Resistant schizophrenia associated with low IQ and family history

According to a new study published on November 12, 2019, in the journal Molecular Psychiatry, individuals with schizophrenia resistant to treatment are more likely to have a family history and a lower IQ compared to other schizophrenic patients. This finding could help design more effective therapies for this subgroup of patients, as for instance, drugs that improve mental processes.


Schizophrenia is a mental illness with fundamental effects on the individual’s thinking, emotions, and behavior. As a result, the person may speak and behave in atypical ways, appear to be unaware of the surroundings, and experience hallucinations, seeing or hearing things which are not real. Moreover, such individuals show abnormal thought and decision-making patterns. In short, such individuals are often thought to have lost touch with the real world. In most cases, the disorder becomes obvious when the person turns into the teens or in early adult life.

Image Credit: Cyrsiam / Shutterstock
Image Credit: Cyrsiam / Shutterstock

Schizophrenia affects normal functioning because of the abnormal perceptions and hallucinations, as well as behavior. About 3.5 million people have been diagnosed with schizophrenia in the US, making it a frontrunner among the causes of disability. At least one in three homeless adults, and perhaps as many as half, have schizophrenia.

About one in three schizophrenics fail to respond properly to medication, and are diagnosed with treatment-resistant schizophrenia (TRS). These are patients who do not show adequate response to two or more courses of different medication. These patients are not only more difficult to treat but are more likely to commit suicide. Health care costs for this group of patients are higher, and the social burden is also greater.

The study

The researchers did a long-term study of over 24,000 Swedish adults, for 8.5 years on average, of whom about 4800 had TRS. This large volume of various kinds of data came from several different population registries, including patient registries, prescribed drug registries, multi-generation registers, and military conscription registers. They carried out an analysis to identify the demographic characteristics of TRS patients, their clinical features and genomic attributes.

What they found

The analysis of all this data showed that people who had one or more relatives with schizophrenia, and male patients with a low IQ measured at 18 years, had higher odds of being diagnosed with TRS than the other type of schizophrenia. According to researcher Kaarina Kowalec, this is the first time such findings have been found to predict TRS in such a large group of people drawn from the population in general. Individuals with the highest family history of schizophrenia had 30% greater odds of TRS compared with those who had the lowest.

The study findings also associated other known factors with TRS, such as being male, having more contact with specialists for treatment, a higher number of suicide attempts, and lower educational qualifications.

Poor thinking, memory, judgment, and emotional reactions are also characteristics of schizophrenics, and there are very few or no treatment options specifically designed to address these. The fact is that TRS is so high because there are basically no new drugs that have been shown to be effective in this condition.

The researchers also separated a smaller subgroup of patients for whom fuller information was available on their genetic makeup. This showed that there were no genetic links between TRS and any of four other mental disorders, namely, schizophrenia, bipolar disorder, depression and autism. The last three have been shown to be linked genetically.


The fact that despite a link between TRS and a family history of schizophrenia, there is no association between the genes seen in TRS and in schizophrenia leads researchers to think that a patient’s response to schizophrenia drugs may possibly depend at least in part upon common environmental factors rather than genetic factors alone. A confirmation of this hypothesis will require larger studies on the genes involved in TRS and other genes.

Moreover, the study highlights two important aspects of schizophrenia: one, effective new drugs are desperately required, in view of the high prevalence of treatment resistance. Secondly, in Kowalec’s words, “Our finding of lower premorbid IQ in TRS compared to TRS is especially interesting given that it could be important in efforts to design novel drug treatments improving cognition.” The need to improve cognitive aspects of health is crucial to promoting self-care, supportive relationships, skilled employment, safety and general satisfaction with life.

Journal reference:

Kowalec, K., Lu, Y., Sariaslan, A. et al. Increased schizophrenia family history burden and reduced premorbid IQ in treatment-resistant schizophrenia: a Swedish National Register and Genomic Study. Mol Psychiatry (2019) doi:10.1038/s41380-019-0575-1,

Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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