Schizophrenia - Neuroanatomy

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Perinatal brain development

It is thought that causal factors can initially come together in early neurodevelopment, including during pregnancy, to increase the risk of later developing schizophrenia. One curious finding is that people diagnosed with schizophrenia are more likely to have been born in winter or spring (at least in the northern hemisphere). However, the effect is not large. Some researchers postulate that the correlation is due to viral infections during the third trimester (4-6 months) of pregnancy. There is now significant evidence that prenatal exposure to infections increases the risk for developing schizophrenia later in life, providing additional evidence for a link between in utero developmental pathology and risk of developing the condition.

A study by Sweden's Karolinska Institute and Bristol University in the UK, looked at the medical records of over 700,000 people and calculated that 15.5% of cases of schizophrenia seen in the group may have been due to the patient having a father who was aged over 30 years at their birth, the researchers argue this is due to build up of mutations in the sperm of elder fathers.

Women who were pregnant during the Dutch famine of 1944, where many people were close to starvation, had a higher chance of having a child who would later develop schizophrenia. Similarly, studies of Finnish mothers who were pregnant when they found out that their husbands had been killed during the Winter War of 1939–1940 have shown that their children were much more likely to develop schizophrenia when compared with mothers who found out about their husbands' death after pregnancy, suggesting that even psychological trauma in the mother may have an effect.

Childhood and adolescent development

Schizophrenia is most commonly first diagnosed during late adolescence or early adulthood suggesting it is often the end process of childhood and adolescent development. Studies have indicated that genetic dispositions can interact with early environment to increase the risk of developing schizophrenia, including through global neurobehavioral deficits, a poorer family environment and disruptive school behaviour, poor peer engagement, immaturity or unpopularity or poorer social competence and increasing schizophrenic symptomology emerging during adolescence These developmental problems have also been linked to socioeconomic disadvantage or early experiences of traumatic events.

There is on average a somewhat earlier onset for men than women, with the possible protective influence of the female hormone oestrogen being one hypothesis made and sociocultural influences another.

Data from a PET study suggests that the less the frontal lobes are activated (red) during a working memory task, the greater the increase in abnormal dopamine activity in the striatum (green), thought to be related to the neurocognitive deficits in schizophrenia.

Adult brain structure

Differences in the size and structure of certain brain areas have been found in some adults diagnosed with schizophrenia. Early findings came from the discovery of ventricular enlargement in people diagnosed with schizophrenia with negative symptoms most prominent. However, this finding has not proved particularly reliable on the level of the individual person, with considerable variation between patients. The role of antipsychotic medication, which nearly all those studied had taken, in causing such abnormalities is also unclear.

More recent studies have shown a large number of differences in brain structure between people with and without diagnoses of schizophrenia. However, as with earlier studies, many of these differences are only reliably detected when comparing groups of people, and are unlikely to predict any differences in brain structure of an individual person with schizophrenia.

Neuropsychology and brain function

Studies using neuropsychological tests and brain imaging technologies such as fMRI and PET to examine functional differences in brain activity have shown that differences seem to most commonly occur in the frontal lobes, hippocampus, and temporal lobes. These differences are heavily linked to the neurocognitive deficits which often occur with schizophrenia, particularly in areas of memory, attention, problem solving, executive function and social cognition.

Electroencephalograph (EEG) recordings of persons with schizophrenia performing perception oriented tasks showed an absence of gamma band activity in the brain, indicating weak integration of critical neural networks in the brain. Those who experienced intense hallucinations, delusions and disorganized thinking showed the lowest frequency synchronization. None of the drugs taken by the persons scanned had moved neural synchrony back into the gamma frequency range. Gamma band and working memory alterations may be related to alterations in interneurons that produced the neurotransmitter GABA.

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