disorder (although it may co-occur with any of these disorders).

F. Criterion A should be confirmed by prospective daily ratings during at least two symptomatic cycles. (Note: The diagnosis may be made provisionally prior to this confirmation).

G. The symptoms are not attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication, other treatment) or another medical condition (e.g., hyperthyroidism).

What are the treatment options for PMDD?

Medications

FDA Approved: Fluoxetine, Paroxetine, Sertraline

Venlafaxine, Duloxetine

  • Birth control pills. The FDA has approved a birth control pill containing drospirenone (droh-SPIR-uh-nohn) and ethinyl estradiol (ETH-uh-nil es-truh-DEYE-ohl)
  • Over-the-counter pain relievers may help relieve physical symptoms, such as cramps, joint pain, headaches, backaches, and breast tenderness:

Ibuprofen, Aspirin, Naproxen

Other Treatment Modalities

  • Stress management, such as relaxation techniques
  • Lifestyle changes such as eating a healthy combination of foods across the food groups, cutting back on salty and sugary foods, and getting more physical activity

References

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