Psychosis in Machado-Joseph Disease: Clinical Correlates, Pathophysiological Discussion, and Functional Brain Imaging. Expanding the Cerebellar Cognitive Affective Syndrome.

Machado-Joseph disease (MJD) is the most common spinocerebellar ataxia worldwide with a broad range of clinical manifestations, but psychotic symptoms were not previously characterized. We investigated the psychiatric manifestations of a large cohort of Brazilian patients with MJD in an attempt to characterize the presence of psychotic symptoms. We evaluated 112 patients with clinical and molecular diagnosis of MJD from February 2008 to November 2013. Patients with psychotic symptoms were referred to psychiatric evaluation and brain perfusion single-photon emission computed tomography (SPECT) analysis. A specific scale-Positive and Negative Syndrome Scale (PANSS)-was used to characterize psychotic symptoms in MJD patients. We also performed an autopsy from one of the patients with MJD and psychotic symptoms. Five patients presented psychotic symptoms. Patients with psychotic symptoms were older and had a late onset of the disease (p < 0.05). SPECT results showed that MJD patients had significant regional cerebral blood flow (rCBF) decrease in the cerebellum bilaterally and vermis compared with healthy subjects. No significant rCBF differences were found in patients without psychotic symptoms compared to patients with psychotic symptoms. The pathological description of a patient with MJD and psychotic symptoms revealed severe loss of neuron bodies in the dentate nucleus and substantia nigra. MJD patients with a late onset of the disease and older ones are at risk to develop psychotic symptoms during the disease progression. These clinical findings may be markers for an underlying cortical-cerebellar disconnection or degeneration of specific cortical and subcortical regions that may characterize the cerebellar cognitive affective syndrome.

Recognition of bipolar disorder type I before the first manic episode: challenges and developments.

Bipolar disorder (BD) usually follows a neurobiological progression pathway, but a relatively long interval between the first symptoms of the disorder and the correct diagnosis and treatment takes place in most patients. Strategies used to recognize BD at an early stage and even prior to the first manic episode could help identify the risk and modifying factors that influence the onset and course of disease, and improve outcomes. Drawing on current research results, this article presents considerations on risk factors for the development of BD, including genetic/familial risk, endophenotypes and clinical characteristics. Taken together, this article provides a framework and tools for research on the BD prodrome, as well as for the early recognition and timely treatment of patients prior to and immediately after the emergence of BD.