Warrick J. Brewer

Key theories of autism implicate orbitofrontal cortex (OFC) compromise, while olfactory identification (OI) deficits are associated with OFC dysfunction. This study aimed to complete a 5-year follow-up of children with high-functioning autism (HFA) who previously lacked the normal age-OI association; and compare unirhinal-OI in children with HFA, Asperger’s disorder (ASP), and controls. While both HFA and controls had improved birhinal-OI at follow-up, reduced OI in some HFA participants suggested OFC deterioration and heterogeneous OFC development. Unirhinal-OI was impaired in HFA but not ASP relative to controls, suggesting orbitofrontal compromise in HFA but integrity in ASP. Differing IQ-OI relationships existed between HFA and ASP. Findings support the hypothesis of separate neurobiological underpinnings in ASP and HFA, specifically differential orbitofrontal functioning.

It is widely accepted that most psychiatric disorders are associated with cognitive impairment and that neuropsychological approaches can help unravel the mechanisms underlying brain function and help us develop a better understanding of these disorders. In this book, a panel of the world's leading experts describe the development of neuropsychological approaches to the investigation, description, measurement and management of a wide range of mental illnesses. Part One explains the rationale for examining neuropsychological processes within clinical disorders, leading into Part Two summarizing and critiquing the methodological approaches to study. Part Three covers each of the major psychiatric disorders and provides a summary of the neuropsychological findings for each condition. The final section brings together the perspectives of neuroscientists, psychiatrists and philosophers. Essential reading for all those studying the healthy as well as the disordered brain, The Neuropsychology of Mental Illness will appeal to specialists from the fields of mental health, psychology, clinical neuroscience and philosophy.

Background: Due to neuropsychological conceptualizations of orbitoprefrontal cortex (OFC) dysfunction underpinning impulsive aggression and the incidence of such behaviour in post-traumatic stress disorder (PTSD), this study aimed to explore olfactory identification (OI) ability in war veterans with PTSD as a probe of putative OFC dysfunction; and to explore the utility of OI ability in predicting aggressive and impulsive behavior in this clinical population.Method: Participants comprised 31 out-patient male war veterans with PTSD (mean=58.23 years, s.d.=2.56) recruited from a Melbourne Veterans Psychiatry Unit, and 31 healthy age- and gender-matched controls (mean=56.84 years, s.d.=7.24). All participants were assessed on clinical measures of PTSD, depression, anxiety, and alcohol misuse; olfactory identification; neurocognitive measures of dorsolateral prefrontal, lateral prefrontal and mesial temporal functioning; and self-report measures of aggression and impulsivity.Results: War veterans with PTSD exhibited significant OI deficits (OIDs) compared to controls, despite uncompromised performance on cognitive measures. OIDs remained after covaring for IQ, anxiety, depression and alcohol misuse, and were significant predictors of aggression and impulsivity.Conclusions: This research contributes to emerging evidence of orbitoprefrontal dysfunction in the pathophysiology underlying PTSD. This is the first study to report OIDs as a predictor of aggression and impulsivity in this clinical population. It prompts further exploration of the potential diagnostic utility of OIDs in the assessment of PTSD. Such measures may help delineate the clinical complexity of PTSD, and support more targeted interventions for individuals with a greater susceptibility to aggressive and impulsive behaviors.

Objective: Cognitive deficits, particularly those related to executive function and behavioural control, are a core feature of patients with schizophrenia and implicate disturbances of the prefrontal cortex (PFC). Consistent with this, functional imaging studies have identified abnormalities of PFC activity in chronically affected patients. The objective of the current study was to investigate executive-control related neural activity from first onset of the illness through to symptom stabilization. Method: The authors examined eight neuroleptic-naïve first-episode psychosis (FEP) patients within 3 days of first presentation and eight healthy agepremorbid-IQ, and gender-matched controls (CTL). All FEP patients were later confirmed with a diagnosis of schizophrenia. Subjects underwent H2-15O positron emission tomography (PET) while performing the Stroop interference task that has previously been shown to engage the PFC in healthy samples. In a double-blind paradigm, FEP patients were randomly treated with either haloperidol or risperidone for 8 weeks, after which CTLs and all but one of the FEP patients were re-scanned. Results: Behaviorally, there was no change in task performance from baseline to follow up for either the FEPs or CTLs. However, there were significant changes in functional activation in both groups across the same period. For CTLs, task-performance was associated with greater recruitment of posterior brain regions at follow up compared to baseline, while for FEP this involved greater recruitment frontal regions. Concurrently, FEP also showed significant improvement in positive symptomatology. Conclusions: These findings suggest that disturbances of the PFC often seen in FEP may be, at least partially, associated with acute symptom expression. However, it is still unclear whether this increase in frontal activity is due to symptom stabilization per se, the effects of medication, a lack of neurophysiological ‘learning’ with experience/practice, or a combination of these factors. In the context of the CTLs performance, we interpret the patient findings as reflective of greater neurophysiological effort required for task accomplishment relative to the learned, more automated, processing apparent in the CTLs.

This chapter shows how olfactory testing could be applied to investigations of orbitofrontal cortex (OFC) function and related behavioural outcomes. It discusses how tasks such as olfactory identification may offer insights into the development and maintenance of substance use disorders (SUD). Although imaging and neuropsychological studies demonstrate abnormalities in OFC function within addicted populations, it is unclear whether these deficits are related to premorbid vulnerability, a direct consequence of chronic exposure to addictive substances, or a combination of both. In humans, there is growing evidence that an earlier onset age of substance abuse may be related to more marked neurobiological and cognitive deficits. Adolescence is a developmental period associated with increased risk-taking and experimentation with drugs, and is also a time of increased vulnerability to the development of SUD. Experimentation with drugs also occurs during a period of substantial brain development and remodelling.

Cognitive impairment associated with schizophrenia (CIAS) includes neuropsychological deficits in attention, working memory, verbal learning, and problem solving. These deficits have been shown to be linked to impairment in functional status (eg, social behavior, work performance, and activities of daily living) among patients with schizophrenia in cross-sectional studies. Less is known about the relationship between cognitive and functional change over time, such as potential functional implications of treatment-related improvement in CIAS. The purpose of this review is to summarize research on the association between change in CIAS and change in functional status, to discuss responsiveness of functional outcomes measures, and to provide recommendations for future research and measure development. Nine longitudinal studies were located on the link between CIAS and functional status, and 8 functional outcomes measures were used across these studies. The 9 studies offer initial support for a link between change in cognitive function and change in functional status. However, inconsistent findings across studies indicate that available research is preliminary, and substantial questions remain unanswered. Shortcomings of functional status measures are noted: most instruments were not developed for the target population, and none have demonstrated responsiveness to cognitive change among schizophrenic patients. It is recommended that new functional outcome measures be developed that are specifically designed to be responsive to change in cognition, with domains previously shown to be related to cognitive ability. When creating new functional outcomes measures for assessment of patients with schizophrenia, responsiveness to change in CIAS should be evaluated as part of the development and validation process.

OBJECTIVE: While cognitive deficits are frequently reported in psychotic disorders, it is unclear whether these impairments predate the onset of illness and to what extent they are predictive of la...