Yale researchers have just published a study showing abnormalities in brain function in schizophrenics. It’s an intriguing new piece to the puzzle of this complex mental disorder. It also adds further evidence to the already well accepted concept that schizophrenia is a neurological disorder – although one that has psychiatric manifestations.

Schizophrenia is not split personality – although that is a common misconception. Rather, it is a brain disorder that results in a number of psychological symptoms. The primary dysfunction is a thought disorder known as psychosis – which basically means having thoughts that are disconnected from reality. “Reality testing” is actually an active process of the human brain, and if this malfunctions or functions sufficiently suboptimally, the result is the inability to separate our internal thoughts from external reality. This psychosis takes many forms, the most common of which among schizophrenics are paranoid delusions (the idea that people and events are conspiring against them), ideas of reference (the sense that everything that happens is being directed specifically to them – even the news announcer on TV), and other types of delusions, such as delusions of grandeur. Schizophrenics may also suffer from visual or auditory hallucinations. They may have so-called “positive” symptoms of pressured speech and agitation, or “negative” symptoms of flat affect and withdrawal, and in extreme cases catatonia (a complete mental shut down).

It is important to note that schizophrenia is a heterogenous clinical disorder – it is defined based upon the presence of a constellation of symptoms. It is not a single disease. It is probably a category of disorders – multiple underlying brain problems causing similar dysfunction and overlapping symptoms. For this reason studies looking at various parameters of brain function (such as the activity of certain neurotransmitters like dopamine) do often show statistical differences between schizophrenics and normal controls, but they are inconsistent – not all schizophrenics have the patterns associated with schizophrenia.

The new study, co-authored by Godfrey Pearlson, M.D., a professor of psychiatry at Yale, looked at 21 patients with schizophrenia and 22 healthy controls. They imaged brain function with functional MRI scanning (fMRI – an amazing tool that has spawned a tide of new brain research). They found that during a task of auditory processing, the healthy controls displayed slow activity resonating between the various brain regions (a pattern being called the “default mode”). This represents, it is believed, active communication among various distinct brain regions. The subjects with schizophrenia displayed increased activity, but it was significantly more irregular – it did not display the default mode activity. This evidence supports the hypothesis that schizophrenics lack the proper neural wiring that allows for robust communication among the various higher cognitive regions of the brain. This leads to a lack of integration of information and processing. One manifestation of this is impaired reality testing – analyzing sensory input or internal thoughts against a model of reality.

This study represents just one tiny piece of information about a very complex class of disorders – but is highlights well, in my opinion, where we are scientifically in approaching subtle and complex brain disorder like schizophrenia. The classic model of schizophrenia was that it was purely a “software” problem – a psychological disorder brought on by cold mothers. This paradigm gave way to a more biological model, based in part on data that schizophrenia has a genetic component, and then later on studies that show differences in brain function. The first attempts at understanding schizophrenia physiologically focused on neurotransmitters – mainly dopamine – showing that the amount and pattern of dopamine activity is different in schizophrenic brains. We are now moving into a more sophisticated paradigm – looking at the pattern of hardwiring in the brain and how these neural networks interact with each other.

Over the years treatment strategy has tracked along with these conceptual paradigms. Psychotherapy was tried, without success. We are still relying on pharmacological treatments bluntly altering the amount of dopamine activity in the brain (although second generation pharmaceuticals have been able to target dopamine subtypes to give some specificity to the target brain regions and decrease side effects).

Perhaps this new research indicates that in the future our therapies will involve changing the hard-wiring of the brain (or compensating for it). At present we don’t have the technology to do this, but there are indications that such technology is on the horizon. Researchers have already succeeded in merging computer chips and neurons, and within 5-10 years we may have chips that can actually be implanted in human brains to replace or augment function. Perhaps such chips could be designed to augment the “default mode” of neural activity lacking in schizophrenia.

As an aside – there persists a subculture of “mental illness deniers” who maintain that schizophrenia is not a legitimate disorder at all – and in fact there is no such thing as mental illness or any mental disorder. This kind of research, however, directly contradicts such denial. This is a complex topic I will address in much greater detail in future blogs.