High-frequency stimulation (HFS) of the subthalamic nucleus (STN) alleviates the cardinal symptoms of Parkinson's disease, but the mechanisms underlying these clinical results remain to be clarified. The HFS of STN is associated with the release of dopamine (DA) in the striatum. This study examines possible mechanisms by which HFS-STN release DA. The experiments were performed in rats anesthetized with urethane. The STN was stimulated by electrical HF and chemical microinjections of an antagonist and an agonist of GABA(A) receptors, the bicuculline, and the muscimol, respectively. The extracellular striatal DA-DOPAC (3-4-dihydroxyphenilacetic acid) content was collected by means of intracerebral microdialysis cannula and analyzed with HPLC with an electrochemical detector. The HFS of STN and microinjection of bicuculline intrasubthalamic produced a significant increase of extracellular striatal DA, whereas DOPAC levels were unchanged. The microinjection of muscimol depresses spontaneous release of DA, without changes in DOPAC. The kainic acid lesion of the globus pallidus (GP) and the substantia nigra pars reticulata (SNr), ipsilateral to dialyzed striatum, did not modify the release of DA-DOPAC. These data provide evidence that the STN has a tonic action on the substantia nigra pars compacta (SNc), and the release of striatal DA by HFS-STN may be due to activation of the STN acting directly on SNc neurons.

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The aim of this study was to identify predictors of high psychosocial functioning in patients with bipolar disorder (BD). One hundred forty-five outpatients with BD and 50 healthy controls were included. Patients were categorized as having high psychosocial functioning if they concomitantly met three conditions: a) General Assessment of Functioning greater than 90, b) full-time employment, and c) full functional recovery. Clinical, demographical, and neurocognitive variables were assessed and considered as potential predictors of high functioning in regression models. We found that 22.8% (n = 33) of patients exhibited high psychosocial functioning. BD type II, higher educational level, and better performance in verbal memory, attention, and executive functions were independent predictors of high psychosocial functioning. Our results provide evidence that functional outcomes are heterogeneous in BD, including a percentage of patients who maintain good to excellent psychosocial functioning despite their illness. Neurocognitive functioning could be one of the most influential factors to explain this heterogeneity.

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ObjectiveIn this study, we aimed to evaluate the role of cognitive performance and measures of clinical course—including both syndromal and subsyndromal symptomatology—as determinants of the functional outcome of patients with Bipolar Disorder (BD) during a mean follow‐up period of more than 4 years.MethodsSeventy patients with euthymic BD completed a neurocognitive battery at study entry. Clinical course was assessed prospectively for a period longer than 48 months by two measures: time spent ill (documented using a modified life charting technique) and density of affective episodes (defined as the number of depressive and hypo/manic episodes per year of follow‐up). Psychosocial functioning was assessed during euthymia using the Functioning Assessment Short Test (FAST) total score at the end of follow‐up period.ResultsBaseline deficits in phonological fluency, a measure of executive functions (β = −2.49; 95% CI = −3.98, −0.99), and density of hypo/manic episodes during follow‐up (β = 6.54; 95% CI = 0.43, 12.65) were independently associated with FAST total score at the end of study.ConclusionsAlthough interrelated, manic morbidity and executive function impairments independently contribute to long‐term psychosocial dysfunction in BD and could be potential targets of intervention.