Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysis

Fleming, Shelley K.; Blasey, Christine; Schatzberg, Alan F.

doi:10.1016/s0022-3956(03)00100-6

Cited by 95 publications

(68 citation statements)

References 29 publications

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“…This raises the question whether the results also have relevance for the study of depression; in particular, whether simulation findings for low 5-HT can help in understanding memory deficits found in depression. These deficits might just be secondary to mood, but the idea that depression is accompanied by neuropsychological deficits independent of mood is gaining wider currency (Fleming et al, 2004). A link between 5-HT and memory deficits in depression is suggested by the fact that serotonergic antidepressants have been found to improve memory before mood improved (Allain et al, 1992;Fudge et al, 1990;Siegfried and O'Connolly, 1986).…”

Section: Discussionmentioning

confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT 1A and 5-HT 3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT 1A agonists ameliorate memory deficits in depression. INTRODUCTIONHypofunction of the 5-hydroxytryptamine (5-HT) system has emerged as a leading candidate cause for depression (Naughton et al, 2000;Middlemiss et al, 2002). At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999). This mirrors findings in depression, which is accompanied by moderate to severe memory deficits (Johnson and Magaro, 1987;Schaub et al, 2003). However, manipulations that increase 5-HT concentration or 5-HT receptor activation also lower memory performance, as indicated by receptor agonist studies in both humans (Riedel et al, 2002) and animals (Altman and Normile, 1988). Up to now, it is not known why both increased and decreased 5-HT activation have adverse effects on memory.5-HT binds to a large and disparate family of CNS receptors, which have effects that are sometimes opposite. Thus, many effects of different receptors seem to cancel each other out. In a review (see Supplementary Information on internet), we identify two robust effects of 5-HT in the hippocampus. First, 5-HT exerts a hyperpolarizing influence on principal cells; directly, via 5-HT 1A receptors, and indirectly, via facilitation of GABA release from local interneurons through 5-HT 3 receptors (Burnet et al, 1995;Piguet and Galvan, 1994). Activation of 5-HT 2A and 5-HT 2C receptors has been suggested to induce depolarization in principal cells (Piguet and Galvan, 1994;Barnes and Sharp, 1999), but these effects appear to be dominated by the depolarizing effects of 5-HT, as bath application of 5-HT will hyperpolarize principal cells in slice preparations of the dentate gyrus (Piguet and Galvan, 1994). In addition, through 5-HT 2C , 5-HT 4 , and 5-HT 7 receptors, afterhyperpolarizing (AHP) currents are downregulated, leading to reduced adaptation in principal cells (Torres et al, 1996;Bac...

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Section: Discussionmentioning

confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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“…A single meta-analysis confirmed that patients with psychotic depression are cognitively more impaired compared with their nonpsychotic counterparts. 14 Studies that investigated the effect of psychotic features on cognitive deficits in BD found less consistent findings: while some studies reported more severe cognitive deficits in working memory, verbal memory, and executive functions, others did not find a between-group difference. [15][16][17][18] There is emerging evidence indicating that cognitive deficits are quite common in AP.…”

Section: Introductionmentioning

confidence: 99%

Cognitive Impairment in Affective Psychoses: A Meta-analysis

Bora

Yücel

Pantelis

2009

Schizophrenia Bulletin

120

100

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It has recently been suggested that cognitive impairment should be included in the diagnostic criteria of schizophrenia. One of the main arguments in support of this suggestion has been the hope that cognitive impairment can help distinguish schizophrenia from bipolar disorder (BD). However, recent evidence shows that cognitive deficits occur in BD and persist beyond euthymia. Further, mood disorders with psychotic features might be expected to manifest greater cognitive impairment, which further complicates the potential to differentiate these disorders. The goal of the current meta-analysis was to examine the magnitude and characteristics of cognitive impairments in affective psychoses (AP). A systematic search of the existing literature sourced 27 studies that met the inclusion criteria. These studies compared cognitive performances of 763 patients with AP (550 BD and 213 major depressive disorder) and 1823 healthy controls. Meta-regression and subgroup analyses were used to examine the effects of moderator variables. Meta-analyses of these studies showed that patients with AP were impaired in all 15 cognitive tasks with large effect sizes for most measures. There were no significant differences between the magnitude of impairments between the BD and major depressive disorder groups. The largest effect size was found for symbol coding, stroop task, verbal learning, and category fluency, reflecting impairments in elementary and complex aspects of attentional processing, as well as learning and memory. In general, the pattern of cognitive impairments in AP was similar to reported findings in euthymic patients with BD, but relatively more pronounced.

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“…There are considerable data suggesting that PMD is a distinct syndrome from nonpsychotic major depression (NPMD), as evidenced by significant differences on a number of different dimensions: neuropsychological testing Fleming et al, 2004;Hill et al, 2004), response to treatment (Spiker et al, 1985), and morbidity and mortality (Rothschild, 2003;Vythilingam et al, 2003). PMD patients also show a number of biological characteristics that are distinct from NPMD patients.…”

Section: Introductionmentioning

confidence: 99%

“…Most notably, they demonstrate excessive hypothalamic-pituitary-adrenal (HPA) axis activity, as evidenced by elevated urinary free cortisol levels (Kathol et al, 1989), elevated evening and night time cortisol levels (Sachar et al, 1973), and high rates of dexamethasone nonsuppression (Nelson and Davis, 1997). Administration of glucocorticoids to healthy controls (Lupien et al, 1999;Newcomer et al, 1999) results in cognitive deficits similar to those seen with PMD Fleming et al, 2004;Hill et al, 2004). In addition, a number of years ago, we hypothesized that the psychotic features of PMD were due to excessive glucocorticoid activity (Schatzberg et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Clinical and Biological Effects of Mifepristone Treatment for Psychotic Depression

Flores

Kenna

Keller

et al. 2005

Neuropsychopharmacol

188

106

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Psychotic major depression (PMD) is found to be a relatively common psychiatric condition that affects up to nearly 20% of patients with major depression. Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone, in addition to restoring a more normal afternoon cortisol release. The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed. In total, 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a randomized double-blind manner. The Hamilton Depression Rating Scale (HDRS) and the Brief Psychiatric Rating Scale (BPRS) were administered at baseline and again after 8 days of treatment. Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment. Significantly, more patients in the mifepristone group (seven of 15) showed a 50% or greater decline on the BPRS positive symptom subscale, an index of psychotic symptoms, as compared to the placebo group (two of 15). Patients who received mifepristone had lower HDRS and BPRS scores at study completion compared to those who received placebo, but these differences were not statistically significant. In addition, mifepristone significantly elevated cortisol and ACTH levels and steepened ascending slopes from 1800 to 0100 and from 0100 to 0900 as compared to placebo. Clinical and biological effects of mifepristone were comparable among males and females. Age was found to significantly and positively correlate with changes in cortisol and ACTH. These results suggest that short-term use of mifepristone may be effective in the treatment of PMD and may reregulate the HPA axis. Additional blinded studies are warranted.

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Neuropsychological correlates of psychotic features in major depressive disorders: a review and meta-analysis

Cited by 95 publications

References 29 publications

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Cognitive Impairment in Affective Psychoses: A Meta-analysis

Clinical and Biological Effects of Mifepristone Treatment for Psychotic Depression

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