What does “mood” mean? What are mood disorders?

What Does “Mood” and “Affect” Mean?

Affects and moods refer to different aspects of emotion. 

Affect is communicated through facial expression, vocal inflection, gestures, and posture and is intended to move human beings and other primates to appraise whether an individual is satisfied, distressed, disgusted, or in danger. Thus, joy, sadness, anger, and fear are basic affects that serve a communicative function in primates as well as many in other mammalian species. Affects tend to be short-lived expressions reflecting momentary emotional contingencies. 

Moods convey sustained emotions; their more enduring nature means that they are experienced long enough to be felt inwardly. Moods are also manifested in subtle ways, and their accurate assessment often requires empathic understanding by the interviewer. The words that persons use to describe their inner emotions may coincide with the technical terms used by researchers or clinicians and often vary from
one culture to another. 

The inward emotion and the prevailing affective tone may be discordant. This conflict could be due to deliberate simulation (i.e., the person does not wish to reveal his or her inner emotion), or it could result from a pathological lesion or process that has altered the emotions and their neural substrates.
 

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 themselves are not pathological and many of us have experienced a 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.” Symptoms of mood disorders usually occur in discrete periods we call episodes. Episodes can last 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.

What are common signs and symptoms of Unipolar Depression?

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)

Rule Out Medical Causes

Common Symptoms associated with Depression due to medical problems:
  • Low Mood
  • Irritability
  • Fatigue/tiredness
  • Concentration problems
  • Memory problems
  • Sleep disturbances (insomnia/excessive sleep)
  • Dizziness
  • Weakness
  • Anxiety
  • Unexplained weight changes

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 Causes Depression?

The cause of depression remains unknown. Based on current evidence, the cause of depression is likely multifactorial and variable. Our current understanding is that depression is probably 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)

What does the prognosis of depression look like?

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

Treatment of Depression

Therapy

  • Cognitive Behavioral Therapy
  •  Interpersonal Psychotherapy
  •  Supportive Psychotherapy
  •  Psychodynamic Psychotherapy
Medications
  • 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

Depression Treatment Algorithm

Bipolar Disorder

  • Mania is defined as a distinct period of abnormally and persistently elevated, expansive, or irritable mood with abnormally and persistently increased goal-directed activity or energy that lasts at least 1 week.
  • Hypomania is similar to mania but less severe. A hypomanic episode is a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy that lasts at least four consecutive days. Hypomanic episodes are typically not severe enough to cause marked impairment in social or occupational functioning or to necessitate hospitalization. If there are psychotic features, the episode is, by definition, manic.
  • During a manic or hypomanic episode, a combination of the following symptoms is present and represents a noticeable change in behavior (see below).
 
  • If drugs, medications, or a medical condition cause the above symptoms, then we do not consider this a manic or hypomanic episode. 
  • However, a full manic or hypomanic episode that emerges during antidepressant treatment (e.g., medication, electroconvulsive therapy) but persists beyond the physiological effect of that treatment is sufficient evidence for a manic or hypomanic episode and, therefore, a bipolar diagnosis.

Bipolar Subtypes

The Neurobiology of Bipolar Disorder

  • Bipolar disorder is a complex disorder. A combination of genetic risk factors and environmental risk factors (e.g., childhood trauma) likely result in changes at numerous levels (intracellular, intercellular, network, etc.) that manifest behaviorally as 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. This is further supported by the lack of efficacy of classic antidepressants in bipolar depression. In fact, there is evidence that classic antidepressants may induce mania and/or cause rapid cycling in patients with underlying bipolar disorder.
  • Human studies have found increased concentrations of noradrenaline (norepinephrine) and dopamine (DA) and decreased concentrations of serotonin (5-HT) in manic patients. This suggests that norepinephrine and dopamine dysregulation may play a primary role in manic symptoms. 
  • In addition to monoamine dysregulation, there is evidence implicating the glutamate and GABA systems in the pathophysiology of bipolar disorder.
  • Animal studies suggest increased glutamatergic neurotransmission via NMDA receptors in manic patients. In addition, the efficacy of anticonvulsants, NMDA antagonists (e.g., ketamine), and benzodiazepines in the treatment of bipolar disorder suggests that glutamate and GABA systems are involved.
  • Circadian rhythms are consistently disturbed in patients with bipolar disorder. Researchers are investigating whether circadian rhythm disturbances might lead to mania given the fact that lithium deactivates the transcription factor GSK3B enzyme which is thought to reset the circadian clocks and restore normal brain functioning.
  • Functional Neuroimaging Studies have demonstrated or suggested that the following areas are implicated in bipolar disorder: prefrontal cortex, limbic areas such as the hippocampus, amygdala, anterior cingulate, and the ventral striatum (nucleus accumbens). 
  • A number of brain circuits have been implicated in the pathophysiology of bipolar disorder. Many of these circuits are involved in the regulation of emotion and cognition. 
  • Decreased activation of the orbitofrontal (OFC) circuits during a go-no go test in manic patients may explain the impulsive behaviors. Recall that the OFC is an important region within the prefrontal cortex involved in impulse-control and compulsive behaviors. 
  • The dorsolateral prefrontal cortex is involved in attentional processes and its dysfunction may also play a role in the pathophysiology of bipolar disorder.
  • Decreased size and activity of the prefrontal cortex (PFC) has been demonstrated in patients with bipolar disorder—similar to that found in patients with unipolar depression.
  • Interestingly, after four weeks of lithium treatment (but no valproic acid) there was an increase in gray matter volume in bipolar patients.
  • Amygdalae are larger and more active in the bipolar patients.
  • Bipolar disorder may be the result of abnormal interactions between the PFC and subcortical regions such as the amygdala—an abnormality not usually seen with unipolar depression.
  • Reasons for the reduction in brain volumes and cell loss remain a mystery but could be from environmental stressors, neurodevelopmental abnormalities, and/or dysfunction in neurotransmitter systems.

Treatment Overview

  • The management of bipolar disorder is multidimensional.
  • Because this course has a psychopharmacology focus, we will review the pharmacological management of Bipolar Depression, Bipolar Mania/Hypomania/Mixed states, and Bipolar Maintenance. 

Bipolar Depression

  • Most evidence supporting efficacy: Quetiapine monotherapy; Lamotrigine +/- Lithium; Lurasidone (Latuda); Lithium
  • Some evidence supporting efficacy: Valproic Acid, Aripiprazole
  • Little evidence supporting efficacy: Antidepressants

Bipolar Mania and Mixed States

  • Most evidence supporting efficacy: Risperidone, Olanzapine, Aripiprazole, Quetiapine, Ziprasidone, Asenapine, Cariprazine, Paliperidone, Valproate (serum levels >94 ug/ml show greatest effect), Carbamazepine, Lithium (high risk of relapse on rapid discontinuation)
  • Benzodiazepines: For short term restoration of sleep-wake cycle (insomnia), Augmentation of Atypical Antipsychotic (short term) – Clonazepam, Lorazepam, Diazepam, Alprazolam

Bipolar Maintenance

  • Observational studies suggest that with each episode of illness the time between episodes shortens. This highlights the importance of relapse prevention, which may improve long-term prognosis. 
  • For Mania Prevention: Lithium (Reduces suicide rates and overall mortality), Aripiprazole, Quetiapine, Olanzapine, Valproic Acid. 
  • For Depression Prevention: Quetiapine, Lamotrigine, Lithium (Reduces suicide rates and overall mortality), Lurasidone
  • NOTE: Patients with Bipolar may be more vulnerable to Extrapyramidal Symptoms (EPS)

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 of PDD

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

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
  • Selective Serotonin Reuptake Inhibitors (FDA Approved: Fluoxetine, Paroxetine, Sertraline)
  • Serotonin Norepinephrine Reuptake Inhibitors (e.g., 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

  1. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Washington, DC.
  2. Arciniegas, Yudofsky, Hales (editors). The American Psychiatric Association Publishing Textbook Of Neuropsychiatry And Clinical Neurosciences. Sixth Edition.
  3. Bear, Mark F.,, Barry W. Connors, and Michael A. Paradiso. Neuroscience: Exploring the Brain. Fourth edition. Philadelphia: Wolters Kluwer, 2016.
  4. Charney DS. Monoamine dysfunction and the pathophysiology and treatment of depression. Journal of Clinical Psychiatry. 1998;59(Suppl):11–14.
  5. Cooper, J. R., Bloom, F. E., & Roth, R. H. (2003). The biochemical basis of neuropharmacology (8th ed.). New York, NY, US: Oxford University Press.
  6. Higgins, E. S., & George, M. S. (2019). The neuroscience of clinical psychiatry: the pathophysiology of behavior and mental illness. Philadelphia: Wolters Kluwer.
  7. Hillhouse, T. M., & Porter, J. H. (2015). A brief history of the development of antidepressant drugs: from monoamines to glutamate. Experimental and clinical psychopharmacology23(1), 1–21. doi:10.1037/a0038550
  8. Iversen, L. L., Iversen, S. D., Bloom, F. E., & Roth, R. H. (2009). Introduction to neuropsychopharmacology. Oxford: Oxford University Press.
  9. Mendez, M. F., Clark, D. L., Boutros, N. N. (2018). The Brain and Behavior: An Introduction to Behavioral Neuroanatomy. United States: Cambridge University Press.
  10. Papakostas GI, Thase ME, Fava M, Nelson JC, Shelton RC. Are antidepressant drugs that combine serotonergic and noradrenergic mechanisms of action more effective than the selective serotonin reuptake inhibitors in treating major depressive disorder? A meta-analysis of studies of newer agents. Biological Psychiatry. 2007.
  11. Papakostas GI. Serotonin norepinephrine reuptake inhibitors: Spectrum of efficacy in major depressive disorder. Primary Psychiatry. 2009;16(Suppl 4):16–24.
  12. Schatzberg, A. F., & DeBattista, C. (2015). Manual of clinical psychopharmacology. Washington, DC: American Psychiatric Publishing.
  13. Schatzberg, A. F., & Nemeroff, C. B. (2017). The American Psychiatric Association Publishing textbook of psychopharmacology. Arlington, VA: American Psychiatric Association Publishing.
  14. Neuroscience, Sixth Edition. Dale Purves, George J. Augustine, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, Richard D. Mooney, Michael L. Platt, and Leonard E. White. Oxford University Press. 2018.
  15. Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY, US: Cambridge University Press.
  16. Hales et al. The American Psychiatric Association Publishing Textbook of Psychiatry. 6th Edition.
  17. Benjamin J. Sadock, Virginia A. Sadock. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Tenth Edition. Philadelphia. Wolters Kluwer. 2017.

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TASK 6: THE VOICES

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TASK 5: THE SOUND

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