A renovation of psychiatry is needed

Strakowski et al carefully discuss the benefits and risks of broadening the diagnosis of bipolar disorder, from treatment and research perspectives. Their conclusion that it is premature to broaden the bipolar disorder diagnosis before the identification of an etiology common to bipolar spectrum disorders is quite reasonable.

It is theoretically apparent that patients currently receiving a diagnosis of “major depression” include those who will develop bipolar disorder in later life. However, those patients cannot be identified just by clinical interviews. Only after the neurobiological basis of bipolar disorder is discovered and an in vivo identification of such neurobiological signature becomes feasible, it will be possible to reliably diagnose potential bipolar disorder in depressive patients. If we make a bipolar spectrum disorder diagnosis based solely on clinical interview, false positive cannot be avoided. Some patients might benefit from a correct diagnosis of potential bipolar disorder, but others will be misdiagnosed and receive inadequate treatment.

Recently, family and genome wide association studies have shown that bipolar disorder and schizophrenia share some common genetic background. The risk of schizophrenia is increased in first-degree relatives of probands with bipolar disorder, and the risk of bipolar disorder is increased in first-degree relatives of probands with schizophrenia, with relative risks between 2.4 and 5.2 1. In the study by the International Schizophrenia Consortium, the involvement of thousands of common alleles of very small effect was suggested in schizophrenia. It was shown that this polygenic component also contributes to the risk of bipolar disorder 2. This finding apparently supports the idea of a continuum between these two disorders. However, it should be noted that 7% of patients with schizophrenia were also diagnosed as having bipolar disorder in the former study. Can we discriminate between “existence of common pathology between these two disorders” and “difficulty in differential diagnosis of these two disorders” using currently available research schemes? If we loosen the diagnostic boundary based on the interpretation that these two disorders share common pathology, future research will suffer from lack of adequate clinical validity. If we deconstruct psychosis and combine these two disorders, we will only return to the chaos before Kraepelin.

We psychiatrists have been trying to differentiate mental disorders based on clinical interviews since the era of Kraepelin. After an extensive effort, we realize now that our diagnostic criteria are not perfect. Because there was little progress in psychiatric diagnosis in the last century, refinement of DSM can make only modest improvement, if any. To further refine psychiatric diagnosis, the only way is to establish a new disease classification based on the neurobiological features of each mental disorder.

A recent study of 153 brains of non-demented elderly people reported that patients receiving a diagnosis of depression during their life by interview showed more Lewy bodies in locus coeruleus. At the same time, neurofibrillary tangles were also more frequently seen in this region 3. Can we differentiate depression in the early stages of diffuse Lewy body or Alzheimer’s disease from depression without neuropathology only by clinical interviews? We psychiatrists should be aware that we cannot identify “diseases” only by interviews. What we are doing now is just like trying to diagnose diabetes mellitus without measuring blood sugar.

Medicine is fundamentally based on pathology. Psychiatry should also be based on pathology rather than psychology. When the concept of Alzheimer’s disease was established more than 100 years ago, there were few staining methods, such as silver and Nissl staining. After one century, we have completely sequenced the human genome, and we can potentially stain tens of thousands of molecules in the brain by mRNA in situ hybridization or immunohistochemistry. All the technologies we need to refine psychiatry have already been established. What we should do is to study the neurobiological basis of mental disorders using updated technologies and give rise to the renovation in psychiatry.