Although delusions and hallucinations might represent the most known and distinctive elements of schizophrenia and other psychosis, the presence of cognitive dysfunction is also considered a core feature that is associated with multiple functional disabilities observed in many people with psychoses.

Deficits of episodic and working memories, executive functions and intellectual functioning are typically the most common cognitive dysfunctions seen such instances. These have been identified even before the illness onset, suggesting a decline of cognitive functions from the premorbid period to the active phase of this condition. However, surprisingly few studies have longitudinally tracked such cognitive changes over a long period of time, so the course of any such decline is far less well established. Further, it has been debated if this decline was generalised or specific to individual neuropsychological functions, and if cognitive decline was specific to schizophrenia or if it was present in other types of psychosis.

A longitudinal study conducted by Zanelli et al (2019) redresses this; the authors identifying how cognitive decline manifested after the first episode was established, determining neurocognitive profiles, and exploring differences between schizophrenia and other psychosis.

Methods

For this study participants with a diagnosis of schizophrenia (N=65) and other psychoses (N=41) were assessed at baseline (first psychotic episode) and at follow-up (10 years later), using a set of neuropsychological tests that measured general intellectual ability (IQ), and other specific functions (memory, verbal knowledge, processing speed, working memory, language and visuospatial ability). To provide better estimate of cognitive changes over time, healthy comparison subjects (N=103) were also assessed at baseline and follow-up. Age, sex, ethnicity and education level were recorded at baseline and follow-up for all participants in the study.

In addition to the neuropsychological and diagnostic assessments, symptom severity and treatment history were also recorded to examine the effect of these variables on cognitive functions. Symptom severity was classified as absent, mild, moderate and severe, whilst treatment history included information regarding the use of either first or second generation antipsychotic medication.

Results

Overall, patients with schizophrenia and patients with other psychosis showed deficits in IQ and some neuropsychological functions at baseline. However, at follow-up, patients with schizophrenia present significantly worse cognitive impairment compared with patients with other psychoses.

Across time, compared with healthy participants, patients with schizophrenia showed a significant IQ decline, and showed a score reduction in the tests assessing memory (verbal learning, immediate recall and delayed recall) and verbal knowledge (decline on vocabulary). These differences were not attenuated when adjusted for sex, age, ethnicity or education level.

Regarding patients with other psychoses, there was no IQ decline compared with the comparison group at follow-up. However, patients with other psychoses did show a decline in the memory domain (verbal learning) of the neuropsychological tests compared with the healthy group.

Although the use, or duration, of first or second generation antipsychotics did not seem to have an effect on IQ changes, the severity of the illness was associated with a significant cognitive decline (memory tests) in those with severe symptoms of schizophrenia compared with those with mild or moderate presentations. There was no association between the symptoms’ severity in those with other psychoses and changes in cognitive functions.

The authors also examined the IQ of participants of the comparison group who had lower IQ (<90) at baseline and again at follow-up. In contrast with patients with schizophrenia, there was no evidence of changes in the IQ of these subjects.

Conclusions

• These findings support the so-called “IQ decline hypothesis”: people with schizophrenia and other type of psychoses not only experience cognitive dysfunctions at onset, but they also continue to experience a decline across a range of neuropsychological functions over the course of their illness.
• However, this decline is not generalised, or similar in magnitude, to every neuropsychological function; and deficits differ from people with schizophrenia to people with other psychoses.
• This suggests that different pathophysiological mechanisms could be involved in the cognitive deficits presented in people with schizophrenia.

Strengths and limitations

For this study, participants from a population-based case-control study were assessed after 10 years of having experienced a first episode of psychosis. This approach allowed the authors to identify important cognitive changes between patients with schizophrenia, patients with other types of psychosis and healthy comparison subjects (inclusion of this last group is relatively novel and removes the confounder of any age-related changes). The follow-up period of ten years was much longer than most parallel work on the topic that tracked people for typically one to two years. However, the relatively small sample size and the high rate of dropouts at follow-up (43%), did not allow authors to identify significant cognitive differences with the other psychosis group, which was formed by patients with bipolar disorder or mania, depressive psychosis, delusional disorder and non-specified psychosis, disorders that differ on their nature and progression. Some important potential confounders, notably social isolation, smoking status, illicit drug use, and general health status could not be accounted for.

Although the authors managed to assess patients after 10 years, having conducted only one follow-up assessment after 10 years, and not at other intervals (i.e. 2, 4, 6 and 8 years), limits this study’s ability to more accurately define the temporal progression of cognitive functions. For example, Meier et al, 2014, studied individuals at different stages of their lives from childhood (ages 7-13) to adulthood (age 38), and identified a gradual decline of processing speed from childhood to early teen years, but an early appearance of verbal deficits which remain static through adulthood. Interestingly, Rund et al, 2016, assessed a group of individuals with psychosis at baseline and at 1, 2, 5 and 10 years after inclusion. However, they did not identify cognitive deficits occurring after the illness onset (deficits were presented already by the time of the diagnosis); it is not clear why those results appear so contradictory to what was reported in this study.

One of the main findings of Zanelli et al. (2019) was that in patients with schizophrenia, processing speed and executive functions did not reduce after the onset of the illness, and that the main cognitive decline in this group of patients was in verbal knowledge and memory. However, Meier et al, 2014, identified greater deficits in learning, processing speed and executive functions in people with schizophrenia. Similarly, in a recent review (Sheffield et al, 2018) authors identified that verbal memory and processing speed were the cognitive functions more affected in patients with schizophrenia. However, in that same review, the authors concluded that cognitive dysfunctions in patients with schizophrenia tend to remain stable after onset.

Implications for practice

The results of Zanelli et al. provide much needed evidence about cognitive decline in people with schizophrenia and other psychoses after illness onset, though these results need further consideration:

• First, if people with psychosis continue suffering a neuropsychological deterioration after the first episode, then clinicians need to continue to consider these changes with their clients when they assess individuals at different stages of their illness, and more importantly, when they develop appropriate treatment plans. Clinicians should be mindful that some aspects of cognitive functioning are more likely than others to deteriorate, and that there are differences between those with a diagnosis of schizophrenia, and those with other psychoses.
• Second, the findings risk (unintentionally) perpetuating stigma and negativity that schizophrenia “cannot” be adequately treated, and imbuing a sense of personal or professional helplessness or defeatism about the future, in those who use services, their friends and loved ones, and professionals. We hope that this is not the case: the findings remind us of the challenges those with psychoses can face, but must serve to renew our joined desire to work for the best care possible.
• This leads us to a final point: there has been interest in psychological, cognitive, and neuromodulatory (e.g. ‘transcranial direct current stimulation’ or tDCS) approaches to slowing decline and indeed enhancing cognitive functioning in schizophrenia. These findings might help direct the specific subdomains where interventions might be optimised for targeting.

Conflicts of interest

None.

Links

Primary paper

Zanelli J, Mollon J, Sandin S, Morgan C, Dazzan P, Pilecka I, Reis Marques T, David AS, Morgan K, Fearon P, Doody GA, Jones PB, Murray RM, Reichenberg A. (2019) Cognitive Change in Schizophrenia and Other Psychoses in the Decade Following the First Episode. Am J Psychiatry. 2019 Jul 1:appiajp201918091088. doi: 10.1176/appi.ajp.2019.18091088.

Other references

Meier MH, Caspi A, Reichenberg A, Keefe RS, Fisher HL, Harrington H, Houts R, Poulton R, Moffitt TE. (2014) Neuropsychological decline in schizophrenia from the premorbid to the postonset period: evidence from a population-representative longitudinal study. Am J Psychiatry. 2014 Jan;171(1):91-101. doi: 10.1176/appi.ajp.2013.12111438.

Rund BR, Barder HE, Evensen J, Haahr U, ten Velden Hegelstad W, Joa I, Johannessen JO, Langeveld J, Larsen TK, Melle I, Opjordsmoen S, Røssberg JI, Simonsen E, Sundet K, Vaglum P, McGlashan T, Friis S. (2016) Neurocognition and Duration of Psychosis: A 10-year Follow-up of First-Episode Patients. Schizophr Bull. 2016 Jan;42(1):87-95. doi: 10.1093/schbul/sbv083. Epub 2015 Jun 21.

Sheffield JM, Karcher NR, Barch DM. (2018) Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective.Neuropsychol Rev. 2018 Dec;28(4):509-533. doi: 10.1007/s11065-018-9388-2. Epub 2018 Oct 20. [PubMed abstract]