Evolving Notions of Schizophrenia as a Developmental Neurocognitive Disorder

Abstract

We review the changing conceptions of schizophrenia over the past 50 years as it became understood as a disorder of brain function and structure in which neurocognitive dysfunction was identified at different illness phases. The centrality of neurocognition has been recognized, especially because neurocognitive deficits are strongly related to social and role functioning in the illness, and as a result neurocognitive measures are used routinely in clinical assessment of individuals with schizophrenia. From the original definitions of the syndrome of schizophrenia in the early 20th century, impaired cognition, especially attention, was considered to be important. Neurocognitive impairments are found in the vast majority of individuals with schizophrenia, and they vary from mild, relatively restricted deficits, to dementia-like syndromes, as early as the first psychotic episode. Neurocognitive deficits are found in the premorbid phase in a substantial minority of pre-teenage youth who later develop schizophrenia, and they apparently worsen by the prodromal, high-risk phase in a majority of those who develop the illness. While there is limited evidence for reversibility of impairments from pharmacological interventions in schizophrenia, promising results have emerged from cognitive remediation studies. Thus, we expect cognitive interventions to play a larger role in schizophrenia in the coming years. Moreover, because youth at risk for schizophrenia can be identified by an emergent high-risk syndrome, earlier interventions might be applied in a preemptive way to reduce disability and improve adaptation. The notion of schizophrenia as a developmental neurocognitive disorder with stages opens up a window of possibilities for earlier interventions. (JINS, 2017, 23, 881-892)

Nonsocial and social cognition in schizophrenia: current evidence and future directions

“…Several converging lines of evidence support the conceptualization of nonsocial cognitive impairments as core features of the illness. Nonsocial cognitive impairments are largely independent of positive psychotic symptoms, cannot be explained by antipsychotic medications or their side effects, are present at comparable levels at the time of illness onset, are relatively stable over time until late life, and are detectable at attenuated levels in unaffected biological relatives of patients and in prodromal samples (i.e., samples considered to be at high risk for psychosis).…”

Cognitive Deficits in Psychotic Disorders: A Lifespan Perspective

“…This model conceptualizes cognitive dysfunction in schizophrenia as aberrant neurodevelopment during the first two decades of life (Bora 2015; Dickson et al 2012; Khandaker et al 2011; MacCabe et al 2013), with deficits in the acquisition of cognitive abilities compared to normative individuals (Bora and Pantelis 2015; Kremen et al 1998; Reichenberg et al 2010). The presence of cognitive deficits years prior to the onset of psychotic symptoms suggests that cognitive dysfunction is at the core of schizophrenia, with abnormal neurodevelopment manifesting through performative lag as early as preschool age (Seidman and Mirsky 2017). As outlined elegantly by Kahn & Keefe (2013), multiple lines of evidence converge on the notion that schizophrenia is a cognitive illness that is neurodevelopmental in nature: cognitive deficits exist prior to psychosis onset, cognitive ability is influenced by genetics, and cognition is an independent predictor of functional outcome(Kahn and Keefe 2013).…”

“…S. Keefe et al 2005). Cognitive impairment early in illness is therefore a critical piece of evidence for abnormal neurodevelopment and should be considered a core feature and risk-factor for symptom manifestation later in life (Seidman and Mirsky 2017). …”

In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia

“…In 1972, Plum stated that "schizophrenia is a graveyard for neuroanatomists" as no single pathological lesion could be found. On the other hand, Mirsky concluded in 1969 that there was evidence of brain dysfunction in SZ from cognitive, neurological, and electroencephalographic examinations [7]. This was further confirmed by Seidman in 1983 who searched for the neurobiological basis of SZ, in an era when computer tomography (CT) and positron emission tomography (PET) began to be applied to patients with SZ.…”

“…Moreover, Bleuler considered the alteration of associations as the only symptom which is both basic and primary [6]. Kraepelin and Bleuler speculated that brain dysfunction is responsible for SZ symptoms, in particular that frontal and/or temporal lobe dysfunctions are linked with cognitive abnormalities [7]. However, they were not able to prove this hypothesis with the tools of their era.…”