Neurobehavioural Functioning – PGO en Colleges
College 1 – Schizophrenia
Schizophrenia basics
Misconceptions: violence and dangerous.
Diagnosis: positive and negative symptoms.
• Positive; hallucinations/illusions (difference ?),
delusions (fixed beliefs), disorganized thinking,
abnormal motor behaviour
• Negative; diminished emotional expression,
avolition (decreased motivation), anhedonia
(decreased pleasure), alogia (diminished speech),
asociality (social withdrawal)
• Cognitive impairments; 75-85% has this → poor
executive functioning, problems with working
memory, problems with paying attention.
• There are no subtypes anymore!
• Attentuated psychocis syndrome.
• A better title would be psychosis spectrum
disorder. There are a lot of other psychotic disorders.
Epidemiology
Mental and substance a use disorders: 5th in the proportion of total disability adjusted life years.
22.9% have lived with their disability (even terug naar slide met table?). All psychotic disorders: 3.6%
Schizophrenia prevalence: 1% with a relatively high mortality rate due to more somatic diseases and
suicide. Affects more men than women and age of onset is around 12 – 35.
In treatment, there is more relapse for positive symptoms and a lot of substance abuse.
Psychotic experiences in the general population
Lifetime prevalence about 5-8%, but about 80% is transitory. 20% is persistent of which only 7%
develops a disorder. There is a shared genetic and socio-environmental risk factors. This there is a
transdiagnostic psychosis phenotype.
Risk factors
Both prenatal (infections, malnutrition, season of birth, complications) and postnatal risk exposure.
Childhood trauma such as sexual, physical, emotional abuse and neglect. Also bullying. They have an
OR of 2.78 → about 3 times more likely to develop schizophrenia. Stressfull life events have a similar
OR.
Evidence has been found for a correlation between the onset of a psychotic disorder and cannabis.
The OR is 3.2 which can increase to 5 for daily users. There is also a 2-3 higher chance of getting
psychosis when you have migration background. Could be explained by social status and education
etc. Also, there is higher prevalence of schizophrenia for people with an urban background. Could
be due to neighbourhood cohesion, population density, ethnic and social fragmentation, especially in
high developing countries.
1
,Problem: reverse causality? → when someone has a psychotic disorder (first), they start to abuse
substances to cope or are bullied because they are different (later).
Important: environment x gene interactions. The more risk-factors combined, the higher the risk for
developing such an disorder.
Most risk factors are pleiotropic. It means that the risk factor is only a risk factor for psychotic
disorders and schizophrenia, but also for other mental diseases and disorders. These factors are also
not independent → correlation, confounding, mediation, moderation. They are also time and dose
sensitive, such as the duration of a cannabis addiction and frequency.
Genetics
Highly heritable. In order to research this, you can link candidate genes to behaviour and
phenotypes. You select genes based on known relevance. You could also use genome wide
association studies. This is a hypothesis free approach. A number of proteins and receptors have
been found. Also calcium channels and D2 receptor have been implicated. You can also calculate a
polygenic risk score. → even terug naar deze slides over genen en GWAS!
Most important: it is always a gene x environment interaction. Furthermore, there re not only risk
factor but also a lot of resilience factors, such as social support, positive atmosphere, low-
rumination, etc.
Putative underlying mechanisms
Dopamine hypothesis → most prominent model.
Dopamine antagonists and stimulants could induce
psychosis. There is an increases presynaptic striatal
dopamine synthesis and release = Corticostriatal
dopaminergic dysregulation. This can be already in
the prodromal phase (just before the actual onset).
Funnily, in mania and depression which are often
comorbid with schizophrenia, this dysregulation has
not been found.
Neurotransmitter systems and circuits
Dopamine and its interaction with environmental factors is a major aspect. Further, reductions in
grey and white matter have been found. There are no clear anatomical or functional abnormalities
which are specific to schizophrenia alone. This is due to the complexity and heterogeneity of the
psychopathology. There is no biological test for schizophrenia.
Stress sensitivity
When people are exposed to trauma, some may experience minor stressors as more stressful. High
stressful event → high psychosis. Dit niet helemaal gevolgd, even terugkijken!
Integrated sociodevelopmental-cognitive model
2
,Treatment
D2 blockers mostly, and antipsychotics such as clozapine. These also work on other
neurotransmitters. These mainly reduce positive symptoms, but do not ‘treat’ someone. Also, a lot of
side effects are common. Pharmacotherapy only used if needed. Usually try CBT or family therapy etc
first. Novel approaches are brain stimulation, VR and meta cognition training. Early intervention
therapies may precede psychotic symptoms when given in the prodromal stage.
Take home message
• Schizophrenia and other related disorders are common.
• Typically occurs in late adolescence or early adulthood.
• Major cause of the disease burden worldwide.
• Complex aetiology; genes, neurodevelopment, socio-environmental risk exposure and all
these interactions.
• Treatment is complex and need to be sustained.
• Important to have a holistic approach: not only pharmacotherapy, also CBT etc.
• Early intervention strategies important.
• The concept of schizophrenia is currently subject of debates and represent more severe
outcomes of a psychosis spectrum phenotype.
3
, PGO 1 – Neurobehavioural functioning
Leerdoel 1: What are the main components of neurobehavioural functioning and how do
they relate to each other?
Leerdoel 2: What are the strengths and weaknesses of dichotomy and continuum
approaches to diagnostics and how do they relate to the concept of neurobehavioural
functioning?
Leerdoel 3: How is neurobehavioural functioning typically assessed?
Leerdoel 4: What are the potential benefits and limitations that could result from combining
modern neuroimaging with assessments?
https://maastrichtuniversity.zoom.us/j/94274121970 → Zoom meeting
https://drive.google.com/drive/folders/1uduMwivqEwpuwFPG4wQOatqziwgVeIrS → Dropbox
https://drive.google.com/drive/folders/1Pe-F0bkK1Y_8qSONdcQhadybGMperIZo → Literatuur beide
vakken.
Artikel: Adam – on the spectrum
Introduction
David Kupfer is a psychiatrist who wants to move away from the categorical approach taken in the
DSM and move towards a more dimensional approach, in which mental illnesses may overlap, as is
often the case in clinical settings. Disorders are thought to be a product of shared risk factors.
However, others say this idea is still premature. More and more evidence in favour of this idea comes
to light, but it is hard to change an already existing clinical doctrine.
Manual evolution
Around 1960, the DSM was mostly influences by Freud and his ideas on conflicts between internal
drives that cause mental illnesses. Around 1980 things got more empirical because of Emil Kraeplin.
He came up with the idea that schizophrenia and bipolar disorder were separate disorders. This
thinking was turned into a more categorical approach in the DSM.
The problem is that symptoms are so varied between and within patients, that it frequently occurs
that a patient fulfilling criteria for one disorder, often does also for two others. Therefore, many
psychiatrists have created new categories. There is not much evidence, but there is some that
suggests that DSM disorders in fact do overlap.
Example: anxiety and mood disorder share hyperactive amygdala. Or; schizophrenia and PTSS
unusual activity in the PFC. A large study also found that there are genetic risk factors that share five
major disorders (autism, ADHD, bipolar, MDD, schizophrenia).
4
,Rival approach
The dimensional approach is gaining support. An example comes from the frequent comorbidity of
schizophrenia and OCD. Some suggest a schizo-obsessive spectrum. Craddock and Owen introduced
a radical dimensional spectrum on which five classes of disorders are arranged: mental retardation–
autism–schizophrenia–schizoaffective disorder–bipolar disorder/unipolar mood disorder. It is
simplified but it does seem to work: more people show the signs of both mental retardation and
autism, for example, than of both mental retardation and depression.
Psychiatrists would place people on the scale by assessing the severity of a series of traits that are
affected in these conditions, such as cognitive impairment or mood disruption.
Kupfer and colleagues hoped to make the switch to the dimensional approach around 2007. Yet the
proposed scales got a lot of critiques. No one had experience using them (too many different
conclusions were dwrawn) and they were not based on enough strong evidence. Also patient groups
and insurances companies and charities had their doubts.
Change of tack
In 2011, the DSM-5 task-force admitted their defeat; too little had changed and they were too
optimistic. However, there are some previous separate categories that are now merched into one
spectrum: autism spectrum (including Asperger’s), obsessive-compulsive disorder (including
hairpulling), substance-use disorder (including substance dependence and abuse.
Currently, anhedonia (a symptom, not a diagnosis) is being researched. If mechanism could be
identified, this could be treated without there being an overall diagnosis.
One of the big challenges is to get the drug regulators on board with the idea that the DSM
categories are not the only way to prove the efficacy of a medicine.
Conclusion: All involved agree on one thing. Their role model now is not Freud or Kraepelin, but the
genetic revolution taking place in oncology. Genetics and brain imaging are especially important.
Artikel: Esterberg – The psychosis continuum and categorical versus dimensional diagnostic
approaches
Abstract
This overview briefly presents recent thinking on the dimensional approach to understanding psychotic experiences. First,
evidence is provided for a continuum of psychosis ranging from self-reported infrequent psychotic symptoms in the general
population, to schizotypal traits, to schizotypal personality disorder, and finally to full-blown psychosis resulting in a
diagnosable primary psychotic disorder. Variation within each of these types of psychotic experience is discussed. Then, a
comparison is presented between categorical and dimensional approaches to the diagnosis of psychosis by highlighting four
advantages of each approach. In doing so, it is emphasized that the categorical approach is beneficial primarily in terms of
reliability, whereas the dimensional approach would enhance validity.
Introduction
In recent years, a dimensional approach for the diagnosis of psychotic disorders is considered. Still,
the categorical approach is dominant. This approach was started by Kraepelin (distinction between
schizophrenic disorders and manic-depressive disorders. This is referred to as the Kraepelinian
dichotomy.
Studies found that the prevalence of psychotic symptoms in the general population is much higher
than originally thought, and might even be comparable to depression and anxiety prevalences.
5
, EVIDENCE FOR A CONTINUUM OF PSYCHOSIS
Self-reported psychotic symptoms in the general population
There seems to be a psychotic continuum in the general population where only the tip of that
continuum is actually diagnosed with a psychotic disorder. Many people have experienced
hallucinations, delusions, paranoia, etc. without it bothering them so much that they needed help.
There do seem to be relationships between psychotic experiences and demographic factors; SES,
ethnicity, women, younger people and sensory deficits. Also, relationships may exist between
symptoms and stress, depression, lower quality of life.
Schizotypy, schizotaxia and schizotypal personality disorder
• Schizotypy = psychosis-related experiences representing a portion of the schizophrenia
spectrum spanning from minimally impairing character traits to diagnosable personality
disorder. Thus, schizotypy encompasses a continuum of traits ranging from psychotic-like
experiences that occur in the general population to more severe symptoms that lead to a
schizotypal personality disorder (SPD) diagnosis or indicate the impending onset of a full-
blown psychotic disorder such as schizophrenia.
o Rado’s concept of schizotypal is a nonpsychotic syndrome related to schizophrenia.
Most of these people do not become psychotic.
o Kendler described some cases: distortion of bodily selves, extreme interpersonal
difficulties, cognitive disorganization and difficulties with anger and fear.
• Schizotaxia = genetic and biological liability for schizophrenia. Meehl described schizotypy as
a clinical manifestation of schizotaxia but later noted that not all individuals with schizotaxia
develop schizotypal features, SPD, or schizophrenia. Nowadays schiotaxia is considered a
condition with neuropsychological deficits and negative symptoms.
• Schizotypal personality disorder = people in the general population that do not display
normal variations In schizotypy, but clinically relevant levels. It is a pervasive pattern of social
and interpersonal defi cits marked by acute discomfort with, and reduced capacity for, close
relationships as well as by cognitive or perceptual distortions and eccentricities of behavior,
beginning by early adulthood and present in a variety of contexts.
o At least five of the following nine: ideas of reference; odd beliefs or magical thinking;
unusual perceptual experiences; odd thinking and speech; suspiciousness or paranoid
ideation; inappropriate or constricted affect; odd, eccentric, or peculiar
behavior/appearance; lack of close friends; and excessive social anxiety
• All in all, factor analyses have shown that schizotypy and SPD are multidimensional. There
also may be different schizotypal disorders. This heterogeneity led us to believe tat the
nature of SPD is best captured by a dimensional diagnostic approach.
• Continuum → ranges from self-reported infrequent psychotic symptoms in the general
population, to schizotypal traits, to SPD, and fi nally to full-blown psychosis resulting in a
DSM-IV-TR–defi ned primary psychotic disorder.
Psychosis and psychotic disorders
In clinical practice, diseases are (too bad) often seen as all or non principles. Psychotic disorders are
grouped together. The symptoms include interpersonal, occupational or other domains of
dysfunctioning. The aim of the current criterion based descriptive symptoms is to enhance reliability.
The problem of the whole dimensional continuum spectrum is that symptoms lack specificity.
Specificity is what is needed to set the boundaries between a sever schizophrenia from a normal
schizotypy. Currently, what sets the boundary is the psychological disability. More than the
descriptive symptoms. It is vague.
6
