Serious conditions can cause long-term delusions: Schizophrenia, paranoia, mania, psychosis, severe OCD; or temporary delusional states: acute toxicity, delirium or drug reactions. Dopamine imbalances are often a major factor.
A specific obsessive delusion can be very destructive, as seen in Holocaust Deniers and survivalist Conspiracy Theorists. Temporal lobe epilepsy is also frequently found in delusions of hyper-salience or grandiosity (feelings of being chosen, having a mission, being a spiritual channel, etc.)
Localized brain damage can cause Cotard’s, Capgras and other bizarre conditions.
Deluded people are unable to perceive that they are deluded. Hallucinations (sensory distortions) are also common but do not necessarily impair self-insight.
Delusions can also be based on direct perceptual distortions—As when an anorexic perceives fat on her skeletal frame.
Someone can also have a monothematic or compartmentalized delusion that may not interfere with other intellectual work. HIV denialist Peter Duesberg [who has had a terrible effect on millions of people by convincing African leaders to question the science of HIV/AIDS] is still contributing solid work in cancer research.
Normal people can also have simple “glitches” that lead to blindspots that can appear delusional. And we all tend to confabulate to fill in the blanks.
Brain Damage and neurological disabilities
Reasoning can be compromised by many conditions: HIV infection, Parkinson’s, multiple sclerosis, Huntington’s disease, Korsakoff’s syndrome, Alzheimer’s and many, many more. TBI, stroke and other acquired damage can undermine any aspect of reasoning.
Inability to recognize that one has an obvious illness or disability
For example, lesions to insular somatosensory cortex results in anosognosia, apathy and placidity, loss of empathy and inability to recognize emotion and facial expression. Stroke victims who lose control of left side of body often are not aware that they have lost function.