The Psychology and Neurobiology of Late Onset Psychosis

Summary

Title: The psychology and neurobiology of late onset psychosis

PhD student: Lies Van Assche

Promotors: Prof. Dr. Mathieu Vandenbulcke, Prof. Dr. Patrick Luyten

The first onset of psychosis in late life is a highly incapacitating syndrome which is more common than previously assumed, presenting in approximately 10-62% of nursing home residents, 5-15% of elderly psychiatric inpatients and 27% of psychiatric outpatients. Yet the etiological mechanisms triggering its onset are still unclear.

     Research in early adulthood suggests that mentalizing difficulties, possibly related to childhood adversity and insecure attachment patterns, as well as cognitive deficits and neurodevelopmental alterations are risk factors to psychosis. Similarly, mild cognitive dysfunction and abnormal brain aging have been associated with late onset psychosis. However, little is known about the involvement of childhood adversity and attachment. We hypothesize that pre-existing vulnerability related to childhood adversity as well as accelerated brain aging and associated cognitive impairment interactively contribute to late onset psychosis.

     First, to gain insight in attachment patterns in non-psychotic elderly persons, we conducted a systematic review on attachment and aging which pointed to a deleterious effect of attachment insecurity on psychological wellbeing. In line with these findings, our empirical research showed more anxiety and depression in community dwelling older adults (n=81) with higher levels of attachment insecurity. Consistent with our general hypothesis, older adults with very-late-onset schizophrenia-like psychosis (VLOSLP, n=49), defined as a first incidence of psychosis after the age of 60 years and in the absence of a neurological or a major affective disorder, reported more childhood trauma and exhibited reduced mentalizing skills compared with healthy controls (n=49) who were matched for age, gender and education. Still, individuals with VLOSLP did not show higher levels of attachment insecurity than controls.

     Second, we studied cognitive and neurobiological changes in VLOSLP. A systematic review revealed a specific set of deficiencies pertaining to the domains of attention, executive function, processing speed, (working) memory and to a lesser degree mentalizing. Neurobiological underpinnings consisted of white matter pathology, an increased ventricle-to-brain ratio, and atrophy or hypo-metabolism in the frontal, subcortical and temporal brain areas. The cognitive profiles of our VLOSLP cohort were largely consistent with the findings of the systematic review. In addition, the profiles in our cohort showed a surprising overlap with those in neurodegenerative conditions with concomitant psychosis. Specifically, we compared individuals with VLOSLP (n=57), dementia with Lewy Bodies (DLB; n=49) and Alzheimer’s type dementia with psychosis (AD+P; n=35) who were matched for general level of cognitive function and found that they were equally impaired on processing speed, attention and executive function, whereas individuals with AD+P experienced relatively more consolidation difficulties and patients with DLB exhibited greater visuoconstructive deficits. Finally, we studied whether lower hippocampal volumes constitute a vulnerability marker to late onset psychopathology and are related to memory dysfunction. We found hippocampal volume reductions in VLOSLP (n=36) and late onset depression (LOD, n=34) and these were indeed associated with memory dysfunction, whereas such an association did not exist in age and gender matched healthy controls who generally had larger hippocampal volumes (n=36). This suggests that there is a threshold effect for the impact of hippocampal volume reduction on memory function.

     In summary, late onset psychosis is a heterogeneous condition in which pre-existing vulnerability related to childhood adversity and accelerated, possibly stress-related neurobiological alterations likely interact leading to the first incidence of psychosis only later in life in individuals who had earlier attained an adequate level of professional and personal functioning.