Schizophrenia is a complex and heterogeneous neuropsychiatric disorder characterised by delusions, hallucinations, disorganisation in behaviour, profound deficits in motivation and social interactions, and impairments in cognitive functions like attention and concentration. Schizophrenia is prevalent in about 1 per cent of the population over the age of 18.
Over the past decade, our team at the translational psychiatry laboratory at the National Institute of Mental Health and Neurosciences (Nimhans) has been involved in studies examining the origins and development of the disorder. These studies have examined patients at the Schizophrenia Clinic in Nimhans. Our observations support the view that the cause of this disorder is determined by genes and environment. It is increasingly being established that adverse events (obstetric complications, maternal infections, etc) during the prenatal development might have a major impact on the aetiology of the disorder.
Not everyone who carries the genetic risk, or are exposed to adversities, develops this disorder. While the genetic factors and prenatal insults add to the vulnerability of a person, it is believed that environmental factors related to early development (childhood and adolescence) along with certain biological factors (neuroendocrine and neuroimmunological) culminate in neurotransmitter abnormalities. Together, all these factors precipitate the peri-adolescent onset of this disorder.
We have been involved in brain imaging studies using a variety of techniques such as magnetic resonance imaging (MRI), functional MRI, magnetic resonance spectroscopy and diffusion tensor imaging. In simple words, the brain of a schizophrenia patient is reduced in overall volume, with an increase in the size of the ventricles, which contain cerebrospinal fluid. Certain parts like hippocampus, superior temporal gyrus and prefrontal cortex are more affected than others.
Interestingly, several researchers believe that schizophrenia might be an offshoot of human evolution. I, too, share this belief. One of the reasons behind the belief is that despite adverse fertility and fecundity, this disorder has been persistent over thousands of years. Given the strong genetic basis of this disorder, one would expect this to have become extinct a long time ago. This is the “central paradox of schizophrenia”.
Studies, including that of ours, suggest that this disorder might be related to evolutionarily significant factors like acquisition of complex language and skills, and protection from certain disease conditions. Certain anecdotal observations―Albert Einstein’s son suffered from schizophrenia, Isaac Newton developed symptoms late in his life, Nobel laureate John Nash is a schizophrenic―along with population-based studies showed increased prevalence of exceptional skills in relatives of schizophrenia patients. This supports the creativity-insanity link. Such a link with adaptive evolutionary factors might have facilitated the persistence of this disorder. Similarly, it has been observed that schizophrenia patients are less likely to have cancer or certain auto-immune diseases like rheumatoid arthritis.
I am of the view that the evolutionary biological factors that underpin the development of exceptional skills, or those that influence various medical diseases, interact with the risk for developing schizophrenia. For example, there could be potential persistent antagonistic co-evolutionary processes between genes with conflict of interests. This is called “Red Queen effect”, named after the character in Lewis Carroll’s Through the Looking Glass, who says, “It takes all the running you can do to stay in the same place”.
Cutting-edge research has substantially increased our understanding of the aetiology and pathogenesis of schizophrenia. However, given the complex and heterogeneous status of schizophrenia, the findings are yet to be clinically applied. Antipsychotic medications form the mainstay of the treatment of the disorder. Nonetheless, psychopharmacological treatment must be complemented with intensive psychological, social and adaptive lifestyle-based interventions with active contribution and involvement from family members.
Recently, we started treating schizophrenia patients with ‘transcranial direct current stimulation (tDCS)’ with striking clinical benefits. I would say treating a patient with schizophrenia is a challenge in terms of balancing the “science” (bio-psycho-social factors and medication-related side effects) and the “arts” (choosing the optimal combination of treatment options that will address the needs of a patient). To facilitate this, we have initiated a program called “InSTAR” (individualised schizophrenia treatment and reintegration) at the Schizophrenia Clinic in Nimhans.
Venkatasubramanian is additional professor of psychiatry at the Schizophrenia Clinic & Translational Psychiatry Laboratory, Nimhans, and senior fellow at Wellcome Trust/DBT India Alliance