Schizophrenia

Schizophrenia is a prevalent and debilitating mental disorder, typically beginning in late adolescence or early adulthood, affecting >21 million individuals across the globe¹.

Positive symptoms of schizophrenia include hallucinations (such as hearing voices when no-one is around), delusions (falsely held beliefs, such as, that their thoughts are being ‘broadcasted’), and disorganised speech.

Negative symptoms of schizophrenia include loss of drive, blunting of mood, and poverty of speech. The precise symptoms experienced by individuals with schizophrenia are variable, and may change over time.

For a formal diagnosis of schizophrenia, the symptoms must persist for a given period of time: the International Classification of Diseases (ICD-11) specifies one month, while the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) specifies continuous signs of disturbance for at least six months.

Schizophrenia and related disorders, left untreated, can have a profound negative impact on the ability of people to form social relationships, undertake academic studies, and pursue career goals.

Affected individuals are at increased risk of social disability, early mortality, social stigma, and negative impact on carers and friends/family^{2, 3}.

As well as the personal cost of psychotic disorders, they are also economically costly. For example, in a US study, the economic consequences of schizophrenia were found to be similar to those of common medical conditions such as diabetes⁴.
 

Pathology and functional impact of Schizophrenia

As with most psychiatric disorders, the brain basis of schizophrenia is not fully understood. There is considerable evidence that schizophrenia is a neurodevelopmental disorder, in which there is a deviation of brain development from the expected trajectories⁵.

Implicated etiological factors include genetics (the disorder is up to 80% heritable), and environmental factors, e.g. perinatal complications, winter births, and older paternal age. While these factors can influence risk of developing schizophrenia, there is generally no clear cause in individual cases.

There is neuroimaging evidence for reduced structural integrity of white matter tracts (structural connectivity), and abnormal communication between discrete brain regions or ‘nodes’ (so-termed functional connectivity)⁶.

Reductions in grey matter are frequently observed, especially in prefrontal and temporal cortical regions, which play key roles in high-level cognitive functions including working memory, planning, and associative learning^{7, 8}.

As a consequence of these underlying brain changes, cognitive impairment is common in people with schizophrenia, and tends to involve many different domains⁹.

It has been suggested that increased striatal dopamine plays a key role in the positive symptoms of schizophrenia, while cognitive impairment and negative symptoms are likely to stem from other neurochemical and immune abnormalities, such as involving the glutamate system and inflammatory pathways¹⁰.

 

Research and development in Schizophrenia

Multiple evidence-based treatment options exist for schizophrenia and related disorders, but the precise choice of treatments should be determined on an individual basis following assessment by a healthcare professional, taking into consideration relevant local guidelines.

Psychotherapy, in the form of cognitive behavioural therapy (CBT; with or without family therapy) is recommended for people with established schizophrenia, and also for people who are at heightened risk of developing psychosis in future.

Antipsychotic medication represents a first-line treatment for psychosis, and there are multiple options in this category of medication, with potentially different benefits and risks.

In addition to considering schizophrenia itself, it is important for healthcare professionals to screen for other mental disorders (e.g. substance use disorders, anxiety disorders, history of trauma) and to treat comorbidities as well. The physical health of people with schizophrenia should also be monitored closely, including in relation to medication side effects.

While treatments are available for schizophrenia and related conditions, in some cases individuals cannot tolerate particular medications due to side effects and/or the need for physical health monitoring; or may find engaging with therapy difficult.

Current mainstream antipsychotic medications do have side effects in common: a meta-analysis suggested that nearly all currently available antipsychotic medications result in weight gain¹¹.

Another limitation of existing treatment options is that, while some antipsychotic medications appear to be associated with improvement in some cognitive domains, these represent relatively small effects¹². Therefore, many people with schizophrenia will experience cognitive deficits despite first-line interventions.

Negative symptoms of schizophrenia (e.g. problems with motivation, emotional blunting) are widely regarded as being resistant to current first-line medication options. The search is on for treatments that can fully ameliorate cognitive impairment in psychosis, as well as reduce positive and negative symptoms, in order to maximise long-term outcomes and quality of life.

 

You might also be interested in…

Barbato, A. (1998). Schizophrenia and Public Health. Nations for Mental Health. World Health Organization.

Barnett, J., et al (2010). Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev.

Kahn R.S. and Sommer I.E. (2015). The neurobiology and treatment of first-episode schizophrenia. Mol Psychiatry.

Barnett J.H., et al (2005). Visuospatial learning and executive function are independently impaired in first-episode psychosis. Psychol Med. 

 

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1. _{World Health Organization. Overview on schizophrenia, 2015. http://www.who.int/mental_health/management/schizophrenia/en/}
2. _{Barbato, A. Schizophrenia and Public Health. Nations for Mental Health. World Health Organization, 1998.}
3. _{Revier CJ, Reininghaus U, Dutta R, Fearon P, Murray RM, Doody GA, Croudace T, Dazzan P, Heslin M, Onyejiaka A, Kravariti E, Lappin J, Lomas B, Kirkbride JB, Donoghue K, Morgan C, Jones PB. Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study.J Nerv Ment Dis. 2015 May;203(5):379-86.}
4. _{Pantelis C, Barnes TR. National Advisory Mental Health Council. (1993). Health care reform for Americans with severe mental illnesses: Report of the National Advisory Mental Health Council. American Journal of Psychiatry, 150: 1447-1465.}
5. _{Selemon LD, Zecevic N. Schizophrenia: a tale of two critical periods for prefrontal cortical development. Transl Psychiatry. 2015 Aug 18;5:e623. doi: 10.1038/tp.2015.115.}
6. _{Narr KL, Leaver AM. Connectome and schizophrenia. Curr Opin Psychiatry. 2015 May;28(3):229-35.}
7. _{Zipursky RB, Lim KO, Sullivan EV, Brown BW, Pfefferbaum A. Widespread cerebral gray matter volume deficits in schizophrenia. Arch Gen Psychiatry. 1992;49:195–205.}
8. _{Veijola J, Guo JY, Moilanen JS, Jääskeläinen E, Miettunen J, Kyllönen M, Haapea M, Huhtaniska S, Alaräisänen A, Mäki P, Kiviniemi V, Nikkinen J, Starck T, Remes JJ, Tanskanen P, Tervonen O, Wink AM, Kehagia A, Suckling J, Kobayashi H, Barnett JH, Barnes A, Koponen HJ, Jones PB, Isohanni M, Murray GK. Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. PLoS One. 2014 Jul 18;9(7):e101689.}
9. _{Barnett JH, Robbins TW, Leeson VC, Sahakian BJ, Joyce EM, Blackwell AD. Assessing cognitive function in clinical trials of schizophrenia. Neurosci Biobehav Rev. 2010 Jul;34(8):1161-77.}
10. _{Kahn RS, Sommer IE. The neurobiology and treatment of first-episode schizophrenia. Mol Psychiatry. 2015 Feb;20(1):84-97.}
11. _{Bak M., et al. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014 Apr 24;9(4):e94112.}
12. _{Désaméricq G, Schurhoff F, Meary A, Szöke A, Macquin-Mavier I, Bachoud-Lévi AC, Maison P. Long-term neurocognitive effects of antipsychotics in schizophrenia: a network meta-analysis. Eur J Clin Pharmacol. 2014 Feb;70(2):127-34.}