Unraveling psychomotor slowing in bipolar disorder.

BACKGROUND/AIMS: In addition to affective and cognitive symptomatology, psychomotor deficits are known to be present in bipolar disorder (BD). Psychomotor functioning includes all of the processes necessary for completing a movement, from planning to initiation and execution. While these psychomotor symptoms have been studied extensively in schizophrenia and major depressive disorder, only simple measures have been conducted in BD. The present study examines psychomotor functioning in BD. METHODS: Twenty-two euthymic BD patients and 21 healthy controls performed three computerized copying tasks varying in cognitive load. Movement times (MT), reflecting fine motor processing, and initiation times (IT), reflecting cognitive processing of visual-spatial information, were separately measured in each group. RESULTS: The BD patients had longer IT but not MT in the simplest task and the opposite pattern of longer MT but not IT in the complex task. However, when controlling for residual mood symptoms, the MT were no longer significantly slower in the BD group. CONCLUSIONS: The longer MT and IT in BD reflect overall psychomotor slowing. Specifically, the results provide evidence for cognitive slowing in BD. In addition, the longer MT in the complex task reflect a slowed motor component of movement when the cognitive load is high and when depressive symptoms are present. These findings extend the current knowledge of the nature of psychomotor slowing in BD and may have important prognostic implications for patients.

Electrophysiological (EEG) evidence for reduced performance monitoring in euthymic bipolar disorder.

OBJECTIVES: Apart from mood episodes, many cognitive deficits are present in bipolar disorder (BD). Performance monitoring is an important aspect of executive functioning and involves continuous monitoring of behavior and making subsequent changes when an error is made. On a neurophysiological level, the error-related negativity (ERN), an event-related brain potential (ERP) generated in the anterior cingulate cortex (ACC), reflects this process of performance monitoring. Abnormal ERN amplitudes have been observed in many major psychiatric disorders. However, despite conflicting evidence regarding the role of the ACC in BD, no studies to date have investigated performance monitoring as reflected in the ERN in BD. METHODS: Sixteen patients with BD in a euthymic state and 14 matched healthy controls performed a speeded two-choice reaction-time paradigm (Flankers Task) while electroencephalogram (EEG) measures were obtained. Behavioral and ERP measurements were analyzed for the two groups. RESULTS: The patients with BD, although euthymic, scored higher on depressive symptoms than healthy controls. While no behavioral group differences were found, patients with BD displayed lower ERN amplitudes than healthy controls when controlling for effects of residual mood. CONCLUSIONS: The lower ERN amplitudes in the BD group reflect reduced performance monitoring and extend current knowledge of executive functioning in BD. Importantly, these findings go a long way to resolving the contradictory results regarding ACC involvement in BD by showing that taking into account residual mood may greatly influence error-related ACC activations and is critically important in understanding cognitive deficits in BD.

Longitudinal evaluation of the psychomotor syndrome in schizophrenia.

Little is known about the longitudinal course of psychomotor signs and symptoms after illness onset in schizophrenia. Therefore, a 1-year follow-up study was conducted in which patients with schizophrenia were assessed three times with an extensive battery of psychomotor rating scales and tests. The syndromic structure of psychomotor symptoms was also studied. In accordance with a neurodevelopmental view on schizophrenia, psychomotor functioning was found to remain stable or improve slightly. Prospective studies with longer follow-up periods are needed to rule out the possibility of neurodegeneration in subgroups of patients and to evaluate possible covariation in the course of psychomotor symptoms.

Pharmacological augmentation strategies for schizophrenia patients with insufficient response to clozapine: a quantitative literature review.

BACKGROUND: When schizophrenia patients have insufficient response to clozapine, pharmacological augmentation is often applied. This meta-analysis summarizes available evidence on efficacy of pharmacological augmentation of clozapine treatment in schizophrenia spectrum disorder. METHODS: Only double-blind randomized controlled studies were included. Primary outcome measure was total symptom severity, and secondary outcome measures were subscores for positive and negative symptoms. Effect sizes were calculated from individual studies and combined to standardized mean differences (Hedges's g). RESULTS: Twenty-nine studies reporting on 15 different augmentations were included. Significant better efficacy than placebo on total symptom severity was observed for lamotrigine, citalopram, sulpiride, and CX516 (a glutamatergic agonist). The positive effect of lamotrigine disappeared after outlier removal. The other positive findings were based on single studies. Significantly better efficacy on positive symptom severity was observed for topiramate and sulpiride. The effect of topiramate disappeared after outlier removal. Results for sulpiride were based on a single randomized controlled trial. Citalopram, sulpiride, and CX516 showed better efficacy for negative symptoms than placebo, all based on single studies. CONCLUSIONS: Evidence for efficacy of clozapine augmentation is currently scarce. Efficacy of lamotrigine and topiramate were both dependent on single studies with deviating findings. The effect of citalopram, sulpiride, and CX516 were based on single studies. Thus, despite their popularity, pharmacological augmentations of clozapine are not (yet) demonstrated to be superior to placebo.