Notes: Neuroscience Models of Schizophrenia

Schizophrenia is a condition characterized by : 1. hallucination, 2. thought disorder, 3. absence of behavior, and 4. lack of motivation.

►Basic symptoms are: associative, affective and personality disturbances, autism and ambivalence.

►Secondary symptoms are: hallucinations, delusions, catatonia and speech disturbances (neologisms, “word salad”)

►Kurt Schneider: Symptoms of 1. and 2. degree (diagnosis of S., if at least one symptom of 1. degree present).

►First degree: acoustic (commenting) hallucinations, disturbances of thinking (incoherent, obsessive, stereotypical, elusive), will (ambivalent, helpless) and perception (derealization, depersonalization)

►Second degree: coenesthetic, optical, olfactory and gustatory hallucinations

►Plus (positive) and minus (negative) symptoms.

►Positive symptoms: delusions, hallucinations, thinking disturbances, bizarre behavior.

►Negative symptoms: affect and speech impoverishment, apathy, disturbed vigilance and concentration

►Affective disturbances dominate in almost 100%, followed by formal thinking disturbances (90%), drive disturbance (85%), diminished attention (84%) and delusions (70%).

Several clinical types:

►Paranoid (hallucinatory) type (ICD 10: F 20.0. DSM-IV 295,30)

►Hebephrenic S. (F 20.1)

►Catatonic S. (F 20.2)

►Undifferentiated S. (F 20.3)

►S. simplex (F 20.6)

►Other S.’s (F 20.8) (e.g. jealousy delusions)

Types of Schizophrenia Symptoms

Paranoid Type:

►Delusional ideas, mostly accompanied by acoustic hallucinations and other S. symptoms.

►Examples of delusional ideas are: persecution, megalomania, particular (religious or other) mission, particular connections.

►Hallucinations consist of commenting or commanding voices (possibly driving to suicide)

► Olfactory or coenesthetic hallucinations may occur

Hebephrenic Type:

►Affective disturbances are predominant

►Inappropriate mood, with affectation, smiling or laughing, grimaces, mannerisms

►Thinking disturbed, speech longwinded, often ridiculous behavior.

►Delusions and hallucinations are short and less severe

Catatonic Type:

►Mainly psychomotor disturbances between stupor and excitement

►Behavior is often characterized by robot-like automatism, rigid and bizarre bodily positions are kept for long time

►Rare in Western countries.

►Often intensive scenic hallucinations

►Severe state with high lethality, emergency state

Other Types:

►Undifferentiated type: Characteristic schizophrenic symptoms without fitting into one of the specific types.

►S. simplex: rare form with only few symptoms, strange behavior, cognitive faculties progressively disturbed, apparently less psychotic than the previously described types. As a rule no delusions or hallucinations. Diagnosis often difficult.

►Postschizophrenic depression (ICD 10: 20.4) consists of mainly negative symptoms, depression, lack of initiative, low level functioning.



Epidemiology of Schizophrenia

►Prevalence: 0.5 – 1% (about the same all over the world)

►Yearly incidence: 0.01%

►Life prevalence: 0.6

►males = females

►Illness begin on average at 21 years (males) and 26 years (females). Hebephrenic form begins with puberty, paranoid-hallucinatory form in about the 4th decade. “Late schizophrenia” begins after 40.



  • Higher familial occurence (Häfner 1993)
  • Family and twin studies: concordance rate in monozygotic twins reaches 44-50%, in heterozygotic twins 10-12%, in siblings 7%.
  • However, no single gene is related to the aetiology of S.;
  • Polygenetic heredity seems to cause the illness.

►Adoption studies (Tienari 1991)

  • “Multifactorial” aetiology
  • Certain neurophysiological or biochemical changes may take place in the brain, leading to higher vulnerability and predisposition.
  • Unfavorable social conditions heighten the chances to develop S. in vulnerable individuals.
  • Coping strategies or protective factors favor better prognosis or subclinical illness.

►Association studies

  • Searching for a gene, genotype, an allele, or a certain DNA sequence variant occuring more frequently than expected in S. populations as risk factor.
  • “Candidate genes” as genetic risk carriers: genes for various dopamine-receptor constellations, e.g. on chromosome 6.

►Morphological and neuropathological findings

  • S. patients have larger brain ventricles than normal population. Atrophic process concentrates mainly on the temporal lobe and the limbic system (thalamus, pallidum, s. nigra, temporal lobe, corpus callosum etc.), diminishing the amount and the arrangement of neurons.
  • Such atrophic processes seem to begin at an early age
  • Brain imaging makes it possible not only to find morphological correlations to S., but also to “observe” dynamic processes occuring in the brain of “normal” and psychotic individuals. Reduced blood perfusion and metabolism could be located in the frontal area
  • Findings are heterogeneous and show great variability.

►Biological hypotheses

  • Dopamine hypothesis: (Experience through dopaminergic drugs: neuroleptics as dopamine-D²-antagonists. Dopamine agonists cause psychotic symptoms) Dopaminergic hypoactivity in the frontal area (leading to “negative symptoms”) and dopaminergic hyperactivity in the mesolimbic system (® “positive symptoms”)
  • Cholinergic hypothesis: also based on the mechanism of cholinergic side-effects of neuroleptics
  • Glutamate hypothesis: Hypofunction of the glutamatergic receptor system (narrowly associated with dopaminergic system)
  • Serotonergic system: Receptor Serotonin-5HT-2a (atypical neuroleptic drugs inhibit these receptors)
  • Complex receptor systems involved (dopaminergic, glutamatergic, serotonergic, gabaergic): balance and interactions between the different systems disturbed
  • Thalamus function disturbance: striato-thalamic pathways filter sensory stimuli reaching the brain cortex. Through disturbance of this mechanism the cortex is poorly protected and thus overstimulated
  • Immunological hypothesis: changes affecting the immune system may follow viral infections. Inconstant findings involving higher antibody titers to cytomegalic, herpes, influenza or measles viruses.

►Psychosocial hypotheses

  • “Schizophrenogenic mother” (Fromm-Reichmann 1950): dominant, possessive, overprotective, rigid and emotionally cold mother “driving” child into “madness” (S.)
  • Double bind hypothesis (Bateson et al. 1956): pathological (double bind) communication between mother and infant, which lead to intellectual and emotional confusion. Lack or passivity of father increases helplessness and frustration of the child, who reacts with withdrawal into psychosis. First group dynamic hypotheses.
  • “Expressed emotions” hypothesis (EE): High emotional level and overprotective-hostile behavior could be found in the families of s. patients, which may lead to frequent s. episodes. Relapse risk predictable by high EE-score (Vaugh & Leff 1976). No specific theory for S., but for all psychiatric conditions
  • “Life Event” hypothesis (Brown & Birley 1970): In about 50% of cases, important life events were found three weeks prior to the beginning of a s. episode. LE are considered as precipitating factors, but not involved in the genesis of the disease
  • Multifactorial theory: Genetic and familial factors concurring (Tienari 1991). At present, multifactorial theory is favorized in all psychiatric and psychosomatic conditions
  • Group dynamic hypothesis (Ammon 1971): Destructive dynamics of the primary group (hostile, manipulative, parentifying, abusive, emotionally traumatizing and confusing atmosphere provoking guilt feelings) interiorized by the child and later enhanced by and acted out in other significant groups (school, work etc.)

Detailed information is found in this lecture:

Schizophrenia is not one disease (in some cases the term disease is not appropriate). There are subtypes of schizophrenia syndromes and  it also occurs in a spectrum.

What Neuroscience has uncovered and theorized so far:

1. Imaging: reduction of brain tissue and dysconnectivity (Gruber, Meisenzahl, Koutsouleris),


2. Global Circuitry /models : cortex-striatal complex-thalamus-cortex; cortex-brain stem (Carlsson; Grace)

3. Local / regional networks: ”dysconnection” hypothesis; cerebral PFC (Murray & Wang, Deco & Hugues)

Impaired coupling of local and global functional feedbacks that underlies abnormal synchronization and negative symptoms of schizophrenia. (Woh 2013)

These are results from Magnetic encephalography (MEG) studies. “In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia.”

4. Neurotransmission: dopamine (+), serotonin (+), glutamate (-), GABA (-); (Antipsychotics: Gründer)

The differences in the excitation-inhibition balance in patients with normal and schizophrenic symptoms can be explained by observing these:

Smaller & fewer dendritic spines, reduced GABA synthesis, increased suppression of GABA release, fewer GABA a1 receptors, reduced GABA re-uptake and more GABA 2 receptors.

a) Working memory task induces lower change in activation in schizophrenia compared to healthy subjects.

b) NMDA-receptor antagonist ketamine evokes similar patterns

c) A computational model of working memory, comprised of task-activated (top) and task-deactivated (bottom) modules highlighting a possible mechanism for deactivation, followed by results. We tested whether ‘disinhibition’ via reduced NMDA receptor conductance onto GABA cells (E–I) (small red arrow) would resemble activation/deactivation BOLD findings under ketamine and observations in schizophrenia.


  1. Synaptic specifities: D2R / D1R predominance e.g. PFC (signal / noise ratio in information processing; Voit)

6. Subcellular molecular networks (Gebicke-Haerter)

7. Genes:for enzymes, receptors … susceptibility genes, including neuregulin-1, ErbB4, nNOS, PICK1, and DISC1, (Rujescu, Schmitt)


Ammon, G. (1971): Auf dem Wege zu einer Psychotherapie der Schizophrenie (Towards a psychotherapy of schizophrenia). Dyn. Psychiat. 4: 9-28 (English summary)
Bateson, G. et al. (1956): Toward a theory of schizophrenia. Behav. Science 1: 251-264
Fromm-Reichmann, F. (1950): Principles of intensive psychotherapy. Chicago: Univ. Chicago Press
Gaebel, W. (2005): New developments and treatment issues in schizophrenia. In: Christodoulou, G. N. (Ed.): Advances in Psychiatry, Vol. 2. World Psychiatric Association, 45-52
Kaplan & Sadock’s Synopsis of Psychiatry (2003) (KSSP). Philadelphia: Lippincott Williams & Wilkins, 471-504
Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, 2 Vol. (2000) (KSCT). Philadelphia: Lippincott Williams & Wilkins, 1096-1231
Vaugh, C., Leff, J (1976): The measurement of expressed emotions in the families of psychiatric patients. Brit. J. Soc. Psychol. 15: 157-165

Narrative Impoverishment in Schizophrenia: Lysaker & Lysaker

“Schizophrenia is characterized by the profoundly diminished ability to experience and represent one’s life as an evolving story” (Lysaker & Lysaker 2006). Disorganized communication about facts, affects and thoughts is involved in disability and a cause of anguish, and a sense of self that lacks depth. There is a lostness of the self amidst an evolving life, and a sense of being an object of social control. The narratives are impoverished.

The article cited is interesting because it provides for a model of schizophrenia that allows us an idea about how we can work towards a functioning psychotherapeutic alliance with clients who aren’t able to easily provide a clear narrative or dialogue.

Read about Notes: Bakhtin’s Polyphonic Novel and the Dialogical Self

Since the work of psychotherapy involves also narratives, how and what can be understood in order to overcome the obstacle of the lack of ability in the client to form coherent narratives?

Dialogical Theory of the Self is used to understand the typology of the experience of self in schizophrenia.

Barren, monological and cacophonous narratives in schizophrenia

The authors asked these questions:

  1. How could someone lose a sense of him or herself amidst a life where there was formerly coherence?
  2. When one’s sense of self appears to be perishing, just what is it that seems to be vanishing (Lysaker & Lysaker, 2001)?

The answer to understanding this is the dialogical models of the self as written by Dimaggio et. al, 2003, Hermans 2004, Nietzsche 1966. That our sense and story of ourselves are part of inner dialogues of different self positions.

It is to be assumed that (p. 59) :

(1) narratives in schizophrenia may become impoverished when processes that allow for the shifting hierarchies within the self are compromised, and

(2) that the loss of sense of self may fundamentally involve the experience of the loss of dialogue.

Thus impoverished narratives may be reflections of diminished dialogical processes rather than merely weak stories.

Forms of narrative impoverishment and the sustenance of dialogue in psychotherapy

Lysaker and Lysaker suggests that other than forcing the client into narrating cohesively, more attention should be paid to the here-and-now relationship between client and therapist.

The client who has no stories to tell, has difficulty  putting into words or bringing to the mind, events and  people from the past experiences. The client can be encouraged to describe his/her experiences in the therapy room and his/her relationship with the therapist. The therapists encourages the client on, by sharing his/her own experiences.

If the relationship can be narrated it seems that other relationships might subsequently be narrated as well – leading ultimately to richer narration of internal feelings and conflicts.

For clients who get stuck in monologues, the therapist can bring the client back to the here-and-now by asking what is being experienced as the stories are being told.  The therapist can continually make statements or ask questions that encourage the client to relate his/her narratives to his/her experiences in the present.

(W)ith the monologue it may be more important to begin by understanding the suffering of a self that is dominated by a limited number of themes. This could include empathic reflections about how specific thoughts take control and make it impossible for the client to think of anything else. By reflecting on the weight of a delusional theme on the daily life and social relationships, the therapist may avoid agreement or disagreement with a delusion or obsessive theme while building the relationship.

Only after the contact through empathic listening is made, and the client is able to relate his/her experiences of the narrated themes, the therapy can move into the more cognitive approach of reality checking these themes.

From a dialogical perspective we reason that this cognitively-based process may diminish the power of the dominant self-positions and allow other self-positions to begin to contribute to the conversation.

In the case of the cacophonous narratives, the central methodology is the continual mirroring and reflection of what the client is saying at the present moment.  In the midst of the fragmented talk, there are pieces of self positions that, with the therapist’s validation, will take foothold.

In this manner independent self-positions might be thought to gather strength to the point where they the can again participate in internal conversations.

Relating to Gestalt Therapeutic Process

Taking the psychotherapeutic relationship to the here-and-now is a very strong feature presented in this article. This is also a major principle in gestalt therapy practice. We also get to appreciate how useful gestalt therapy can be for working with clients diagnosed with schizophrenia.

The other aspect mentioned in this article that I find is closely related to gestalt therapy, is that of phenomenology. Although the word is not mentioned, it is implicit when we bring to the awareness the experiences of creating the dialogue, while not getting sucked in by the content of the narratives. The therapist is handed the task of observing what is happening in the session, and not only focussed on what is being said.

Like most humanistic therapies, unconditional positive regard is the foundation of the work, which requires time and also patience.




Read also : Christopher Bollas on Mental Pain


Lysaker, P. H., & Lysaker, J. T. (2006). A typology of narrative impoverishment in schizophrenia: Implications for understanding the processes of establishing and sustaining dialogue in individual psychotherapy. Counselling Psychology Quarterly19(01), 57-68.