The effects of early life stress on reward processing

May combine two claims.

Other factors such as sex of the animal or duration of separation did not account for variation in results.

“Other factors, such as sex of animal or duration/length of separation, did not account for variation in results.”

May combine two claims.

In marmoset monkeys, daily isolation from parents during the first month of life left free consumption of a sweet solution unchanged at seven months but decreased effort expenditure on a progressive reinforcement schedule.

“In one frequently cited study in marmoset monkeys, daily bouts of isolation from parents for the first month of life resulted in unchanged free consumption of a sweet solution at seven months, but decreased effort expenditure on a progressive reinforcement schedule (Pryce et al., 2004).”

• cites Pryce et al., 2004 sourceNot checked yet

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Deficits in reversal learning have been reported with parental deprivation in monkeys and maternal separation in rats.

“Deficits in the ability to alter behavior based on changing reward cues, known as reversal learning, have also been reported with parental deprivation in monkeys (Pryce et al., 2004) and maternal separation in rats (Matthews et al., 1996a).”

• cites Pryce et al., 2004 sourceNot checked yet

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• cites Matthews et al., 1996aNot checked yet

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Maternal separation was associated with decreased conditioned locomotor activity to food-related cues and decreased conditioned place preference to chocolate, indicating decreased reward valuation or incentive salience within approach motivation.

“Maternal separation was also associated with decreased conditioned locomotor activity to food-related cues (Matthews et al., 1996b, 1996a) as well as decreased conditioned place preference to chocolate (Sasagawa et al., 2017) indicative of a decreased reward valuation/incentive salience function within the approach motivation construct.”

• cites Matthews et al., 1996bNot checked yet

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• cites Matthews et al., 1996aNot checked yet

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• cites Sasagawa et al., 2017 sourceNot checked yet

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Maternal separation is associated with changes to the opioid system, but results conflict depending on methodology, showing both increases and decreases in endogenous peptide levels and ligand sensitivity.

“Changes to the opioid system are also apparent with maternal separation, but conflicting results also exist based on specific methodology, demonstrating both increases and decreases in levels of endogenous peptides (Ploj et al., 2003; Vazquez et al., 2005) as well as sensitivity to ligands (Kalinichev et al., 2001; Vazquez et al., 2005).”

• cites Ploj et al., 2003 sourceNot checked yet

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• cites Vazquez et al., 2005 sourceNot checked yet

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• cites Kalinichev et al., 2001 sourceNot checked yet

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Several studies found that maternal separation alone did not change sucrose preference, but a second stressor in adolescence or adulthood reduced sucrose preference.

“Several studies found that while maternal separation by itself did not result in changes in sucrose preference, occurrence of a second stressor or challenge in adolescence or adulthood resulted in reduced sucrose preference (Hill et al., 2014; Klug and van den Buuse, 2012; Uchida et al., 2010).”

• cites Hill et al., 2014 sourceNot checked yet

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• cites Klug and van den Buuse, 2012Not checked yet

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• cites Uchida et al., 2010 sourceNot checked yet

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Cognitive remediation, including working memory training and mindfulness, can enhance reward processing in non-clinical individuals with high trait social anhedonia and in prescription opioid abusers.

“there are data showing that cognitive remediation, including working memory training and mindfulness, can enhance reward processing in non-clinical populations with high trait social anhedonia (Li et al., 2016) and in prescription opioid abusers (Garland, 2016).”

• cites Li et al., 2016Not checked yet

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• cites Garland, 2016 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Data were extracted by at least two independent authors to ensure accuracy and limit bias.

“Data were extracted by no fewer than two separate authors to ensure accuracy and limit bias (Tables 1, 2).”

May combine two claims.

Deficits in reward processing occur in major depressive disorder, substance use disorders, posttraumatic stress disorder, schizophrenia, and ADHD.

“Deficits in reward processing are found in MDD (Admon and Pizzagalli, 2015), substance use disorders (Garfield et al., 2014; Tobler et al., 2016), posttraumatic stress disorder (PTSD) (Kalebasi et al., 2015), schizophrenia (McCarthy et al., 2016), and ADHD (van Hulst et al., 2016).”

• cites Admon and Pizzagalli, 2015 sourceNot checked yet

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• cites Garfield et al., 2014 sourceNot checked yet

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• cites Tobler et al., 2016 sourceNot checked yet

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People with major depressive disorder show similar hedonic responses to sweet solutions as controls but are less willing to engage in tasks requiring higher effort.

“individuals with MDD have similar hedonic responses to sweet solutions compared to controls (Berlin et al., 1998), but are less likely to engage in tasks requiring higher amounts of effort (Treadway et al., 2012).”

• cites Berlin et al., 1998 sourceNot checked yet

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• cites Treadway et al., 2012 sourceNot checked yet

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The particular psychopathological trajectory may depend on the type of early life stress, the developmental window when stress occurred, and genetic or epigenetic risk and protective factors.

“The particular psychopathological trajectory might depend on the type of ELS (Carr et al., 2013) and the developmental window in which the stress was experienced (Andersen et al., 2008), as well as genetic and epigenetic risk and protective factors (Caspi et al., 2003; Palma-Gudiel and Fañanás, 2016).”

• cites Carr et al., 2013 sourceNot checked yet

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• cites Andersen et al., 2008Not checked yet

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• cites Caspi et al., 2003 sourceNot checked yet

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Early life stress has been associated with both increased and decreased HPA axis reactivity to stress, and both patterns have been linked to psychopathology.

“Early life stress has been found to both exaggerate and attenuate the activity of the HPA axis in response to stress, both phenomena which have been linked to psychopathology (Carpenter et al., 2009; Heim C et al., 2000; Tyrka et al., 2008).”

• cites Carpenter et al., 2009 sourceNot checked yet

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• cites Heim C et al., 2000 sourceNot checked yet

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• cites Tyrka et al., 2008 sourceNot checked yet

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Receptors for CRF and glucocorticoids are distributed throughout the brain's reward circuitry, and their activation or blockade influences reward-related neurotransmission and behavior.

“receptors for CRF and glucocorticoids are located throughout the reward circuitry of the brain, with their activation or blockade affecting reward-sensitive neurotransmission and behaviors (Bryce and Floresco, 2016; Craenenbroeck et al., 2005; Walsh et al., 2014).”

• cites Bryce and Floresco, 2016Not checked yet

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• cites Craenenbroeck et al., 2005 sourceNot checked yet

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• cites Walsh et al., 2014 sourceNot checked yet

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Because stress and reward neurobiology overlap, changes in stress neurobiology are likely to affect reward processing.

“This overlap between stress neurobiology and reward neurobiology suggests that any change in stress neurobiology is likely to influence reward.”

Classified as probably not a substantial claim. May combine two claims.

Animal models cannot fully replicate the complexity of human early life stress, and the relevance of their findings to human conditions is not always clear.

“However, animal models cannot replicate the complexity of human ELS, and the significance of findings for human conditions is not always clear.”

Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

The precision of the paradigm limits how well the RDoC framework can parse reward processes, and several paradigms engage more than one process.

“It should be noted that parsing of various reward processes using the RDoC framework is limited by the precision of the paradigm used, with several paradigms engaging more than one process.”

May combine two claims.

Alterations in reward processing predict later diagnoses of major depressive disorder, substance use disorder, and conduct disorder even in people who do not meet full diagnostic criteria.

“Even in individuals who do not meet full diagnostic criteria, alterations in reward processing predict later diagnoses of MDD (Nelson et al., 2016), substance use disorder (Castellanos-Ryan et al., 2011; Garfield et al., 2014), and conduct disorder (Rubia et al., 2009).”

• cites Nelson et al., 2016 sourceNot checked yet

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• cites Castellanos-Ryan et al., 2011 sourceNot checked yet

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• cites Rubia et al., 2009 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Variability and co-variation of early life stress factors pose a major challenge in human studies.

“Variability and co-variation of these factors represent a major challenge in human studies.”

May combine two claims.

Blocking dopamine receptors or depleting dopamine in the ventral striatum, specifically the nucleus accumbens, reduces the effort an animal will expend for reward but often leaves reward consumption and positive hedonic responses intact.

“Antagonism of dopamine receptors or dopamine depletion in the ventral striatum (specifically the nucleus accumbens) reduce the amount of effort an animal will expend to obtain a reward, but often leave intact reward consumption and positive hedonic responses (e.g., affective facial expressions) (Berridge and Robinson, 1998; Salamone and Correa, 2002).”

• cites Berridge and Robinson, 1998 sourceNot checked yet

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• cites Salamone and Correa, 2002 sourceNot checked yet

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Maternal separation interferes with the mother's postnatal regulatory influence on the animal's physiology and development and is considered by many to be an analog of human child neglect.

“Maternal separation interferes with the postnatal regulatory influence that the mother has on the animal’s physiology and development, and is considered by many to be an analog of human child neglect (Carlyle et al., 2012; Pryce et al., 2005).”

• cites Carlyle et al., 2012 sourceNot checked yet

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• cites Pryce et al., 2005Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Reward responsiveness also involves the nucleus accumbens, but opioids and endocannabinoids are the major neurochemical mediators of this component.

“Responsiveness to reward also involves the nucleus accumbens (in addition to other regions, such as the ventral pallidum), but opioids and endocannabinoids are the major neurochemical mediators of reward responsiveness (Mahler et al., 2007; Peciña and Berridge, 2005).”

• cites Mahler et al., 2007 sourceNot checked yet

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• cites Peciña and Berridge, 2005Not checked yet

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Dopamine in the nucleus accumbens appears necessary for approach motivation but less involved in hedonic experience or initial responsiveness to reward.

“Thus, dopamine in the nucleus accumbens appears to be necessary for the approach motivation aspects of reward processing, but is less involved in the hedonic experience/initial responsiveness to reward.”

May combine two claims.

Human brain development is protracted compared with other species, so despite having a more mature brain at birth than rats, humans remain vulnerable to insult.

“development of the human brain is protracted compared to other species (Clancy et al., 2001; Miller et al, 2012; Semple et al., 2013), so despite having a more “mature” brain at birth compared to rats, vulnerability to insult remains.”

• cites Clancy et al., 2001 sourceNot checked yet

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• cites Miller et al, 2012 sourceNot checked yet

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• cites Semple et al., 2013 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

A common use of the sucrose preference test is to assess stress-induced anhedonia in animal models of depression, where reduced sucrose consumption is considered indicative of depressive-like behavior.

“One of the most common uses of the sucrose preference test is to assess stress-induced anhedonia in animal models of depression, where reduced consumption of sucrose is considered indicative of depressive-like behavior (Willner et al., 1996).”

• cites Willner et al., 1996 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The reward prediction error, in which changes in dopamine firing encode differences between expected and actual reward outcomes, enables dynamic learning from experience and updates in reward expectations.

“The reward prediction error, in which changes in dopamine firing encode differences between an expected vs. actual reward outcome, allows for dynamic learning from experience and updates in reward expectations (Gradin et al., 2011; Schultz, 2016).”

• cites Gradin et al., 2011 sourceNot checked yet

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• cites Schultz, 2016 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Because most components of reward processing are subjective, their occurrence in animals can only be inferred from behavior.

“Because most components of reward processing are ultimately subjective phenomena (motivation, hedonic experience), their occurrence in animals can only be inferred by the measurement of behavior.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The most common animal manipulations used to model early life stress are maternal and peer separation.

“the most common manipulations in animals to model ELS consist of maternal and peer separation.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In this reward circuit, information about reward cues, reward value, and required effort is processed and integrated to guide decision-making, motivation, action readiness, and pleasure.

“It is in this circuit that information about reward cues, reward value, and required effort is processed, communicated, and then integrated to guide decision-making, facilitate motivation and readiness for action, and eventually result in the experience of pleasure (Rizvi et al., 2016) (Figure 2).”

• cites Rizvi et al., 2016 sourceNot checked yet

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Dopamine from the nucleus accumbens is important for rewarding cues to acquire incentive salience and elicit instrumental behavior.

“dopamine from the nucleus accumbens is important for the ability of rewarding cues to gain incentive salience and elicit instrumental behavior (Peciña et al., 2003; Wyvell and Berridge, 2000).”

• cites Peciña et al., 2003 sourceNot checked yet

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• cites Wyvell and Berridge, 2000Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In the prefrontal cortex, the orbital frontal cortex encodes and maintains reward value, while the anterior cingulate cortex monitors and determines the effort required to obtain rewards.

“Within the PFC, the orbital frontal cortex encodes and maintains reward value, while the anterior cingulate cortex plays a role in monitoring and determining effort required to obtain rewards (for review see (Rushworth et al., 2011)).”

• cites Rushworth et al., 2011 sourceNot checked yet

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Reversal learning depends on an intact orbitofrontal cortex to inhibit the previously learned response.

“Such reversal is known to depend on an intact orbitofrontal cortex to inhibit the prior learned response (Placek et al., 2013; Rolls, 2016).”

• cites Placek et al., 2013 sourceNot checked yet

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• cites Rolls, 2016 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Observation of orofacial movements is probably the only measure of liking independent of learning or motivational processes, but it is rarely studied.

“Observation of orofacial movements is probably the only measure of liking independent of any learning or motivational process (Berridge and Robinson, 1998), but this is rarely studied.”

• cites Berridge and Robinson, 1998 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Conditioned place preference can be conceptualized as probing reward valuation within approach motivation, though expectancy is also likely involved.

“conditioned place preference can be conceptualized as probing the “reward valuation” subconstruct within approach motivation, but expectancy is arguably also involved, given the presence of Pavlovian conditioned approach behavior (Flagel et al., 2009; NIMH Research Domain Criteria).”

• cites Flagel et al., 2009 sourceNot checked yet

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• cites NIMH Research Domain CriteriaNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Regions of the prefrontal cortex and amygdala are additional key brain areas in reward circuitry.

“regions of the prefrontal cortex (PFC) and amygdala are additional key brain areas involved in reward circuitry.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The amygdala encodes reward value and deviations between expected and actual outcomes through its projections to the prefrontal cortex.

“Reward value and deviations of expected and actual outcomes are encoded via the amygdala through its projections to the PFC (Lichtenberg et al., 2017; Wassum and Izquierdo, 2015).”

• cites Lichtenberg et al., 2017 sourceNot checked yet

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• cites Wassum and Izquierdo, 2015Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Multiple well-validated tests of reward behavior in animals allow some differentiation among reward components, but close scrutiny often shows that more than one component is involved.

“While there are multiple well-validated tests of reward behavior in animals that allow some differentiation between various reward processing components, close scrutiny often reveals that more than one component is likely involved.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Dopamine signaling to the basal ganglia, including the nucleus accumbens, contributes to the reward prediction error.

“Dopamine signaling to the basal ganglia, including the nucleus accumbens, also plays a role in what is known as the reward prediction error, a subconstruct of approach motivation.”

• cites Gradin et al., 2011 sourceNot checked yet

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• cites Schultz, 2016 sourceNot checked yet

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Stressors earlier in life may be more likely to affect subcortical reward functions such as approach motivation and reward responsiveness, whereas stressors later in adolescence may more likely affect learning, valuation, and effort prediction.

“Thus, stressors occurring earlier in life might be more likely to affect subcortical reward functions (approach motivation and reward responsiveness), with those later in adolescence more likely affecting learning, valuation, and effort prediction.”

May combine two claims.

Normative development of reward-related brain regions involves structural and functional changes from childhood to adulthood, with prefrontal cortex maturation typically delayed relative to subcortical regions.

“Normative development of the brain regions involved in reward processing demonstrates structural and functional changes from childhood to adulthood, with maturation of PFC regions typically delayed compared to that of subcortical regions (Galvan et al., 2006; Mills et al., 2014; Somerville et al., 2011).”

• cites Galvan et al., 2006 sourceNot checked yet

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• cites Mills et al., 2014 sourceNot checked yet

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• cites Somerville et al., 2011 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

Conditioned place preference is thought to measure incentive motivation to seek out cues previously associated with reward.

“The conditioned place preference task is thought to measure incentive motivation to seek out cues previously associated with reward (Bardo and Bevins, 2000).”

• cites Bardo and Bevins, 2000Not checked yet

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Post-weaning social isolation during the juvenile and adolescent period produces sensory processing deficits and increases in fear and anxiety-like behavior.

“While pre-weaning maternal separation is often conceptualized as early life neglect and results in a depressive-like phenotype (Pryce et al., 2005), post-weaning social isolation during the juvenile and adolescent period produces sensory processing deficits and increases in fear and anxiety-like behavior (Fone and Porkess, 2008; Lukkes et al., 2009).”

• cites Fone and Porkess, 2008Not checked yet

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• cites Lukkes et al., 2009 sourceNot checked yet

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Pre-weaning maternal separation is often conceptualized as early life neglect and produces a depressive-like phenotype.

“While pre-weaning maternal separation is often conceptualized as early life neglect and results in a depressive-like phenotype (Pryce et al., 2005), post-weaning social isolation during the juvenile and adolescent period produces sensory processing deficits and increases in fear and anxiety-like behavior (Fone and Porkess, 2008; Lukkes et al., 2009).”

• cites Pryce et al., 2005Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The neonatal rat depends on the dam for protection from predators, nutrition, thermoregulation, and waste elimination.

“The neonatal rat relies upon the dam for protection from predators, nutrition, thermoregulation, and proper elimination of waste (Hofer, 1996).”

• cites Hofer, 1996 sourceNot checked yet

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These findings support a two-hit model in which early life stress confers vulnerability to psychiatric symptoms, but symptom onset occurs only after a subsequent stressor.

“These studies support a “two hit” model in which ELS, such as maternal separation, confers vulnerability to symptoms of psychiatric illness, but with symptom onset only occurring after exposure to a subsequent stressor (Bayer et al., 1999; Maynard et al., 2001).”

• cites Bayer et al., 1999 sourceNot checked yet

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• cites Maynard et al., 2001 sourceNot checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

This link is an important concept in addiction and is hypothesized to mediate the relationship between early life stress and increased risk of substance use disorders.

“This is an important concept in the field of addiction (Burke and Miczek, 2014b; George et al., 2012; Sinha, 2008), that is hypothesized to mediate the relationship between ELS and increased risk of substance use disorders (Andersen and Teicher, 2009).”

• cites Burke and Miczek, 2014bNot checked yet

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• cites George et al., 2012 sourceNot checked yet

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• cites Sinha, 2008 sourceNot checked yet

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Other studies show enhanced mesolimbic dopamine function, with increased nucleus accumbens dopamine release in response to stress or amphetamine and increased locomotion in response to cocaine.

“other studies demonstrate enhanced mesolimbic dopamine function, as evidenced by increased nucleus accumbens dopamine release in response to stress (Brake et al., 2004) or amphetamine (Hall et al., 1999), as well as increased locomotion in response to cocaine (Brake et al., 2004).”

• cites Brake et al., 2004 sourceNot checked yet

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• cites Hall et al., 1999 sourceNot checked yet

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These changes suggest that high maternal care enhances HPA axis regulation, allowing greater control of the endocrine stress cascade and better regulation of emotional behavior.

“These changes suggest that high levels of maternal care enhance HPA axis regulation and allow more control of the endocrine stress cascade and better regulation of emotional behavior.”

May combine two claims.

Matthews and colleagues found decreased sensitivity to amphetamine's enhancing effects and increased sensitivity to D2 antagonists' blunting effects on approach motivation behaviors after maternal separation.

“Matthews and colleagues have demonstrated decreased sensitivity to the enhancing effects of amphetamine and increased sensitivity to the blunting effects of D2 antagonists on behaviors related to approach motivation (Matthews et al., 1996bMatthews and Robbins, 2003).”

• cites Matthews et al., 1996bNot checked yet

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• cites Matthews and Robbins, 2003Not checked yet

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Reduced conditioning to predictive appetitive cues may reflect decreased motivation but may also indicate impairments in associative learning.

“reduced conditioning to predictive appetitive cues, while possibly reflecting decreased motivation, might also indicate impairments in associative learning (Matthews et al., 1996a, 1996b).”

• cites Matthews et al., 1996aNot checked yet

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• cites Matthews et al., 1996bNot checked yet

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Maternal separation results in a greater peak and longer duration of glucocorticoid release after stress, decreased glucocorticoid receptor expression, increased CRF expression, and reduced benzodiazepine receptor binding.

“maternal separation results in a greater peak and duration of glucocorticoid release in response to stress, decreased GR expression, increased CRF expression, and reduced benzodiazepine receptor binding (Sánchez et al., 2001).”

• cites Sánchez et al., 2001 sourceNot checked yet

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Because maternal separation deprives rat pups of maternal care, it would be expected to produce changes opposite to those seen with high maternal care, and this appears to be the case.

“Given that maternal separation deprives rat pups from opportunities for maternal care, this paradigm would be expected to result in changes opposite to that seen in rats exposed to high levels of maternal care, and this does appear to be the case (Ladd et al., 2000).”

• cites Ladd et al., 2000Not checked yet

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Pups raised by dams with high maternal care show increased hippocampal synaptogenesis, increased glucocorticoid receptor mRNA, decreased hypothalamic CRF mRNA, and increased benzodiazepine receptor binding in emotion-regulating brain regions.

“Pups raised by dams who exhibit high levels of maternal care demonstrate increases in hippocampal synaptogenesis (Liu et al., 2000), increased glucocorticoid receptor (GR) mRNA, decreased hypothalamic CRF mRNA (Liu et al., 1997), and increased benzodiazepine receptor binding in brain regions regulating emotion (Caldji et al., 2000b).”

• cites Liu et al., 2000Not checked yet

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• cites Liu et al., 1997 sourceNot checked yet

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• cites Caldji et al., 2000bNot checked yet

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Classified as probably not a substantial claim.

Differences in the timing and duration of separation may explain divergent findings on sucrose preference.

“One explanation for these divergent findings might be the existence of differences in the timing and duration of separation.”

• cites McCool and Chappell, 2009Not checked yet

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• cites Panksepp, 1981 sourceNot checked yet

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Post-weaning social isolation leads to deficits in reversal learning and attentional set shifting.

“This paradigm also results in deficits in reversal learning (Amitai et al., 2014; Li et al., 2007), as well as in learning new strategies based on a previously unrelated cue (attentional set shifting) (Schrijver and Würbel, 2001).”

• cites Amitai et al., 2014 sourceNot checked yet

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• cites Li et al., 2007Not checked yet

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• cites Schrijver and Würbel, 2001Not checked yet

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Probably not a substantial claim: may not pass S3 (load-bearing).

By depriving animals of play experiences that normally guide cortical development, post-weaning social isolation is conceptualized as a rodent model of adolescent adversity with long-lasting effects on neurobiology and behavior.

“By depriving animals of the play experiences that normally guide cortical development, post-weaning social isolation is conceptualized as a rodent model of adolescent adversity with long-lasting effects on neurobiology and behavior (Fone and Porkess, 2008; Lukkes et al., 2009; Robbins, 2016).”

• cites Fone and Porkess, 2008Not checked yet

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• cites Lukkes et al., 2009 sourceNot checked yet

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• cites Robbins, 2016 sourceNot checked yet

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Most studies report lower striatal activation in motivation and reward tasks, but not when the stressor is parental warmth variation.

“While most studies demonstrate decreased activation of the striatal regions in tasks engaging motivational and reward responsiveness processes, this was not the case when the specific stressor investigated was variations in parental warmth.”

May combine two claims.

Even though socially isolated rats show greater approach motivation, they obtain less reward on low-effort tasks because of perseveration.

“For example, despite enhanced approach motivation compared to socially housed controls, when a reward task requires fewer lever presses, socially isolated rats end up receiving less reward due to perseveration (Morgan and Einon, 1975).”

• cites Morgan and Einon, 1975Not checked yet

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One study found lower ventral striatum and putamen activity during anticipation but higher activity during delivery, and only for positive verbal feedback rather than money.

“However, in one study, while activation in the ventral striatum and putamen was decreased during anticipation, activity was increased during the delivery phase, but only for positive verbal feedback as opposed to monetary reward (Boecker et al., 2014).”

• cites Boecker et al., 2014 sourceNot checked yet

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Social isolation generally increases sucrose preference in rodents, though some studies report discrepant results.

“In tasks measuring liking, social isolation generally results in increased sucrose preference (Brenes and Fornaguera, 2008, 2009; Colonnello et al., 2011; Hall et al., 1998a; Van den Berg et al., 2000), although there are some discrepant reports (McCool and Chappell, 2009; Pisu et al., 2011).”

• cites Brenes and Fornaguera, 2008, 2009Not checked yet

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• cites Colonnello et al., 2011 sourceNot checked yet

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• cites Hall et al., 1998aNot checked yet

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Findings on positive emotional stimuli diverge: institutionalized children show lower ventral striatal response to positive faces, whereas abused adolescents show greater reactivity to positive social cues.

“While institutionally reared children had decreased ventral striatal response to positive emotional faces (Goff et al., 2013), adolescents with a history of physical and sexual abuse demonstrated increased reactivity to positively valenced social stimuli (Dennison et al., 2016), suggesting a potential difference in the effects of neglect vs abuse.”

• cites Goff et al., 2013 sourceNot checked yet

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• cites Dennison et al., 2016 sourceNot checked yet

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These tasks each include an anticipation phase and a delivery phase; brain activity during these phases is used to infer motivation and reward responsiveness, respectively.

“Both tasks have two phases, an anticipation phase, in which the subject is given information about the potential for reward, and a delivery phase, in which the reward is received. By measuring brain activity during the anticipation and delivery phases, a motivational component and a reward responsiveness component can be inferred, respectively (Knutson et al., 2000; Lutz and Widmer, 2014; Wang et”

• cites Knutson et al., 2000 sourceNot checked yet

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• cites Lutz and Widmer, 2014Not checked yet

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• cites Wang et al., 2016 sourceNot checked yet

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Human fMRI and animal studies differ notably: animal work relies almost entirely on behavior, whereas human studies report behavior far less often.

“A major difference between the human fMRI studies and the animal studies is that while the animal studies rely almost solely on behavioral measures to infer reward processes, behavioral measures (reaction times, performance) are reported much less frequently in the human literature.”

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Together, these studies suggest that low maternal warmth can heighten brain sensitivity to reward anticipation, with effects varying by sex and by the timing of stress and testing.

“These two studies suggest that, depending on gender and developmental timing of stressor and testing, low maternal warmth may increase the brain’s sensitivity to anticipation of reward.”

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Adolescent female rats given variable stressors later consume less sucrose, whereas males do not.

“there is some indication that female rats exposed to variable stressors in adolescence (restraint, social defeat) demonstrate subsequent deficits in sucrose consumption (Bourke and Neigh, 2011; Pohl et al., 2007) while male animals do not (Bourke and Neigh, 2011; Novick et al., 2013; Pohl et al., 2007; Toth et al., 2008).”

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• cites Pohl et al., 2007 sourceNot checked yet

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• cites Novick et al., 2013 sourceNot checked yet

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Social isolation increases indices of approach motivation, including enhanced responding for increasing sucrose concentrations and greater conditioned responses to sucrose-related stimuli.

“Increased indices of approach motivation are also found following social isolation, with evidence of enhanced responding for increasing concentrations of sucrose (Cuenya et al., 2015; Hall et al., 1997), as well as greater conditioned responses to sucrose-related stimuli (Jones et al., 1990).”

• cites Cuenya et al., 2015 sourceNot checked yet

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• cites Hall et al., 1997 sourceNot checked yet

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• cites Jones et al., 1990 sourceNot checked yet

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Social isolation after weaning increases HPA axis sensitivity, particularly in males, and leads to an anxiety-like profile.

“As with maternal separation, post-weaning social isolation results in enhanced sensitivity of the HPA axis, especially in male rats (Holson et al., 1991; Viveros et al., 1988; Weiss et al., 2004), as well as an overall anxiogenic phenotype.”

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• cites Viveros et al., 1988Not checked yet

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• cites Weiss et al., 2004 sourceNot checked yet

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That link was significant for stress in early childhood (kindergarten to grade 3) but not for later stress.

“This relationship was significant when the stress was experienced earlier in life (kindergarten through grade 3) but not later (Hanson et al., 2016).”

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Adolescent girls with low early-adolescent maternal warmth show a similar increase in striatal activation during reward anticipation, and that increase is linked to more depressive symptoms.

“A similar association was found for adolescent females with low maternal warmth in early adolescence, although increased activity was associated with increased depressive symptoms (Casement et al., 2014).”

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On a probabilistic reward task, reduced reinforcement learning appears in women with childhood sexual abuse and MDD, physically abused adolescents, and young adults with many early-life adversities.

“For example, women with a history of both childhood sexual abuse and MDD (Pechtel and Pizzagalli, 2013), adolescents exposed to physical abuse (Hanson et al., 2017), and young adults who had high levels of various adversities in early life (Birn et al., 2017) demonstrate decreased reinforcement learning.”

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• cites Hanson et al., 2017 sourceNot checked yet

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• cites Birn et al., 2017 sourceNot checked yet

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Reward-processing changes did not mediate the ELS-ADHD association, although similar ventral striatal activity patterns appeared.

“While changes to reward processing did not mediate the association between ELS and ADHD, similar patterns of ventral striatal activity were found (Boecker et al., 2014).”

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ELS probably changes fundamental affect and cognition, increasing vulnerability to psychopathology.

“As posited in the introduction, ELS likely alters core aspects of affect and cognition that in turns makes individuals susceptible to psychopathology.”

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Two studies reported longer reaction times on the monetary incentive delay task in people with prior ELS, while children with reactive attachment disorder had shorter reaction times on a gambling task; other studies either did not assess behavior or found no differences.

“Dillon et al. (2009) and Boeker et al. (2014) found increased reaction times in individuals with prior ELS in the monetary incentive delay task, while decreased reaction times were noted in children with reactive attachment disorder in a gambling task (Takiguchi et al., 2015), although the remainder of studies either did not measure behavior (Casement et al., 2015, 2014; Goff et al., 2013; Hanson”

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• cites Boecker et al., 2014 sourceNot checked yet

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• cites Takiguchi et al., 2015 sourceNot checked yet

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Lower striatal responsiveness in humans is associated with anhedonia and depression, yet research on its behavioral consequences is scarce.

“While it does appear that decreased striatal responsiveness in humans is linked to anhedonia and depressive symptoms, studies measuring how this impacts actual behavior are lacking.”

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No interventions yet target subclinical anhedonia or reinforcement-learning deficits in at-risk groups, but evidence suggests they could work.

“To our knowledge, interventions meant to target subclinical anhedonia or impairments in reinforcement learning in at risk populations have yet to be tested, however there is evidence for potential efficacy.”

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• cites Garland, 2016 sourceNot checked yet

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• cites Acheson et al., 2013 sourceNot checked yet

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Many human studies link lower basal ganglia activation during reward anticipation or receipt to depressive symptoms, and this activation often mediates the ELS-depression relationship.

“in many of the human studies reviewed, decreased activation in regions of the basal ganglia to the anticipation or receipt of reward was not only associated with depressive symptoms (Dillon et al., 2009; Goff et al., 2013), but often found to mediate the relationship between ELS and depression (Corral-Frías et al., 2015; Hanson et al., 2015).”

• cites Dillon et al., 2009 sourceNot checked yet

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• cites Goff et al., 2013 sourceNot checked yet

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• cites Corral-Frías et al., 2015 sourceNot checked yet

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The monetary incentive delay and reward guessing tasks suit imaging well but are poorer at detecting behavioral differences in reward processing.

“The monetary incentive delay task and the reward guessing task, while well adapted for use with imaging, are less suited to capturing differences in reward behavior.”

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Several fMRI studies using the monetary incentive delay task find ventral striatal activation changes without reaction-time changes, which suggests reaction time may be an insensitive reward-processing marker.

“It should be noted that in various studies utilizing fMRI and the monetary incentive delay task, changes in ventral striatal activation are often found in the absence of changes in reaction time (Jansma et al., 2013; Saji et al., 2013; Smoski et al., 2011), suggesting that reaction time may lack sensitivity as a marker for reward processing.”

• cites Jansma et al., 2013 sourceNot checked yet

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• cites Saji et al., 2013 sourceNot checked yet

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• cites Smoski et al., 2011 sourceNot checked yet

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After behavioral activation therapy, people show greater ventromedial PFC activation while anticipating loss on a monetary incentive delay task, which is thought to support continued rewarding activity despite negative mood.

“When individuals who have completed behavioral activation therapy are challenged with a monetary incentive delay task, they demonstrate increased activation of the ventromedial PFC during anticipation of a loss, which is interpreted as allowing for ongoing engagement in rewarding activity despite negative emotions (Mori et al., 2016).”

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Taken together, the small human literature indicates that ELS relates to lower neural reward responsiveness on both motivation and reward responsiveness measures, except in studies of low maternal warmth.

“Overall, a limited literature in humans does suggest that ELS is associated with decreased neural responsiveness to reward on both measures of approach motivation and reward responsiveness, although studies evaluating decreased maternal warmth appear to be an exception.”