Methamphetamine-Associated Psychosis (MAP) – The Clinical Spectrum

METHAMPHETAMINE ASSOCIATED PSYCHOSIS

A range of psychotic phenomena has been reported in association with MA use, from transient states during periods of intoxication to more persistent syndromes that resemble schizophreniform disorder.

Psychotic features with methamphetamine use have a prevalence of 15-30% in the recreational setting and <60% in some inpatient settings. [4], [5]

Risk factors include the chronicity of methamphetamine use as well as an individual’s genetic susceptibility. (see below)

Moreover, these are also important factors in determining if psychotic symptoms are just transient episodes during methamphetamine use or if it develops into a more persistent psychotic disorder. [6]

Risk Factors for Psychosis

Although there is great variability in the literature on what represents a significant risk factor for the development of MAP, a recent systematic review has identified several factors but with varying degrees of consistency: [7]

• There is strong evidence of chronicity of methamphetamine use (i.e. increased frequency and dose amount) with MAP
• A diagnosis of methamphetamine dependence with duration of usage and age of onset also shown to be important factors
• Alcohol and other non-stimulant drug (primarily cannabis use) dependency have been strongly linked with MAP however these results were inconsistent
• The literature supports a possible relationship between psychiatric comorbidities such as antisocial personality disorder or schizotypal personality traits with the development of MAP
• A family history of schizophrenia or bipolar disorder may be more common in individuals with MAP
• A history of childhood trauma with one study showing that people with three or more types of adverse childhood experiences had 4.5 times higher odds of reporting a lifetime MA-induced psychotic disorder
  higher odds of reporting a lifetime MA-induced psychotic disorder
• Sociodemographic factors such as age, gender, employment status and level of education were not predictive of MAP

Genes associated with MAP

Furthermore, genetic polymorphisms that are associated with schizophrenia have also been previously suggested to play an important role in the development of MAP. [8], [9]

1.Dysbindin-1 candidate gene (DTNBP1) has been linked to signalling pathways that involve the neurotransmitters, dopamine and glutamate. The DTNBP1 gene has already been shown to be important for synaptic homeostasis and variation in this gene may affect cognitive abilities as well as an individual’s risk of developing schizophrenia.

2. Other genes that have a role in dopamine system function, such as SNCA (alpha-synuclein) or CLN3 and FBP1, have also been implicated in both MAP and schizophrenia.

CLINICAL FEATURES OF METHAMPHETAMINE PSYCHOSIS

The DSM-V states that if psychotic symptoms persist for longer than a month, then this is evidence of a persistent primary psychotic disorder.

In the context of MAP, the transition from an initial acute MAP episode to a primary psychotic disorder is estimated as highly likely (19 to 33%). [6]

This estimate is derived from population-based studies examining hospital admissions for psychosis and thus there exists the possibility of misdiagnosis of some of these cases of primary psychotic disorder as MAP.

Psychotic symptoms

Methamphetamine intoxication is commonly associated with hallucinations and paranoid delusions, which are not too dissimilar from acute psychosis in cases of schizophrenia. [10]

Visual and tactile hallucinations and particularly formication, the sensation of insects crawling under the skin, are reported to be more common in MAP in comparison to other types of psychoses.

The presence of negative symptoms or first-rank symptoms may correlate with a more persistent type of psychosis that resembles primary psychotic disorders, such as schizophrenia or bipolar disorder.

However, a recently published study has suggested that there is evidence of different subsets of positive psychotic symptoms. [11]

These are differentiated by their symptom patterns, which has been suggested to identify whether an individual will progress to psychosis:

• Type 1 – Most prevalent type (43% of the population studied) with a high degree of persecutory delusions present but with a smaller probability for hallucinations or first-rank symptoms.
• Type 2 – Was represented by 35% of the population studied and these subjects also experienced the same types of delusions as Type 1 subjects but that they were more likely to experience hallucinations, unlike Type 1.
• Type 3 – Although only representing 22% of the population studied, these subjects showed similar symptoms as Type 2 but that they had a much higher probability for Schneider’s first-rank symptoms as well as delusional symptoms.

Schneider’s first-rank symptoms are often described as bizarre, and the presence of bizarre thinking has been suggested as a risk factor for the onset of psychosis. [12]

However, bizarre thinking is not a good predictor for schizophrenia as most patients with schizophrenia do not exhibit first-rank symptoms.

In contrast, another study in a hospitalised sample of participants with
MAP found that delusions of thought broadcasting were more common in schizophrenia, while auditory hallucinations of voice conversing were more common in MAP; but overall, there was no significant difference between the MAP and schizophrenia groups for any other first-rank symptoms. [13]

Overall, MAP can be considered a heterogenous syndrome however more research into the complex relationship between methamphetamine use, polydrug abuse, specific psychotic symptoms, and comorbid mood disorders is required to identify symptom typologies that may predict the onset of psychosis.

Cognitive Symptoms:

Methamphetamine abuse is linked to cognitive dysfunction with impairments in executive functioning (impulsivity and impaired decision making), psychomotor functioning, and memory deficits (verbal memory and fluency). [14]

Neuroimaging studies show that dopamine and serotonin networks are affected by methamphetamine use:

• Methamphetamine stimulates the release of dopamine, serotonin, and noradrenaline.
• However, all amphetamine-related compounds are lipophilic and can diffuse across membranes, thereby directly modulating neurotransmitter release— this has been referred to as the weak base hypothesis. [15]
• Observations from in vivo and in vitro studies show an increase in dopamine levels in the synapse through the redistribution of dopamine from synaptic vesicles to the cytosol.
• The action of methamphetamine on the neuronal dopamine transporter and the vesicular monoamine transporter-2 causes the reverse transport of dopamine out of the cell as well as competitively inhibiting dopamine reuptake.
• Methamphetamine use has also been shown to block not only dopamine transporters but also reduce the expression of these transporters.

Moreover, it is interesting to note that the symptoms of cognitive dysfunction in MAP are different in methamphetamine abusers that do not exhibit psychotic symptoms. Persistent psychotic symptoms may indicate a risk for cognitive decline among meth users.[16]

In subjects diagnosed with MAP, there are substantial impairments in attentiveness, executive functioning, and processing speed—which is more akin to the symptoms of chronic schizophrenia—in comparison to subjects with no symptoms of psychosis.

As previously discussed, the type of psychotic symptoms may be used as a possible predictor for the onset of psychosis. However, it can similarly be suggested that cognitive deficits are not only a sign of the underlying neurobiological dysfunction but that it can also be compared to the cognitive profile of psychotic disorders.

In summary, methamphetamine-associated psychosis lies along a spectrum ranging from no psychotic symptoms and cognitive impairment to the presence of persistent psychotic symptoms and cognitive impairment at the severe end.

CONCLUSION

Methamphetamine is a highly addictive psychostimulant and extended use is associated with substantial neurotoxicity with cognitive dysfunction and psychotic symptoms contributing to the increased morbidity and mortality in users.

There are many similarities between MAP and psychosis with a subset of methamphetamine users experiencing persistent psychotic symptoms that extend beyond cessation of methamphetamine use.

Understanding the MAP spectrum raises the opportunity of treating MAP within the context of mental health paradigms for early psychosis, rather than purely within the context of drug and alcohol services.

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