Antipsychotic treatment effects on progression of brain pathomorphology in first episode schizophrenia

Lieberman, J.A.; Charles, H. Cecil; Sharma, Tonmoy; Zipursky, R.; Kahn, R.S.; Gur, Ruben; Tohen, Mauricio; Green, A.I.; McEvoy, Joseph P.; Perkins, D.; Hamer, Robert M.; Nemeroff, Charles B.; Rothschild, Anthony J.; Kuldau, John M.; Strakowski, S. M.; Tollefson, Gary D.

doi:10.1016/s0920-9964(03)80491-7

Cited by 19 publications

(17 citation statements)

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“…Atypical antipsychotics are also found in several studies to show greater beneficial effects than typical antipsychotics on cognitive functions (e.g. Keefe et al, 1999Keefe et al, , 2004 ; for reviews see Meltzer and McGurk, 1999 ;Sharma, 1999), brain activity (Braus et al, 1999 ;Honey et al, 1999) and brain structural volumes (Corson et al, 1999 ;Chakos et al, 2005 ;Garver et al, 2005 ;Lang et al, 2004 ;Lieberman et al, 2005). It should be noted, however, that PPI in patients treated with risperidone or olanzapine, although within the normal range, was still somewhat lower than PPI seen in controls.…”

Section: Discussionmentioning

confidence: 99%

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics

Kumari

Antonova

Geyer³

et al. 2006

Int. J. Neuropsychopharm.

114

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A key feature of schizophrenia is the inability to screen out irrelevant sensory input. Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable opportunity to study this feature. PPI is reliably impaired in schizophrenia. Animal models of disrupted PPI have proved valuable for the evaluation of antipsychotic substances. The cortico-striato-pallido-thalamic circuitry is primarily responsible for modulation of PPI in animals. We examined PPI and its brain correlates, using functional magnetic resonance imaging (fMRI), in men with schizophrenia treated with typical or atypical antipsychotics. Thirty men with schizophrenia on stable doses of typical antipsychotics (n=10), risperidone (n=10) or olanzapine (n=10 ; 9 with usable fMRI data) and 12 healthy men underwent psychophysiological testing and fMRI during a tactile PPI paradigm. The results showed reduced PPI of the eye-blink startle response in patients compared with healthy controls. Within the patient group, those on typical antipsychotics showed significantly impaired PPI but risperidone-or olanzapine-treated patients showed a milder (non-significant) deficit. Increased activity in the striatum, thalamus, insula, hippocampal, temporal, inferior frontal and inferior parietal regions occurred in association with PPI in controls. Patients treated with risperidone or olanzapine, but not with typical antipsychotics, showed significant activation in PPI-relevant regions. Our findings provide preliminary evidence that atypical antipsychotics positively influence PPI and partially restore associated brain functions in schizophrenia. Imaging data buttress the validity of PPI as a useful animal model of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics

Kumari

Antonova

Geyer³

et al. 2006

Int. J. Neuropsychopharm.

114

View full text Add to dashboard Cite

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“…In vivo imaging studies have reported decreased prefrontal cortical volume in schizophrenia (Hirayasu et al, 2001;Selemon et al, 2002), and a recent multicenter study of first-episode schizophrenic subjects has concluded that treatment with the atypical APD olanzapine, but not a typical APD, slows the progressive loss of gray matter volume (Lieberman et al, 2003a). A slowing or reversal of the cortical volume loss in schizophrenia by appropriate APD treatment could involve an increase in the number of newly generated cortical cells.…”

Section: Introductionmentioning

confidence: 99%

Effects of Antipsychotic Drugs on Neurogenesis in the Forebrain of the Adult Rat

Wang

Dunnavant

Jarman

et al. 2004

Neuropsychopharmacol

154

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The generation of new cells in the adult mammalian brain may significantly modify pathophysiological processes in neuropsychiatric disorders. We examined the ability of chronic treatment with the antipsychotic drugs (APDs) olanzapine and haloperidol to increase the number and survival of newly generated cells in the prefrontal cortex (PFC) and striatal complex of adult male rats. Animals were treated with olanzapine or haloperidol for 3 weeks and then injected with 5-bromo-2 0 -deoxyuridine (BrdU) to label mitotic cells. Half of the animals continued on the same APD for two more weeks after BrdU challenge, with the other half receiving vehicle during this period. Olanzapine but not haloperidol significantly increased both the total number and density of BrdU-labeled cells in the PFC and dorsal striatum; no effect was observed in the nucleus accumbens. Continued olanzapine treatment after the BrdU challenge did not increase the survival of newly generated cells. The newly generated cells in the PFC did not express the neuronal marker NeuN. Despite the significant increase in newly generated cells in the PFC of olanzapine-treated rats, the total number of these cells is low, suggesting that the therapeutic effects of atypical APD treatment may not be due to the presence of newly generated cells that have migrated to the cortex.

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“…This is of particular interest since it was suggested that typical antipsychotics were related to a more pronounced loss while atypical medication (olanzapine in particular) was related to less pronounced loss. This was not only the case in first-episode patients (Lieberman et al 2005) but also in a sample consisting of first-episode and chronically ill patients who had all been medicated for more than a few weeks at baseline measurement (van Haren et al 2008). Moreover, to investigate the effects of medication in an unbiased fashion randomized control trials are essential ; therefore, it is justified to place more weight on the results of the only large randomized trial, even though it was funded by the manufacturers of olanzapine.…”

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confidence: 99%

“…Second, as different antipsychotic drugs act on different neurotransmitter systems it would not be surprising that type of medication is a crucial factor. Indeed, two of the largest follow-up MRI studies (including the only randomized trial) (Lieberman et al 2005 ;van Haren et al 2008) found evidence for differential effects from different kinds of antipsychotics on global brain volumes. This is of particular interest since it was suggested that typical antipsychotics were related to a more pronounced loss while atypical medication (olanzapine in particular) was related to less pronounced loss.…”

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confidence: 99%

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Letter to the Editor: A comment on ‘A systematic review of the effects of antipsychotic drugs on brain volume’ by Moncrieff & Leo ()

Haren

Kahn

2010

Psychol. Med.

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Antipsychotic treatment effects on progression of brain pathomorphology in first episode schizophrenia

Cited by 19 publications

References 0 publications

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics

A fMRI investigation of startle gating deficits in schizophrenia patients treated with typical or atypical antipsychotics

Effects of Antipsychotic Drugs on Neurogenesis in the Forebrain of the Adult Rat

Letter to the Editor: A comment on ‘A systematic review of the effects of antipsychotic drugs on brain volume’ by Moncrieff & Leo ()

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