The Pathophysiology of Schizophrenia

Schizophrenia is a physiological phenomenon. The fact that the disorder is so symptomatically dynamic is one of the main reasons it is considered one of the most complex degenerative brain disorders in existence. Physiologically, what we do know about schizophrenia is that regardless of the behavioral aspect or classification of the symptom, they all derive from dysfunction of an individual’s neurobiological makeup.

The etiology of schizophrenia is still widely debated, however we can say with a few hundred research studies worth of security that the physiological expression of the disorder is due mainly to disruptions in neurotransmitter function and abnormal neurological structures. In turn, these are thought to be due to genetic mutations or changes in an individual’s genetic expression.

For the purpose of providing a clear explanation, the following sections are divided into positive and negative symptoms, however the distinction between positive and negative symptoms of schizophrenia is mainly of categorical use as it does very little to simplify the understanding of the symptoms themselves as they are the product of combinations of neurotransmitter function.

Positive Symptoms of Schizophrenia

Pathophysiologically, positive symptoms of schizophrenia are related to the function of a combination of neurotransmitters, primarily the overproduction of dopamine or inhibition of dopamine reuptake. Dopamine monitors energy levels and controls metabolism and as evident by the manic-like characteristics of positive symptoms, dopamine can also produce physiological effects similar to those induced by amphetamines.

Dopamine also plays a role in cognition, mood, attention, and learning, which accounts for symptoms like thought disorders (disorganized thinking and thought blocking), movement disorders (catatonic stupor or catatonic excitement), delusions (persucutory, erotomanic, grandoise, somatic, or broadcasting), hallucinations, and in paranoid schizophrenia, capras syndrome.

Auditory hallucinations are the most distinctive symptom of schizophrenic patients. Research on cerebral blood flow in schizophrenic patients suffering from auditory hallucinations indicates that this symptom, common to schizophrenic patients, is experienced biologically in Broca’s area, a region in the frontal lobe whose function is speech production. Therefore, if I am speaking aloud or to myself, Broca’s area would be activated. Wernike’s area,  a region in the cerebral cortex located in the left posterior temporal lobe is responsible for speech comprehension, which means that this area should become activated during auditory stimulation. However, during auditory hallucinations, schizophrenics experience more intense activation of Broca’s area. Physiologically, as indicated by activation of Broca’s area, the patient is hearing his/her own voice. Psychologically, as indicated by non-activation of Wernike’s area, the patient cannot distinguish between his/her host voice or the voice of his/her perceived narrator. Behaviorally, the patient appears to speak to him/her self, which validates the finding that physiologically, the patient is indeed producing the speech he or she is hearing.

Hallucinatory and delusional symptoms can be attributed to abnormalities in acetylcholine pathways as well. Acetylcholine is the regulatory neurotransmitter responsible for processing sensory input and accessing stored information. Abnormalities at this level can result in misreading sensory information and memory problems.

Negative Symptoms of Schizophrenia

Although negative symptoms can also be related to dopamine, other neurotransmitters such as gamma-aminobutyric acid (GABA), serotonin, and acetylcholine can also account for the depression-like symptoms experienced on the other extreme of the schizophrenic symptom spectrum.

GABA is the primary inhibitory neurotransmitter of the nervous system and is responsible for producing endorphins. Under peak functionality, GABA promotes relaxation, however abnormalities in its production or distribution can have opposing effects which result in negative symptoms. Negative symptoms consist primarily of emotional and physical apathy.

Patients suffering from schizophrenia with mainly negative symptoms are often misdiagnosed with depression as abnormalities in the neurotransmitter serotonin can cause lack of appetite, an inability to enjoy life, relationships or friendships, insomnia, anxiety, paranoia, dread, and a general lack of motivation that is projected onto every event in the patient’s life.

The similarities between negative schizophrenic symptoms and major depressive disorder are extremely problematic. Physiologically, both disorders have a similar proposed etiology, however the pharmacological treatment of schizophrenia and depression has shown that our understanding of neurobiology is faulty and this can have extremely harmful effects on patients.

Symptoms of schizophrenia are caused by multiple neurotransmitters, and dopamine, although associated mainly with positive symptoms, is still hypothesized to be responsible on a more complex level with the general biochemical structure of the disorder.

The treatment of patients diagnosed with depression generally consists of anti-depressants such as selective serotonin, dopamine, or norepinephrine reuptake inhibitors. This is problematic for schizophrenics misdiagnosed and treated for depression because it completely rearranges the dynamics of neurochemical function which can worsen symptoms of schizophrenia. In turn, this creates more symptoms which are then treated with more medication, causing the patient’s neurobiological makeup to become an artificial and dangerously unstable entity.

Schizophrenia and Neurological Abnormalities

In order to understand the pathophysiology of schizophrenia, we also have to take into account neurological structure. Research on the brains of high risk infants has proven that even in early development, schizophrenics show structural abnormalities, the most visually noticeable being enlarged ventricles and deficits in gray matter volume in the temporal and frontal lobes.

Studies show that the deficit of gray matter seems to occur mainly in the right superior temporal gyrus and the loss of tissue is progressive and directly related to the severity of symptoms. The lower the amount of gray matter volume, the more severe the symptoms. Symptomatically, reductions in the volume of gray matter are manifested through the expression of mainly positive symptoms such as delusions, hallucinations, psychotic thinking and depression.

It is immensly fascinating  that on a pathophysiological level, the cognitive, emotional, and physical symptoms of schizophrenia are due to  neurostructural abnormalities and neurobiological dysfunction. Disorders like schizophrenia show us exactly how intricate neurological function is and how very little we understand of its details.