Negative symptoms: A review of schizophrenia, melancholic depression and Parkinson's disease.

Negative symptoms generally refer to a reduction in normal functioning. In schizophrenia they encompass apathy, anhedonia, flat affect, avolition, social withdrawal and, on some accounts, psychomotor retardation. Negative symptoms have been identified in other psychiatric disorders, including melancholic depression, and also in neurological disorders, such Parkinson's disease. Achieving a better understanding of negative symptoms constitutes a priority in mental health. Primarily, negative symptoms represent an unrelenting, intractable and disabling feature for patients, often amounting to a severe burden on families, carers and the patients themselves. Identifying and understanding subgroups within disorders may also contribute to the clinical care and scientific understanding of the pathophysiology of these disorders. The purpose of this paper is to review the current literature on negative symptoms in schizophrenia and explore the idea that negative symptoms may play an important role not only in other psychiatric disorders such as melancholic depression, but also in neurological disorders, such as Parkinson's disease. In each disorder negative symptoms manifest with similar motor and cognitive impairments and are associated with comparable neuropathological and biochemical findings, possibly reflecting analogous impairments in the functioning of frontostriatal-limbic circuits.

Self-paced saccades and saccades to oddball targets in Parkinson's disease.

Patients with Parkinson's disease (PD) manifest difficulty in initiation and execution of movements, particularly when movements are sequential, simultaneous or repetitive. Eye movements are particularly effective in evaluating motor impairments. We utilized a series of saccadic eye movement paradigms to explore the ability of 13 patients with mild-moderate PD and 13 age-matched healthy controls to self-pace saccades between two continuously illuminated targets, before and after an externally cued tracking period, and respond to unexpected changes in task demand. The latter was explored by measuring saccadic responses to unexpected "oddball" targets that appeared during a well-learned reciprocating sequence of saccades, in either the opposite direction to that expected or at twice the anticipated extent. Results indicated that all participants demonstrated a marked increase in saccade amplitudes from the externally cued saccade tracking to the self-paced saccades. Unexpectedly, this difference was magnified in PD patients. Self-paced saccades before externally cueing were also more frequent than requested in the PD group, but timing improved following external cueing. The second key finding was that while patients were able to respond to unexpected changes in target amplitude, performance was more variable (in terms of latency and accuracy) when responding to unexpected changes in target direction. Hence, beneficial effects of external cueing on the timing of self-paced saccades may be mediated through cortical regions, placing less emphasis on striatal regions known to be compromised in PD. Additionally, responding to changes in saccade direction (but not amplitude) may rely on basal ganglia circuitry.

Ocular motor differences between melancholic and non-melancholic depression.

BACKGROUND: Major depressive disorder may be a heterogeneous disorder, yet melancholic depression is the most consistently described subtype, regarded as qualitatively different to non-melancholic depression in terms of cognitive and motor impairments. Eye movement studies in depression are infrequent and findings are inconclusive. METHODS: This study employed a battery of saccadic eye movement tasks to explore reflexive saccades, as well as higher order cognitive aspects of saccades including inhibitory control and spatial working memory. Nineteen patients with major depressive disorder (9 melancholic; 10 non-melancholic) and 15 healthy controls participated. RESULTS: Differences were revealed between melancholic and non-melancholic patients. Melancholia was associated with longer latencies, difficulty increasing peak velocities as target amplitudes increased, and hypometric primary saccades during the predictable protocol. In contrast, the non-melancholic depression group performed similarly to controls on most tasks, but saccadic peak velocity was increased for reflexive saccades at larger amplitudes. LIMITATIONS: Most patients were taking antidepressant medication. CONCLUSIONS: The latency increases, reduced peak velocity and primary saccade hypometria with more severe melancholia may be explained by functional changes in the fronto-striatal-collicular networks, related to dopamine dysfunction. In contrast, the serotonergic system plays a greater role in non-melancholic symptoms and this may underpin the observed increases in saccadic peak velocity. These findings provide neurophysiological support for functional differences between depression subgroups that are consistent with previous motor and cognitive findings.

Hypometric primary saccades and increased variability in visually-guided saccades in Huntington's disease.

Eye movement abnormalities can be distinctive and suggestive of a specific pathophysiology. To further investigate the deficits in the control of saccades in patients with Huntington's disease (HD), we investigated the ability of 11 HD patients and 11 matched controls to perform visually-guided saccades. We adopted reflexive saccade tasks involving predictable and unpredictable sequences, at different amplitudes of target step (10 degrees, 20 degrees, 30 degrees, 40 degrees ), as well as voluntary self-paced saccades. Prolongation of initiation was observed in the HD group as the target amplitude of predictable saccades increased. During the self-paced saccade task, the HD patients had increased intersaccadic intervals, performed fewer saccades in the allocated time and displayed an increased temporal variability in comparison to the controls. Furthermore, hypometric primary saccades, and an increased number of corrective saccades, were observed during both reflexive and voluntary saccades in the HD group. The delayed initiation of large saccades, deficits in voluntary, self-paced saccades, impaired saccadic accuracy and increased corrective saccades in HD, were interpreted in light of other ocular motor and limb studies, and appear to be due to damage to the fronto-striatal loop, including the supplementary eye fields, as well as possible brainstem and cerebellar involvement.