Rather impairment which includes the presence of

Rather
than a medical condition in its own right, psychosis
is a symptom of many mental disorders (MacGill, n.d.) and it manifests as a
severe impairment in mental functioning. According to Stenberg, Holder and
Tallur (1998), the impairment which includes the presence of hallucinations and
delusions, is “so substantial that the individual is unable to carry on normal
activities of daily living” (p.5). To quote from Waters and Stephane (2014),
“the term reality is often opposed to
the world of psychosis” (p.22).

Characterized by positive
symptoms including psychosis, thought disorganization, and negative symptoms
like avolition, disorganized speech and catatonic behaviour (American
Psychiatric Association, 2013),
schizophrenia is one of the most typically associated mental disorders
to psychosis. Jablensky (1987) describes schizophrenia as “a condition of
obscure origin and no established etiology” (p. 162). While theories on psychogenic, environmental and
genetic factors have attempted to explain its etiology, research has focused on
identifying a biological basis for this complex disorder – the dopamine hypothesis.
This report seeks to discuss the supporting and disproving
evidences concerning the hypothesis and how they have contributed to existing
understandings on dopamine’s role in this context.   

The
classical dopamine hypothesis of schizophrenia evolved largely from the
knowledge of how medications treating psychiatric disorders work (Wyatt, 1982).
The idea is that, since antipsychotic medication
or neuroleptics block dopamine activity (Carlsson & Lindqvis, 1963;
Birtwistle & Baldwin, 1998), a schizophrenic patient would supposedly have “a
functional excess of brain dopamine” (Wyatt, 1982, p.225). In other words, if
antipsychotic drugs blocked dopamine activity and improve schizophrenic
symptoms, then those symptoms must be caused by excess dopamine activity. Dopamine
is a neurotransmitter that plays a crucial role in motor function, learning, memory,
motivation and reward. Disturbances in its levels may thus lead to a range of
psychiatric symptoms. Hence, the hypothesis postulates
that schizophrenic symptoms are a result of excess synaptic activity at the
dopamine receptor.

An investigation on the action of major neuroleptic drugs
upon the brain’s metabolic processes was among the earliest supporting
evidences. Carlsson and Lindqvist (1963) studied chlorpromazine, a
first-generation antipsychotic medicine used to treat schizophrenia, on small
rodents. The drug was found to have enhanced the turnover of dopamine in the mouse
brain, whereas no such effect arose with promethazine, a compound “chemically
related to chlorpromazine but devoid of antipsychotic efficacy” (Spiegel, 2003).
Researchers attributed this
finding to the idea that neuroleptics act by blockage of dopamine receptors; chlorpromazine
and other neuroleptic drugs were thus recognized as dopamine antagonists. Middleton (2015) believes these antagonists work by
blocking receptor binding sites to prevent neurotransmitter activation and
release. A measure of how strongly a drug binds to a given receptor is also
known as affinity (p.63). Chlorpromazine has high dopamine affinity necessary to
suppress dopamine buildup in the brain. When the receptors are blocked, less
dopamine is taken up, thus the effects of excess dopamine are avoided. This in
turn reduces positive schizophrenic symptoms including psychosis and supports
the hypothesis of excess dopamine causing schizophrenia.

The second line of
support derives from psychostimulant drugs. When
evaluating its effects in healthy controls, “chronic or sustained use of
psychostimulants, specifically amphetamine, has been shown to induce a toxic psychosis”
(Angrist & Gershon, 1970 as cited in Lieberman, Kane & Alvir, 1987), closely
resembling the positive symptoms of schizophrenia. This syndrome is termed as
the amphetamine psychosis and is best
supported by Calipari and Ferris (2013), who stressed that amphetamine is known
to elevate dopamine levels and prolong the signaling of dopamine brain
receptors (p.8923). Even at smaller doses, amphetamine was found to exacerbate
psychosis in existing schizophrenics. However, psychotic symptoms due to amphetamine
abuse can generally be resolved with medications for schizophrenia. Results
cited in Shoptaw, Kau and Ling (2009) which suggests that chlorpromazine
effectively reverses amphetamine psychosis, further supports the dopamine
hypothesis.

Evidences in
favour of the hypothesis did not end there, for research on Parkinson’s disease
also revealed more support. Patients with Parkinson’s disease are often administered
with L-Dopa to counter the
insufficient dopamine levels in them. L-Dopa functions to increase levels of
dopamine however, it cautions of schizophrenic-like side effects specifically
psychosis. In contrast,
chlorpromazine which reduces dopamine activity, can produce side effects
resembling Parkinson’s disease. To quote from Nelson (1994), this
indicates that antipsychotic drugs “mimic Parkinson’s disease by blocking
dopamine in these same areas” (p.123). Taken together, chlorpromazine reduces
the severity of schizophrenic symptoms whereas amphetamine and L-Dopa which increase
dopamine levels, either worsen or produce these symptoms. Such evidence clearly
attests to the involvement of dopamine in schizophrenia.

Finally,
post-mortem studies also provided evidence for dopamine dysregulation. When comparisons were made with
aged-matched controls, Bird, Spokes and Iverson (1979) found high
concentrations of dopamine in the left amygdala of brains in schizophrenics.
This contrasted with symmetrical distributions of dopamine concentrations in
the left and right amygdala of brains from healthy controls. However, there
have been criticisms implying that the increased dopamine levels may have
occurred after death.

            As
compelling as the dopamine hypothesis may be, it has also been the subject of scrutiny.
The above evidence linking schizophrenia and dopamine is largely correlational,
causing difficulty in establishing the direction of causality. This means whether
the increased dopamine activity is a causal factor, or a result of
schizophrenia remains ambiguous. Another issue concerns the treatment aetiology
fallacy, a common misconception that the success of a certain form of treatment
reveals the cause of the disorder (Eysenck, 2014). In this case, the fact that
dopamine antagonist drugs alleviate schizophrenic symptoms does not necessarily
indicate dopamine as the direct cause of the disorder. In fact, the
aforementioned evidence of successful neuroleptics seems to only account for
positive schizophrenic symptoms, with little impact on negative ones. This shows
that the role of dopamine in other symptoms is equivocal and that the
hypothesis may not be a sufficient theory of etiology for schizophrenia.

Contrary to the hypothesis’
predictions, antipsychotic drugs like chlorpromazine do not act immediately in
reducing symptoms, although they immediately affect dopamine levels. As Spiegel
(2003) explains, the blockade of dopamine receptors by antipsychotic drugs is
an immediate effect whereas the therapeutic action of these drugs becomes
apparent only after several days or weeks. For
instance, it was recently published in a medicine and drug reference guide that
risperidone, another type of
antipsychotic drug treating schizophrenia and mania, required up to 3 weeks
before onset of effect (O’Shaughnessy,
2015, p.377). If dopamine levels
are directly responsible for schizophrenic symptoms, one would assume
that symptom improvement would begin immediately. Thus, such
delayed drug effects are puzzling.

The role of dopamine is again questioned
as statistics reveal that antipsychotics are not effective for all
schizophrenics – about 25% of patients with schizophrenia do not respond to
antipsychotic medication (Carr, 2001) despite high levels of dopamine. This
argues that blocking dopamine receptors in some patients have minimal to no
effect on their symptoms. In these drug-resistant patients, clozapine emerged as more effective than
classical neuroleptic drugs like chlorpromazine. Clozapine prompted new
research which discovered that its broad spectrum of receptor affinities
accounted for its antipsychotic efficacy in drug-resistant patients: clozapine
had a substantially higher affinity for serotonin receptors than dopamine receptors (Weyandt, 2006). Not only was it able to treat
positive symptoms, clozapine was also proven effective in alleviating negative
symptoms unlike typical antipsychotics (Sharafi 2005; Khan & Zaidi, 2017). Having
been criticized as a reductionist explanation, the hypothesis fails to factor
the involvement of other neurotransmitter systems, that is serotonin. Given
this evidence, the emerging picture is that at least two neurotransmitters
could be involved in schizophrenia: serotonin and dopamine.                                 

To date, the efficacy of antipsychotic drugs still depend on its
dopamine-suppressing abilities. Thus despite its shortcomings, the dopamine
hypothesis has not been entirely disproved and remains as one of the
most enduring ideas about the disorder. The present report has shown that
evidence for a role for dopamine in the etiology of schizophrenia is compelling
but not completely irrefutable. If,
as Karl Popper (1959) says, the value of a hypothesis lies not so much in
whether it is right or wrong but in its capacity to stimulate attempts to
refute it, then the dopamine hypothesis has been extraordinarily successful. 

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