Hypofrontality in Schizophrenia

Hypofrontality, or reduced activity in the brain's frontal lobes, is a well-established feature of schizophrenia. The frontal lobes are responsible for various executive functions, such as planning, decision-making, working memory, and inhibitory control, which are often impaired in individuals with schizophrenia.

Proposed mechanisms

Several studies using neuroimaging techniques, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), have shown reduced activation or metabolism in the frontal lobes of individuals with schizophrenia compared to healthy controls. This hypofrontality has been linked to the negative symptoms and cognitive impairments commonly observed in schizophrenia.

• reduced blood flow
• reduced dopaminergic activation
• reduced metabolism

However, it is important to note that hypofrontality's exact nature and causes in schizophrenia are not yet fully understood and require further research. Additionally, hypofrontality is not specific to schizophrenia and may also be present in other psychiatric conditions.

References

1. Lawrie, S. M., & Abukmeil, S. S. (1998). Brain abnormality in schizophrenia: a systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry, 172(05), 110-120.
2. Peltier, S., & Casanova, M. F. (2015). The anatomy of schizophrenia: A review of structural brain imaging studies. Journal of the International Neuropsychological Society, 21(4), 235-255.

ICD-11Criteria for Schizophrenia or Other Primary Psychotic Disorders (BlockL1‑6A2)

Schizophrenia and other primary psychotic disorders are characterised by significant impairments in reality testing and alterations in behaviour manifest in positive symptoms such as persistent delusions, persistent hallucinations, disorganised thinking (typically manifest as disorganised speech), grossly disorganised behaviour, and experiences of passivity and control, negative symptoms such as blunted or flat affect and avolition, and psychomotor disturbances. The symptoms occur with sufficient frequency and intensity to deviate from expected cultural or subcultural norms. These symptoms do not arise as a feature of another mental and behavioural disorder (e.g., a mood disorder, delirium, or a disorder due to substance use). The categories in this grouping should not be used to classify the expression of ideas, beliefs, or behaviours that are culturally sanctioned.

Coded Elsewhere:  

• Substance-induced psychotic disorders
• Secondary psychotic syndrome (6E61)

REFERENCE:

International Classification of Diseases Eleventh Revision (ICD-11). Geneva: World Health Organization; 2022. License: CC BY-ND 3.0 IGO.

https://creativecommons.org/licenses/by-nc-nd/3.0/igo/

ICD-11 Criteria for Schizophrenia (6A20 )

Schizophrenia is characterised by disturbances in multiple mental modalities, including thinking (e.g., delusions, disorganisation in the form of thought), perception (e.g., hallucinations), self-experience (e.g., the experience that one's feelings, impulses, thoughts, or behaviour are under the control of an external force), cognition (e.g., impaired attention, verbal memory, and social cognition), volition (e.g., loss of motivation), affect (e.g., blunted emotional expression), and behaviour (e.g., behaviour that appears bizarre or purposeless, unpredictable or inappropriate emotional responses that interfere with the organisation of behaviour). Psychomotor disturbances, including catatonia, may be present. Persistent delusions, persistent hallucinations, thought disorder, and experiences of influence, passivity, or control are considered core symptoms. Symptoms must have persisted for at least one month in order for a diagnosis of schizophrenia to be assigned. The symptoms are not a manifestation of another health condition (e.g., a brain tumour) and are not due to the effect of a substance or medication on the central nervous system (e.g., corticosteroids), including withdrawal (e.g., alcohol withdrawal).

Exclusions:             

• Schizotypal disorder (6A22)
• schizophrenic reaction (6A22)
• Acute and transient psychotic disorder (6A23)

6A20.0        Schizophrenia, first episode

Schizophrenia, first episode should be used to identify individuals experiencing symptoms that meet the diagnostic requirements for Schizophrenia (including duration) but who have never before experienced an episode during which diagnostic requirements for Schizophrenia were met.

6A20.00       Schizophrenia, first episode, currently symptomatic

All definitional requirements for Schizophrenia, first episode in terms of symptoms and duration are currently met, or have been met within the past one month.

6A20.01       Schizophrenia, first episode, in partial remission

All definitional requirements for Schizophrenia, first episode in terms of symptoms and duration were previously met. Symptoms have ameliorated such that the diagnostic requirements for the disorder have not been met for at least one month, but some clinically significant symptoms remain, which may or may not be associated with functional impairment. The partial remission may have occurred in response to medication or other treatment.

6A20.02       Schizophrenia, first episode, in full remission

All definitional requirements for Schizophrenia, first episode in terms of symptoms and duration were previously met. Symptoms have ameliorated such that no significant symptoms remain. The remission may have occurred in response to medication or other treatment.

6A20.0Z       Schizophrenia, first episode, unspecified

6A20.1         Schizophrenia, multiple episodes

Schizophrenia, multiple episode should be used to identify individuals experiencing symptoms that meet the diagnostic requirements for Schizophrenia and who have also previously experienced episodes during which diagnostic requirements were met, with substantial remission of symptoms between episodes. Some attenuated symptoms may remain during periods of remission, and remissions may have occurred in response to medication or other treatment.

6A20.10       Schizophrenia, multiple episodes, currently symptomatic

All definitional requirements for Schizophrenia, multiple episodes in terms of symptoms and duration are currently met, or have been met within the past one month.

6A20.11       ZSchizophrenia, multiple episodes, in partial remission

All definitional requirements for Schizophrenia, multiple episodes in terms of symptoms and duration were previously met. Symptoms have ameliorated such that the diagnostic requirements for the disorder have not been met for at least one month, but some clinically significant symptoms remain, which may or may not be associated with functional impairment. The partial remission may have occurred in response to medication or other treatment.

6A20.12       Schizophrenia, multiple episodes, in full remission

All definitional requirements for Schizophrenia, multiple episodes in terms of symptoms and duration were previously met. Symptoms have ameliorated such that no significant symptoms remain. The remission may have occurred in response to medication or other treatment.

6A20.1Z         Schizophrenia, multiple episodes, unspecified

6A20.2         Schizophrenia, continuous

Symptoms fulfilling all definitional requirements of Schizophrenia have been present for almost all of the illness course over a period of at least one year, with periods of subthreshold symptoms being very brief relative to the overall course.

6A20.20       Schizophrenia, continuous, currently symptomatic

All definitional requirements for Schizophrenia, continuous in terms of symptoms and duration are currently met, or have been met within the past one month.

6A20.21        Schizophrenia, continuous, in partial remission

All definitional requirements for Schizophrenia, continuous in terms of symptoms and duration were previously met. Symptoms have ameliorated such that the diagnostic requirements for the disorder have not been met for at least one month, but some clinically significant symptoms remain, which may or may not be associated with functional impairment. The partial remission may have occurred in response to medication or other treatment.

6A20.22     Schizophrenia, continuous, in full remission

All definitional requirements for Schizophrenia, continuous in terms of symptoms and duration were previously met. Symptoms have ameliorated such that no significant symptoms remain. The remission may have occurred in response to medication or other treatment.

6A20.2Z                 Schizophrenia, continuous, unspecified

6A20.Y                   Other specified episode of schizophrenia

6A20.Z                    Schizophrenia, episode unspecified

REFERENCE:

International Classification of Diseases Eleventh Revision (ICD-11). Geneva: World Health Organization; 2022. License: CC BY-ND 3.0 IGO.

https://creativecommons.org/licenses/by-nc-nd/3.0/igo/

Causes of Increased Mortality in Schizophrenia

The mortality rate is elevated in patients with schizophrenia. The following are the common natural and unnatural causes of increased mortality in patients with schizophrenia. 

Unnatural Causes 

Approximately 60% of the increased mortality is because of unnatural causes, especially suicide and accidents.

Natural Causes 

Nearly 40% of the increased risk is because of natural causes, such as:

• Cardiovascular disease
• Smoking
• Sedentary lifestyle
• Obesity
• Medication side effects

Differences between Typical and Atypical Antipsychotics: Efficacy and Adverse Effects

Typical Versus Atypical Antipsychotics

By definition, typical antipsychotics are those which produce extrapyramidal side effects, while atypical antipsychotics do not. However, at the doses used today, most atypical antipsychotics do not produce extrapyramidal side effects. Whether typical and atypical antipsychotics differ in efficacy in a long-held debate. Except for clozapine, there are no significant differences in the efficacy of typical and atypical antipsychotics. 

Two large pragmatic studies, CATIE in the United States, and CutLASS in the United Kingdom, in 2005 and 2006, respectively, produced similar conclusions. Another meta-analysis, in 2009 showed that risperidone, olanzapine, and amisulpride were more effective compared to typical antipsychotics. 

Overall, typical antipsychotics are more likely to produce extrapyramidal side effects, while atypical ones are more likely to produce metabolic side effects, including weight gain, hyperlipemia, and diabetes. 

Clozapine is more effective than both typical and other atypical antipsychotics. 

Assessment and Management of The Risk of Violence in Schizophrenia

Assessment and Management of The Risk of Violence in Schizophrenia

Scenario

A 21-year-old lady with the diagnosis of schizophrenia informs you she will kill her neighbour tomorrow as she has ruined her life. She tells not to disclose this to anyone.

1. How will you assess the homicidal risk in this patient?
2. What treatment and follow up recommendations will you make in this case?

Clinical Assessment 

Listen to the patient and develop a therapeutic relationship. 

begin the assessment and enquire about her demographics. 

Enquire about the issue that she brought up—she will kill her neighbour. 

Elaborate on how she thinks her neighbour has ruined her life. 

Explore her thoughts and whether the patient may have persecutory delusions

Assess how much resentment she feels?

Follow up with inquiry about her mood, esp. about irritability and depression

How she plans to commit the act

Has she threatened the person?

Whether she has done so in the past

If so, what provoked such an incident

Whether the provoking factor is still present

Whether she possesses a weapon.

How easily she can access her

Whether she uses alcohol or substance

Psychiatric history and mental state

Whether she has other psychotic symptoms, e.g., commanding hallucinations

Negative symptoms (reduced likelihood)

Elicit relevant personal history

Especially whether she is single, divorced or separated

Who she lives with?

Her socioeconomic circumstances

Any stressful circumstances she might be passing through

 

Tools to Assess the Risk of Violence

Buss-Durkee Hostility Inventory

•       75 (true/false)-item questionnaire

•       Used to assess cynicism and distrust

Hostility and Direction of Hostility Questionnaire

The 51-item self-report questionnaire with 5 subscales. 

Used to assess the range of manifestations of aggression, hostility, and punitiveness; distinguishes hostility as they direct it either externally (extra-punitive: psychopathic, paranoid, hysterical) or internally (internal-punitive: guilt, self-criticism)

Aggression Risk Profile

•       39-item rating scale

• Identifies the characteristics of chronically aggressive patients, to foresee future manifestations of violent behaviour

Suicide and Aggression Survey

• Semi-structured clinician-administered interview and research tool; divided into 5 parts

• Elicits a brief medical history, recent and lifetime suicidality, and tendency to social violence; measures recent and past aggressiveness expressed by suicidal acts and thoughts

Management

1. Clozapine for schizophrenia, which also reduces the risk of violence (Farooq and Taylor 2011)
2. Address the modifiable risk factors identified
3. Inform the potential victim as a precautionary measure (which is also a legal/ethical responsibility)
4. If community services are available, we should consider assertive outreach.
5. If the patient is violent, we can also consider ECT.
6. Family therapy, CBT and other psychosocial interventions for schizophrenia.