Prodrome

Prodrome also known as early symptoms or premonitory symptoms, is a medical term that refers to early signs and symptoms of a disease that precede the characteristic manifestations of the acute, fully developed disease. Identification of a prodrome is important because it might allow doctors to diagnose disease earlier. With the emergence of disease-modifying therapies, identification of patients in the preclinical phase of the disease might improve disease outcomes. For example, migraine prodrome is a constellation of symptoms that include food cravings, unexplained mood changes, lethargy, uncontrollable yawning, fluid retention, and increased urination occurring 24 hour before a migraine headache.  Viral prodrome may include fever, malaise, headache and anorexia (lack of desire to eat).

Prodromal psychosis

Psychosis is a mental health condition that causes people to perceive or interpret things differently from those around them. Psychosis is characterized by loss of contact with reality and may involve severe disturbances in perception, cognition, behavior, and feeling. Psychosis might involve hallucinations or delusions.

In psychiatry, prodrome is referred to as “the initial prodrome” and “relapse prodrome” ¹. The widely accepted definition of prodrome was given by Keith and Matthews in 1991 as a “heterogeneous group of behaviors temporally related to the onset of psychosis. Loebel et al. ² defined it as the time interval from the onset of unusual behavioral symptoms to onset of psychotic symptoms ² and Beiser et al. ³ defined it as the period from first noticeable symptoms to first prominent psychotic symptoms. The concept of prodrome does not refer to a hardbound set of signs and symptoms. It is an evolution over time ¹. Docherty et al. in 1978 ⁴ described it as a “moment to moment march of psychological changes.”

The evolution of prodrome has been categorized into two main patterns.

• Pattern 1 was described as certain nonspecific changes, followed by specific prepsychotic symptoms, and then eventually leading to psychosis.
• Pattern 2 explains the evolution to begin with early specific changes followed by neurotic symptoms as a reaction to these and then psychosis.

Chapman in 1978 described 5 patterns of disturbances which are disturbances in attention, perception, speech production, motor functions, and thought block. From the above-mentioned symptoms, disturbance in motility occurs secondary to disturbance of attention and perception ⁵. Huber et al. ⁶ coined the term “basic symptoms” which can be subjective complaints of emotional, cognitive, or autonomic impairment. Another consideration was “symptomatic psychosis at-risk state” which finally paved way to the ultrahigh risk criteria which was set at a high threshold in an attempt to reduce misdiagnosis among psychiatrists ⁷. This is in contrast to at-risk mental state (ARMS) which defines a syndrome that may or may not develop into psychosis. A person at at-risk mental state (ARMS) may manifest symptoms such as depressed mood, anxiety, and psychosis but may not necessarily meet ultrahigh risk criteria. The finding of duration of untreated psychosis and early intervention at this particular point has provided a new insight into the etiopathological progress of the illness ⁸. Studies have indicated better socio-occupational functioning in patients who have received intervention ⁸. Although the boundary between the at-risk mental state (ARMS) and actual psychosis might be narrow and vaguely demarcated ⁹, “close-in” follow-up strategy, which involves shortening the periods of follow-up helps us to observe the transition to psychosis.

The 2 main symptoms of psychosis are:

• hallucinations – where a person hears, sees and, in some cases, feels, smells or tastes things that do not exist outside their mind but can feel very real to the person affected by them; a common hallucination is hearing voices
• delusions – where a person has strong beliefs that are not shared by others; a common delusion is someone believing there’s a conspiracy to harm them

The combination of hallucinations and delusional thinking can cause severe distress and a change in behavior.

Experiencing the symptoms of psychosis is often referred to as having a psychotic episode.

Approximately 3% of people will experience a psychotic episode at some stage in their life. Usually a person’s first episode occurs in adolescence or early adult life, an important time for the development of identity, relationships and long-term vocational plans.

The terms “psychosis” and “psychopath” should not be confused.

Someone with psychosis has a short-term (acute) condition that, if treated, can often lead to a full recovery.

A psychopath is someone with an antisocial personality disorder, which means they:

• lack empathy – the capacity to understand how someone else feels
• are manipulative
• often have a total disregard for the consequences of their actions

People with an antisocial personality can sometimes pose a threat to others because they can be violent. Most people with psychosis are more likely to harm themselves than others.

The prodromal phase is the period during which the individual is experiencing changes in feelings, thought, perceptions and behavior although they have not yet started experiencing clear psychotic symptoms such as hallucinations, delusions or thought disorder. Depending on the type of psychotic condition, the prodrome may or may not be apparent.

Changes in prodromal phase vary from person to person and some people may not experience a prodromal phase. The duration of prodromal phase is also quite variable, although it is usually over several months. In general, the prodrome is fluctuating and fluid, with symptoms gradually appearing and shifting over time. Some prodromal signs and symptoms include:

• Changes in Affect: Feelings of vague suspiciousness, depression, anxiety, tension, irritability, anger or mood swings.
• Changes in Cognition (Thinking): Difficulty in concentration and memory, thoughts feel slowed down or speeded up, odd ideas, vague speech.
• Changes in Sense of Self, Others or the World: Feeling somehow different from others or that things in the environment may seem changed.
• Physical and Perceptual Changes: Sleep disturbances, appetite changes, bodily complaints, loss of energy or motivation and perceptual aberrations.

Family and friends may notice when a person’s behavior changes, their studies or work deteriorate, they become more withdrawn or isolated, they are no longer interested in socializing or they become less active.

Clearly, these changes are non-specific and can result from a number of psychosocial difficulties, physical disorders and psychiatric disorders.

The initial episode of psychotic disorders can be particularly confusing and traumatic for the person and their family. A lack of understanding of psychosis often leads to delays in seeking help. As a result, these treatable illnesses are left unrecognized and untreated. Even when appropriate help seeking does occur, further delays in diagnosis and treatment may result from skill and knowledge gaps among professionals.

Early intervention involves diagnosis of psychotic disorders at the earliest possible time and ensuring that appropriate specialist treatment is initiated. This should be at the first sign of positive psychotic symptoms, but it may also be possible to intervene during the period prior to development of psychotic symptoms (the prepsychotic or prodromal phase).

It’s important psychosis is treated as soon as possible, as early treatment can be more effective. Early intervention in first-episode psychosis is aimed at shortening the course and decreasing the severity of the initial psychotic episode, thereby minimizing the many complications that can arise from untreated psychosis. It is a strategy that can provide considerable long-term benefits.

Psychosis diagnosis

You should visit a doctor if you’re experiencing symptoms of psychosis. It’s important to speak to a doctor as soon as possible because earlier treatment can be more effective.

Your doctor may ask you some questions to help determine what’s causing your psychosis.

Your doctor should also refer you to a mental health specialist for further assessment and treatment.

Initial assessment

There’s no test to positively diagnose psychosis. However, your doctor will ask about your symptoms and possible causes.

For example, they may ask you:

• whether you’re taking any medicines
• whether you’ve been taking illegal substances
• how your moods have been – for example, whether you’ve been depressed
• how you’ve been functioning day-to-day – for example, whether you’re still working
• whether you have a family history of mental health conditions, such as schizophrenia
• about the details of your hallucinations, such as whether you’ve heard voices
• about the details of your delusions, such as whether you feel people are controlling you
• about any other symptoms you have

Referral to a mental health specialist for further assessment and treatment

The evidence supporting the early treatment of psychosis means you’re likely to be referred to a specialist urgently.

Who you’re referred to will depend on the services available in your area. You may be referred to:

• a community mental health team – a team of mental health professionals who provide support to people with complex mental health conditions
• a crisis resolution team – a team of mental health professionals who treat people who would otherwise require treatment in hospital
• an early intervention team – a team of mental health professionals who work with people who have experienced their first episode of psychosis

These teams are likely to include some or all of the following healthcare professionals:

• a psychiatrist – a qualified medical doctor who has received further training in treating mental health conditions
• a community mental health nurse – a nurse with specialist training in mental health conditions
• a psychologist – a healthcare professional who specializes in the assessment and treatment of mental health conditions

Your psychiatrist will carry out a full assessment to help identify and diagnose any underlying mental health condition that could be causing your symptoms. This will help when planning your treatment for psychosis.

Getting help for others

The lack of insight and level of distress associated with psychosis means people experiencing it are not always able to recognize their symptoms.

They may be reluctant to visit a doctor if they believe there’s nothing wrong with them. You may need to help them get support and treatment.

Someone who has had psychotic episodes in the past may have been assigned a mental health worker, who works in mental health or social services, so try to contact them.

If someone has very severe psychosis, they can be compulsorily detained at hospital for assessment and treatment under the Mental Health Act.

If you’re concerned about someone you know, you could contact a doctor for them.

If they’re receiving support from a mental health service, you could contact their mental health worker.

If you think the person’s symptoms are severe enough to require urgent treatment and could be placing them at possible risk, you can:

• take them to the nearest emergency department, if they agree
• call their doctor or local out-of-hours doctor
• call your local emergency services number and ask for an ambulance

A number of mental health helplines are also available that can offer expert advice.

Causes of psychosis

There are multiple causes of psychosis, which include substance abuse or withdrawal, exposure to severe stress, inherited and acquired medical conditions or diseases, and mood disorders. However, the most common cause of psychosis is schizophrenia.

It’s sometimes possible to identify the cause of psychosis as a specific mental health condition, such as:

• schizophrenia – a condition that causes a range of psychological symptoms, including hallucinations and delusions
• bipolar disorder – a mental health condition that affects mood; a person with bipolar disorder can have episodes of low mood (depression) and highs or elated mood (mania)
• severe depression – some people with depression or feelings of persistent sadness also have symptoms of psychosis when they’re very depressed, including postnatal depression, which some women experience after having a baby

Psychosis can also be triggered by:

• a traumatic experience
• stress or anxiety
• drug misuse
• alcohol misuse
  • A person can also experience a psychotic episode if they suddenly stop drinking alcohol or taking drugs after using them for a long time. This is known as withdrawal.
• lack of sleep
• side effects of prescribed medicine. In rare situations, psychosis can also occur as a side effect of some types of medicine or as a result of an overdose of that medicine.
• General medical conditions. The following medical conditions have been known to trigger psychotic episodes in some people:
  • HIV and AIDS
  • malaria
  • syphilis
  • Alzheimer’s disease
  • Parkinson’s disease
  • hypoglycemia (an abnormally low level of glucose in the blood)
  • lupus
  • multiple sclerosis
  • brain tumor
• Drugs known to trigger psychotic episodes include:
  • cocaine
  • amphetamine (speed)
  • methamphetamine (crystal meth)
  • mephedrone (MCAT or miaow)
  • MDMA (ecstasy)
  • cannabis
  • LSD (acid)
  • psilocybins (magic mushrooms)
  • ketamine

It’s also possible to experience psychosis after drinking large amounts of alcohol or if you’re high on drugs.

The underlying psychological cause often influences the type of psychotic episode someone experiences. For example, a person with bipolar disorder is more likely to have grandiose delusions. Someone with depression or schizophrenia is more likely to develop persecutory delusions.

How often a psychotic episode occurs and how long it lasts can depend on the underlying cause.

Psychosis symptoms

Someone who develops psychosis will have their own unique set of symptoms and experiences, according to their particular circumstances.

But in general, 3 main symptoms are associated with a psychotic episode:

1. hallucinations
2. delusions
3. confused and disturbed thoughts

Hallucinations

Hallucinations are where someone sees, hears, smells, tastes or feels things that do not exist outside their mind.

• sight – seeing colors, shapes or people
• sounds – hearing voices or other sounds
• touch – feeling touched when there is nobody there
• smell – an odor that other people cannot smell
• taste – a taste when there is nothing in the mouth

Delusions

A delusion is where a person has an unshakeable belief in something untrue.

A person with persecutory delusions may believe an individual or organization is making plans to hurt or kill them.

A person with grandiose delusions may believe they have power or authority. For example, they may think they’re the president of a country or they have the power to bring people back from the dead.

People who have psychotic episodes are often unaware that their delusions or hallucinations are not real, which may lead them to feel frightened or distressed.

Confused and disturbed thoughts

People with psychosis sometimes have disturbed, confused, and disrupted patterns of thought. Signs of this include:

• rapid and constant speech
• disturbed speech – for example, they may switch from one topic to another mid-sentence
• a sudden loss in their train of thought, resulting in an abrupt pause in conversation or activity

Postnatal psychosis

Postnatal psychosis, also called puerperal psychosis, is a severe form of postnatal depression, a type of depression some women experience after having a baby.

It’s estimated postnatal psychosis affects around 1 in every 1,000 women who give birth. It most commonly occurs during the first few weeks after having a baby.

Postnatal psychosis is more likely to affect women who already have a mental health condition, such as bipolar disorder or schizophrenia.

As well as the symptoms of psychosis, symptoms of postnatal psychosis can also include changes in mood:

• a high mood (mania) – for example, feeling elated, talking and thinking too much or too quickly
• a low mood – for example, feeling sad, a lack of energy, loss of appetite, and trouble sleeping

Contact a doctor immediately if you think you or someone you know may have developed postnatal psychosis as it is a medical emergency.

If you think there’s an imminent danger of harm, call your local emergency services number and ask for an ambulance.

Psychosis complications

People with a history of psychosis are more likely than others to have drug or alcohol misuse problems, or both. Some people use these substances as a way of managing psychotic symptoms. But substance abuse can make psychotic symptoms worse or cause other problems.

Self-harm and suicide

People with psychosis have a higher than average risk of self-harm and suicide.

If you think a friend or relative is self-harming, look out for signs of unexplained cuts, bruises or cigarette burns, usually on the wrists, arms, thighs and chest.

People who self-harm may keep themselves covered up at all times, even in hot weather.

Psychosis treatment

Treatment for psychosis involves using a combination of:

• antipsychotic medicine – which can help relieve the symptoms of psychosis
• psychological therapies – the 1-to-1 talking therapy cognitive behavioural therapy (CBT) has proved successful in helping people with psychosis, and family interventions (a form of therapy that may involve partners, family members and close friends) have been shown to reduce the need for hospital treatment in people with psychosis
• social support – support with social needs, such as education, employment or accommodation

Some people are recommended to take antipsychotics on a long-term basis (and possibly for the rest of their lives). Other people may be able to gradually reduce their dosage and then stop taking them altogether if there is a marked improvement in symptoms.

Do not stop suddenly taking any prescribed medicines as this could trigger a relapse of your symptoms.

If a person’s psychotic episodes are severe, they may need to be admitted to a psychiatric hospital for treatment.

Prodromal schizophrenia

Schizophrenia is a severe long-term mental health condition. It causes a range of different psychological symptoms. Doctors often describe schizophrenia as a type of psychosis. This means the person may not always be able to distinguish their own thoughts and ideas from reality.

Symptoms of schizophrenia include:

• hallucinations – hearing or seeing things that do not exist outside of the mind
• delusions – unusual beliefs not based on reality
• muddled thoughts based on hallucinations or delusions
• losing interest in everyday activities
• not caring about your personal hygiene
• wanting to avoid people, including friends

Schizophrenia does not cause someone to be violent and people with schizophrenia do not have a split personality.

Prodromal symptoms of schizophrenia

The prodrome of schizophrenia and other psychotic disorders is characterized as a process of changes or deterioration in heterogeneous subjective and behavioral symptoms that precede the onset of clinical psychotic symptoms.

The Diagnostic and Statistical Manual (DSM)-III-R (American Psychiatric Association 1987) ¹⁰ focuses mainly on observable behavioral changes in its description of the prodromal features of schizophrenia. It provides an operationalized criteria of nine symptoms for schizophrenic prodrome ¹⁰:

1. Marked social isolation or withdrawal
2. Marked impairment in role functioning
3. Markedly peculiar behavior
4. Marked impairment in personal hygiene and grooming
5. Blunted or inappropriate affect
6. Digressive, vague, overelaborate or circumstantial speech, or poverty of speech, or poverty of content of speech
7. Odd beliefs or magical thinking
8. Unusual perceptual experiences
9. Marked lack of initiative, interests, or energy.

This list of criteria has been dropped from the DSM-IV (American Psychiatric Association 1994). The International classification of diseases (ICD)-10 (World Health Organization 1994) acknowledges a prodrome as part of the schizophrenic syndrome; prodromal symptoms are not included in its description of schizophrenia ¹. The whole picture of this prodromal phase should also be compared to the DSM-IV concepts of fully psychotic disorders that have not been present for long enough to meet the criteria for schizophrenia or schizoaffective disorder. These DSM-IV concepts are psychotic disorders not otherwise specified, brief psychotic disorders, and schizophreniform disorders. Yung et al. in 1996 gave the criteria for the diagnosis of schizophrenia and divided it as three main categories ¹¹:

• Category 1, the patient should have at least one of the following attenuated (i.e., subthreshold) positive symptoms: ideas of reference, odd beliefs, or magical thinking; perceptual disturbance; odd thinking and speech; paranoid ideation; and odd behavior or appearance.
• Category 2 consists of participants who have experienced transient psychotic symptoms, which have spontaneously resolved within a week.
• Category 3 is a combination of genetic risk (i.e., being the first-degree relative of an individual with a diagnosis of schizophrenia) with changes in functioning. The patient must have undergone a substantial decline in the previous year. The criteria in the first two categories have been largely derived from positive symptoms, and that negative signs and symptoms were not utilized as the basis of any of the categories ¹².

Researchers have also attempted to describe the course of the prodrome. Evidence suggests that the following course is typically observed ¹³. First, individuals commonly experience negative or nonspecific clinical symptoms, such as depression, anxiety symptoms, social isolation and school/occupational failure. This is often followed by the emergence of basic symptoms, attenuated positive symptoms or brief, intermittent attenuated positive symptoms of moderate intensity. Most proximal to psychosis, individuals commonly exhibit more serious attenuated positive symptoms that remain subpsychotic in terms of frequency (once or twice a month), duration (often lasting for only a few minutes and usually less than a day) and intensity (skepticism as to the veracity of hallucinations or delusions can still be induced) ¹⁴. During this final high-risk period, individuals often exhibit predelusional unusual thoughts, prehallucinatory perceptual abnormalities or prethought disordered speech disturbances.

Cognitive deficits including memory, attention, and concentration are the most commonly documented clinical findings. This may incorporate relative disturbance in speed and verbal memory, social reasoning, and emotional processing. Various mood changes such as anxiety, depression, mood swings, sleep disturbances, irritability, anger, and suicidal ideas are reported as part of prodromal symptoms. Patient may also present with spectrum of conditions including obsessive-compulsive phenomenon and dissociative disorders. Even subtle changes such as social withdrawal, school refusal, deterioration in school work may be considered as part of prodrome and may require intervention if the person is under ultra-high-risk category. The fact that these symptoms and experiences negatively impact social, emotional and cognitive development makes early detection and intervention especially important.

It was reported that 75% of the patients with schizophrenia passed through the stages of prodromal symptoms. Subthreshold psychotic symptoms were reported 1 year preceding the onset and nonspecific anxiety and affective symptoms much before this ¹⁵. Only a proportion goes on to develop psychotic disorder. Current estimates suggest that 1 in 4 of the patients who can be categorized as high risk will convert to schizophrenia and hence warrant intervention. According to different studies, only 20%–40% of those who meet ultra high risk criteria convert to psychosis within 2–4 years. Studies conducted in both Australia and the United States showed that young people with “subthreshold” psychotic symptoms and some evidence of functional decline with a history of genetic risk for schizophrenia were ascertained and followed longitudinally for the development of psychosis ¹⁶. In a few earlier studies, it was seen that prodromal status was associated with a 40%–50% rate of conversion to psychosis in 1–2 years. A more modest rate of transition was explained by a group of researchers in North America. In Australia, 1-year transition rates for patients have steadily decreased over time 50% in 1995, 32% in 1997, 21% in 1992, and 12% in 2000 ¹⁶.

Prodromal schizophrenia diagnosis

The recent resurgent interest in the field of prodromal research has led to the development of various assessment tools. These tools can identify symptoms in the phase which calls for intervention. The various tools include:

• Instrument for the retrospective assessment of onset of schizophrenia ¹⁷
• Bonn Scale for the assessment of basic symptoms ¹⁸
• Structured Interview for Prodromal Symptoms (SIPS) ¹⁹
• Scale for prodromal symptoms (SOPS) ¹⁹
• Multidimensional assessment of psychotic prodrome ¹²
• Comprehensive assessment of ARMS (CAARMS) ²⁰

In an attempt to better categorize the prodromal period of schizophrenia and other psychotic disorders, and to elucidate the process of change or deterioration that represents a deviation from an individual’s previous experience or behavior, researchers have proposed several diagnostic and classification systems for individuals at high risk of developing a psychotic disorder ²¹.

The Personal Assessment and Crisis Evaluation (PACE) clinic in Melbourne, Australia, was the first to develop a standardized classification of prodromal syndromes, which they referred to as the ‘ultra-high-risk’ (UHR) states. Risk factors such as age, family history of psychosis and symptom scores were combined in a multifactorial index of risk ²². From this work came the creation of the CAARMS, which takes into account the intensity, frequency and duration of emerging positive symptoms, as well as declines in functioning. Help-seeking individuals between the ages of 14 and 29 years are categorized as ultra-high-risk if they experienced attenuated positive symptoms during the past year, experience brief limited intermittent psychotic symptoms (BLIPS), and/or have schizotypal personality disorder or a family history of psychosis in concert with a significant decrease in functioning during the past year.

Shortly after the CAARMS was developed, the Prevention through Risk Identification, Management, and Education (PRIME) prodromal research team at Yale University (CT, USA) developed the Structured Interview for Prodromal Syndromes (SIPS) and an accompanying scoring system termed the SOPS with criteria for the ultra-high-risk/prodromal state (the Criteria of Prodromal Syndromes [COPS]). The COPS and the CAARMS prospectively operationalize the prodrome using almost identical criteria, with only small differences in ratings of frequency and duration criteria and, thus, are often used interchangeably ²³. Some of the symptoms included in these measures were derived partly from the previously mentioned ‘basic symptoms’ included in the BSABS.

Structured interviewing technique was followed in all these scales. The SIPS and SOPS to rate the prodromal symptoms were developed by research team from Yale University called The Prevention through Risk Identification, Management, and Education. Among these, the most widely used measure is the SIPS. It enhances positive predictive power, thus increasing the true-positives ²⁴. The SIPS is a diagnostic interview used to diagnose the prodromal syndromes and similar to the structured clinical interview for DSM-IV. The CAARMS defined the at-risk criteria and included in it the vulnerable groups, attenuated positive symptom groups, and the brief limited intermittent psychotic symptoms ²⁵. The other symptoms and syndromes which are measured in these scales include genetic risks and deterioration, brief-limited psychotic symptoms, and attenuated positive symptoms; brief limited psychotic symptoms includes transient psychotic symptoms at a specified frequency over a given period. Unusual perceptual experiences and ideations that do not meet the level of conviction and severity required for hallucinations and delusions are characterized as attenuated positive symptoms. These are vital in ultra high risk criteria and charted by all of these measures.

Imaging studies and biomarkers

Much of the work on imaging and biomarkers was done by Pantelis et al. in 2003. Their studies focused on structural changes in the gray matter and following up these individuals at a later phase after they developed psychosis. The structures affected include right medial temporal, lateral temporal bilateral cingulated cortex, and inferior frontal cortex. On rescanning the individuals who developed psychosis, there was a reduction in gray matter in the left parahippocampal, fusiform, orbitofrontal, and cerebellar cortices whereas longitudinal changes were restricted to only cerebellum in those who did not become psychotic. This progressive change which was studied in adolescence was considered to be due to a combination of several factors. Genetic factors like those resulting from altered expression of genes are critical for neurodevelopmental processes such as glutaminergic N-methyl- D-aspartate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor expression or altered dynamics of dopaminergic or GABAergic neurotransmitter systems ²⁶. Hormonal changes such as reproductive steroids could modulate brain maturational processes such as synaptic pruning or myelination. Psychosocial and environmental factors also have a role in dendritic arborization. Biomarkers which have a role in early identification of psychosis have also been evaluated in studies by Schoebel et al. in 2009 ²⁷. Different categories of biomarkers representing inflammation, oxidative stress, endocannabinoids, glucocorticoids, and biogenic amine systems are dysregulated and interact with each other in the early phase of schizophrenia. Biomarkers for impending psychosis might identify high-risk individuals and thus help in halting the progression of aberrant neurodevelopmental processes ²⁸. This was also studied in researches in mouse models of maternal immune activation which revealed that interventions directed at maternal inflammatory cytokines protected against neurodevelopmental abnormalities in the offspring ²⁹. Targeting risk genes and environmental factors in the signaling pathway are found to restore functionality in a more efficacious way in these individuals. Studies have also indicated that treatments which reduce molecular deficits produced by genetic variants like folate supplementation in people with certain risk alleles have actually caused a decline in relapse rates ³⁰. Drugs which act on Val 158 and decreases catechol-o-methyl transferase activity when given at an early stage have improved the socio-occupational functioning in affected individuals ³¹.

Prodromal schizophrenia management

The importance of early detection focuses on prevention of the psychological and social disruption which results from psychosis. Minimizing the delay between the onset of psychosis and treatment is the primary objective for this diagnosis. Medications that decrease the stress levels have been found to reduce clinical deterioration in individuals with biological susceptibility for schizophrenia. Anti depressants, anxiolytics and mood stabilizers might in some cases enhance At Risk individual’s ability to tide over stressful situations ³². Studies have shown that combination of low dose Risperidone together with cognitive behavior therapy or supportive psychotherapy have shown a conversion rate of 9.7% (3/31) over 6 months in the experimental group compared to 35.7% (10/28) in the control group. Over a 12 month follow up period it was seen that 20 subjects became psychotic. Therefore, the 12 month transition rate was 40.8% (20/49). Similar placebo controlled and double blind trial of olanzapine focusing on symptoms over 8 weeks, also showed improvement in prodromal patients primarily limited to the SOPS and PANSS scales. In this study it was seen that there was a higher transition rate in the group where olanzapine was discontinued ³³. 15 patients were observed over 8 weeks in an open label study administering Aripiprazole. Significant improvement was seen in symptomatology in these patients ³⁴. The prevalence of sub-threshold psychosis was higher in subjects at genetic risk ³⁵. Antipsychotic medications for such people seem to be a logical extension for treatment protocol as a whole ³⁶. In a double blind, randomized, placebo controlled treatment study; patients were supplemented with omega 3 fatty acids. They carried out the trial on 81 ultra high risk individuals. The experimental group was given 1.2g/day omega 3 fatty acids. It was observed that after 40 weeks monitoring period 2 of the 41 in the experimental group and 11 of the 40 in the placebo group had converted to psychosis. The patients materialized improvement in positive, negative and general symptoms with betterment in functioning in comparison to the placebo group ³⁷. Besides pharmacological interventions, study of the effect of psychosocial modification on the vulnerable individuals helps the young person to regain their capacity for psychological well-being and improved quality of life. Psycho education assists the young person and their family in understanding psychosis as a brain disorder rather than a mental illness. Individuals should be taught about the coping and problem solving skills to better help the people deal with the manifestations of the illness.

Psychological interventions have been explored as cost-effective, well-tolerated adjuncts to pharmacological agents. In patients with schizophrenia, research indicates that social skills, cognition and interaction training programs lead to improvements in measures of social functioning ³⁸. Psychoeducational family interventions also improve social adjustment as well as quality of life, family burden and treatment adherence ³⁹. When provided as an adjunct to other treatments, cognitive remediation has been shown to improve psychosocial functioning, functional outcomes and cognition ⁴⁰. Regarding symptom amelioration, cognitive–behavioral therapy (CBT) has been used to guide patients to challenge and modify thoughts, emotions and behaviors, as well as improve coping strategies as a means of decreasing the level of conviction of delusions and hallucinations (and therefore severity). One meta-analysis found an effect size for reduction of psychotic symptoms with CBT of 0.65 ⁴¹. Lasting results were found with 6- to 12-month post-treatment follow-up analyses (e.g., effect size = 0.93) ⁴². Thus, meta-analyses and reviews strongly support the use of adjunct psychological interventions in patients with schizophrenia. Considerably less research has been conducted in prodromal individuals.

One early intervention study examining a small sample using a nonstandardized treatment design found that psychosocial stress management in concert with neuroleptic treatment on an as-needed basis might have reduced the incidence of schizophrenia in one catchment area in the UK ⁴³. In Australia, 10 years later, risperidone augmented with CBT was compared with standard supportive psychosocial intervention in prodromal individuals ⁴⁴. As previously noted, the results do not allow for examination of the relative contributions of risperidone and CBT, but the encouraging findings that psychosis may have been delayed or prevented spurred further studies. In the UK, 58 help-seeking ultra-high-risk patients were randomly assigned to 6 months of cognitive therapy (median number of sessions = 11) or treatment as usual (mean of 12 sessions) and then followed-up 12 months later. Cognitive therapy significantly reduced the likelihood of transition to psychosis over 12 months and the likelihood of being prescribed an antipsychotic medication. The intervention group also had significantly improved APS. The low withdrawal rate (14%) led researchers to conclude that the treatment was well-tolerated and that further research was warranted ⁴⁵. A total of 49% (n = 17) of participants in the cognitive therapy condition and 43% (n = 10) in the monitoring-only condition were followed-up 3 years later ⁴⁶. Participants in the cognitive therapy condition continued to evidence a decreased likelihood of being prescribed antipsychotics, but the previous main effect of cognitive therapy-assigned participants’ decreased transition to psychosis was not maintained on standard measures of conversion. The authors cite the low follow-up rate as a possible explanation for the findings. Another randomized controlled trial compared CBT to supportive counseling in 67 prodromal individuals. The researchers did not find a statistically significant difference between the two types of treatment; both were associated with improvements in work and global functioning ratings as well as social functioning ⁴⁷.

Expert commentary

Adolescents and young adults who appear to be prodromal or at ultra-high-risk should be monitored and provided with symptom-targeted treatments (e.g., antidepressants, psychosocial treatments) ⁴⁸. Antipsychotics should be used as soon as frank psychosis emerges. For the investigational treatments reviewed herein, prodromal-appearing adolescents and young adults should be referred to specialized research programs when possible. The potential benefits, and minimal risks, associated with omega-3 fatty acids suggest that this treatment is promising as an early intervention.

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