This chapter discusses the diagnosis and epidemiology of panic disorder (PD). Genetic studies, while instrumental, cannot alone address the etiological complexities of most psychiatric disorders. The chapter turns to two integrative approaches that combine genetics with other clinical or biological methods to target the underlying mechanisms. First, it discusses exploiting the relationship between psychiatric and non-psychiatric medical manifestations (the expanded spectrum approach). This approach is particularly relevant to PD, where the panic attacks are accompanied by a range of physiological responses that may be central to the etiology. Second, the chapter describes neurobiological phenotypes, and in particular, on using measures of brain structure and function to identify genetic variation, and studies the mechanisms via which genes can impact behavior. The chapter concludes with an overview of imaging genetic studies of PD, and particularly, of how data from imaging studies can be used to enhance the tractability of genetic targets.

The biological basis for electroencephalogram (EEG)/average evoked potential (AEP) correlations to intelligence measures is not yet clear. Neural transmission speed (often measured as nerve conduction velocity) and the degree of myelination surrounding neurons have been proposed as potentially important variables for individual differences in intelligence. This chapter discusses neuroimaging studies that include positron emission tomography (PET), magnetic resonance imaging (MRI), and parieto-frontal integration theory (P-FIT) model of intelligence to emphasize the importance of information flow. Structural neuroimaging studies with large samples continue to relate intelligence to brain development. A number of new functional imaging studies use sophisticated experimental designs to examine cognitive and psychometric components of intelligence. The combination of neuroimaging and genetic research is one of the most powerful new approaches to understanding the neural basis of intelligence. Studies show that regional gray matter and white matter are largely under genetic control and share common genes with intelligence.

This chapter describes cited contemporary models of intelligence for each of the three levels: psychometric, physiological, and social. The contemporary models that bridge more than one level are examined. The chapter discusses the extended theory of fluid and crystallized intelligence (Gf-Gc theory), the three-stratum theory, the Cattell-Horn-Carroll (CHC) theory, and critique of the psychometric level and its models. According to the dual process (DP) theory intelligent behavior can be explained through a hierarchical structure of directed and spontaneous mental processes. Sternberg notes that his analytic, practical, and creative aspects of intelligence could be applied to Gardner's domains of intelligences. Similarly, neuroimaging studies could examine areas of the brain that are activated before and after the acquisition of expertise. The psychometric, physiological, and social levels and their current models have headed the field of intelligence down three productive paths. Perhaps the time has come for these paths to converge into one.

This chapter discusses the recent neuroimaging studies that have started to unravel some of the mysteries behind the behavior and cognitive manifestations of Parkinson's disease (PD). In-vivo anatomical and functional confirmation of the cortico-striatal loops in humans comes from magnetic resonance imaging (MRI) techniques. In the early stages of PD, frontal lobe dysfunction most likely reflects deafferentation in relation to dopamine deficiency. In keeping with neuropathological studies, which have demonstrated Lewy bodies and cell loss in medial temporal lobe areas high-resolution MRI images have demonstrated hippocampal atrophy in PD. There is pathological and in-vivo positron emission tomography (PET) evidence that other neurotransmitters, particularly cholinergic pathways, are involved in PD dementia (PDD). In-vivo PET studies are currently investigating whether concomitant amyloid pathology may contribute to dementia in PD subjects, although at this point, it appears that amyloid deposition is associated more with dementia with Lewy bodies (DLB) than with PDD.

Neuroimaging studies have provided new insights in neural brain circuits and neuroreceptor functions of eating disorders and as a consequence have contributed to a change of the conceptual framework of the pathophysiology and aetiology of eating disorders. Changes in brain structure and metabolism during resting conditions showed several brain alterations in eating-disordered patients. Brain imaging studies using neurotransmitter ligands have offered new opportunities to study neurotransmitter functions and pathways, as well as their relation to pathological behaviour. Neuromediators such as dopamine (DA) and serotonin (5-HT) are believed to be involved in eating disorder pathology. This chapter has summarised findings of neuroimaging research in eating disorders across a wide range of different methods and tools. A promising challenge in the future will be to consider how genetic, developmental and environmental influences shape brain circuit structure and function.

Neuropsychological, structural and functional imaging studies have broken new ground in demonstrating the existence of physiological and anatomical abnormalities in the olfactory system in schizophrenia. Since the pioneering psychophysical studies of odour recognition memory in patients with schizophrenia by Australian researchers Campbell and Gregson, a number of investigators have reported that schizophrenia patients exhibit olfactory dysfunction. In a 10-year longitudinal study, the presence of deviant olfactory experiences was found to significantly predict the development of future psychosis. The causes of olfactory impairments are numerous, including chemical, infectious, traumatic, metabolic and hormonal disturbances. Recent years have brought rapid expansion of structural and functional imaging technologies, including high-resolution structural magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT) and event-related potential (ERP). To characterise more directly the functional status of the olfactory system, ERPs have been employed to assess the physiological brain response to odour stimuli.

The concept of schizophrenia as a neurodegenerative disorder has a long and somewhat controversial past. The absence of a histopathological phenotype in schizophrenia has been cited as evidence against a neurodegenerative hypothesis. However, studies of schizophrenia increasingly demonstrate subtle yet consistent histopathological deficits in addition to evidence of progressive clinical and neuroimaging findings. It is believed that schizophrenia can be considered as a limited neurodegenerative disorder with neurodevelopmental antecedents. Studies from clinical, neurocognitive, neuroimaging, and neuropathological domains are reviewed in critical analysis of this hypothesis. The conclusion is increasingly supported by neuroimaging studies that find progressive neurostructural changes, especially in gray matter content and ventricle size, and studies that report limited progression of clinical symptoms and neurocognitive function. Future studies utilizing high-resolution neuroimaging and sophisticated neuropsychological testing techniques will undoubtedly provide greater insight on the timing, regionality, and degree of progression in the early stages of schizophrenia.

Neuroimaging studies in patients with early acquired damage will primarily seek to identify enhanced activations in regions outside a structural lesion. By comparison, imaging studies in developmental disorders will typically look for an absence or abnormality of activation that is assumed to reflect a particular cognitive or affective impairment. This chapter deals with evidence indicating vulnerability effects in non-human animals and human patients with early structural lesions. It discusses the interaction of vulnerability and compensatory events in developmental disorders, with exemplary focus on autism, developmental language impairment (DLI), and dyslexia. The chapter presents developmental disorders both in terms of the obvious effects of maturational vulnerability and in terms of the typically more elusive effects of compensatory reorganization. It focuses on autism and Asperger's syndrome. In the discussion presented here on bottom-up and top-down approaches, there are interesting parallels in the debates about developmental disorders of spoken and of written language.