Psychosis is a mental health condition characterized by a disconnect from reality. The main symptoms of psychosis include delusions, hallucinations, disorganized thinking and speech, and abnormal motor behavior. Psychosis occurs in psychiatric disorders like schizophrenia, bipolar disorder, major depressive disorder with psychotic features, and substance-induced psychotic disorder. Researchers have found that there are structural and functional abnormalities in certain brain regions that are associated with psychosis. Understanding what parts of the brain are affected in psychosis can provide important insights into the underlying biology and potential treatments for these disorders.
The Prefrontal Cortex
One of the main brain regions implicated in psychosis is the prefrontal cortex. This region is located at the front of the brain and is responsible for complex cognitive functions like planning, decision-making, personality expression, moderating social behavior, and regulating emotions. Studies using neuroimaging techniques like MRI have shown that prefrontal cortex volumes are reduced in people with schizophrenia and bipolar disorder. The prefrontal cortex is made up of several sub-regions that each have distinct functions:
Dorsolateral Prefrontal Cortex
The dorsolateral prefrontal cortex (DLPFC) is involved in working memory, executive functioning, and cognitive flexibility. Dysfunction in this area is thought to underlie symptoms like disorganized thinking and behavior, difficulty concentrating, impaired reasoning, and cognitive inflexibility in psychosis. The DLPFC shows decreased activation during cognitive tasks in schizophrenia.
Ventromedial Prefrontal Cortex
The ventromedial prefrontal cortex (VMPFC) plays a key role in emotional regulation, decision-making, and processing risk and fear. Abnormalities here are associated with inappropriate emotional reactions, poor judgment, and lack of insight often seen in psychotic disorders.
Orbitofrontal Cortex
The orbitofrontal cortex (OFC) supports reward processing, impulse control, and socially appropriate behaviors. OFC dysfunction could lead to disinhibition, irritability, and odd or repetitive behaviors in psychosis.
The Temporal Lobe
The temporal lobe, located on the sides of the brain above the ears, is also heavily implicated in psychosis. Key temporal lobe structures include:
Superior Temporal Gyrus
The superior temporal gyrus is involved in auditory processing and language comprehension. In psychosis, abnormalities here could contribute to patients hearing voices or having trouble understanding speech.
Hippocampus
The hippocampus plays a major role in memory formation and retrieval. Hippocampal deficits are linked to memory problems and difficulty learning new information in psychotic disorders.
Amygdala
The amygdala regulates emotions like fear and is part of the brain’s threat response system. Amygdala overactivity could produce paranoia and anxiety in psychosis.
The Parietal Lobe
The parietal lobe at the top back of the brain integrates sensory information and body awareness. Key parietal lobe regions include:
Superior Parietal Lobule
The superior parietal lobule integrates visual, auditory, and sensory information. Dysfunction here may contribute to disorganized thinking, confusion, and inability to localize sensations that can occur in psychosis.
Inferior Parietal Lobule
The inferior parietal lobule is involved in language processing and sense of self. Abnormalities in this region could produce thought and speech disturbances, as well as a distorted sense of body or self in psychotic disorders.
The Occipital Lobe
The occipital lobe located at the back of the brain contains the primary visual cortex which processes visual information. Occipital lobe abnormalities could lead to visual hallucinations and deficits in facial emotion recognition associated with psychosis.
The Cerebellum
The cerebellum coordinates motor activity and is involved in cognition and emotional regulation. Cerebellar dysfunction is linked to problems with movement, coordination, and emotional control in psychotic disorders like schizophrenia.
The Basal Ganglia
The basal ganglia are a group of nuclei involved in motor activity, motivation, reward, and habit formation. Disruptions here may contribute to reduced motivation, movement abnormalities, and repetitive behaviors seen in psychosis.
The Thalamus
The thalamus acts as a relay station filtering sensory inputs. Thalamic deficits could overwhelm cortical regions with too much sensory information leading to symptoms like hallucinations.
White Matter Tracts
White matter tracts are bundles of axons that allow different brain regions to communicate with each other. Damage to white matter connectivity has been observed in schizophrenia and bipolar disorder. This could impair coordination between brain areas contributing to cognitive dysfunction.
Neurotransmitter Systems
Imbalances in neurotransmitters like dopamine, glutamate, serotonin, acetylcholine, and GABA have been identified in psychotic disorders. These chemical messengers regulate signaling between neurons throughout the brain. Disruptions to these systems affect widespread brain communication.
- Dopamine: Excess dopamine activity is linked to positive symptoms like hallucinations and delusions. Antipsychotic medications block dopamine receptors.
- Glutamate: Hypoactive glutamate systems are associated with negative and cognitive symptoms of psychosis. Glutamate-modulating drugs are being researched.
- Serotonin: Low serotonin levels may contribute to mood disturbances in psychosis.
- Acetylcholine: Reduced acetylcholine is connected to cognitive deficits in schizophrenia.
- GABA: GABA dysfunction could lead to neuronal overexcitability and symptoms of psychosis.
Brain Network Dysconnectivity
Research shows that psychosis stems from disruptions in the coordinated activity of distributed brain networks rather than isolated regions. Key networks impacted include:
- Default mode network: involved in internal mentation and self-referential processing.
- Central executive network: regulates high-level functions like attention, planning, decision-making.
- Salience network: determines which stimuli are deserving of attention.
- Reward network: processes motivation and hedonic experience.
Abnormalities in how these normally integrated networks interact are proposed to generate many symptoms of psychosis.
Neurodevelopmental Factors
Psychotic disorders like schizophrenia are increasingly recognized to be neurodevelopmental in origin, with brain changes beginning years before full onset. The leading hypothesis is that genetic and environmental factors such as prenatal infection, malnutrition, or stress disrupt normal brain development in utero or during key maturation periods in childhood/adolescence. This produces brain abnormalities that eventually manifest as psychosis later in life when the brain undergoes normal maturation and pruning processes, particularly in the prefrontal cortex. Supporting this, mild cognitive, motor and behavioral impairments are often observable in childhood long before psychosis onset. Brain scans also show progressive loss of grey matter as people approach the usual age of schizophrenia onset.
Genetic Influences
Twin and family studies confirm psychotic disorders have a strong genetic component, likely involving multiple genes. Specific risk genes associated with schizophrenia play roles in synaptic plasticity, immune function, and neurotransmitter signaling. How these genetic variants interact with each other and the environment to impact brain development and function are active research questions.
Conclusion
In summary, psychosis originates from dysfunction in a distributed network of brain regions and circuits rather than a single focal lesion. Key areas implicated include the prefrontal cortex, temporal lobe, basal ganglia, thalamus, and cerebellum. White matter connectivity defects and imbalances in dopamine, glutamate, and other neurotransmitters also contribute. While the precise mechanisms are still being elucidated, abnormal neurodevelopment rooted in genetics and early environmental influences appear central to the emergence of schizophrenia and related psychotic disorders. Understanding the neurobiology of psychosis remains an active, evolving field of psychiatric research that will enable advances in treatment and prevention.