Cognition in Schizophrenia: The Missing Piece of the Therapeutic Puzzle.

What kind of mental image springs to mind upon reading the word ‘schizophrenia’? Many envisage individuals locked in dark institutions, plagued by non-existent voices and vivid hallucinations. Fortunately, modern antipsychotic drugs combating symptoms like hallucinations have allowed many patients to successfully function and flourish within their communities. So, why do so many schizophrenia patients still fail to achieve independent living, find employment, and form relationships? Even more alarmingly, why are rates of symptomatic relapse so high? The answer lies in the debilitating cognitive disturbances suffered by patients, too often overlooked by research and – crucially – neglected by current drug therapies.

Schizophrenia is a staggeringly heterogeneous disorder, with symptoms manifesting very differently in each patient. Patients often struggle in areas of verbal learning, processing speed, and working memory. But do these impairments really have a major impact? In the context of a disorder characterized by terrifying hallucinations and debilitating delusions, cognitive difficulties might not seem like an urgent therapeutic priority.

In fact, the true impact of cognition upon disease outcomes in schizophrenia is only recently coming to light. A plethora of studies have drawn links between poor cognitive performance and impaired psychosocial functioning. One might argue that this is a rather obvious association. But closer consideration reveals the enormous impact this has on daily life: if a schizophrenia patient is unable to speak clearly, perform hygiene-related tasks, or keep up with their medications, they have little hope of finding employment or successfully integrating into community living. Indeed, a 2015 review calculated employment rates in schizophrenia ranging from 4% to 50.4%.

As recently as January 2020, research has emphasized the detrimental effects of impaired cognition. An Ecuadorian study conducted at the psychiatric Kennedy Hospital used the SCIP (Screening of Cognitive Deterioration in Psychiatry), which is a test of cognitive functioning that requires patients to complete tasks like remembering a list of words or naming all the words they can think of in a specific category that start with a certain letter. This test, along with questionnaires about their experiences, revealed that patients suffering greater cognitive difficulties had a poorer quality of life.

Even considering the impact of untreated cognitive symptoms upon quality of life, it is still reasonable to pose the question: so what? The sad reality is that for many patients, cognitive difficulties make antipsychotic drugs a futile intervention, leading to symptomatic remission and a substantial waste of resources. Beyond material concerns, a Swedish study following over 500 schizophrenia patients made the staggering finding that executive function independently predicted premature death.

In the face of such alarming data, it is unsurprising that the cognitive deficits of schizophrenia have become an urgent therapeutic target. But how can cognition be elevated? Amongst the most promising interventions are drugs targeting NMDA receptors. These receptors are located on the surface of neuronal cells and mediate signaling crucial for learning and memory functions. One such NMDA-inhibiting medication is memantine, which has shown some promise in schizophrenia patients.

Unfortunately, using pharmacological treatments to improve cognition is far from straightforward. It is critical to remember that these patients still rely upon antipsychotics to manage positive symptoms, which often interfere with the activity of cognition-targeting drugs. Even without this complication, is it rational to expect modifying a single receptor to be effective in treating such a complex, multi-faceted disorder? This is where cognitive remediation therapy comes in. Using behavioral training, this technique is not only shown to improve performance across numerous cognitive domains, but also delay the relapse of symptoms.

As research continues to search for successful schizophrenia treatment strategies, one thing is becoming worryingly clear: one size does not fit all. A particular cocktail of drugs and behavioral therapies allowing one patient to thrive may be completely unsuccessful in another. Encouragingly, current efforts are directed toward identifying patients most likely to benefit from certain treatment strategies, using biological indicators or ‘biomarkers’.

There is an undeniably long way to go before schizophrenia patients will be able to make a complete recovery, with a low risk of relapse and a satisfactory quality of life. But recognizing cognition as the wrongly neglected aspect of schizophrenia is certainly a step in the right direction.

Written by Jessica Brown on behalf of LIVE with Scientists (originally written for Knowing Neurons).

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