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Samenvatting Neuropsychology And Psychiatric Disorders (PSMNB-3)

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This is a summary of all articles that need to be studied for the course 'Neuropsychology and psychiatric disorders'.

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  • October 9, 2022
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  • 2022/2023
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Lecture 2: schizophrenia

Duration of untreated psychosis and neurocognition in first-episode psychosis:
a meta-analysis

Schizophrenia is associated with significant cognitive impairment which has a significant
effect on the level of functioning in those individuals. Cognitive deficits are also at first
episode (FEP). Neurodevelopmental models suggest that cognitive deficits in schizophrenia
are mostly a consequence of problems in acquisition of cognitive abilities (developmental
lag or arrest) during development. Neurodevelopmental factors play a significant role in
cognitive impairment in schizophrenia. Also, emergence of psychotic symptoms might
interfere with normal maturation of advanced cognitive abilities (i.e., planning/problem
solving) which are complete until late adolescence/early adulthood. However, neurotoxicity
hypothesis of psychosis suggests that cognitive deficits might also emerge as a consequence
of untreated active psychosis in early years of the illness. The time elapsing between onset
of first psychotic symptoms and initiation of first effective intervention has been defined as
the duration of untreated psychosis (DUP). The neurotoxicity hypothesis suggests that
longer DUP can lead to structural brain changes and cognitive deficits in FEP. There is a
modest but significant relationship.

Discussion
The current meta-analysis sought to provide a systematic overview of studies investigating
the relationship between neurocognition and DUP. In general, DUP had no significant
impact on the severity of cognitive impairment. However, there was an exception for the
planning/ problem-solving domain; longer DUP was very modestly but significantly
associated with low performance in planning/problem-solving. In general, these findings do
not support the notion that DUP has a “toxic” effect on cognitive abilities. These findings are
consistent with the neurodevelopmental hypothesis of schizophrenia, which suggests that
cognitive deficits are mostly neurodevelopmental in origin and precede the onset of
psychotic disorder. Longer DUP might be a severity marker of poor prognosis, rather than
being the cause of poor outcome in psychotic disorders. Insidious rather than acute onset of
psychotic symptoms is associated with poor outcome in psychotic disorders and insidious
onset is expected to be related to longer DUP. For example, deficits in planning ability have
been associated with poor insight and poor functional outcome and both are related to
longer DUP in schizophrenia.
Neurodevelopmental theory of psychosis can also provide an explanation for the modest
but significant relationship between DUP and planning ability; the patients with more severe
neurodevelopmental abnormalities are expected to have a poorer prognosis and insidious
onset of psychosis.

,Approaching a consensus cognitive battery for clinical trials in schizophrenia:
the NIMH-MATRICS conference to select cognitive domains and test criteria

Cognitive deficits in this context refer to a wide range of performance deficits in areas such
as attention, memory, speeded responses, or problem solving. A cognitive deficit reflects a
disturbance in one of these underlying cognitive processes that may, or may not, be
detected by standard clinical instruments or informal clinical observation but can be
detected by appropriately designed cognitive performance tasks.

The rationale for the psychopharmacologic treatment of cognition in schizophrenia rests on
a few premises. One premise is that the cognitive deficits of schizophrenia are a core feature
of the illness. A core feature means that the cognitive performance deficits are not simply
the result of the symptoms, nor of the current treatments of schizophrenia. Instead, these
deficits represent a fundamental aspect of the illness.

Evidence that cognitive deficits are core features of schizophrenia comes from various
sources:
 Many patients demonstrate clear cognitive impairments before the onset of
psychotic symptoms and before the start of other clinical features.
 Some first-degree relatives of schizophrenic patients who have no evidence of
psychosis also demonstrate a pattern of cognitive impairments that is similar to that
found in schizophrenia.
 On some measures of cognition, the level of impairment shown by patients during a
psychotic episode is similar to that seen in the same patients when their symptoms
are under control or when they are in full remission. Hence, cognitive impairment
may occur independently, and even in the absence of clinical symptoms of
schizophrenia.
 The correlations between psychotic symptom severity and measures of cognitive
performance are typically near zero.
 The types of cognitive deficits seen in schizophrenia tend to fit a typical profile that
differs from the pattern of deficits seen in dementia, bipolar disorder, and
depression.

A second premise, one that is related to the idea that these deficits are a core feature, is
that cognitive deficits are relatively common in schizophrenia. Almost all schizophrenia
patients are performing at a level below what would be expected in the absence of illness.

A third key premise for targeting cognition in the treatment of schizophrenia is that the
cognitive deficits are related to the daily functioning of patients, and these relationships are
generally stronger than those between psychotic symptoms and functional outcome.

A fourth premise is that patients’ performance on cognitive tasks can be improved through
psychopharmacologic treatment.

Overview of MATRICS
The MATRICS contract has four main goals: 1) to promote development of novel compounds

,to enhance cognition in schizophrenia, 2) to catalyze regulatory acceptance of cognition in
schizophrenia as a target for drug approval, 3) to help focus the economic research power of
industry on a neglected clinical target, and 4) to identify promising compounds and support
proof of concept trials for cognition in schizophrenia.

The first steps in the process of developing a consensus cognitive battery were to 1) identify
the cognitive domains that should be represented in the battery and 2) prioritize criteria by
which tests were to be selected for inclusion in the battery.

The subgroup of the Neurocognition Committee concluded that six separable factors had
been replicated in multiple studies of schizophrenic patients and were appropriate for the
consensus cognitive battery for clinical trials:
1. Working memory
2. Attention/vigilance
3. Verbal learning and memory
4. Visual learning and memory
5. Reasoning and problem solving
6. Speed of processing

Social cognition is defined in various ways and broadly refers to the mental operations
underlying social and emotional interactions, including the human ability and capacity to
perceive the intentions and dispositions of others. This factor was eventually added as the
seventh factor. Data suggest that social cognition is closely related to functional outcome
and may be an intervening variable between basic (nonsocial) cognition and outcome.

, Pathways to functional outcome in schizophrenia spectrum disorders: meta-
analysis of social cognitive and neurocognitive predictors

There is a strong link between functional outcomes in schizophrenia and impairments in
both social cognition (SC) and neurocognition (NC). Social cognition possibly serves as a
mediator between NC and functional outcomes. Despite this relationship, the majority of
interventions target either NC or SC impairments.

Domains of NC included: attention and vigilance, processing speed, reasoning and problem
solving, verbal comprehension, verbal fluency, verbal learning and memory, visual learning,
and memory, working memory, and combined neurocognition.

Domains of SC included: attribution bias, emotion perception and processing, social
knowledge and perception, theory of mind, and combined social cognition.

Domains of functional outcomes included: community functioning (e.g., activities of daily life
and relationships), social behaviour in the milieu (e.g. observed behaviours in a specific
context), social problem solving (e.g. abilities to address a social problem or generate
solutions), and social skills (e.g. social interaction abilities like eye contact and conversation
skills).

Discussion
With respect to a priori aims, (1) domains of NC and SC demonstrated small to medium
relationships with functional outcomes. Specific NC domains of verbal learning and memory
(community functioning), working memory (social behavior in the milieu and social skills)
and reasoning and problem solving (social problem solving) demonstrated the strongest
relationships with specific functional outcomes. For SC, the strongest associations were
present for social knowledge and perception (com- munity functioning) and theory of mind
(social behavior in the milieu and social skills). (2) Relationships between overall NC and SC
with functional outcomes were not significantly different in bivariate analyses. However, SC
did explain more unique variance in functioning than NC, suggesting distinct relationships
for respective domains of cognition with functional outcomes; (3) Relationships were not
moderated by FEP sample status, suggesting similar associations between NC and SC with
functional outcomes are already present in the early stages of illness; 4) Consistent with
previous theoretical and empirical work, the role of SC as a partial mediator between NC
and functional outcomes was substantiated.

According to the proximal-distal approach, the proximity of SC to functional outcomes offers
support for SC as a primary treatment target for optimal improvement in functioning.
However, correlation analyses demonstrated medium effect sizes from both NC and SC
domains and seem to support the increasing focus on integrated interventions targeting
both domains of NC and SC in schizophrenics.

Additionally, results recommend consideration of the desired type of functional outcome
improvement when planning interventions. Unsurprisingly, SC was particularly more
strongly associated with measures of outcome that are social skill and behaviourrelated
(e.g., social behaviour in the milieu and social skills) while NC and SC seemed to be equally

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