Schizophrenia, schizotypal

and delusional disorders

Ján Pečeňák

Psychiatrická klinika LF UK

ICD-10Schizophrenia, schizotypal and delusional disorders

F20 Schizophrenia

F20.0 Paranoid schizophrenia

F20.1 Hebephrenic schizophrenia

F20.2 Catatonic schizophrenia

F20.3 Undifferentiated schizophrenia

F20.4 Post-schizophrenic depression

F20.5 Residual schizophrenia

F20.6 Simple schizophrenia

A fifth character may be used to classify course:

.x0 Continuous

.x1 Episodic with progressive deficit

.x2 Episodic with stable deficit

.x3 Episodic remittent

.x4 Incomplete remission

.x5 Complete remission

F21 Schizotypal disorder

F22 Persistent delusional disorders

F23 Acute and transient psychotic disorders

F23.0 Acute polymorphic psychotic disorder without symptoms of schizophrenia

F23.1 Acute polymorphic psychotic disorder with symptoms of schizophrenia

.x0 Without associated acute stress

.x1 With associated acute stress

F24 Induced delusional disorder

F25 Schizoaffective disordersF25.0 Schizoaffective disorder, manic type

F25.1 Schizoaffective disorder, depressive type

F28 Other nonorganic psychotic disorders

F29 Unspecified nonorganic psychosis

DSM 5

B 00 Schizophrenia

B 01 Schizotypal Personality Disorder

B 02 Schizophreniform Disorder

B 03 Brief Psychotic Disorder

B 04 Delusional Disorder

B 05 Schizoaffective Disorder

B 06 Attenuated Psychosis Syndrome

B 07-14 Substance-Induced Psychotic Disorder

B 15 Psychotic Disorder Associated with a Known General

Medical Condition

B 16 Catatonic Disorder Associated with a Known GeneralMedical Condition

B 17 Other Specified Psychotic Disorder

B 18 Unspecified Psychotic Disorder

B 19 Unspecified Catatonic Disorder

ICD-11

Schizophrenia or other primary psychotic disorders

• 6A20 Schizophrenia

• 6A21 Schizoaffective disorder

• 6A22 Schizotypal disorder

• 6A23 Acute and transient psychotic disorder

• 6A24 Delusional disorder

• 6A25 Symptomatic manifestations of primary psychotic disorders

• 6A2Y Other specified schizophrenia or other primary psychotic disorders

• 6A2Z Schizophrenia or other primary psychotic disorders, unspecified

Catatonia

• 6A40 Catatonia associated with another mental disorder

• 6A41 Catatonia induced by psychoactive substances, including medications

• 6A4Z Catatonia, unspecified

Schizophrenia

• clinical syndrome

– greatly variable

– profoundly affecting ill person

– psychopathology affects• perception, thinking, emotion, cognition,

and multiple aspects of behavior

– (endogenous) psychosis• hallucinations

• delusions

• disorganization

– change of personality

Schizofrénia

• schisis σχίζειν

• phrein φρήν - mind

development of concept

Dementia praecox

• Emil Kraepelin (1856–1926)

– dementia praecox (Morel`s term)

• long-term deteriorating course

• hallucinations and delusions

– Kraepelin distinguished dementia praecox from

illness with periodic course - manic-depressive

psychosis

• paranoia

Schizophrenia(s) and Four AS

• Eugene Bleuler (1857–1939) – replaced dementia praecox

for schizophrenia

• it is not split personality, but the presence of schisms between thought, emotion, and behavior

– schisis σχίζειν – cleavage

– phrein φρήν – mind

– The Four As

• fundamental (or primary) symptoms of schizophrenia

– Associations

– Affect

– Autism

– Ambivalence

• accessory (secondary) symptoms

– hallucinations and delusions

Schneider's first-rank symptoms

• Kurt Schneider (1887 – 1967)

He emphasized that in patients who showed no first-rank symptoms, the disorder could be diagnosed

exclusively on the basis of second-rank symptoms and an otherwise typical clinical appearance

Audible thoughts Auditory hallucinations of a person’s voice being spoken aloud

Voices arguing or discussingAuditory hallucinations of two or more voices arguing or discussing, usually about the

person

Voices commenting on

patient’s actions

Auditory hallucinations commenting on a person’s behaviors

Somatic passivity Tactile or visceral hallucinations that are imposed by some external agent; can be

combinations of different somatic hallucinations

Thought withdrawal Sensation of thoughts being actively removed from a person’s mind

Thought insertion Thoughts inserted into a person’s mind by some external agent

Thought broadcastingThe sense that a person’s thoughts are experienced as real phenomena by others —the

thoughts are made audible or may be experienced by others through telepathy

Made feelings Feelings that are not a person’s own are imposed on that person by an external agent

Made impulses or drives An impulse for action is imposed on a person by some external agent

Made volitional actsA person’s actions are from and are controlled by an external agent; the person is a

passive participant in the action

Delusional perceptionA perception that has a unique and idiosyncratic meaning for a person, which

leads to an immediate delusional interpretation

Epidemiology

• life time prevalence ~ 1%

– more in urban area

• poverty, drug abuse

Age and sex distribution at the time of diagnosis

0

10

20

30

40

50

60

70

15 20 25 30 35 40 45 50 55 60 65 70 75 80 85

vek v rokoch

Muži Ženy

Castel DJ, 1999

Familiar risk

Austin JC, Peay HL., Clin Genet 2006

2

2

4

5

6

6

8

13

17

17

46

48

0 5 10 15 20 25 30 35 40 45 50

Uncle/aunt

Nephew/niece

Cousin

Grand child

Parent

Half sibling

Sibling

Child (1 parent ill)

Sibling (1parent ill)

DZ twin

Child (2 parents ill)

MZ twin

Etiology/course

Etiology

• genetic factors 80%– DISC1

– COMT

– velo-cardio-facial syndrome (di George) deletion in localization 22q11.2

• environmental factors– older age of father

– season of birth

– infections

– drug abuse

– nutrition

Stage of

illness Premorbid Prodromal Progressive Residual

Developmental

stage

Clinical

signs

& symptoms

Pathologicalprocess

Developmental

Process/Events

Mild impairment

motor

cognitive

social

minor physical

anomalies No

ns

pe

cif

ic

be

ha

vio

ral

ch

an

ge

Symptoms

positive

negative

cognitive

mood

Symptoms

positive

negative

cognitive

Patterning

Migration

Apoptosis

Dysconnectivity DA?

GLU?

Neurodegenaration

sym

pto

ms

, d

isa

bil

ity

Sever

InductionDifferentiation

SynaptogenesisPruning

Myelination

Stress, Life Events, Substance Use

Normal

adapted from Lewis DA, Lieberman, JA, Neuron, 2000

Time to the first hospitalisation

(Häfner et al.)P

sychosis

15 % > 1 month < 1 year

18 % < 1 month

68% 1 year

prodroms: 4,3 years, median 2,33

psychotic pre-phase 1,3 year, median 0,8 year

Meyer-Lindenberg A, Weinberger DR. Neurosci. 2006.

Dopamine theory

• effect of antipsychotics– D2 blocade

• dopaminergic drugs are increasing risk for psychosis

Dopaminergic pathways

Mravec B. In: Psychofarmakológia, 2016

1

2

43

1 mesocortical

2 mesolimbic

3 nigro-striatal

4 tubero-infundibular

cortex

GLU GLU GABA GABA GLU GLU

SN/VTA

GABA5-HT

AChGABA

DA

NA

LC

Ncc. raphe

striatum

muscimol

(GABAA)

PCP

(NMDA)

PCP

(NMDA)

PCP

(NMDA)

PCP

(NMDA)atropine

(M1)

amphetamine

(releasing of

NA, DA)

LSD

(5-HT2)

LSD

(5-HT2)

secondary to Carlssson

Cognitive symptoms:

attentionmemoryexecutive functions

Positive symptoms:

delusionshallucinationsdisorganized speechcatatonia

Symptoms/syndromes of Schizophrenia and Overall Functioning

Occupational

Interpersonal

Self-care

Social

Work

Negativesymptoms:

affective flatteningalogiaavolitionanhedonia

Mood symptoms:

dysphoriasuicidalityhelplessness

Symptoms of Schizophrenia

• Five factors of PANSS :– positive

– negative

– excitement

– disorganization

– depression

• Domains of negative symptoms:– blunted affect

– alogia

– asociality (social withdrawal)

– anhedonia

– avolitionMarder SR, Davis JM, Chouinard G. J Clin Psychiatry. 1997 Dec;58(12):538-46.

Lindenmayer JP, Grochowski S, Hyman RB. Schizophr Res. 1995 Feb;14(3):229-34;

Kay, S.R., Fisbein, A., Opler, L.A.. Schizophr. Bull. 1987, 13, 261– 276

Cognitive symptoms

• Inherent part of schizophrenia– Measured by neuropsychological testing

– Probably correlated to the basic pathophysiological processes

• “cognitive dysmetria” (Andreasen N. et al, 1996)

Pronounced impact on functional outcome

• 20%-60% of variance in functional outcome can be explained by differences in neurocognition– Cognition is better correlated with adaptive functioning

than negative syndrome and a very little or no correlation was found for positive symptoms

Green MF, Kern RS, Braff DL, Mintz J. Schizophr Bull. 2000;26(1):119-36.

Peuskens J, Demily C, Thibaut F. Clin Ther. 2005;27 Suppl A:S25-37.

Andreasen NC et al. Sep 3;93(18):9985-9990.

http://www.matrics.ucla.edu/

Depressive symptoms

• range 17% to 83% (mean about 30%)

• traditionally - better outcome (?)

– need to differentiate pre-psychotic

and post-psychotic continuous symptoms

• risk factor for treatment adherence,

suicidality, quality of life

The Calgary Depression

Scale for Schizophrenia

Rybakowski JK et al. Eur Neuropsychopharmacol.

2012 Dec;22(12):875-82.

pri

ma

ryn

on

-p

ers

isti

ng

secondary primary

dete

rio

rati

on

pre

-mo

rbid

deficit or primarypersisting

EP

S

dep

ressio

n

en

vir

on

men

tal

fac

tors

Composition of Negative Syndrome

“p

sych

osis

”

Tandon R, Jibson MD, Taylor SF, DeQuadro JR. American Psychiatric Press; 1995:109–124.; Buchanan RW. Schizophr

Bull. 2007 Jul;33(4):1013-22.

Diagnostic criteria

Diagnosis -ICD 10

• G1. Either at least one of the syndromes, symptoms, and signs listed under (1) below, or at least two of the symptoms and signs listed under (2) should be present for most of the time during an episode of psychotic illness lasting for at least 1 month (or at some time during most of the days).

1. At least one of the following must be present: – thought echo, thought insertion or withdrawal, or thought broadcasting;

– delusions of control, influence, or passivity, clearly referred to body or limb movements or specific thoughts, actions, or sensations; delusional perception;

– hallucinatory voices giving a running commentary on the patient's behavior, or discussing the patient among themselves, or other types of hallucinatory voices coming from some part of the body;

– persistent delusions of other kinds that are culturally inappropriate and completely impossible (e.g., being able to control the weather, or being in communication with aliens from another world).

2. Or at least two of the following: – persistent hallucinations in any modality, when occurring every day for at least 1 month, when

accompanied by delusions (which may be fleeting or half-formed) without clear affective content, or when accompanied by persistent overvalued ideas;

– neologisms, breaks, or interpolations in the train of thought, resulting in incoherence or irrelevant speech;

– catatonic behavior, such as excitement, posturing or waxy flexibility, negativism, mutism, and stupor;

– “negative” symptoms, such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses (it must be clear that these are not due to depression or to neuroleptic medication).

Diagnosis DSM-IV

B. Social/occupational dysfunction:– one or more major areas of functioning such as work,

interpersonal relations, or self-care are markedly below the level achieved prior to the onset

C. Duration:

• Continuous signs of the disturbance persist for at least 6 months.

– at least 1 month of symptoms (or less if successfully treated) that meet Criterion A

– may include periods of prodromal or residual symptoms• During these prodromal or residual periods, the signs of the

disturbance may be manifested by only negative symptoms or two or more symptoms listed in Criterion A present in an attenuated form (e.g., odd beliefs, unusual perceptual experiences).

Schizophrenia subtypes

• Paranoid• Preoccupation with one or more delusions or frequent

auditory hallucinations.

• None of the following is prominent:

disorganized speech, disorganized or catatonic

behavior, or flat or inappropriate affect.

• Disorganized type

– All of the following are prominent:

• disorganized speech

• disorganized behavior

• flat or inappropriate affect

Schizophrenia subtypes

• Catatonic type • motoric immobility as evidenced by catalepsy (including waxy

flexibility) or stupor

• excessive motor activity (that is apparently purposeless and not influenced by external stimuli)

• extreme negativism (an apparently motiveless resistance to all instructions or maintenance of a rigid posture against attempts to be moved) or mutism

• peculiarities of voluntary movement as evidenced by posturing (voluntary assumption of inappropriate or bizarre postures), stereotyped movements, prominent mannerisms, or prominent grimacing

• echolalia or echopraxia

• Undifferentiated type

• Residual type– Absence of positive symptoms, negative symptoms, attenuated

form of symptoms

ICD 10

Hebephrenic schizophrenia

A. The general criteria for schizophrenia must be met.

B. Either of the following must be present: 1. definite and sustained flattening or shallowness of affect;

2. definite and sustained incongruity or inappropriateness of affect.

C. Either of the following must be present: 1. behavior that is aimless and disjointed rather than goal-

directed;

2. definite thought disorder, manifesting as speech that is disjointed, rambling, or incoherent.

D. Hallucinations or delusions must not dominate the clinical picture, although they may be present to a mild degree.

ICD 10

Simple schizophreniaA. There is slow but progressive development, over a period of at least 1

year, of all three of the following: 1. a significant and consistent change in the overall quality of some aspects

of personal behavior, manifest as loss of drive and interests, aimlessness, idleness, a selfabsorbed attitude, and social withdrawal;

2. gradual appearance and deepening of “negative” symptoms such as marked apathy, paucity of speech, underactivity, blunting of affect, passivity and lack of initiative, and poor nonverbal communication (by facial expression, eye contact, voice modulation, and posture);

3. marked decline in social, scholastic, or occupational performance.

B. At no time are there any of the symptoms referred to in criterion G1 for general schizophrenia, nor are there hallucinations or well-formed delusions of any kind; i.e., the individual must never have met the criteria for any other type of schizophrenia or for any other psychotic disorder.

C. There is no evidence of dementia or any other organic mental disorder.

Treatment of schizophrenia

Treatment of schizophrenia

• antipsychotics• recommended at least for two years after

the first episode

– often life-long treatment

• to control acute symptoms

– relapse prevention

• functionality/quality of life

• data about protective effect on the

brain ??

Antipsychotics available in Slovakia

„TYPICALS“

LAI*

flupenthixol yes

fluphenazine yes

haloperidol yes

chlorpromazine no

chlorprotixen no

levopromazine

tiaprid no

zuclopenthixol yes

„ATYPICALS“

LAI LAI

amisulpride quetiapine

aripiprazol yes risperidon yes

asenapine sertindole

clozapine sulpird

olanzapine yes ziprasidone

paliperidon yes

* Long Acting Injectable (depot)

ECT in Schizophrenia

• catatonic subtype

– treatment resistant

– profound negative symptomatology

rTMS in Schizophrenia

• negative symptoms

– chronic hallucinations

Non-biological treatment

• psychosocial interventions

– cognitive training

– training of social competences

– cognitive – behavioral therapy for

delusions

Prognosis

• Late onset

• Obvious precipitating factors

• Acute onset

• Good premorbid social, sexual, and work histories

• Mood disorder symptoms (especially depressive disorders) or affective disorders in family history

• Married, good social support system

• Positive symptoms

• Young onset

• No precipitating factors

• Insidious onset

• Bad premorbid social status

• Withdrawn, autistic behaviorfamily history of schizophrenia

• Bad family/social support background

• Negative symptoms, neurological disturbances, perinatal complications, no remission in 3 years, relapses, non-compliance

Good Poor

Schizophrenia, schizotypal and delusional disorders

F20 Schizophrenia

F20.0 Paranoid schizophrenia

F20.1 Hebephrenic schizophrenia

F20.2 Catatonic schizophrenia

F20.3 Undifferentiated schizophrenia

F20.4 Post-schizophrenic depression

F20.5 Residual schizophrenia

F20.6 Simple schizophrenia

A fifth character may be used to classify course:

.x0 Continuous

.x1 Episodic with progressive deficit

.x2 Episodic with stable deficit

.x3 Episodic remittent

.x4 Incomplete remission

.x5 Complete remission

F21 Schizotypal disorder

F22 Persistent delusional disorders

F23 Acute and transient psychotic disorders

F23.0 Acute polymorphic psychotic disorder without symptoms of schizophrenia

F23.1 Acute polymorphic psychotic disorder with symptoms of schizophrenia

.x0 Without associated acute stress

.x1 With associated acute stress

F24 Induced delusional disorder

F25 Schizoaffective disordersF25.0 Schizoaffective disorder, manic type

F25.1 Schizoaffective disorder, depressive type

F28 Other nonorganic psychotic disorders

F29 Unspecified nonorganic psychosis

Schizotypal (personality) disorder

• lasting at least 2 years

• pervasive pattern of social and interpersonal deficits

• constricted affectivity

• ideas of reference– not delusion of reference

• involvement in paranormal phenomena– not clearly “dereistic”, has influence of behavior

• e.g. to wear sun glasses during the night, because of space radiation

• complicated, unusual construction of speech/phrasing – “pseudophilosophy”, “unproductive vague speech”,

– specific/odd argumentation

– but not clear formal disturbances of thinking

• strange clothing– outside of trends or socially acceptable norms

• inability to understand jokes, teasing remarks, metaphors

• can be transient psychotic experience like illusion, depersonalization

• differential diagnosis from personality disorders (schizoid, paranoid)– marked eccentricity or oddness

• she/will not change odd clothing because of dress code in company

Delusional Disorder (Paranoia)• Delusions

– A false belief based on incorrect inference about external reality that is firmly sustained despite what almost everyone else believes

• non-bizarre (or not so bizarre as in schizophrenia)

– may be systematic and stable

• function could not be disturbed outside of delusional system

• Delusions of

– persecution – persecutory type

– grandeur (inflated self-esteem, exceptional abilities, delusion of origin)

– delusions of jealousy

– hypochondriacal

• monosymptomatic hypochondriacal psychosis– delusional parasitosis, halitosis (delusion of body odor)

– delusion of pregnancy (pseudocyesis)

– different dysmorphophobic delusion

– erotomanic delusions (delusions of love)

• erotomania, Clerembault`s syndrome

• if some hallucinations, they are not prominent or hardly distinguished from disturbance of thinking (like in

prasitosis)

• personality, behavior and emotional reaction can be normal outside of delusional content

• sometimes the crucial event - change in life situation present at the beginning

• must last at least 3 months

F23 Acute and transient psychotic disorders

In DSM-5 Brief Psychotic Disorder

F23.1 Acute polymorphic psychotic disorder with symptoms of schizophrenia

F23.0 Acute polymorphic psychotic disorder without symptoms of schizophrenia

• acute onset = ≤ 2 weeks– specify if less than 48 hours

• psychoreactive, toxic for differential diagnosis

• not longer prodromal phase !! – remember schizophrenia– symptoms rapidly, both in nature and intensity

– duration of the episode ≤ 3 months = if more, the diagnosis should be changed

» most commonly few days to 1 month

• perplexity/qualitative change of consciousness– but not “organic” reason

• dg. often used for first episode of schizophrenia – reasons mainly more social

• patients with recurrent episodes– is it schizophrenia? - cycloid psychoses

Shared Psychotic Disorder

(Induced Delusional disorder)

• A delusion develops in an individual in the context of a close relationship with another person(s), who has an already-established delusion.– often isolated from society

• The delusion is similar in content to that of the person who already has the established delusion.

Schizoaffective DisorderF25.0 Schizoaffective disorder, manic typeF25.1 Schizoaffective disorder, depressive typeF25.2 Schizoaffective disorder, mixed type

Difference from schizophrenia:• cyclic course• affective disturbance as the condition, but usually no flat affect

!• better prognosis than for schizophrenia, worse than for mood

disorders

During the same period of illness, there have been delusions or

hallucinations for at least 2 weeks in the absence of prominent

mood symptoms.

• DSM-5 requires that “symptoms that meet criteria for a major

mood episode are present for the majority of the total duration

of the active and residual portions of the illness”

• Clinical consequence

– often combination of medication (antipsychotics, mood stabilizers,

antidepressants)

Paraphrenia

• = late onset schizophrenia ?

• = paranoia ?

In our concept

• distinguished from schizophrenia– older age

– more common in women

– relatively compact personality

– spectrum of delusions and hallucinations • erotic type – like touches, rapes, erotomanic

delusions