Exploring Etiology: What Part Of The Brain Is Affected By Schizophrenia?

Schizophrenia is a mental health disorder usually characterized by hallucinations, delusions, and disorganized thoughts and speech. It can influence how an individual perceives and interacts with the world and may significantly impact daily life, productivity, and interpersonal relationships. 

Like many mental illnesses, the workings of schizophrenia can be complex. A deeper understanding of its causes and contributing factors may be integral to developing more effective treatments for the disorder. It’s thought that brain regions like the prefrontal cortex, amygdala, hippocampus, thalamus, and striatum may be affected by schizophrenia. Often, symptoms can be managed with doctor-prescribed medication and therapy.

Learn more about schizophrenia from an expert

Connect with a licensed therapist online

The neuroanatomy of schizophrenia

Key regions associated with schizophrenia

Research suggests that differences and dysfunction in the following areas of the brain could be linked to schizophrenia.

The prefrontal cortex (PFC)

This part of the brain generally occupies the frontal lobe's orbital, medial, and lateral areas. The PFC is primarily responsible for executive function, including planning, working memory, attention, reactivity, and judgment. Research indicates that people with schizophrenia typically have cortical brain abnormalities compared to people with no history of schizophrenia. 

Amygdala

The amygdala is usually involved in processing emotions like fear and aggression. Dysregulation of this area of the brain has been linked to emotional distress and decreased cognitive function in schizophrenia patients. 

Hippocampus

Located in the temporal lobe, this part of the brain generally plays a significant role in memory formation, spatial navigation, learning, and emotions. Dysfunction in the hippocampus can be linked to both cognitive deficits and positive symptoms like hallucinations and delusions.

Thalamus

The thalamus usually serves as a relay station for sensory information processing and the regulation of consciousness. Abnormalities in thalamic structure and function appear to contribute to sensory processing deficits and altered perception in people with schizophrenia.

Striatum

The striatum, particularly the mesolimbic dopamine pathway, can be implicated in the reward system and motivational processes. Dysregulation of dopamine neurotransmission in the striatum may be associated with anhedonia and other negative symptoms present in schizophrenia. 

Structural brain abnormalities

• Grey matter generally covers the brain's surface and contains nerve cells. Its function is primarily to control sensory perception and muscles. Studies involving first-episode schizophrenic patients typically show a progressive brain volume decrease in grey matter during the early stages of the disorder, although updated evidence may be necessary
• Residing deep within the brain's tissues, white matter normally contains nerve cells and fibers from which the body requires signals to function. Brain changes in white matter structure in some people with schizophrenia appear to contribute to its development. 

Neurodevelopmental hypothesis

The neurodevelopmental hypothesis in schizophrenia is generally centered around the idea that abnormal structural brain changes during the first and second trimesters of pregnancy may play a vital role in the emergence of psychotic symptoms in adolescence or early adulthood. These abnormalities have been associated with genetic and environmental factors. 

Role of neurotransmitters in the pathophysiology of schizophrenia

The dopamine, glutamate, and GABA hypotheses can offer potential insights into the role of neurotransmitters in schizophrenia.

The dopamine hypothesis

Some experts posit that dysregulation of dopamine neurotransmission in the subcortical, limbic, and prefrontal cortex regions may contribute to negative and positive schizophrenia symptoms. Recent studies may offer evidence to support the dopamine hypothesis and the efficacy of antipsychotic medications targeting dopamine receptors.

The glutamate hypothesis

This hypothesis proposes that a deficiency in activity at the glutamate synapse, particularly in the prefrontal cortex and hippocampus, may contribute to negative and cognitive symptoms of schizophrenia.

The GABA hypothesis

Studies on the neurotransmitter GABA suggest that a loss of neurotransmission in some regions of the prefrontal cortex and hippocampus could contribute to cognitive impairments and psychotic symptoms in individuals with schizophrenia. 

Future implications 

Because of groups like The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium, advancements in neuroimaging techniques yield daily discoveries that can enhance our understanding of schizophrenia's symptoms and origins.

However, because schizophrenia can be seen as a heterogeneous disorder with diverse symptom profiles, the affected brain regions can vary among individuals. As such, ongoing interdisciplinary research may be necessary to develop more effective treatments targeting the underlying neurological mechanisms impacting individuals with schizophrenia.

For example, a recent study published in Nature Neuroscience revised long-standing beliefs about how antipsychotic medications (typically the first line of treatment for schizophrenia) may impact the brain's dopaminergic functioning. These findings likely have significant implications for developing more effective medications to successfully treat schizophrenia patients for whom antipsychotics weren't effective. This new generation of antipsychotics may also reduce adverse side effects associated with traditional antipsychotics, potentially encouraging better treatment adherence. 

Schizophrenia symptoms, stages, and diagnostic criteria

Understanding schizophrenia symptoms and how they manifest over time can be integral to establishing a diagnosis and treatment plan. Symptoms are typically categorized into three types: positive, negative, and cognitive.

Positive symptoms of schizophrenia

"Positive" symptoms can be defined as those involving a break with reality. They typically manifest outwardly and may be observable by others. Positive symptoms can include the following:

• Hallucinations: Auditory hallucinations tend to be the most common and often involve hearing voices. However, some individuals experience hallucinations associated with other sensory experiences, like sight, touch, smell, and taste. 
• Delusions: Delusions can refer to false thoughts and beliefs an individual holds despite evidence to the contrary. They may be paranoid, neutral, or grandiose in nature.
• Disorganized thinking and speech: People with schizophrenia sometimes experience disorganized thinking that surfaces in odd or nonsensical speech patterns. 
• Disorganized behaviors: Individuals with schizophrenia might display behaviors that appear odd or erratic to others. They can range from severe agitation to lack of movement or affect (catatonia).

Negative symptoms

These symptoms tend to be associated with the individual's emotional state and interpersonal relationships. They may range from mild to severe and often mirror symptoms of other mental conditions, like major depressive disorder and generalized anxiety disorder. Common negative symptoms of schizophrenia may include those listed below:

• Anhedonia: Lack of or decreased ability to experience pleasure
• Blunted affect: Diminished ability to express emotions
• Avolition: Lack of or diminished motivation
• Asociality: Aversion to social interaction
• Alogia: Decreased ability to speak clearly

Cognitive symptoms

Cognitive symptoms generally refer to those affecting an individual's memory, concentration, problem-solving abilities, learning, and executive function. These symptoms can create challenges in all areas of an individual's life, including academics and employment. 

Episodic phases

Whether one is referring to schizophrenia's core positive symptoms or lingering negative symptoms, the disorder’s signs tend to emerge in phases.

Prodromal stage

It's usually during this phase that signs of schizophrenia begin to surface in the form of negative symptoms. Friends and loved ones might notice the individual becoming significantly withdrawn, unmotivated, and depressed during this time. They may not take pleasure in activities they once enjoyed, seeming emotionally "flat" and indifferent.  

Symptoms of this stage often mimic those of other disorders, such as depression or bipolar disorder, making misdiagnosis a common occurrence. 

Acute stage

Positive symptoms like delusions and hallucinations normally emerge during the acute phase. Some may believe they can communicate with unseen forces or that random people are "out to get them." Others may experience delusions of grandeur, believing they're godlike or famous. They might appear disoriented or separated from reality, and they may have trouble communicating coherently. 

Residual stage

The residual stage is usually marked by a decrease in positive symptoms and a return to negative symptoms. Though it may be the least intense phase for some, it can severely affect the individual's self-esteem, leaving them feeling isolated. 

Although symptoms like these are generally accepted as resulting from the distress associated with psychotic episodes, studies suggest that loneliness and isolation might play a role in the development of psychotic symptoms, too. This can create a self-perpetuating cycle in which isolation or alienation leads to diminished social support, which, in turn, can cause a greater risk of relapse. 

Schizophrenia etiology

Experts still don't know exactly what causes schizophrenia. However, existing studies reveal it's likely the result of a combination of genetics, environmental factors, and neurological dysfunction.

• Genetics: Twin and family studies indicate that roughly 80% of schizophrenia cases are genetically linked. It may be worth noting, however, that not everyone with a relative who has schizophrenia will develop schizophrenia and vice versa. 
• Neurobiology: Researchers believe there may be a bi-directional relationship between schizophrenia and brain dysfunction involving neurochemical activity, brain structure, and other neurological factors.  
• Environment is thought to play a role in the development of schizophrenia when combined with genetics and neurobiological factors. For example, research suggests that environmental conditions may play a regulatory role in gene expression. 

Childhood adversity, obstetric complications, infections, socioeconomic status, and living in a migratory group have been associated with schizophrenia emergence. 

Additionally, while substance misuse isn't thought to cause schizophrenia, it's commonly cited as a risk factor. 

The importance of comprehensive treatment

Currently, a comprehensive treatment program including medication, psychotherapy, and psychosocial interventions is considered the most effective method for helping people with schizophrenia manage their symptoms, develop healthy coping strategies, and live productively. 

Despite the importance of treatment, schizophrenia has a relatively low treatment adherence rate. Individuals may find antipsychotic side effects difficult to tolerate, prompting them to discontinue medication. Some people with schizophrenia may experience availability or financial difficulties that make it challenging to participate in psychotherapy and psychosocial programs. 

Many mental health advocacy programs offer resources to individuals with schizophrenia and their families to neutralize those obstacles. Alternative treatment options, such as virtual talk therapy, may also be helpful.

While it may not be appropriate for everyone, studies indicate that internet-delivered cognitive behavioral therapy (iCBT) may reduce symptoms associated with schizophrenia and encourage greater treatment adherence for some people.

Online therapy platforms usually offer flexibility in scheduling, as well as access to a diverse pool of mental health professionals with varying specialties. Individuals may switch therapists at any time. Additionally, online therapy is often more affordable than in-person treatment without insurance.