Notre Dame University-Louaize

Faculty of Natural and Applied Sciences

Psychosis: Genetically Predisposed or Drug

Induced
Aya Homsi and Selena Chemaly

BIO220: Genetics

Dr. Katherine Yaacoub

Abstract:
Background: Psychosis is a mental state where one experiences hallucinations and delusions. It
is the main symptom of some mental disorders and a common symptom of others. Such mental
disorders include schizophrenia spectrum disorders, mood disorders, and substance use disorder.
Psychosis is mostly heritable and genetically based, however, it may be induced. The purpose of
this report is to analyze the available research examining the etiology of psychosis.

Methods: Several research articles were carefully read and analyzed. The articles included
several forms of genetic studies such as linkage studies, genome-wide associations, twin studies,
etc.

Results: Several genes were found to be involved in psychosis for schizophrenia spectrum
disorder such as Disrupted-in-schizophrenia-1 (DISC1), Neuregulin, and Dysbindin. Linkage
studies found regions of chromosomes for psychosis in mood disorders such as 8p and 13q. The
intake of drugs such as LSD and Amphetamine dysregulate neurotransmitters in the brain like
dopamine, glutamate, and serotonin which are similar to the neurotransmitter dysregulations
caused by genetic predispositions.

Conclusion: Psychosis in schizophrenia spectrum disorders and mood disorders is highly

genetic, however, there is a genetic overlap between the disorders that needs to be further
examined. Drug induced psychosis is not genetic but leads to the same psychotic behaviors and
experiences.

Keywords: psychosis, schizophrenia, schizophrenia spectrum disorders, mood disorders,

depression, bipolar, substance use disorder, LSD, amphetamine, genetics

Introduction:
Psychosis is a common symptom of various mental disorders. In the past, the exact
definition of psychosis had been unclear and highly debatable. Today, the Diagnostic and
Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) defines psychosis as a state where
one exhibits hallucinations, delusions, or both (Arciniegas, 2015).

Hallucinations are sensory experiences such as auditory or visual with a lack of external
stimuli (Laroi et al., 2007). Most hallucinations such as sleep hallucinations or hearing one’s
own name are experienced by healthy individuals and are not considered abnormal since they do
not disturb daily functioning or cause distress (Arciniegas, 2015). The hallucinations with the
absence of insight (cannot be distinguished from reality) are considered abnormal and psychotic
symptoms (Arciniegas, 2015).
 Delusions are false beliefs that are irrational or abnormal (Kiran et al., 2009). Even when
presented with contradictory evidence, the beliefs remain firmly fixed and do not change (Kiran
et al., 2009). There are two main types of delusions, ordinary and bizarre. Ordinary delusions are
irrational beliefs and interpretations of experiences and the environment (Arciniegas, 2015). For
example, believing that the TV host is sending a message to the person watching, or that the song
on the radio was written specifically for that person. Bizarre delusions are beliefs that are
physically impossible and are often related to culturally ‘taboo’ topics e.g. sexuality or religion
(Arciniegas, 2015). For example, one might believe that they are the next Jesus Christ, or believe
that they have lost their genitals.

For the past couple of years, psychosis has been a popular topic in psychological and
neurological research due to it being a common symptom of various mental disorders. Psychosis
is one of the core symptoms of schizophrenia spectrum disorders (schizophrenia, brief psychotic
disorder, etc.), a common symptom of mood disorders (e.g. depression), and a feature of
substance use disorder (Arciniegas, 2015). Even though the environment is a significant
contributing factor, the development of psychosis and psychotic disorders is highly genetic.

Discussion and Interpretation:

Schizophrenia Spectrum Disorders:
Schizophrenia spectrum disorders are psychotic disorders that are highly distressing and
cause dysfunction to the patient’s daily life. These disorders include schizophrenia, delusional
disorder, schizoaffective disorder, schizotypal personality disorder, schizophreniform disorder,
and brief psychotic disorder (Barch, 2024). It is now quite known that schizophrenia spectrum
disorders have a common genetic basis (Lichtermann et al., 2000). A research study on 150
randomly selected cases of schizophrenia found that 78.01% (117 cases) had genetic factors that
led to the development of the disorder (Barrett, 2006). These findings were equal to the
percentage of psychosis in general which strongly support the claim that psychosis is highly
heritable (Barrett, 2006).

To begin with, results from linkage studies of genome scans have found genes that are
factors in schizophrenia predisposition (Lichtermann et al., 2000). The genes that were found to
be associated with development of schizophrenia were found on chromosomes 8p, 13q, and 22q
(Craddock et al., 2005). Additional research also found evidence for specific regions on
chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p (Craddock et al., 2005). However,
regions 8p and 22q are by far the most strongly supported (Craddock at al., 2005).

In addition, genome-wide association studies have found three major genes for
schizophrenia: Disrupted-in-schizophrenia-1 (DISC1), Neuregulin, and Dysbindin (Ham et al.,
2017). These three genetic mutations cause abnormal brain development and dysregulation of the
neurotransmitter dopamine which consequently leads to psychotic behaviors (Ham et al., 2017).

The combination of these genetic factors leads to abnormal brain development which is
the predisposition for the disorder (Tsuang, 2000). Individuals with such predispositions have a
higher probability to develop schizophrenic disorders due to certain environmental factors that
would cause further brain malfunctioning (Tsuang, 2000). These environmental factors include
birth complications, malnutrition, socioeconomic stressors, and child abuse (Tsuang, 2000).
Moreover, identical twin studies have shown a concordance rate of 50% (100% if environment
not accounted for) due to the role of environmental factors (Tsuang, 2000). More recent studies
have found that schizophrenia follows a polygenic model with a mix of different genetic
mutations (Gejman et al., 2010). This means that a predisposition for schizophrenia depends on
the mutation of several genes and not just one. Today, the genetic architecture of schizophrenia
still remains unknown, however, the evidence that is present shows that it is highly heritable
(Gejman et al., 2010).

Mood Disorders:
Mood disorders are mental disorders characterized by dysregulation of mood which
impacts one’s functioning, emotions, and motivation (Rakofsky, 2018). The two most common
mood disorders are major depressive disorder and bipolar disorder (Rakofsky, 2018). Major
depressive disorder is characterized by constant low mood that would lead to a lack of energy,
impaired decision-making, crying, self-criticism, irritability, and lack of interest in social
interactions (Molina et al., 2012). Bipolar disorder is characterized by fluctuations in mood
where an individual would experience a depressive state which is followed by a manic state or a
high (Grande et al., 2016).

Some cases of major depressive disorder develop psychotic symptoms or go into a state
of psychosis (Rothschild, 2013). These individuals would struggle with a combination of
depressive symptoms and psychotic symptoms (hallucinations and delusions) and are much more
challenging to treat (Rothschild, 2013). Genetic research studies such as the Vietnam Era Twin
Registry have revealed that major depressive disorder with psychosis has a heritability of 39%
(Domschke, 2013). However, this heritability is not specific, meaning the predisposition is
shared with schizophrenia and schizoaffective disorder (Domschke, 2013). Linkage studies
provide evidence of an overlap between the disorders on chromosomes 6p, 8p22, 10p13-12,
10p14, 13q13-14, 13p32, 18p, and 22q11-13 (Domschke, 2013). Researchers are now suggesting
a dimensional view or a spectrum of psychotic disorders including psychotic depression due to
the recent genetic discoveries (Domschke, 2013). In addition, family studies have shown higher
rates of psychotic depression within the families of patients diagnosed with psychotic depression
in contrast to those diagnosed with nonpsychotic depression (Domschke, 2013). Finally, the
delusions observed with individuals diagnosed with psychotic depression are due to lower
dopamine beta-hydroxylase (DBH) plasma levels which are higher in patients that have
depression without psychosis (Domschke, 2013). These low DBH levels are caused by a genetic
mutation in the DBH gene known as the variant 444G/A (Domschke, 2013).

Many cases of bipolar disorder exhibit psychotic features or psychosis. Many argue that
bipolar disorder with psychosis is on a spectrum with schizophrenia due to the shared genetic
basis (van Bergen et al., 2018). Results of linkage studies on the genetic basis of bipolar disorder
have proven the role of chromosomes 8p and 13q which have also been found to be associated
with schizophrenia and psychotic depression (Goes et al., 2008). Other linkage studies found
evidence for regions on chromosomes 9p22.3-21.1, 10q11.21-22.1, 14q24.1-32.12, and some
specific regions on chromosome 18 (Craddock et al., 2005). In addition, association studies have
found positive correlations between genes associated with schizophrenia (DAOA/G30 and
Dysbindin) and psychotic bipolar disorder (Goes et al., 2008).

Substance Use Disorder:

Substance use disorder is characterized by the use or abuse of drugs or alcohol (Han et
al., 2008). Psychosis is a common feature of substance use disorder; however, the psychosis is
drug induced and not genetically based. Certain drugs such as amphetamine and LSD can cause
the user to experience psychosis (Ham et al., 2017). The symptoms of drug induced psychosis
are so strong and are exactly identical to those experienced by schizophrenia patients (Ham et al.,
2017). The only difference between the psychoses is that schizophrenia psychosis is mainly
heritable while the other is drug induced (Ham et al., 2017). The drugs that are used or abused
alter neurotransmitter levels in the brain (e.g. dopamine) and lead to psychosis. For example
amphetamine is a stimulant drug that is commonly abused by people that work during night
shifts to be able to stay alert. Amphetamine increases levels of dopamine and glutamate in the
brain, similarly to patients with schizophrenia (Ham et al., 2017). The dysregulation of these
neurotransmitters causes the abuser to experience psychosis (Ham et al., 2017).

The most powerful hallucinogen drug today is D-Lysergic Acid Diethylamide or more
commonly known as LSD or Acid as it leads to extreme psychotic behaviors and experiences in
very low doses (Ham et al., 2017). LSD increases levels of the neurotransmitters dopamine,
serotonin, and glutamate in the brain which leads to the psychosis (Ham et al., 2017). The drug
was first studied by Albert Hofmann, a Swiss chemist, in 1943 (Carhart-Harris et al., 2016). He
intentionally ingested a high dose of 250 mg of LSD in his laboratory to study the effect of the
drug (Carhart-Harris et al., 2016). He wrote a report a few days later describing his experience as
unpleasant due to strong feelings of paranoia and terror (Carhart-Harris et al., 2016). He also
experienced hallucinations such as seeing his neighbor as an evil witch with colored skin
(Carhart-Harris et al., 2016).

Conclusion:

To sum up, psychosis is a symptom of many mental disorders, however, it can be

heritable or induced. The evidence provided supports the claim that schizophrenia spectrum
disorders and psychotic mood disorders have a strong genetic basis. However, there is significant
overlap between the genetic mutations of psychotic mood disorders and schizophrenia spectrum
disorders. The genetic predisposition is not specific and there are environmental factors that play
a huge role in the development of the disorders This overlap needs to be further investigated to
be able to determine if they are separate disorders or whether they lie on a spectrum. Other states
of psychosis are drug induced such as in substance use disorder and are not genetic. The effects
of these drugs need to be further examined, and the availability and use of the drugs need to be
restricted.
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