White Matter and Cognition in Adults Who Were Born Preterm

BACKGROUND AND PURPOSE: Individuals born very preterm (before 33 weeks of gestation, VPT) are at risk of damage to developing white matter, which may affect later cognition and behaviour. METHODS: We used diffusion tensor MRI (DT-MRI) to assess white matter microstructure (fractional anisotropy; FA) in 80 VPT and 41 term-born individuals (mean age 19.1 years, range 17-22, and 18.5 years, range 17-22 years, respectively). VPT individuals were part of a 1982-1984 birth cohort which had been followed up since birth; term individuals were recruited by local press advertisement. General intellectual function, executive function and memory were assessed. RESULTS: The VPT group had reduced FA in four clusters, and increased FA in four clusters relative to the Term group, involving several association tracts of both hemispheres. Clusters of increased FA were associated with more severe neonatal brain injury in the VPT group. Clusters of reduced FA were associated with lower birth weight and perinatal hypoxia, and with reduced adult cognitive performance in the VPT group only. CONCLUSIONS: Alterations of white matter microstructure persist into adulthood in VPT individuals and are associated with cognitive function

Lithium and cognitive enhancement: leave it or take it?

Lithium is established as an effective treatment of acute mania, bipolar and unipolar depression and as prophylaxis against bipolar disorder. Accumulating evidence is also delineating a neuroprotective and neurotrophic role for lithium. However, its primary effects on cognitive functioning remain ambiguous. The aim of this paper is to review and combine the relevant translational studies, focusing on the putative cognitive enhancement properties of lithium, specifically on learning, memory, and attention. These properties are also discussed in reference to research demonstrating a protective action of lithium against cognitive deficits induced by various challenges to the nervous system, such as stress, trauma, neurodegenerative disorders, and psychiatric disorders. It is suggested on the basis of the evidence that the cognitive effects of lithium are best expressed and should, therefore, be sought under conditions of functional or biological challenge to the nervous system

Effects of age and cognitive reserve on cognitive remediation therapy outcome in patients with schizophrenia

OBJECTIVES:: Older people with a diagnosis of schizophrenia seem to show fewer benefits following cognitive remediation therapy (CRT). It is not clear whether cognitive reserve modifies the relationship with age. METHODS:: A total of 134 individuals with schizophrenia were pooled from one randomized control trial and one observational trial. Eighty-five participants received more than 20 sessions of CRT and 49 participants received fewer than 20 sessions of CRT or treatment as usual. Participants were divided into two groups according to their age (younger than 40 years: younger, N = 77; and 40 years or older: older, N = 57). Cognition (working memory, cognitive flexibility, and planning) was assessed at baseline and posttreatment. Premorbid IQ and vocabulary at baseline were used as cognitive reserve proxies. RESULTS:: There was a significant effect of CRT on working memory in younger but not older participants. Better premorbid IQ was associated with better working memory performance in younger participants irrespective of treatment. No significant effects of treatment or cognitive reserve were revealed in older participants. Cognitive reserve proxies did not modify CRT treatment effect. CONCLUSION:: In conclusion, the effects of CRT were limited in older people with schizophrenia. Cognitive reserve could not be shown to influence the relationship of age with CRT efficacy. Better premorbid IQ was associated with increased practice effects on working memory in younger but not older individuals

Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive-compulsive disorder

Rationale We have proposed rewarded T-maze alternation as a model of obsessive-compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP) increments persistence therein, 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 increase, counteracted by mCPP pretreatment. Objectives This study (a) further explores the cross-tolerance between fluoxetine and mCPP and (b) extends the model by investigating its sensitivity to dopaminergic manipulations (D-2,D- 3 agonism-quinpirole). Materials and methods In both experiments, baseline and drug testing were 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 (2.5 mg/kg), (3) low-dose mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other with high-dose mCPP (2.5 mg/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 D-2,D- 3 receptor 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

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, 2.5 mg/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. (C) 2013 Elsevier B.V. All rights reserved

Diffusion tensor MRI of the corpus callosum and cognitive function in adults born preterm

Very preterm birth (before 33 weeks gestation) is associated with the white matter damage, and a common sequel is reduced size and altered shape of the corpus callosum. We used diffusion tensor MRI to assess the corpus callosum in 63 very preterm and 45 term-born young adults. Indices of white matter microstructure [fractional anisotropy (FA) and mean diffusivity (MD)] were obtained for the genu, body and splenium. Very preterm females had higher MD in the genu than term-born females, indicating altered white matter microstructure. This was associated with lower performance IQ. The groups demonstrated different patterns of correlations between verbal learning and tract-specific FA and MD, consistent with the reorganization of white matter structure in adults born very preterm