Impaired probabilistic reversal learning in youths with mood and anxiety disorders

“All participants were evaluated by graduate-level clinicians with high inter-rater reliability (k>0.75) using the Kiddie-Schedule for Affective Disorders Present and Lifetime version (K-SADS-PL) administered to parents and children separately (Kaufman et al. 1997).”

“BD and SMD subjects completed the Young Mania Rating Scale (YMRS; Young et al. 1978).”

“Nevertheless, previous studies have demonstrated that ANX subjects, including those with trait anxiety, have deficits in paradigms requiring goal-directed stimulus attention and task switching, such as the Wisconsin Card Sorting Task (WCST; Eysenck et al. 2007).”

“…2002) and/or a Children’s Depression Rating Scale (CDRS) score >39 (Poznanski et al. 1985) ; (2) a Children’s Global Assessment Scale (CGAS) score<60 (Shaffer et al. 1983) ; and (3) persistent anxiety and/ or depression (consistently elevated PARS and/or CDRS) during 3 weeks of supportive…”

“…and adults after neurosurgical resection indicate that it is mediated by similar regions, including both the frontal cortex (dorsomedial, inferior and ventromedial) and the striatum (Blair et al. 2001 ; Cools et al. 2002, 2004 ; Clark et al. 2004 ; O’Doherty et al. 2004 ; Budhani et al. 2007).”

“2007) whereas the ventral striatum transforms concrete stimulus exemplar information into motor responses (Knutson et al. 2000 ; Cools et al. 2004).”

“…and adults after neurosurgical resection indicate that it is mediated by similar regions, including both the frontal cortex (dorsomedial, inferior and ventromedial) and the striatum (Blair et al. 2001 ; Cools et al. 2002, 2004 ; Clark et al. 2004 ; O’Doherty et al. 2004 ; Budhani et al. 2007).”

“For the BD group, children with irritable mania only, without elevated or expansive mood, were excluded (Geller et al. 1998 ; Leibenluft et al. 2003).”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“That is, irritability in youths may be due in part to the frustration that occurs when they are unable to adapt to changing reward contingencies in the environment (Blair & Cipolotti, 2000 ; Blair, 2004).”

“PRR is of particular interest because the circuitry mediating its performance has been well studied in humans and non-human primates (Cools et al. 2002 ; Fellows & Farah, 2003 ; Clark et al. 2004 ; Izquierdo & Murray, 2004 ; Budhani et al. 2007 ; Bellebaum et al. 2008).”

“However, it is important to note that the WCST is thought to rely on attentionally based category shifting (Robbins et al. 1998).”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“…study in healthy adults found that those taking the selective serotonin reuptake inhibitor citalopram had impaired probabilistic learning but unaltered response inhibition, whereas the opposite was true for those taking the noradrenaline reuptake inhibitor atomoxetine (Chamberlain et al. 2006).”

“Other regions that may play an accessory role include the parietal cortex, which is implicated in decision making in the presence of uncertainty (Paulus et al. 2001 ; Huettel, 2006 ; Chamberlain et al. 2008).”

“Although some studies show that SMD youths share some deficits with those with narrow-phenotype BD, including face emotion labeling (Guyer et al. 2007 ; Rich et al. 2008), others show differences between SMD and BD, including family history and longitudinal course (Brotman et al. 2006, 2007).”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“PRR is of particular interest because the circuitry mediating its performance has been well studied in humans and non-human primates (Cools et al. 2002 ; Fellows & Farah, 2003 ; Clark et al. 2004 ; Izquierdo & Murray, 2004 ; Budhani et al. 2007 ; Bellebaum et al. 2008).”

“fMRI has not been used to study the circuitry mediating reversal learning in patients with MDD, but several regions of the PFC and the striatum have been implicated in the pathophysiology of depression (Milham et al. 2005 ; Rosenberg et al. 2005 ; Roberson-Nay et al. 2006 ; McClure et al. 2007).”

“Such grouping of ANX youths has been used by the Research Units on Pediatric Psychopharmacology (RUPP, 2001) and in other randomized controlled trials for pediatric anxiety (Birmaher et al. 2003).”

“By contrast, such adolescents did not have alterations in either the dorsomedial or inferior frontal cortex, suggesting an intact ability to alter motor responses (Finger et al. 2008).”

“Prepubertal and early adolescent bipolarity differentiate from ADHD by manic symptoms, grandiose delusions, ultra-rapid or ultradian cycling.”

“…Medicine (2010), 40, 1089–1100. f Cambridge University Press 2009 doi:10.1017/S0033291709991462 ORIGINAL ARTICLE (Blair et al. 2001 ; Clark et al. 2004 ; Cools et al. 2004 ; O’Doherty et al. 2004 ; Budhani et al. 2007) whereas the ventral striatum transforms…”

“However, emerging neuroimaging data using tasks other than reversal learning implicate several frontal regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2…”

“For the BD group, children with irritable mania only, without elevated or expansive mood, were excluded (Geller et al. 1998 ; Leibenluft et al. 2003).”

“…regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2007b ; Leibenluft et al. 2007 ; Nelson et al. 2007 ; Pavuluri et al. 2007, 2008).”

“Moreover, secondary analyses reveal that BD and SMD may show particular difficulty in using reinforcement expectancy information to guide their behavioral choices, as they are more likely to shift away from a correct response whether they have received either a reward or ‘spurious’ punishment (Blair, 2009).”

“Although some studies show that SMD youths share some deficits with those with narrow-phenotype BD, including face emotion labeling (Guyer et al. 2007 ; Rich et al. 2008), others show differences between SMD and BD, including family history and longitudinal course (Brotman et al. 2006, 2007).”

“2007) whereas the ventral striatum transforms concrete stimulus exemplar information into motor responses (Knutson et al. 2000 ; Cools et al. 2004).”

“However, emerging neuroimaging data using tasks other than reversal learning implicate several frontal regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2…”

“Other regions that may play an accessory role include the parietal cortex, which is implicated in decision making in the presence of uncertainty (Paulus et al. 2001 ; Huettel, 2006 ; Chamberlain et al. 2008).”

“Our study suggests that BD youths may have neural alterations in frontostriatal regions mediating reversal learning, especially those involved with the receipt of unexpected, spurious reward and punishment (Ramnani et al. 2004 ; Abler et al. 2008).”

“Specifically, we have shown that BD youths made more errors and required more trials and time to complete a simple reversal than controls (Dickstein et al. 2004).”

“fMRI has not been used to study the circuitry mediating reversal learning in patients with MDD, but several regions of the PFC and the striatum have been implicated in the pathophysiology of depression (Milham et al. 2005 ; Rosenberg et al. 2005 ; Roberson-Nay et al. 2006 ; McClure et al. 2007).”

“One previous study failed to find reversal learning deficits in MDD youths (n=30) versus controls (n=49) using the non-probabilistic ID/ ED task (Kyte et al. 2005).”

“PRR is of particular interest because the circuitry mediating its performance has been well studied in humans and non-human primates (Cools et al. 2002 ; Fellows & Farah, 2003 ; Clark et al. 2004 ; Izquierdo & Murray, 2004 ; Budhani et al. 2007 ; Bellebaum et al. 2008).”

“Although some studies show that SMD youths share some deficits with those with narrow-phenotype BD, including face emotion labeling (Guyer et al. 2007 ; Rich et al. 2008), others show differences between SMD and BD, including family history and longitudinal course (Brotman et al. 2006, 2007).”

“We include youths with SMD because these patients suffer from attention deficit/hyperactivity disorder (ADHD)-like symptoms of hyperactivity plus severe irritability, and their diagnostic status vis-à-vis BD is unclear (Carlson, 1998 ; NIMH, 2001; Leibenluft et al. 2003).”

“fMRI has not been used to study the circuitry mediating reversal learning in patients with MDD, but several regions of the PFC and the striatum have been implicated in the pathophysiology of depression (Milham et al. 2005 ; Rosenberg et al. 2005 ; Roberson-Nay et al. 2006 ; McClure et al. 2007).”

“However, both BD and SMD subjects were impaired on the compound reversal stage (i.e. reversals involving compound stimuli of white line drawings superimposed on purple shapes ; subjects must discern which of the two stimuli is linked to reward) (Dickstein et al. 2007a).”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“Although some studies show that SMD youths share some deficits with those with narrow-phenotype BD, including face emotion labeling (Guyer et al. 2007 ; Rich et al. 2008), others show differences between SMD and BD, including family history and longitudinal course (Brotman et al. 2006, 2007).”

“For the reversal trials, we calculated win-stay and lose-stay percentages for both correct and incorrect responses following the receipt of reward or punishment (Budhani et al. 2006).”

“However, emerging neuroimaging data using tasks other than reversal learning implicate several frontal regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2…”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“fMRI has not been used to study the circuitry mediating reversal learning in patients with MDD, but several regions of the PFC and the striatum have been implicated in the pathophysiology of depression (Milham et al. 2005 ; Rosenberg et al. 2005 ; Roberson-Nay et al. 2006 ; McClure et al. 2007).”

“Our study suggests that BD youths may have neural alterations in frontostriatal regions mediating reversal learning, especially those involved with the receipt of unexpected, spurious reward and punishment (Ramnani et al. 2004 ; Abler et al. 2008).”

“…regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2007b ; Leibenluft et al. 2007 ; Nelson et al. 2007 ; Pavuluri et al. 2007, 2008).”

“PRR is of particular interest because the circuitry mediating its performance has been well studied in humans and non-human primates (Cools et al. 2002 ; Fellows & Farah, 2003 ; Clark et al. 2004 ; Izquierdo & Murray, 2004 ; Budhani et al. 2007 ; Bellebaum et al. 2008).”

“In addition, compared to controls, fewer BD patients achieved this minimal competence (Gorrindo et al. 2005).”

“PRR is of particular interest because the circuitry mediating its performance has been well studied in humans and non-human primates (Cools et al. 2002 ; Fellows & Farah, 2003 ; Clark et al. 2004 ; Izquierdo & Murray, 2004 ; Budhani et al. 2007 ; Bellebaum et al. 2008).”

“However, both BD and SMD subjects were impaired on the compound reversal stage (i.e. reversals involving compound stimuli of white line drawings superimposed on purple shapes ; subjects must discern which of the two stimuli is linked to reward) (Dickstein et al. 2007a).”

“Other regions that may play an accessory role include the parietal cortex, which is implicated in decision making in the presence of uncertainty (Paulus et al. 2001 ; Huettel, 2006 ; Chamberlain et al. 2008).”

“Moreover, reversal learning is mediated by the same frontostriatal circuit implicated in BD, MDD and ANX (Drevets, 2000 ; Thomas et al. 2001 ; Blumberg et al. 2002 ; Monk et al. 2006 ; Krain et al. 2008 ; Pfeifer et al. 2008).”

“However, emerging neuroimaging data using tasks other than reversal learning implicate several frontal regions, including dorsolateral, ventromedial and anterior cingulate cortices, along with the amygdala and striatum in the pathophysiology of pediatric BD (Blumberg et al. 2003 ; Rich et al. 2006 ; Dickstein et al. 2…”

“By contrast, reversal learning tasks rely on the ability to update reinforcement values associated with different responses to objects (Mitchell et al. 2008 ; Xue et al. 2008).”

“By contrast, reversal learning tasks rely on the ability to update reinforcement values associated with different responses to objects (Mitchell et al. 2008 ; Xue et al. 2008).”

“Indeed, recent data suggest that specific deficits in stimulus/reinforcement-based decision making are present in adults with generalized anxiety but not in those with social phobia (Devido et al. 2008).”

“From an affective neuroscience perspective, reversal learning taps into cognitive flexibility, defined as the ability to adapt one’s thinking and behavior in response to changing environmental conditions including rewards (Cools et al. 2004 ; Stemme et al. 2005).”

“We use unexpected context changes to elicit affective responses, motivated in part by the fact that affective disorders are associated with deficiencies in performing this kind of task (Adlerman et al., 2011; Dickstein et al., 2010).”

“Effects on probabilistic reward learning were not found among euthymic children with bipolar disorder (Dickstein et al. 2010, Gorrindo et al. 2005) or in unmedicated adults diagnosed with bipolar depression (Roiser et al. 2009).”

“[12] Dickstein DP, Finger EC, BrotmanMA, Rich BA, Pine DS, Blair JR, et al.”