Episodic Visual Learning/Memory and Attentional Flexibility in Patients With Major Depressive Disorder After Clinically Effective Electroconvulsive Therapy.

OBJECTIVES: This study is a follow-up of a previous one reporting that the neuropsychological profile of pharmacoresistant patients with major depressive disorder referred for electroconvulsive therapy (ECT, ECT group) contrasted with that of their pharmacorespondent counterparts (NECT group). The NECT group exhibited severe visuospatial memory and minor executive deficits; the ECT group presented the reverse pattern. In that same ECT group, the current follow-up study examined the effects of clinically effective ECT on both cognitive domains 2 months later. METHODS: Fifteen ECT patients were administered Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA), Mini-Mental State Examination Scales and 5 tests of Cambridge Neuropsychological Test Automated Battery at intake (pre-ECT), end of ECT course (post-ECT), and 2 months thereafter (follow-up). RESULTS: Electroconvulsive therapy was effective in relieving clinical depression. After a post-ECT decline, the patients exhibited significant improvement in both Cambridge Neuropsychological Test Automated Battery, paired associate learning, and Stockings of Cambridge. By contrast, their major pre-ECT deficit in intra/extradimensional set shifting remained virtually unaffected. CONCLUSIONS: Our findings suggest that attentional flexibility deficits may constitute a neuropsychological trait-like feature of pharmacoresistant, ECT-referred major depressive disorder patients. However, this deficit does not seem generalized, given patient improvement in episodic visual learning/memory and some indication of improvement in spatial planning after ECT.

Cognitive effects of pregabalin in the treatment of long-term benzodiazepine-use and dependence.

OBJECTIVE: Long-term benzodiazepine (BDZ) use and dependence affect cognitive functioning adversely and partly irreversibly. Emerging evidence suggests that pregabalin (PGB) might be a safe and efficacious treatment of long-term BDZ use. The aim of the present study was to investigate the changes in several core cognitive functions after successful treatment of long-term BDZ use and dependence with PGB. METHODS: Fourteen patients with long-term BDZ use (mean duration >15 years) underwent neuropsychological assessment with the mini-mental state examination and four tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) battery before the initiation of PGB treatment and at a two months follow-up after the cessation of BDZs. Patients' CANTAB percentile score distributions were compared with normative CANTAB data. RESULTS: Patients improved on cognitive measures of global cognitive functioning, time orientation, psychomotor speed, and visuospatial memory and learning with strong effect sizes. By contrast, they failed to improve on measures of attentional flexibility. Despite their significant improvement, patients' scores on most tests remained still at the lower percentiles of CANTAB normative scores. CONCLUSIONS: Although preliminary, our findings suggest that successful treatment of long-term BDZ use with PGB is associated with a substantial, though only partial, recovery of BDZ-compromised neuropsychological functioning, at least at a 2-month follow-up.

Patient-reported needs predict perceived psychosocial disability and quality of life beyond symptom severity in schizophrenia.

PURPOSE: We examined whether patient-rated or clinician-rated needs are more strongly associated with perceived psychosocial disability (PPD) and subjective quality of life (SQOL) of schizophrenia patients, beyond symptom severity. METHODS: Hierarchical regression analyses were computed to test patient and clinician-rated unmet and met needs (estimated by eighty-two patient-clinician pairs) as predictors of PPD and SQOL above and beyond demographics and psychopathology. Needs, symptomatology, PPD and SQOL were estimated using Camberwell Assessment of Need (CAN), PANSS, WHODAS 2.0 and WHOQOL-BREF respectively. RESULTS: Needs were significantly associated with all WHODAS 2.0 and WHOQOL-BREF domains above and beyond demographics and PANSS variables. Clinician-rated needs were better predictors of only one WHODAS 2.0 domain, while patient-rated needs were better predictors of all other WHODAS 2.0 and WHOQOL-BREF domains. Patient-rated unmet needs were more strongly than met needs associated with the most WHODAS 2.0 and WHOQOL-BREF subscores. CONCLUSION: This study offers the first evidence that patient-rated needs, especially unmet needs, are strongly associated, above and beyond symptomatology, with global and domain-specific PPD of schizophrenia patients. Accordingly, strong relations of patient-rated needs with SQOL emerged. Identifying and addressing patient-reported needs could facilitate PPD and SQOL improvement more effectively than interventions confined solely to symptom remission.IMPLICATIONS FOR REHABILITATIONSchizophrenia is associated with poor rehabilitation and recovery outcomes, i.e., perceived psychosocial disability (PPD) and subjective quality of life (SQOL).Assessment of patients' needs constitutes the basis of determining treatment goals and planning tailor-made interventions to achieve crucial rehabilitative outcomes.Higher levels of patient-reported unmet needs are associated with poorer SQOL and higher global and domain-specific PPD of schizophrenia patients, above and beyond symptom severity.Addressing patient-reported needs through personalized interventions can facilitate more effectively PPD and SQOL improvement, than treatment confined to symptomatic alleviation.

Bipolar disorder, mood stabilizers and cognitive flexibility: Translationally dissecting illness from drug effects.

Bipolar disorder (BD) effects on cognition are confounded by the putative cognitive impact of its major pharmacological treatments, given the neurotrophic potential of mood stabilizers, particularly lithium. We examined the area of cognitive flexibility (CF), aiming to disentangle BD from medication effects, using translational methodology. CF was assessed by CANTAB-IED (intra- extra-dimensional shift; Study 1, euthymic BD participants) and its animal analog (Study 2, rats). Both studies included groups (1) control, (2) lithium, chronic, current treatment (LI-CHRON-C, A: > 2 years, N = 32; B: 2 months, N = 11); (3) valproate, chronic, current treatment (VPA-CHRON-C, A: > 2 years, N = 30; B: 2 months, N = 12). Study 2 included 2 additional groups; Group 4: LI-CHRON-PAST (2 months, stopped 1 month pretest, N = 13); Group 5: LI-ACUTE (LI on test days only, N = 13). In Study 1, neither total nor stage (discrimination: D; reversal R; intra- extra-dimensional shifts: IED) IED errors differed between groups [Kruskal-Wallis: H(2, N = 94) 0.95 > p > 0.65]. Similarly in Study 2, errors did not differentiate the 5 pharmacological groups. Differences emerged only between LI-ACUTE and Controls in response latencies (D, R, IED ANOVAS: 0.002 > p > 0.0003; contrasts D, R: p = 0.002, 0.0001). In conclusion, LI and VPA BD patients were indistinguishable from Controls in IED errors, as were animals treated with LI-CHRON, current or past, or VPA-CHRON-C vs Controls. LI-ACUTE treatment produced significant latency deficits vs Controls. Within the limitations of translational comparisons, our results suggest that the normal CF noted in euthymic BDs is not attributable to mood stabilizer effects.

5-HT2C receptor involvement in the control of persistence in the reinforced spatial alternation animal model of obsessive-compulsive disorder.

OBJECTIVE: The serotonergic system is implicated in the pathophysiology of obsessive-compulsive disorder (OCD). However, the distinct role of serotonin (5-HT) receptor subtypes remains unclear. This study investigates the contribution of 5-HT2A and 5-HT2C receptors in the modulation of persistence in the reinforced spatial alternation model of OCD. METHODS: Male Wistar rats were assessed for spontaneous and pharmacologically induced (by m-chlorophenylpiperazine: mCPP) directional persistence in the reinforced alternation OCD model. Systemic administration of mCPP (non-specific 5-HT agonist, 2.5mg/kg), M100907 (selective 5-HT2A receptor antagonist, 0.08 mg/kg), SB242084 (selective 5-HT2C receptor antagonist, 0.5 mg/kg) and vehicle was used. Experiment 1 investigated M100907 and SB242084 effects in animals spontaneously exhibiting high and low persistence during the early stages of alternation training. Experiment 2 investigated M100900 and SB242084 effects on mCPP-induced persistence. RESULTS: Under the regime used in Experiment 1, 5-HT2A or 5-HT2C receptor antagonism did not affect spontaneous directional persistence in either high or low persistence groups. In Experiment 2, 5-HT2C but not 5-HT2A receptor antagonism significantly reduced, but did not abolish, mCPP-induced directional persistence. CONCLUSIONS: These findings suggest that 5-HT2C but not 5-HT2A receptors contribute to the modulation of mCPP-induced persistent behaviour, raising the possibility that the use of 5-HT2C antagonists may have a therapeutic value in OCD.