A general cognitive improvement emerged in non-affective psychosis

with and without llicit drug use in the frst month after an acute psychotic
episode. As hypothesized, the psychosis group with illicit drug use showed
the largest increase in performance on the global measure of cognitive
functioning from baseline to follow-up, especially among the youngest
patients in this group. No signifcant differences in cognitive functioning were
found at baseline between the groups in this study. However, a larger
increase in cognitive functioning emerged in the psychosis group with illicit
drug use as compared to the group without from admission to follow-up. This
indicates that the cognitive recovery process is more prominent in the illicit
drug using psychosis group in the acute phase as opposed to the nonaffective

psychosis

only

group.

Possibly,

patients

with

non-affective

psychosis and a history of illicit drug use, like for instance cannabis,
originally have a superior cognitive functioning (Lberg and Hugdahl,2009;
Yuceletal., 2012). Conceivably, use of illicit drugs can induce transient
cognitive defcits, mimicking the cognitive vulnerability that characterizes
patients with schizophrenia at group level (Lberg and Hugdahl,2009). The
results from this study, with larger cognitive changes in the psychosis group
with illicit drug use, are in line with this assumption. Thus, the cognitive
defcits initially in the acute psychosis phase maybe attributed to the effects
ofllicit drugs, like cannabis.
The analyzed interaction model accounted for age differences in the
two groups and showed the group difference to be stronger for younger
patients. This means that the younger patients in the psychosis group with
illicit drug use had the largest cognitive change in the acute phase, and
younger age was not related to poly drug use or having a schizophrenia
diagnoses as opposed to an acute and transient psychosis diagnosis in the
psychosis group with illicit drug use group. Aplausible explanation for a
larger cognitive change among the younger illicit drug using patients is that
their neuro cognitive set-up is more resilient and fexible; their younger
brains may have a larger capacity for plasticity (Kolb and Robbin,2011).

Accordingly, the recovery process of the brain functioning in the acute phase
is larger among these patients. However, one cannot rule out the possibility
of a selection bias. Theoretically the younger patients in this study could
representa better functioning cognition sub-group. The association between
younger age and higher scores on the PANSS negative and general psycho
pathology subscales,and thus higher PANSS total scores, in the psychosis
group with illicit drug use, implies that the younger illicit drug using patients
have more, not less, symptoms at admission. However, inspite of more
symptoms at baseline the youngest illicit drug using patients have the most
improvement on the neuro psychological tests in the acute phase.
Interestingly, this effect of age has been reported previously; a meta-analysis
by Potvin et al.(2008) found that the effect of better global cognition in
schizophrenia patients with mixed substance use or cannabis use decreased
with increased age. Thus, it is important to be aware of the effect of age in
relation to cognitive functioning when drawing conclusions about cognition.
Use of illicit drugs like cannabis and amphetamines, may have led to
disturbances in dopaminergic and endogenous cannabinoid system and
transient cognitive defcits, which ultimately have resulted in expression of a
psychotic

disorder

(Di

Fortietal.,2007;

Bossong

and

Niesink,2010;

Kuepperetal.,2010). This is supported by the fact that having a drug use

disorder, in particular cannabis and amphetamines use disorder (Callaghan
etal.,2012), or earlier cannabis use, is a risk factor for developing
schizophrenia

in

dose

dependent

manner

(Andreasson

etal.,1987;

Henquetetal.,2005; Moore etal.,2007). Thus, illicit drug-using patients may

have become psychotic through an alternative etiological pathway Lberg
andHugdahl,2009; Lberg etal.,2012). Supporting this, less neurological soft
signs(Bersani etal.,2002; Stirlingetal., 2005; Ruiz-Veguillaetal.,2012) and
better social and leisure functioning and more social contacts among drug
using patients with schizophrenia, as compared to psychosis patients without
illicit drug use, have also been found (SalyersandMueser,2001). In addition,
non-affective psychosis patients with cannabis use seem to have a higher

premorbid IQ compared to those without illicit drug use (Leeson etal.,2012).

Furthermore, studies have generally reported an earlier onset of psychosis
among

cannabis

using

patients

with

schizophrenia(Large

etal.,2011;Leesonetal.,
2012;Mylesetal.,2012;DiFortietal.,2013;Donoghueetal.,

2014),

also

suggesting an alternative etiological pathway. Use of illicit drugs, like

cannabis and amphetamines seems to have an additive negative effect on
brain functioning, and in some individuals the thres hold for developing
psychosisis lowered, presumably depending on the brains ability to tolerate
the effects of drugs, amount of drugs taken and genetic and cognitive
vulnerability. The present study is a naturalistic prospective study integrated
in clinical practice. This increases the generaliz ability and clinical relevance
of the study, while at the sametime decreases the ability to control for
confounders and the ability to create a more homogenous drug user group,
since multiple drug use seems to be the norm. It may therefore be diffcult to
attribute the differential effects on cognition a particular illicit drug.
Confounders have been minimized by controlling for group differences by
statistical procedures, but it is a weakness of this study that age onset of
psychosis and number of psychotic episodes were not recorded, this was also
the case with frequency and duration of illicit drug use. Methodological
strengths of the present study were particularly that the patients were
hospitalized

during

the

follow-up

to

minimize

drug

use

and

that

neuropsychological screening instrument had alternative forms to avoid

practice effects. The present study did not include a control group of healthy
individuals. Cognitive functioning has been shown to predict functional
everyday outcomes, like work participation, better than positive symptoms
(Green,1996;Venturaetal.,2009). RBANS total score has also been shown to
be strongly related to work participation in patients with schizophrenia (Gold
etal.,1999). Even though a general cognitive improvement took place in both
groups, indicating that neuropsychological functioning in the acute psychosis
phase is not stable, better cognition in particularly the younger psychosis

patients that are using illicit drugs emerged. This may have positive clinical
implications, suggesting a potential for better functional outcome. It seems
plausible however, that a better prognosis is dependent on abstinence from
illicit drugs (Mullin et al.,2012;Guptaetal.,2013). In line with this, worse
cognitive functioning has been associated with continuous use of illicit drugs
in psychosis (Rabin etal.,2012). Aparallel focus on illicit drug use in the
treatment of psychosisis therefore benefcial also with cognition in mind.

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