Comp. by: VNatarajan Stage : Proof ChapterID: 9780521862899c24 Date:11/5/09 Time:16:36:00 Filepath:H:/01_CUP/3B2/Wood-9780521862899/Applications/3B2/Proof/ 9780521862899c24.3d Chapter 24 Neuropsychological investigation in mood disorders Paul Keedwell, Simon A. Surguladze and Mary Philips Introduction In this chapter we will consider the various approaches to defining neuropsychological abnormalities under- lying major depressive disorder and bipolar disorder. We will consider the methodological limitations, the implications for defining vulnerability markers and the priorities for further research. Major depressive disorder Introduction Major depressive disorder (MDD) remains one of the most debilitating psychiatric illnesses worldwide with an estimated lifetime prevalence of 16% (Kessler et al., 2003). By the year 2020 depressive disorder is predicted to become the second largest cause of disability after ischemic heart disease (World Health Organization, 1999). Major depressive disorder is associated with lost productivity, physical morbidity and suicide (Üstün & Chatterji 2001). Each depressive episode increases risk for subsequent episodes (Mueller et al., 1999; Solomon et al., 1997). Depression is thought to occur due to an interaction between a genetic diathesis and environ- mental stress (Andreasen, 1997; Caspi et al., 2003; Kendler, 1998). However, there are problems with defining a valid phenotypic marker for genetic vulner- ability (a “trait marker”). Such a marker should persist throughout episodes of illness and remission, co-segre- gate within families of affected individuals, and bear some conceptual relationship to MDD (Kraemer et al., 2002). If found it could help to define the endopheno- type – a neurological target for treatment. Negative cognitions Information processing models focus on cognitive processes that guide the selection, transformation, encoding, storage, retrieval and generation of infor- mation. These models suggest that negative cognitive biases are essential elements of depression (state phe- nomena), but they may also represent predisposing factors in vulnerable individuals (trait phenomena). Thus, cognitive theories of depression propose that negatively biased associative processing, especially negative self-referent information, confers cognitive vulnerability to depression (Abramson et al., 1989; Beck et al., 1979; Ingram et al., 1998; Teasdale, 1988). Paradigms that uncover these neurocognitive vulnerability factors could be amenable to integration with neuroimaging and genetic research in order to define an endophenotype. For example, neuropsycho- logical studies of working memory have proved suc- cessful in identifying genes involved in the abnormal functioning of the prefrontal cortex of individuals with schizophrenia (Egan et al., 2001). Emotional bias and executive control in major depression (state effects) It has been proposed (Phillips et al., 2003) that abnor- malities in emotion processing in major depression are associated with structural and functional anomal- ies in ventral (orbitofrontal cortex, ventral anterior cingulate gyrus, ventral striatum, amygdala) and dorsal (dorso-lateral prefrontal cortex, dorsal anterior cingulate gyrus, dorso-medial prefrontal cortex) neural systems. Neuropsychological assessment offers an opportunity to probe particular psychological properties related to these neural systems. Here, we discuss current findings reporting abnormal perform- ance on tests of social cognition and emotional pro- cessing as potential predictors of depressive disorder. Individuals with depression show poor interper- sonal functioning (Gotlib & Whiffen, 1989; Libet & The Neuropsychology of Mental Illness, ed. Stephen J. Wood, Nicholas B. Allen and Christos Pantelis. Published by Cambridge University Press. # Cambridge University Press 2009. 353