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Cognitive Impairment in Schizophrenia and the Circadian Clock

Veeha Verma

Remedial Blog Post for Quiz 6
Schizophrenia has perhaps one of the biggest impacts on cognition, leading to severe cognitive impairment. No case is exempt, the two going hand in hand. However, the factors within the illness that lead to this impairment are not well known or discussed. Due to the sleep disorganization and disruption, the role of the circadian rhythm comes into question. A prolonged disturbance in the exposure to light and dark cycles is known to have extreme effects on cognitive representation, memory and learning. We will now look at whether and what the extent of the influence of the circadian rhythm on cognitive impairment is.
                To begin lets first look at what the circadian clock and the circadian rhythm are. The circadian clock may be thought of as an endogenous clock which runs on a 24-hour cycle, the central mechanism of which is situated in the suprachiasmatic nucleus (SCN) of the hypothalamus in mammals. This rhythm of physiological and cellular processes is modulated and susceptible to external cues in the form of light, which coordinates internal time with environmental changes. The circadian rhythm is any biological process that shows “endogenous, entrainable oscillation of about 24 hours”. Sleep disturbances are a characterizing feature of schizophrenia, some believing it is more important to treat before the actual illness. On the other hand, cognitive functioning itself is closely related to the day-night cycle. The periods of sleep and wakefulness thus play a crucial role in the synchronization with the external world and temporal alignment. So how does this express itself in schizophrenia? The first signs of cognitive impairment begin to show at the very outset of psychosis. The effects of this are not localized, affecting the generalized mental faculties useful in effective negotiation of external activities. These activities could include learning, remembering, planning and strategy formation, as an effect of the specific higher mental processes being disrupted by schizophrenia - working memory, inhibition, memory consolidation and information-processing speed. Most importantly this impairment is a very strong predictor for later social and occupational dysfunction, making intervention in this field of primary importance.
                So let’s break down the exact role of the circadian clock in this. To study its affects and possible remediation, Bromundt and colleagues worked with a sample of “well-characterized” patients with schizophrenia (n=14) by having them wear actigraphs (“Actigraphy is a non-invasive method of monitoring human rest/activity cycles”) for a three-week period, while also monitoring melatonin secretion before and after sleep on several occasions throughout. Patients were entrained to the regular sleep cycle, asleep at night and awake during the day, removing the confound of gross disruptions of circadian activity frequently noted in mental health patients. Hence, circadian disturbances showed in smaller ways, with increased night activity and irregular melatonin secretion in certain patients. In cognitive tests before and after the actigraphy study, results remained mostly stable. The group with a normal circadian rhythm performed within the normal range of published data. In comparison, the group with disrupted circadian cycles performed worse on all but one of the cognitive tests (the tests used were verbal fluency, the Stroop test and the Trail Making test). Interestingly, the study showed that in all patients’ large associations between day and night activity ratio and the cognitive measures. Effect sizes were ranging from 0.66 to 0.83, however, no association between the severity of the symptoms or the duration of the illness was seen. Thus, a specific causation link is observed between abnormalities in the circadian rhythm and impairment of cognitive abilities in schizophrenia.
                The study however, has certain limitations. For instance, it doesn’t specify what it means by “well-characterized” patients. It doesn’t standardize duration of illness or the kind of schizophrenia being exhibited. Further, the sample size is quite small within itself, if then broken into sub-groups it is hard to draw conclusions on such few specimens. However, the basis of these findings appear sound and this data could have great value in the future. Follow-up studies should be conducted so that intervention on this basis can be developed. 


Bibliography:
Circadian rhythms and cognition in schizophrenia. Available from: https://www.researchgate.net/publication/51692459_Circadian_rhythms_and_cognition_in_schizophrenia [accessed May 03 2018].
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