Visuospatial working memory deficits in remitted patients with bipolar disorder: susceptibility to the effects of GABAergic agonists

Objective: Visuospatial working memory (VSWM) deficit under high working memory (WM) load deserves further investigation as a potential trait marker for bipolar disorder (BPD). However, VSWM performances may depend on basic neurocognitive processes and are possibly compromised by neurocognitive effects of psychotropic medications. Methods: A total of 32 remitted BPD patients and 39 healthy controls undertook parametric VSWM tasks and assessments for selective attention, sustained attention, psychomotor speed, mental flexibility, and Wechsler Adult Intelligence Scale-III full IQ. Using a multivariate model and trend analysis and controlling for other basic neurocognitive ability, the effects of mood stabilizers, antipsychotics, GABAergic agonists, and anticholinergics on VSWM performances were explored by post-hoc analysis comparing performances across WM loads between healthy controls and patients treated and not treated with a specific medication. Results: Remitted BPD patients showed more pronounced performance declines in VSWM performances as WM loads increased, indicating inefficient VSWM processing. The VSWM deficits of remitted patients were independent of their impairments in attentional processes or psychomotor speed. Among the medications, only GABAergic agonists were associated with impaired VSWM performances. Conclusions: Remitted BPD patients had WM-load-dependent VSWM processing deficits after controlling for neurocognitive performances. As these deficits were associated with the use of GABAergic agonists, altered GABAergic neurotransmission might be involved with the underlying mechanisms of the impaired VSWM processing of BPD. Since GABAergic agonist use is often continued from the acute to the remitted phase in BPD and might potentially affect the functional recovery, clinicians should be aware of these neurocognitive side effects, even at low dosages. Close monitoring and timely discontinuation of GABAergic agonists is of utmost importance for clinical practice.