Schizophrenia – Physiology, Pathophysiology and Pharmacological Therapies

Schizophrenia has been known to be a psychiatric disorder affecting 1% of the world’s population1, which affects the brain in a physiological approach and it’s known to be a progressive life-long illness1. The brain is part of the nervous system. The central nervous system (CNS) and the peripheral nervous system (PNS) make up the nervous system. The central nervous system consists of both the brain and the spinal chord while the peripheral nervous system consists of the network of nerves, which are all linked to the spinal chord and the brain. The CNS makes up the largest part of the nervous system, which controls everything in the body, both the CNS and the PNS has major impact in the way our behaviour and emotions are controlled (all activities of the body)2.

The brain, which controls our emotions, thoughts and movement, can be found in the cranial cavity, the brain is also known to control the autonomic functions which are our unconscious actions such as heart rate, digestion, breathing etc2. The brain consists of soft delicate neural tissues, which is protected by the skull, meninges and the cerebrospinal fluid. The brain can be divided into three main parts, which are: the forebrain which consist of the cerebrum, thalamus, hypothalamus and the limbic system, the midbrain which consists of the tectum and tegmentum, they tend to make the largest part of the brain stem, and the hindbrain which is made up of the cerebellum, pons and medulla oblongata. The midbrain, the pons and the medulla are sometimes known as the brain stem2

A normal healthy brain functions quickly and automatically by receiving electrical signals from the neurons3. Neurons are known to be electrical nerve cells that can gather information and transit electrical signals. There are lots of different neurons in our brain and body in which they pass electrical signals to other cells through the synapses, once it reaches the end of the axons, it stimulates tiny sacs which are known as neurotransmitters into the synapses, this then allows information to be carried to receptors on the other cells in our brain/body2. The neurotransmitters in our brain include amino acids, monoamines, peptides and acetylcholine, some of these neurotransmitters are known to be excitatory (glutamate) while some are known to be inhibitory (GABA) and some are known to depend on their receptor in order to determine if the transmitter is inhibitory or excitatory (dopamine) neurotransmitter4.

Structure of a typical NEURON

A basic neuron contains the cell body, which is the main part of the neuron as it contains all the necessary parts of the cell i.e. nucleus, mitochondria, ribosomes etc, followed by the axons, which usually carries electrical message, axons are usually covered with myelin, which is made of fat, it helps to speed transmission of a nerve impulse down the axons, followed by the dendrites, which allows connection to other cells as they are arranged at the end of the cell in a branch-like fashion, and finally the axon terminals, which are located at the end of an axon for information output2,6.

These neurotransmitter chemicals in our brain are released and they tend to bind to the receptor sites onto the postsynaptic neurons by crossing the synaptic cleft, the changes that occur when the binding takes place can either continue or inhibit the transmission of the impulse5. An uptake can occur when the function of the neurotransmitter is completed. Once any of these neurotransmitters are altered at the postsynaptic receptor, it can lead to a disease i.e. Schizophrenia3.

Pathophysiology

Schizophrenia was first termed by a Swiss Psychiatrist named Eugen Bleuler in 19117 and it’s known to affect both men and women equally but it tends to affect men at a much earlier stage than women usually in early adulthood8. The precise cause of schizophrenia is unknown but there are a number of factors / hypothesis discovered by various researchers, which include:
Schizophrenia patients can experience either the negative symptoms, positive symptoms and cognitive symptoms14 the positive symptom which is caused by increased dopaminergic activity in the brain includes hallucinations, delusions, thought disorder while the negative symptom which is caused by reduced activation of prefrontal cortex might include emotional and social withdraw14 and the cognitive symptoms can include decrease verbal learning, memory difficulties, loss of concentration, problem solving etc, this disorder prevents sufferers from thinking clearly and recognising reality14,.

Schizophrenia patients are known to have part of their brain affected compared to normal brain. The cerebral ventricles of the brain tends to become larger, which tends to alter the brain structure associated with the disorder, they tend to have reduced brain activity of the frontal lobes of the brain, it is also known that schizophrenia patients tend to have less grey matter in their brain, both the hippocampus and the amygdala are found to be smaller compared to normal brain15,16. The area of the brain, which tends to be affected in schizophrenia, includes the frontal lobe (prefrontal cortex), thalamus, temporal lobe, cerebellum and the cingulated gyrus. All these features observed in schizophrenia brain shows that some connections in the brain are

abnormal, which gives rise to the symptoms of schizophrenia15. Several other method has also shown that these part of the brain is affected in schizophrenia patient, such as positron emission tomography (PET), magnetic resonance imaging (MRI), and single-photon emission computed tomography (SPECT) scanning techniques has widely been used in order to understand better the structure and function of the affected brain to be examined in detail, a number of brain-imaging has helped in showing that abnormal brain morphology is involved in the development of schizophrenia18,19.

Dopamine which partly governs the brain activity has become one of the neurotransmitter known to affect schizophrenia patients, which proposes that the disorder is caused by increased level of dopamine in the brain between neurons, which results in excessive stimulation by combining with receptor on the brain cell. Excessive dopamine in the brain can disrupt emotional functioning as dopamine is involved in mood and control of complex movements, which can lead to schizophrenic psychosis21. The increase in dopamine concentration in affected patients is known to be mostly associated with increased activity of D2 dopamine receptors in the prefrontal cortex, which is found in the region of the frontal lobe, prefrontal cortex is also associated with memory, hence the disordered thinking and thoughts of an affected patient.

Research has also shown that another neurotransmitter called serotonin is involved in causing symptoms of schizophrenia; various researches indicated that patients with schizophrenia felt better with drugs that affect the serotonin in the brain22,23. Other neurotransmitters that might be involved in the pathogenesis of schizophrenia include GABA, glutamate and acetylcholine. GABA is now known to be another hypothesis for the aetiology of the disease.

Although there is no cure for schizophrenia but there are variety of drugs that can be used to treat schizophrenia most of which have similar mode of action and effects. Antipsychotic drugs (Neuroleptic drugs) are the first generation of primary treatment for the symptoms of this disorder; they are only used to control the symptoms but not to cure it. Antipsychotic drugs mainly depresses the action of dopamine which they can disturb its balance with another chemical in the brain (Ach), if an imbalance occurs, it can result in extra-pyramidal side effect, which include restlessness, disorder of movement and parkinsonism.

The drugs also occupy the dopamine D2 receptors by binding onto them, which prevents the effects of excess dopamine in the brain by reducing the transmission of nerve signals; this effectively makes the brain cells become less sensitive to dopamine. Another neurotransmitter blocked by these drugs is the serotonin 2 receptors, which is also involved in causing symptoms of the disorder. Antipsychotic drugs are known to have a response delay of 2 – 3 weeks from administering the drug into observing therapeutic effects26,27,28.

Schizophrenia is a very serious condition. It is the most common psychosis. Schizophrenia affects attention, thinking, social relationships, motivation and emotion. In a serious episode, most find it hard to understand the “reality” and it challenges our basic understanding about …

Research into schizophrenia shows that there is a major genetic component but the fact that concordance rates between identical twins is never 100% means that there must be environmental contributions.’ Discuss biological explanations of schizophrenia. (30 marks) Schizophrenia is a psychiatric disorder …

‘Research into schizophrenia shows that there is a major genetic component but the fact that concordance rates between identical twins is never 100% means that there must be environmental contributions.’ Discuss biological explanations of schizophrenia. (30 marks) Schizophrenia is a psychiatric disorder …

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Schizophrenia is a serious and chronic mental disorder that affects 1% of the world’s population. It is characterized by a range of striking disturbances in mental functioning that can be grouped into both positive and negative symptoms, and also cognitive …

Neurobiology plays a very important path in the causation of OCD. Recently there have been a lot of developments in the understanding we have developed in matters regarding OCD. The basis for this development includes improved imaging techniques of the …

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