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What is Schizophrenia?Schizophrenia is a spectrum disorder with issues such as -*Schizophreniform
*Schizoaffective
*Delusional
*Brief Psychotic disorders, and
*Personality disorder (Schizotypal personality disorder).

All of the above mentioned share features of extreme reality distortion.

Further, schizophrenia is a complex syndrome that disrupts a person’s perception, thought, speech, and movement, and the number of behaviours or symptoms aren’t necessarily shared by all people who are given the diagnosis. 
StatsThe widespread of schizophrenia affects one out of every 100 people at some point in their lives and the consequences of schizophrenia can be severe.

The full recovery from schizophrenia is a low base rate of 1 out of 7 patients (Jååsklåinen et al., 2013)
DiagnosisThe requirement to be diagnosed for schizophrenia requires 2 or more positive, negative and/or disorganized symptoms to be present for at least one month, with one of these symptoms including delusions, hallucinations, or disorganised speech.
SymptomsSymptoms of Schizophrenia

Three categories positive, negative, and disorganised

Positive symptoms:
Traits → Symptoms around distorted reality and have more obvious signs of psychosis, including delusions and hallucinations. Between 50-70% experience delusions, hallucinations OR both (Lindenmayer & Khan, 2006)

Delusion

Types of delusions
– Grandeur
– Persecution
– Unusual delusion (Debryune & Audenaert, 2012; Salvatore et al., 2014)

*Capgras syndrome → Believe that the person they know have been replaced by a double

*Cotard syndrome → Person believe that they are dead
Reasons for believing delusion:
– Motivational view → Look at these beliefs as attempts to deal with and relieve anxiety and stress
– Deficits view → Beliefs as resulting from brain dysfunction that create the disordered cognitions OR perceptions

Hallucinations

Perceptions are real and occur regularly

Individuals experience sensory events without any input from the surrounding environment
Can involve ANY of the senses → Auditory hallucinations is the most common form (70%) experienced by people with schizophrenia followed by visual hallucinations.

People with hallucinations have intrusive thoughts but believe it is coming from somewhere OR someone else

Negative symptoms:
It is the deficits in normal behaviour (speech OR blunted affect, and motivation). The absence of normal behavior are displayed by approximately 25% of the people with schizophrenia (Cohen, Natarajan, Araujo & Solanki, 2013 ; Millan, Fone, Steckler, & Horanm 2014)

Avolition 
Inability to initiate and persist in activities → Individuals show little interest in performing even the most basic day-to-day functions

Alogia
Individuals display relative absence of speech
Responding to a question with brief replies that have little content and may appear uninterested in conversation
Reason for behaviour → Due to negative thought disorder than lack of communication skills

Anhedonia
Presumed lack of pleasure experienced by some people with schizophrenia An indifference to activities that would typically be considered pleasurable (e.g. Eating, sexual relations) 

Asociality
Similar to avolitation OR related to anhedonia, but is considered an independent symptoms → Captures the lack of interest in social interaction (APA, 2013)
Can result from OR be worsened by limited opportunities to interact with others, particularly severely ill patients (Reddy, Horan, & Green, 2016)

Affective Flattening
Approximately 25% of the people with schizophrenia exhibit flat affect
Individuals do not show emotions when you would normally expect them to
Stare at you vacantly, speak in flat tone and toneless manner, unaffected by things going on around them, and may respond to things on the inside though we are unable to see it

Disorganised:
There are a variety of erratic behaviors that affect speech, motor behaviour, and emotional reactions. The prevalence is unclear

Disorganised speech
Eliciting relevant information is especially difficult → Lack of insight and awareness they have a problem
Experience associative splitting/cognitive slippage
This describes speech problems with schizophrenia
Individuals jump topic to topic OR talk illogically
Reply from them can be tangentiality → Off on a tangent
Change topic or conversation to unrelated area → Loose association OR derailment

Inappropriate affect and disorganized behaviour
Individuals laugh and cry at inappropriate times
Exhibit bizarre behaviours → e.g. Hoarding objects OR acting unusual ways in public
Engage in number of other “active” behaviours usually view as unusual

Catatonia → Motor dysfunction that range from wild agitation to immobility

Spectrum
Active → People pace excitedly OR move their fingers or arms in stereotyped ways
Other → Hold unusual posture as if fearful of something terrible happening (Catatonic immobility)
Waxy flexibility → Tendency to keep bodies and limbs in position as if they are put in that way by someone else
Risk FactorsLifetime prevalence rate is roughly equivalent for men and women (0.2%-1.5% of the general population) → 1% of population at some point be affected (Erlich et al.,2014)

Life expectancy is slightly less than average → Partly the higher rate of  suicide and accidents among people with schizophrenia

Onset age (Jablensky, 2012)
– Men → Likelihood diminishes with age, but can still occur after the age of 75

– Women → Lower than men until age 36, relative risk for onset switches, with more women than men being affected later in life
Women have more favourable outcome than do men

Factors

Cultural
Universal
Affecting all racial and cultural groups → Evidence is the shared neuroanatomical similarities (Gong et al., 2015)

Course and outcome → Vary from culture to culture
E.g. lack of adequate mental health infrastructure, significant political, social, and economic problems

Levels of stress associated with factors (stigma, isolation, and discrimination) (Anglin, Lighty, Greenspoon, & Ellman 2014; Pinto, Ashworth, & Jones, 2008)

Genetic Influence
Genes
Genetic inheritance is responsible for making some individuals vulnerable to schizophrenia → Multiple gene variances combine to produce vulnerability (Murray & Castle, 2012)

Family studies
Severity of the parent’s disorder  → Influence the likelihood of the child’s having  schizophrenia
Individuals may inherit a general predisposition for schizophrenia that manifest in the same or different form, from that of your parent

Twin Studies
Identical siblings → have different prenatal and family experience 
Be exposed to varying degrees of biological and environmental stress

Adoption studies
Biological mother had schizophrenia OR one of the related psychotic disorder (delusional disorder OR Schizophreniform disorder) → Risk adopted child would have one of these disorder rise to 22%

Raised away from biological parents → Children still have much higher chance of having the disorder themselves

Offspring of twins
-Parent is an Identical (Monozygotic) twin → 17% chance of having disorder yourself, even if you are the child of an unaffected twin
– Parent is a Fraternal twin → Parent does not have, but the twin does is only 2%. You can be considered as a carrier of schizophrenia.

References 
1. Durand, Barlow, Hofmann (2018) Essentials of Abnormal Psychology (8th ed.). Cengage Learning
Pathophysiology Neuropathology
Schizophrenia is usually termed a neurodevelopmental disorder2 as it manifests before the complete maturation of the brain.It is a cerebral cortical disorder where deficits in GABAergic interneurons1,2 are detected. GABAergic interneurons are necessary to coordinate cognitive processes and complex emotions, which are dysregulated in schizophrenia.

The “GABAergic origin hypothesis” 1 to explain schizophrenia symptoms holds that reduced NMDA receptor functioning at GABAergic interneurons is enough to produce  schizophrenia-like symptoms.
This hypothesis has been evident when: Healthy subjects produced schizophrenia-like symptoms with systemic administration of NMDA receptor antagonists (to induce hypoactivity of NMDA receptors)Transgenic mice with selective deletion of NMDA receptors from cortical and hippocampal GABAergic interneurons produced molecular, physiological and behavioral characteristics similar to human schizophrenia.

The revised dopamine hypothesis3 suggests dopamine transmission is hyperactive in the mesolimbic regions (reflecting positive symptoms) and hypoactive in the prefrontal cortex (reflecting negative symptoms and cognitive difficulties) of schizophrenia patients. 
A recent review article “White matter neurons biology and neuropathology in schizophrenia” (Ryan et al., 2019) discusses the potential involvement of increased interstitial white matter neurons in schizophrenia.
Treatment ModalitiesSchizophrenia treatment in the emergency department4,5

When an acutely agitated patient with schizophrenia is presented, check for the level of risk of harm to themselves and staff. This determines the route and type of medication.

Patients who are more violent need rapidly calming therapies coupled with verbal de-escalation techniques.

Benzodiazepines are the most common medications used for sedation.
For patients who cannot be de-escalated, intramuscular medicines with antipsychotics are used along with physical restraints.

2 types of antipsychotics are used in the emergency setting:
first-generation (typical) and second-generation (atypical).

Limitations of typical antipsychotics led to the development of atypical antipsychotics which are more effective in reducing negative symptoms and improving cognitive function. 

After drug administration, observe the patient’s respiratory status, as adverse events can include hypoxia.

Apart from pharmacologically informed management of schizophrenia, psychologically informed management is also necessary, given the multidimensional nature of the disease. Heightened anxiety is key to the psychotic disintegration of the patient therefore this needs to be managed.

*Take care to avoid unnecessary situations where the patient experiences increased anxiety.
*Do not confront the validity of patients’ delusions, but also do not agree, rather be empathetic and explain there are reasons as to why they are experiencing things differently.
*Build an environment of trust.

*Other treatments for schizophrenia: CBT, ECT6

References
1. Nakazawa, Kazu, Veronika Zsiros, Zhihong Jiang, Kazuhito Nakao, Stefan Kolata, Shuqin Zhang, and Juan E. Belforte. “GABAergic interneuron origin of schizophrenia pathophysiology.” Neuropharmacology 62, no. 3 (2012): 1574-1583.Duchatel, Ryan J., Cynthia Shannon Weickert, and Paul A. Tooney. “White matter neuron biology and neuropathology in schizophrenia.” NPJ schizophrenia 5, no. 1 (2019): 1-9.
2. Brisch, Ralf, Arthur Saniotis, Rainer Wolf, Hendrik Bielau, Hans-Gert Bernstein, Johann Steiner, Bernhard Bogerts et al. “The role of dopamine in schizophrenia from a neurobiological and evolutionary perspective: old fashioned, but still in vogue.” Frontiers in psychiatry 5 (2014): 47.
3. https://www.psychiatrictimes.com/view/schizophrenia-in-the-emergency-department-psychologically-and-psychodynamically-informed-practices
4. da Silva Alves, Fabiana, Martijn Figee, Therese van Amelsvoort, Dick Veltman, and Lieuwe de Haan. “The revised dopamine hypothesis of schizophrenia: evidence from pharmacological MRI studies with atypical antipsychotic medication.” Psychopharmacol Bull 41, no. 1 (2008): 121-32.
5. What is schizophrenia? – Anees Bahji – Bing video (TED-Ed video)

Schizophrenia

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