Peripartum mood disturbances overview

# Overview
Childbirth is a life changing event in a woman's life. Her body undergoes many physiological and psychological changes during pregnancy and childbirth; a causal relationship between hormone changes and mood shifts has been proposed. During the postpartum period, women face many depressive symptoms which varies in severity from mild postpartum blues to serious mood disorders like postpartum depression and postpartum psychosis.  Identification and treatment of these mood disorders is critical to both child and mother's health. These illnesses are classified according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) into 3 types: postpartum blues, postpartum depression, and postpartum psychosis. The most widespread is postpartum blues, second most common is postpartum depression and relatively uncommon is postpartum psychosis. The pathophysiology involves a complex interaction of genes, hormones and immune system. The chemical, psychological and social changes, which occur after the childbirth interact with one another causing the mood disturbances. Various screening tools are used which differs in their sensitivity and specificity. The new mother is screened at the first prenatal visit, second and third trimester, six weeks, 6 months and 12 months postpartum.  Postpartum blues are mostly self limiting and resolve on their own,while pharmacotherapy and non-pharmacotherapy are used for the management of postpartum depression. Postpartum psychosis is a psychiatric emergency and needs uregnt hospitalisation. In severe, suicidal and non responsive patients ECT is used. For prevention of these disorders biological, psychological and psychosocial interventions are used.

# Historical Perspective
In 460 B.C., Hippocrates was the first to mention about postpartum fever, mania, delirium and agitation. His writings reflected how postpartum depression is described today.
In 11th century, a professor of medicine, Trotula of Salerno, first recognized postpartum depression.
In 1547, a Portuguese physician, Joao Rodrigues de Castello Branco(Amatus Lusitanus), briefly described postpartum depression.
Between 16th and 18th centuries about 50 brief reports about Psychosis were published stating that these psychoses were recurrent and could be seen in both non-lactating and lactating females.
In 1797, Osiander, an obstetrician, wrote about 2 cases in detail, that are among the treasures for postpartum psychosis.
In 1819, Esquiro evaluated inpatients in the Salpetriere, which paved the way for long term research.

# Classification
Puerperal psychiatric illnesses may be classified according to Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) into 3 types:
- postpartum blues,
- postpartum depression, and
- postpartum psychosis.
During the postpartum period there is also increased susceptibility to anxiety disorders such as obsessive-compulsive disorder and panic disorder. 

# Pathophysiology
Many pathological mechanisms are involved in postpartum depression which interact with one another.
- Genetics of postpartum depressionEstrogen receptor alpha gene, polymorphisms in the serotonin transporter gene, 5-HTT, and the gene encoding for MAOA and the gene encoding for Catechol-O-methyltransferase (COMT), Genetic variants for the TPH2 gene, a SNP in OXT was predictive of both variation in breastfeeding duration and postpartum depression scores, an interaction between a SNP in the OXTR gene and methylation state was detected in association with postpartum depression. In a genome-wide linkage and association study, the Hemicentin 1 gene (HMNC1) had the strongest association with postpartum depression.
- Epigenetic mechanisms of postpartum depressionIn women with postpartum depression, there was a substantial interaction between OXTR DNA methylation, estradiol, and the ratio of allopregnanolone to progesterone. Alterations in DNA methylation of the OXTR gene are adversely linked with blood estradiol levels in women with postpartum depression. As a result, epigenetic alterations can affect metabolic processes linked to postpartum depression.
- Neuroendocrine mechanisms of postpartum depressionIn postpartum depression, there is an interaction between the Hypothalamus-pituitary-gonadal (HPG) and Hypothalamus-Pituitary-Adrenal(HPA) axis. HPA axis function has been found to be influenced by reproductive hormones and vice versa. As a result, any change in reproductive hormones may cause stress hormone levels to fluctuate, resulting in postpartum depression.  Alterations of the HPA axis' function may also affect reproductive hormone levels, contributing to postpartum depression.
- Neurotransmitters and postpartum depressionGABA-GABA which is an inhibitory neurotransmitter in the brain, its level is inversely related with the depression symptoms in  the postpartum period.
Glutamate-Glutamate is the excitatory neurotransmitter in the brain. In women with postpartum depression its level are increased in the medial prefrontal cortex and decreased in the dorsolateral prefrontal cortex.
Serotonin-The binding of Serotonin to 5HT1A receptors is decreased in the mesiotemporal and  anterior cingulate cortices.
Dopamine-Mutations in DR1 is related to the behaviour of mother paying less attention to the baby.
- Neuroinflammatory mechanisms in postpartum depressionThere is a negative relationship between T-cell number and postpartum depression symptoms, whereas IL-6 and IL-1 have a significant positive relationship with it.
It is thought that in postpartum psychosis, immunoneuroendocrine set point is dysregulated with overactivation of the immune system's macrophage and monocyte arm. 

# Causes
Postpartum depression: drop in estrogen, progesterone and thyroid hormones after the birth of the child, anxiety, lack of sleep , distorted self image : 
postpartum psychosis: sleep disruptions, genetics, immune system dysregulation, family history of mental health conditions, presence of other underlying mental health conditions, extreme hormone fluctuations, thyroid gland dysfunction 
Postpartum blues: are caused mainly by a drop in estrogen and progesterone post delivery, decrease in thyroid hormone, sleep deprivation, not eating properly, emotional issues, anxiety about the care of the newborn and not finding time for oneself.

# Differentiating Postpartum depression from Other Diseases
- Postpartum anxiety : The onset is anywhere between child birth to one year. Presents with feelings of dread, worry, lack of concentration, sleeping and eating problems, nausea, palpitations, dizziness. The  condition does not subside on its own. The patient has to seek medical advice.
- Postpartum blues: They usually occur within a few days after child birth and improve within a week or two. The new mother has low mood, frequent crying, change in appetite and sleep, feeling of inadequacy. This does not impact day to day functioning or the capacity to look after the baby.
- Hyperthyroidism or Hypothyroidism: These pathologies can cause mood diorders along with other physiologic symptoms. These can be differentiated by evaluating free T4 and TSH levels.
- Postpartum Psychosis: This presents within days or weeks post delivery. This is acute in onset and an emergency situation with the risks of suicide and harm to the baby. The mother experiences agitation, delusions, hallucinations, sleep deprivation for several nights and change in behaviour.

# Epidemiology and Demographics
Up to 85% of women have some form of mood disorder during the postpartum period. 
The most widespread is postpartum blues with prevalence ranging from 30%-75%. It exists in a number of nations and cultures, although there is a difference in the prevalence rates.
According to the reports, it ranges from 15% in Japan to 60% in Iran. The disparity in prevalence is because of underreporting of the condition because of cultural beliefs.
The second most common is postpartum depression which affects 10%-15% of new mothers. The average age at presentation is 27 with majority being married and being Akans. On grading them on severity scale, 39% has minimal depression, 22% are affected by moderate depression and mild depression, 6% have moderately severe depression, and 11% are affected by severe depression. There is significant reduction in the symptoms with psychosocial support.
Postpartum psychosis is relatively uncommon which affects 0.1%-0.2% women.  

# Risk Factors
Postpartum blues: History of mood changes during menstrual cycles or pregnancy, multiple pregnancies during lifetime, personal history of major depression or dysthymia or family history of postpartum depression. 
Postpartum depression: Prior history of anxiety and depression, family history of depression, severe premenstrual syndrome,  low social support, difficulty to conceive, stressful life events, teenage pregnancy, pregnancy and labor complications, preterm labor (before 37 weeks) and delivery, multiple babies like twins or triplets, hospitalisation of baby after birth.
Postpartum psychosis: Family history of postpartum psychosis or bipolar disorder, history of bipolar disorder, postpartum psychosis in a previous pregnancy or schizoaffective disorder or schizophrenia, first pregnancy, discontinuation of psychiatric medication for pregnancy and sometimes even without a risk factor. 

# Screening
There are no specific guidelines for screening of postpartum blues.
A variety of depression screening tools are available, their specificity ranges from 77% to 100%, but sensitivity varies and is the deciding factor in choosing the depression screening tool. The most sensitive tools are Edinburgh Postnatal Depression Scale, Postpartum Depression Screening Scale, and Patient Health Questionnaire-9. Other screening tools are given in the table below

# Natural History, Complications, and Prognosis
Postpartum blues are characterized by mild, temporary, and self-limiting mood disturbances.
Postpartum blues puts a woman at risk of postpartum depression, postpartum psychosis and postpartum anxiety disorders.
If left untreated, females with postpartum depression may progress to develop chronic depressive disorder, and are predisposed to major depression in future. This can also result in depression in father. Children of untreated females may have emotional, behavioural issues and language problems. Greater chances of having ADHD, excessive crying, eating and sleeping problems.  This condition can impact bonding between mother and child.
Postpartum psychosis is a psychiatric emergency and patient needs immediate treatment. Majority of individuals with postpartum psychosis react well to therapy and have rapid recovery and remission. Suffering from postpartum psychosis increases its likelihood in future pregnancy.
Common complications of postpartum psychosis, if left untreated include filicide, suicide, and many psychosocial implications. 

# Diagnosis

## Diagnostic Study of Choice
The diagnosis of Postpartum depression is made when at least 5 of the following mentioned diagnostic criteria are met:
- Changes in sleep pattern,
- Feelings of hopelessness or sadness,
- Feelings of restlessness,
- Loss of interest in activities,
- Feelings of guilt,
- Loss of energy,
- Loss of concentration,
- Change in appetite or weight,
- Thoughts of death or suicide.
Patients with postpartum psychosis are diagnosed under the DSM-5, based on their primary mental illness with the addition of the "peripartum onset" if it 
presents during pregnancy or within four weeks after delivery.
The diagnosis of postpartum blues is made if three or four of depressive symptoms are present.
The postpartum blues is defined by International Classification of Diseases  10th Revision (ICD-10) as postpartum depression not otherwise specified.

## History and Symptoms
Postpartum blues symptoms are present for few days to 1-2 weeks after delivery. 
They are sadness, excessive crying, reduced concentration, appetite problem, anxiety, mood swings, sleeping difficulty, feeling overwhelmed.
Signs and symptoms of postpartum depression includes:
- Difficulty bonding with the baby
- Fear that she is not a good mother
- Thoughts of harming herself or her baby
- Crying excessively
- Depressed mood or severe mood swings
- Panic attacks and severe anxiety
- Intense anger and irritability
- Insomnia or excessive sleeping
- Loss of energy or overwhelming fatigue
- Loss of interest and pleasure in activities she used to enjoy
- Withdrawing from friends and family
- Feelings of guilt or inadequacy
- shame or worthlessness
- Hopelessness
- Reduced concentration ability to think clearly or take decisions
- Loss of appetite or excessive eating
- Restlessness
- Repeated thoughts of death or suicide
Most common symptoms of postpartum psychosis include:
- Confusion and disorientation
- Hallucinations and delusions
- Paranoia
- Sleep disturbances
- Obsessive thoughts about the baby
- Attempts to harm herself or the baby
- Excessive energy and agitation

## Physical Examination
There are no specific findings related to peripartum mood disturbances, most of the patients appear normal. A decline in grooming and hygiene and a change in weight is seen in patients with severe symptoms.

## Laboratory Findings
There are no diagnostic laboratory findings associated with peripartum mood disorders. The tests are done in order to rule out any organic causes. These include thyroid function and antithyroid antibody test, CBC, electrolyte panel, viatmin B12, folate and calcium levels.

## Electrocardiogram
There are no ECG findings associated with peripartum mood disturbances.

## X-ray
There are no x-ray findings associated with peripartum mood disturbances.

## Echocardiography and Ultrasound
There are no echocardiography/ultrasound findings associated with peripartum mood disturbances.

## CT scan
There are no CT scan findings associated with peripartum mood disturbances.

## MRI
There are no MRI findings associated with peripartum mood disturbances.

## Other Imaging Findings
There are no other imaging findings associated with peripartum mood disturbances.

## Other Diagnostic Studies
There are no other diagnostic studies associated with peripartum mood disturbances.

# Treatment

## Medical Therapy
To manage postpartum depression efficiently, a multidisciplinary and comprehensive approach is used.
All PPD
- Investigate and manage social stressors, psychiatric and medical comorbidities
- Psychosocial support strategies.
- Self-care
- Sleep protection
- Exercise
PPD: moderate severity or not in remission from self-care and psychosocial strategies
- Psychological treatments, including CBT and IPT
- Add SSRI if insuffiecient response (for lactation safety)
PPD: Severe
- SSRI alone or with psychological intervention (for lactation safety)
- Consider antidepressant switch and augmentation startegies if no response to SSRI alone.
- Consider ECT with severe suicidality, psychosis or treatment resistance.
Additional therapeutic options: bright light therapy, yoga, relaxation training, massage and acupunture.Alternative treatment options are omega-3 PUFAs, such as eicosapentaenoic acid (EPA) and  docosahexaenoic acid (DHA), which have fewer side effects.
Postpartum psychosis is a medical emergency and requires prompt inpatient treatment. Once the organic causes of psychosis are ruled out the treatment is given according to the symptom profile. Antipsychotics, mood stabilizers and benzodiazepines are used in acute therapy. Insomnia should be treated promptly. ECT is used when the condition is treatment resistant or a quicker response is required because of symptoms severity or safety concerns. Antimaniac and antipsychotic agents benefit a patient who has a known history of the illness or a family member has a history.
Before being discharged from the hospital, a strategy must be in place that includes close monitoring, appropriate sleep, and stress reduction.
The majority of cases of Postpartum blues are self-limited and temporary. The mainstay of therapy is supportive care. As a result, it resolves on its own, requiring reassurance, education, validation, and psychological support.

## Interventions
Psycho-educational interventions such as interpersonal therapy, dynamic therapy and cognitive behavioural therapy helps in decreasing the episodes of peripartum mood disturbances in future.

## Surgery
No surgical interventions are used in the treatment of peripartum mood disturbances.

## Primary Prevention
Biological intervention-
- Psychotropic medicines:  Sertraline was shown to be substantially more effective compared to placebo in avoiding depression recurrence.
- Reproductive hormones: High-dose estrogen has been shown to reduce the risk of recurrence.
- Micronutrients: Omega-3 fatty acids, fish oil rich in docosahexaenoic acid, DHA and AA(Arachidonic acid)
- Other biological agents: thyroxine, dietary calcium, and selenium.
Psychological and psychosocial methods
- Psychological intervention: Interpersonal therapy, Cognitive-Behavioral therapy, Postnatal Psychological Debriefing
- Psychosocial interventions: Antenatal and Postnatal Classes, Postnatal support.

## Secondary Prevention
Woman at-risk for postpartum psychosis should see a psychiatrist even before delivery to discuss treatment options to prevent illness during the delivery and postpartum period. In the first 2-4 weeks postpartum, the woman and her family should contact a physician if they find any of these symptoms, that is, confusion, strange beliefs, mood swings, and hallucinations in the new mother.
At the 6-week obstetrical follow-up appointment, it is highly recommended that physicians should inquire about symptoms of postpartum psychosis. If the patient expresses red flags like difficulty caring for her child, confusion, poor self-care or threats to harm herself or others, a psychiatric referral should be made as soon as possible.