Normally, you've got a pretty good grip on reality. You can easily distinguish between external reality and the different kinds of mental states that you routinely experience. But in the course of a life, the ability to stay firmly anchored in reality is not a given.

Rather, we are engaged in an ongoing process of verifying the accuracy of our thoughts, beliefs, and perceptions. If any mental disorder demonstrates the potential for losing touch with reality, it's schizophrenia, a psychological disorder that involves several distorted beliefs, perceptions, and thought processes.

During a schizophrenic episode, people lose their grip on reality. They experience an entirely different inner world, one that is often characterized by mental chaos, disorientation, and frustration.

So the first thing to say is that schizophrenia is a syndrome, not a disease. So when you call it a syndrome, that means that there are a lot of different kinds of symptoms that can appear that don't always appear in every person, and the symptoms that do appear in a particular case can fluctuate over time, so they don't necessarily always look the same.

The characteristic symptoms of schizophrenia can be described in terms of two broad categories— positive and negative symptoms. Positive symptoms reflect an excess or distortion of normal functioning. Positive symptoms include delusions, hallucinations, and several disorganized thought processes, speech, and behavior.

In contrast, negative symptoms reflecting absence or reduction of normal functions, such as greatly reduced motivation, emotional expressiveness, or speech. Simply put, positive symptoms are the presence of inappropriate behaviors, and negative symptoms are the absence of appropriate behaviors.

The definition of a delusion is a false belief. So people have beliefs about their experiences. For example, I've had patients who report the symptom that all of their perceptual experience is being first experienced by some other entity. And then that entity decides what part of their perceptual environment to filter back to them, as though there were another entity interposed between them and the outside world.

Other patients report things like the feeling that thoughts are being put into their head by an alien force. And they often have beliefs that this is being done by, say, extraterrestrial forces, because they're looking for an explanation that has at least some plausibility. Of course, that isn't entirely very plausible, but it's at least in the realm of what people have experienced through science fiction. So they look for those kinds of explanations to attribute their really unusual experiences.

Auditory hallucinations are by far the most common. And sometimes, those are of more or less unformed sounds— crackling noises, not full on voices. But the vast majority of them are full on voices. And they typically take the form of one or more voices commenting on the patient, almost as though they're sports casters keeping a running commentary.

That seems, in some ways, innocuous, because— it could be irritating to have a voice like that. But then, as time goes on, they start to say more derogatory things. And typically, the voices are saying things that the patient finds very disturbing about the patients own value as a person.

Schizophrenia is not only one of the most dreaded psychological disorders, but also one of the most heavily researched. Most of the new research studies have linked the cause of schizophrenia with brain abnormalities and imbalances in brain chemistry.

The patient reliably shows subtle decrements in gray matter density, in very critical parts of the brain for integrating information across different modalities. Patients have these subtle reductions in gray matter. They also have decreases in the integrity of white matter— so the tracks, the axons that connect neurons, neuronal populations in distal regions of the brain to each other. And white matter is defined by the presence of a myelin sheath around the axon, which is, in part, a mechanism to support conduction velocity of the cell or interneuronal communication.

All of these findings are thought to ultimately reflect a state of basically disconnectivity in the brain, whereby region x— say, the prefrontal cortex— and another brain region aren't coordinating their activity in the same way as in a healthy brain. And the result is little snippets of cognition that get isolated because they're not being coordinated with other cognitive processes in an orchestration of the person's cognitive experience.

We actually have been studying this in my lab. And there is a genetic defect associated with schizophrenia, which is an overexpression, overactivity, of a certain kind of dopamine receptor called the D2 receptor in the striatum, which is part of the brain.

And we find when we just selectively overexpress that receptor in the striatum, the mice have a working memory deficit. Working memory importantly involves the prefrontal cortex, which has a defect in not only working memory, but the prefrontal cortex is involved in executive function in general and organizing one's life— getting up in the morning, shaving, put it on a shirt. These things require prefrontal cortical function. And people with schizophrenia have a difficult time with that.

Environmental factors may also be involved in schizophrenia— factors such as exposure to a virus during prenatal development and a psychologically unhealthy family environment. New research has provided hope that there are more breakthroughs to come. Until then, schizophrenia remains prevalent and continues to confront its suffers with unbearable horrors on a daily basis.

Well, for sure, we need to think more carefully about how to coordinate multi-modal treatments. On the biological treatment side, we need to improve our treatments and look at new targets. So the domain system is clearly, in some manner, involved in schizophrenia, but not necessarily as a primary neurobiological deficit.

Patients with these disorders aren't as dangerous as might be the popular impression. Most patients, when they're violent, the violence is towards themselves. There's a very high suicide rate. So it's not as though this is something to be feared. It's something to be understood and then conquered.

And so with less stigmatization, more patients will come into treatment. We'll have fewer patients on the streets. We'll have fewer instances of the behavior that most people right now interpret to be bizarre and frightening.