human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Selective serotonin reuptake inhibitors ( SSRIs ) are typically thought to have a delay of several weeks in the onset of their clinical effects . However , recent reports suggest they may have a much earlier therapeutic onset . A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs . Aims To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces . Method Twenty-six healthy volunteers were r and omised to receive a single oral dose of citalopram ( 20 mg ) or placebo . Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging . Results Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo . Conclusions Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine . Clozapine-induced sedation can worsen cognition and impair social and occupational functioning . OBJECTIVES To evaluate the efficacy , tolerability , and safety of modafinil for negative symptoms , cognition , and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine . METHOD A double-blind , placebo-controlled , flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007 , adding modafinil up to 300 mg/d to stabilized schizophrenia out patients receiving clozapine .  Psychopathology , cognition , and wakefulness/fatigue were assessed with st and ard rating scales . RESULTS Thirty-five patients were r and omly assigned to treatment with study drug and included in the analysis . Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo . Modafinil was well tolerated and did not worsen psychosis . CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms , cognitive deficits , or wakefulness/fatigue in patients on clozapine . However , given our limited power to detect a treatment effect and the clear possibility of a type II error , larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00573417 Rationale Cognitive impairments are important determinants of functional outcome in psychosis , which are inadequately treated by antipsychotic medication . Modafinil is a wake-promoting drug that has been shown to improve attention , memory and executive function in the healthy population and in patients with schizophrenia . Objectives We aim ed to establish modafinil ’s role in the adjunctive treatment of cognitive impairments in the first episode of psychosis , a time when symptoms may be more malleable than at chronic stages of the disease . Methods Forty patients with a first episode of psychosis participated in a r and omised , double-blind , placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning , memory , learning , impulsivity and attention . Results Modafinil improved verbal working memory ( d = 0.24 , p = 0.04 ) , spatial working memory errors ( d = 0.30 , p = 0.0004 ) and strategy use ( d = 0.23 , p = 0.03 ) . It also reduced discrimination errors in a task testing impulsivity . Modafinil showed no effect on impulsivity measures , sustained attention , attentional set-shifting , learning or fluency . Conclusions Modafinil selectively enhances working memory in first episode psychosis patients , which could have downstream effects on patients ’ social and occupational functioning Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression Modafinil , a novel cognitive enhancer , selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder ( ADHD ) . It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission . The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia . Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind , r and omized , placebo-controlled crossover study using a 200 mg dose of modafinil . Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD . Improvement was seen on short-term verbal memory span , with trends towards improved visual memory and spatial planning . This was accompanied by slowed response latency on the spatial planning task . No effect on stop-signal performance was seen . Importantly , significant improvement in attentional set shifting was seen , despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients . Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia , particularly because of its beneficial effects on attentional set shifting Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders , depression , and anxiety . We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders . In all , 12 male volunteers received  citalopram  ( 7.5 mg intravenously ) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go , Loss/No-loss , and covert ( aversive ) face emotion recognition tasks during functional magnetic resonance imaging ( fMRI ) . Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping ( SPM2 ) . The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex ( BA47 ) common to the three tasks . Citalopram pretreatment enhanced the right BA47 responses to the No-go condition , but attenuated this response to aversive faces . Attenuations were seen following citalopram in the medial orbitofrontal ( BA11 ) responses to the No-go and No-loss ( ie relative reward compared with Loss ) conditions . The right amygdala response to aversive faces was attenuated by citalopram . These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific , rather than general effect . The technique of combining drug challenge with fMRI ( pharmacoMRI ) has promise for investigating human psychiatric disorders OBJECTIVES Modafinil has recently been approved for the treatment of shift work sleep disorder , making it potentially available for shift-working emergency physicians . The authors ' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations 
    Output:
    
agent
A review of its effects in schizophrenia suggests that modafinil facilitates cognitive functions , with pro-mnemonic effects and problem solving improvements .
The systematic review on the neurochemical modulation of the modafinil suggests that its mnemonic enhancing properties might be the result of glutamatergic and dopaminergic increased neuronal activation in the hippocampus and in the prefrontal cortex respectively .
Other neurotransmitters were also activated by modafinil in various limbic brain areas , suggesting that the drug acts on these brain regions to influence emotional responses .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background Selective serotonin reuptake inhibitors ( SSRIs ) are typically thought to have a delay of several weeks in the onset of their clinical effects . However , recent reports suggest they may have a much earlier therapeutic onset . A reduction in amygdala responsivity has been implicated in the therapeutic action of SSRIs . Aims To investigate the effect of a single dose of an SSRI on the amygdala response to emotional faces . Method Twenty-six healthy volunteers were r and omised to receive a single oral dose of citalopram ( 20 mg ) or placebo . Effects on the processing of facial expressions were assessed 3 h later using functional magnetic resonance imaging . Results Volunteers treated with citalopram displayed a significantly reduced amygdala response to fearful facial expressions compared with placebo . Conclusions Such an immediate effect of an SSRI on amygdala responses to threat supports the idea that antidepressants have an earlier onset of therapeutically relevant effects than conventionally thought BACKGROUND Patients with schizophrenia often suffer from cognitive deficits and negative symptoms that are poorly responsive to antipsychotics including clozapine . Clozapine-induced sedation can worsen cognition and impair social and occupational functioning . OBJECTIVES To evaluate the efficacy , tolerability , and safety of modafinil for negative symptoms , cognition , and wakefulness/fatigue in DSM-IV-diagnosed schizophrenia patients treated with clozapine . METHOD A double-blind , placebo-controlled , flexible-dosed 8-week pilot trial was conducted between September 2003 and September 2007 , adding modafinil up to 300 mg/d to stabilized schizophrenia out patients receiving clozapine .  Psychopathology , cognition , and wakefulness/fatigue were assessed with st and ard rating scales . RESULTS Thirty-five patients were r and omly assigned to treatment with study drug and included in the analysis . Modafinil did not reduce negative symptoms or wakefulness/fatigue or improve cognition compared to placebo . Modafinil was well tolerated and did not worsen psychosis . CONCLUSIONS Results of this pilot trial do not support routine use of modafinil to treat negative symptoms , cognitive deficits , or wakefulness/fatigue in patients on clozapine . However , given our limited power to detect a treatment effect and the clear possibility of a type II error , larger trials are needed to resolve or refute a potential therapeutic effect of uncertain magnitude . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00573417 Rationale Cognitive impairments are important determinants of functional outcome in psychosis , which are inadequately treated by antipsychotic medication . Modafinil is a wake-promoting drug that has been shown to improve attention , memory and executive function in the healthy population and in patients with schizophrenia . Objectives We aim ed to establish modafinil ’s role in the adjunctive treatment of cognitive impairments in the first episode of psychosis , a time when symptoms may be more malleable than at chronic stages of the disease . Methods Forty patients with a first episode of psychosis participated in a r and omised , double-blind , placebo-controlled crossover design study assessing the effects of a single dose of 200 mg modafinil on measures of executive functioning , memory , learning , impulsivity and attention . Results Modafinil improved verbal working memory ( d = 0.24 , p = 0.04 ) , spatial working memory errors ( d = 0.30 , p = 0.0004 ) and strategy use ( d = 0.23 , p = 0.03 ) . It also reduced discrimination errors in a task testing impulsivity . Modafinil showed no effect on impulsivity measures , sustained attention , attentional set-shifting , learning or fluency . Conclusions Modafinil selectively enhances working memory in first episode psychosis patients , which could have downstream effects on patients ’ social and occupational functioning Abstract : In a double-blind , parallel groups study , 60 healthy student volunteers ( 29 men and 31 women , aged 19 - 22 years ) were r and omly allocated to receive placebo , 100 or 200 mg modafinil . Two hours later , in the early evening , they completed an extensive cognitive battery . The 3 groups did not differ in self-ratings of sleepiness or tiredness before the testing session , and there were no treatment-associated changes in these or in mood ratings during the tests . Modafinil was without effect in several tests of reaction time and attention , but the 200-mg group was faster at simple color naming of dots and performed better than placebo in the Rapid Visual Information Processing test of sustained attention . Modafinil was without effect on spatial working memory , but the 100-mg group performed better in the backward part of the digit span test . Modafinil was without effect on verbal short-term memory ( story recall ) , but 100 mg improved digit span forward , and both doses improved pattern recognition , although this was accompanied by a slowing of response latency in the 200-mg group . There were no significant effects of modafinil compared with placebo in tests of long-term memory , executive function , visuospatial and constructional ability , or category fluency . These results suggest that the benefits of modafinil are not clearly dose-related , and those from 100 mg are limited to the span of immediate verbal recall and short-term visual recognition memory , which is insufficient for it to be considered as a cognitive enhancer in non-sleep-deprived individuals Abstract Rationale . Modafinil , a novel wake-promoting agent , has been shown to have a similar clinical profile to that of conventional stimulants such as methylpheni date . We were therefore interested in assessing whether modafinil , with its unique pharmacological mode of action , might offer similar potential as a cognitive enhancer , without the side effects commonly experienced with amphetamine-like drugs . Objectives . The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests . Methods . Sixty healthy young adult male volunteers received either a single oral dose of placebo , or 100 mg or 200 mg modafinil prior to performing a variety of tasks design ed to test memory and attention . A r and omised double-blind , between-subjects design was used . Results . Modafinil significantly enhanced performance on tests of digit span , visual pattern recognition memory , spatial planning and stop-signal reaction time . These performance improvements were complemented by a slowing in latency on three tests : delayed matching to sample , a decision-making task and the spatial planning task . Subjects reported feeling more alert , attentive and energetic on drug . The effects were not clearly dose dependent , except for those seen with the stop-signal paradigm . In contrast to previous findings with methylpheni date , there were no significant effects of drug on spatial memory span , spatial working memory , rapid visual information processing or attentional set-shifting . Additionally , no effects on paired associates learning were identified . Conclusions . These data indicate that modafinil selectively improves neuropsychological task performance . This improvement may be attributable to an enhanced ability to inhibit pre-potent responses . This effect appears to reduce impulsive responding , suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder OBJECTIVE Antidepressants that inhibit the reuptake of serotonin ( SSRIs ) or norepinephrine ( SNRIs ) are effective in the treatment of disorders such as depression and anxiety . Cognitive psychological theories emphasize the importance of correcting negative biases of information processing in the nonpharmacological treatment of these disorders , but it is not known whether antidepressant drugs can directly modulate the neural processing of affective information . The present study therefore assessed the actions of repeated antidepressant administration on perception and memory for positive and negative emotional information in healthy volunteers . METHOD Forty-two male and female volunteers were r and omly assigned to 7 days of double-blind intervention with the SSRI citalopram ( 20 mg/day ) , the SNRI reboxetine ( 8 mg/day ) , or placebo . On the final day , facial expression recognition , emotion-potentiated startle response , and memory for affect-laden words were assessed . Question naires monitoring mood , hostility , and anxiety were given before and after treatment . RESULTS In the facial expression recognition task , citalopram and reboxetine reduced the identification of the negative facial expressions of anger and fear . Citalopram also abolished the increased startle response found in the context of negative affective images . Both antidepressants increased the relative recall of positive ( versus negative ) emotional material . These changes in emotional processing occurred in the absence of significant differences in ratings of mood and anxiety . However , reboxetine decreased subjective ratings of hostility and elevated energy . CONCLUSIONS Short-term administration of two different antidepressant types had similar effects on emotion-related tasks in healthy volunteers , reducing the processing of negative relative to positive emotional material . Such effects of antidepressants may ameliorate the negative biases in information processing that characterize mood and anxiety disorders . They also suggest a mechanism of action potentially compatible with cognitive theories of anxiety and depression Modafinil , a novel cognitive enhancer , selectively improves neuropsychological task performance in healthy volunteers and adult patients with attention deficit hyperactivity disorder ( ADHD ) . It has been argued that persistent cognitive deficits in patients with schizophrenia are responsible for the failure of many patients to rehabilitate socially even when psychotic symptoms are in remission . The present study examined the potential of modafinil as a cognitive enhancer in schizophrenia . Twenty chronic patients with a diagnosis of schizophrenia were entered into a double-blind , r and omized , placebo-controlled crossover study using a 200 mg dose of modafinil . Modafinil had some cognitive enhancing properties in schizophrenia similar to those observed in healthy adults and adult patients with ADHD . Improvement was seen on short-term verbal memory span , with trends towards improved visual memory and spatial planning . This was accompanied by slowed response latency on the spatial planning task . No effect on stop-signal performance was seen . Importantly , significant improvement in attentional set shifting was seen , despite no effect of modafinil on this task being seen in healthy volunteers or ADHD patients . Modafinil may have potential as an important therapy for cognitive impairment in patients with schizophrenia , particularly because of its beneficial effects on attentional set shifting Methamphetamine (MA)-dependent individuals exhibit deficits in cognition and prefrontal cortical function . Therefore , medications that improve cognition in these subjects may improve the success of therapy for their addiction , especially when cognitive behavioral therapies are used . Modafinil has been shown to improve cognitive performance in neuropsychiatric patients and healthy volunteers . We therefore conducted a r and omized , double-blind , placebo-controlled , cross-over study , using functional magnetic resonance imaging , to examine the effects of modafinil on learning and neural activity related to cognitive function in abstinent , MA-dependent , and healthy control participants .  Modafinil ( 200 mg ) and placebo were administered orally ( one single dose each ) , in counterbalanced fashion , 2 h before each of two testing sessions . Under placebo conditions , MA-dependent participants showed worse learning performance than control participants . Modafinil boosted learning in MA-dependent participants , bringing them to the same performance level as control subjects ; the control group did not show changes in performance with modafinil . After controlling for performance differences , MA-dependent participants showed a greater effect of modafinil on brain activation in bilateral insula/ventrolateral prefrontal cortex and anterior cingulate cortices than control participants . The findings suggest that modafinil improves learning in MA-dependent participants , possibly by enhancing neural function in regions important for learning and cognitive control . These results suggest that modafinil may be a suitable pharmacological adjunct for enhancing the efficiency of cognitive-based therapies for MA dependence Changes in serotonin neurotransmission have also been implicated in the etiology and treatment of impulse control disorders , depression , and anxiety . We have investigated the effect of enhancing serotonin function on fundamental brain processes that we have proposed are abnormal in these disorders . In all , 12 male volunteers received  citalopram  ( 7.5 mg intravenously ) and placebo pretreatment in a single-blind crossover design before undertaking Go/No-go , Loss/No-loss , and covert ( aversive ) face emotion recognition tasks during functional magnetic resonance imaging ( fMRI ) . Blood oxygenation level dependent responses were analyzed using Statistical Parametric Mapping ( SPM2 ) . The tasks activated prefrontal and subcortical regions generally consistent with literature with lateral orbitofrontal cortex ( BA47 ) common to the three tasks . Citalopram pretreatment enhanced the right BA47 responses to the No-go condition , but attenuated this response to aversive faces . Attenuations were seen following citalopram in the medial orbitofrontal ( BA11 ) responses to the No-go and No-loss ( ie relative reward compared with Loss ) conditions . The right amygdala response to aversive faces was attenuated by citalopram . These results support the involvement of serotonin in modulating basic processes involved in psychiatric disorders but argue for a process-specific , rather than general effect . The technique of combining drug challenge with fMRI ( pharmacoMRI ) has promise for investigating human psychiatric disorders OBJECTIVES Modafinil has recently been approved for the treatment of shift work sleep disorder , making it potentially available for shift-working emergency physicians . The authors ' objectives were to determine whether modafinil improved cognitive performance of emergency physicians following overnight shifts and to record symptoms and subjective evaluations 
    Output:
    