We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.
To save content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about saving content to .
To save content items to your Kindle, first ensure no-reply@cambridge.org
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about saving to your Kindle.
Note you can select to save to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
In the rewarded alternation model of obsessive compulsive disorder (OCD), the serotonin agonist m-chlorophenylpiperazine (mCPP) increases persistent behaviour, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI-fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increases, counteracted by mCPP pretreatment.
Objectives:
This study
a. further explores the apparent cross-tolerance between fluoxetine and mCPP and
b. extends the model by investigating its sensitivity to dopaminergic manipulations (D2,3 agonism - quinpirole).
Methods:
In both experiments, baseline and drug testing was carried out under daily T-maze alternation training.
Exp.1:
Matched group (n=8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration):
1. saline,
2. low-dose fluoxetine (2.5mg/kg),
3. low-dose mCPP (0.5mg/kg) or
4. combined fluoxetine+mCPP.
One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10mg/kg), the other with high-dose mCPP (2.5mg/kg).
Exp.2:
One group (n=12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg).
Results:
Exp.1:
Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine+mCPP pretreatment afforded full protection from either challenge.
Exp.2:
Quinpirole significantly increased directional persistence after 13 administration days.
Conclusions:
These results establish the sensitivity of the rewarded alternation OCD model to D2,3receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.
We recently demonstrated that patients with major depression (MDD) with and without electroconvulsive therapy referral (ECTs vs. NECTs) qualitatively differ in neuropsychological profile. ECTs presented severe executive but minor visuospatial memory deficits, suggesting mainly frontostriatal involvement; NECTs presented the opposite pattern, compatible with temporohippocampal involvement. Here we follow up on ECT treatment effects on both cognitive domains.
Method
15 ECTs were assessed with Hamilton Depression (HAMD-24), Hamilton Anxiety (HAMA) and Mini-Mental State Examination (MMSE) scales and 5 tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB) at hospitalisation (PRE-ECT), immediately after ECT (POST-ECT) and 2 months later (FOLLOW-UP). ECTs at FOLLOW-UP were also compared to 15 matched non-psychiatric CONTROLS who underwent neuropsychological testing once.
Results
There was significant clinical improvement (reflected by reduced HAMD-24 and HAMA scores: p < 0.001) between PRE-ECT and FOLLOW-UP. After a minor decline POST-ECT, MMSE scores showed significant increase at FOLLOW-UP (p < 0.02). At FOLLOW-UP, Paired Associates Learning (PAL) showed significant improvement (p < 0.001). Stockings of Cambridge (SOC) performance also improved (decrease in early abandonments, p < 0.04) POST-ECT and at FOLLOW-UP. However, clinical improvement did not result in improvement in Intra / Extradimensional Shift (IED): at FOLLOW-UP, ECT patients were indistinguishable from CONTROLS in all neuropsychological measures except IED (p < 0.04).
Conclusions
Clinically successful ECT treatment was accompanied by improved global cognitive functioning, visuospatial memory and spatial planning, but offered no benefit in attentional flexibility. This residual deficit suggests ‘trait’ frontostriatal involvement in this patient group.
The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses.
Method
Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and nonpsychiatric Controls (matched groups, n = 15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Results
ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p = 0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p < 0.03 ; Control/NECT p < 0.01) and the Spatial Recognition Memory (SRM) task (p < 0.05 ; Controls/NECTs p < 0.05) ; ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p < 0.01 ; Controls/ECTs p < 0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H = 11, p < 0.01) but ECTs who completed SOC performed comparably to the other two groups.
Conclusions
A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT dépressives.
The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses.
Method
Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).
Results
ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups.
Conclusions
A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.
Recommend this
Email your librarian or administrator to recommend adding this to your organisation's collection.