The search for universal transdiagnostic and trans-therapy change processes: Evidence for intolerance of uncertainty

May combine two claims.

Intolerance of uncertainty is higher in people with generalized anxiety disorder than in non-anxious controls and acts as a cognitive vulnerability for worry and GAD.

“Consistent with this model, IU is elevated in individuals with GAD compared to non-anxious controls and is a cognitive vulnerability factor for worry and GAD (Dugas, Gagnon, Ladouceur, & Freeston, 1998;Koerner & Dugas, 2008;Dugas et al., 2007;Laugesen, Dugas, & Bukowski, 2003;Sexton, Norton, Walker, & Norton, 2003).”

• cites Dugas, Gagnon, Ladouceur, & Freeston, 1998 sourceNot checked — no full text of the source
• cites Koerner & Dugas, 2008 sourceNot checked — no full text of the source
• cites Dugas et al., 2007 sourcePartly supported

  The Abstract says people with GAD are more intolerant of uncertainty than people with other anxiety disorders, but it does not give the claimed comparison with non-anxious controls. It also says intolerance of uncertainty may be a causal risk factor for worry/GAD; the claim states that vulnerability more definitively. The Discussion reports an association with GAD and worry severity, not a test of vulnerability. Page numbers are not available in our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

Classified as probably not a substantial claim.

RNT is a well-established vulnerability factor for depression symptoms.

“RNT is a well-established vulnerability factor for depression symptoms (Nolen-Hoeksema, Wisco, & Lyubomirsky, 2008).”

• cites Nolen-Hoeksema, Wisco, & Lyubomirsky, 2008 sourceSupported

May combine two claims.

The disorder-specific foci of our treatments may more specifically target IU within each problem area, and there is evidence that disorder-specific IU explains unique variance in symptoms above and beyond trait IU.

“It may be that the disorder-specific foci of our treatments more specifically target IU within each problem area, and indeed there is evidence that disorder-specific IU explains unique variance in symptoms above and beyond trait IU (Mahoney & McEvoy, 2012a;Thibodeau et al., 2015).”

• cites Mahoney & McEvoy, 2012aNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Thibodeau et al., 2015 sourceSupported

May combine two claims.

In the same sample, change in intolerance of uncertainty was related to symptom reduction in the social anxiety and generalized anxiety groups, but not in the depression group.

“Changes in IU were also associated with symptom relief in the social anxiety disorder and generalized anxiety disorder groups, but not in the depression group.”

May combine two claims.

In the worry and rumination group, there were very large reductions on the PSWQ and RTQ during treatment, and patients continued to improve over the follow-up period.

“There were very large reductions on the PSWQ and RTQ during treatment, and patients continued to improve over the follow up period.”

May combine two claims.

In the worry and rumination group, change on the IUS-12 was associated with change on the RTQ, with an estimate of .35 (95% CI .16-.53, p<.001), and the association remained after controlling for PANAS, with an estimate of .25 (95% CI .06-.45, p=.011).

“Change on the IUS-12 was associated with change on the RTQ, Est = .35,95% CI [.16, .53],p <.001, and the association was still present after controlling for PANAS, Est = .25,95% CI [.06, .45],p = .011.”

May combine two claims.

In the worry and rumination group, IUS-12 and PANAS scores improved substantially, with effect sizes exceeding 1 SD by follow-up.

“IUS-12 and PANAS scores also improved substantially, with effect sizes exceeding 1 SD by follow up.”

May combine two claims.

In the worry and rumination group, within-person change on the IUS-12 was associated with PSWQ scores over treatment, with a coefficient of .47 (95% CI .21-.72, p=.001) without PANAS and .31 (95% CI .06-.56, p=.015) after controlling for PANAS.

“Within-person change on the IUS-12 was associated with PSWQ scores over the course of treatment, and this association persisted even after controlling for change on PANAS scores.”

• Also stated in: § 3.1 Worry and Rumination Group · plain

  “The relevant regression coefficient (for the IUS-12 deviation term) was .47 for the model without the PANAS, 95% CI [.21, .72],p = .001,and .31after controlling for the PANAS, 95% CI [.06, .56],p = .015.”

May combine two claims.

In the worry and rumination group, change on the IUS-12 between post-treatment and follow-up continued at the same rate as during treatment, whereas the rate of change on other variables slowed somewhat.

“The figure suggests that change on the IUS-12 between post-treatment and follow up continued at the same rate as was observed during treatment, whereas the rate of change on other variables slowed somewhat.”

May combine two claims.

The confidence intervals for Inhibitory IU after controlling for PANAS in both cases are wide and consist almost entirely of positive values.

“While the p-values for Inhibitory IU after controlling for the PANAS in both cases are above .05,the confidence intervals are wide and consist almost entirely of positive values.”

May combine two claims.

The hypothesis that changes in IU would be consistently associated with changes in RNT and symptoms across disorders and treatments was supported for RNT and partially supported for symptoms, with the exception being depression symptoms.

“It was hypothesized that changes in IU would be consistently associated with changes in RNT and symptoms across disorders and treatments, which was supported for RNT and partially supported for symptoms with the exception being depression symptoms.”

May combine two claims.

In the social anxiety group, there were very large reductions on the SIAS and SPS, a large reduction on the PANAS and RTQ, and moderate to large reductions on the IUS-12.

“There were very large reductions on the SIAS and SPS, a large reduction on the PANAS and RTQ, and moderate to large reductions on the IUS-12.”

May combine two claims.

In the worry and rumination group, Prospective IU was a statistically significant predictor of RTQ after controlling for PANAS, with an estimate of .44 (95% CI .14-.74, p=.005), while Inhibitory IU was not, with an estimate of .35 (95% CI -.07-.77, p=.102).

“Prospective IU was a statistically significant predictor after controlling for the PANAS (Est = .44,95% CI [.14, .74],p = .005)while Inhibitory IU was not (Est = .35,CI [-.07, .77],p = .102.”

May combine two claims.

In the mood management group, there was a large change on the BDI-II, while changes on the RTQ and PANAS were more modest than for the other groups, and change on the IUS-12 was small.

“There was a large change on the BDI-II, while changes on the RTQ and PANAS were more modest than for the other groups, and change on the IUS-12 was small.”

May combine two claims.

In the worry and rumination group, change in Prospective IU was a statistically significant predictor of PSWQ scores after controlling for PANAS, with an estimate of .50 (95% CI .10-.89, p=.014), whereas Inhibitory IU just failed to achieve statistical significance, with an estimate of .50 (95% CI -.04-1.04, p=.071).

“For the worry and rumination group, change in Prospective IU was a statistically significant predictor of PSWQ scores after controlling for the PANAS, Est = .50,95% CI [,10, .89],p = .014,whereas Inhibitory IU just failed to achieve statistical significance, Est = .50,95% CI [-.04, 1.04], p = .071.”

May combine two claims.

For the Mood Management Group, all changes in outcome during treatment had p-values less than .001 except the pre-treatment to follow-up change on IUS-12, which had p = .005.

“P-values for all changes in outcome during treatment were < .001except for pre-treatment to follow-up change on the IUS-12 (p = .005).”

May combine two claims.

This study found evidence that IU was associated with reductions in RNT across different group treatment protocols for GAD, SAD, and depression, and with reductions in symptoms of GAD and SAD, even after controlling for negative affectivity.

“This study found evidence that IU was associated with reductions in RNT across different group treatment protocols for GAD, SAD, and depression, and with reductions in symptoms of GAD and SAD, even after controlling for negative affectivity.”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

For the Social Anxiety Group, all changes in outcome during treatment had p-values less than .001.

“P-values for all changes in outcome during treatment were < .001.”

Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

For the Worry and Rumination Group, all changes in outcome during treatment had p-values less than .001.

“P-values for all changes in outcome during treatment were < .001.”

May combine two claims.

Negative affectivity was a unique predictor of symptom change (and the sole predictor for depression symptoms) in our study, which is consistent with Talkovsky and Norton's (2014) findings.

“Notwithstanding the differences in findings in relation to IU, it is noteworthy that negative affectivity was a unique predictor of symptom change (and the sole predictor for depression symptoms) in our study, which is consistent with Talkovsky and Norton's (2014) findings.”

May combine two claims.

The observed pattern supports viewing intolerance of uncertainty as a process that operates across diagnoses and across therapies.

“IU was associated with reductions in repetitive negative thinking in all treatments, which is consistent with IU being a transdiagnostic and 'trans-therapy' process of change.”

May combine two claims.

Intolerance of uncertainty and repetitive negative thinking are two central constructs in the Intolerance of Uncertainty Model that have been shown to be transdiagnostic.

“IU and RNT are therefore two key constructs in the Intolerance of Uncertainty Model (Freeston et al., 1994) that have been demonstrated to be transdiagnostic.”

• cites Freeston et al., 1994 sourceNot checked — no full text of the source

May combine two claims.

Higher intolerance of uncertainty is a risk factor for anxiety symptoms and anxiety disorders, with people higher on this trait more likely to react negatively to ambiguity or uncertainty.

“IU is argued to be a risk factor for anxiety symptoms and anxiety disorders, such that individuals higher on this dimension are more likely to experience negative emotions in response to ambiguity or uncertainty (Koerner & Dugas, 2008).”

• cites Koerner & Dugas, 2008 sourceNot checked — no full text of the source

May combine two claims.

In a GAD trial comparing IU therapy, metacognitive therapy, and delayed treatment, both active therapies were highly effective, but metacognitive therapy produced larger reductions in IU than IU therapy.

“While both treatments were highly effective, metacognitive therapy was associated with larger reductions on a measure of IU compared to IU therapy.”

• cites van der Heiden et al.'s (2012) sourceNot checked — no full text of the source

May combine two claims.

Recent evidence indicates that treatments from alternative cognitive behavioural frameworks may reduce intolerance of uncertainty, making it a candidate trans-therapy mechanism.

“Recent evidence that IU may be modified by treatments deriving from alternative cognitive behavioural frameworks suggests that IU could be a candidate trans-therapy mechanism of change.”

May combine two claims.

Self-reported IU significantly reduces and is associated with symptom change during CBT protocols that do not explicitly target IU.

“with evidence that self-reported IU significantly reduces and is associated with symptom change during CBT protocols that do not explicitly target IU (Mahoney & McEvoy, 2012b;van der Heiden et al., 2012).”

• cites Mahoney & McEvoy, 2012bNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites van der Heiden et al., 2012 sourceNot checked — no full text of the source

May combine two claims.

The significant relationships remained after controlling for negative affectivity, supporting the discriminant validity of IU from negative affect and suggesting that changes in IU were incrementally associated with changes in RNT and symptoms for social anxiety and worry beyond reductions in general negative affect.

“The significant relationships remained after controlling for the higher order construct of negative affectivity, thus supporting the discriminant validity of IU from negative affect and suggesting that changes in IU were incrementally associated with changes in RNT and symptoms for social anxiety and worry beyond reductions in general negative affect.”

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

Talkovsky and Norton (2014) found that within their transdiagnostic clinical sample anxiety sensitivity and IU failed to explain unique variance in state anxiety beyond negative affect.

“In contrast, Talkovsky and Norton (2014) recently found that within their transdiagnostic clinical sample anxiety sensitivity and IU failed to explain unique variance in state anxiety beyond negative affect.”

• cites Talkovsky and Norton (2014) sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based). May combine two claims.

The literature showing IU is transdiagnostic and evidence that IU changes across therapies suggest IU may be a universal process linked to change across emotional disorders and treatments.

“The vast literature demonstrating that IU is transdiagnostic, together with evidence that IU changes across different therapies (trans-therapy), suggests that IU may be a universal process associated with change across different emotional disorders and treatments.”

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

Another potential explanation for the lack of association between IU changes and depression symptoms is that the magnitude of change in IU was smaller in the mood management group than other groups, which may have attenuated the association.

“Another potential explanation for the lack of association between changes in IU and changes in depression symptoms is that the magnitude of change in IU was smaller in the mood management group than for the other groups, which may have attenuated the association.”

May combine two claims.

All three treatments in the current study titrated uncertainty by using a graded approach to cognitive and behavioural change, which may have increased treatment acceptability for high IU individuals.

“All three treatments in the current study titrated uncertainty by using a graded approach to cognitive and behavioural change (i.e., least to most challenging), which may have increased treatment acceptability for high IU individuals.”

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

Reductions in IU should reduce the tendency to expect negative outcomes as likely, which should positively impact depression symptoms.

“Reductions in IU should therefore reduce the tendency to expect negative outcomes as being likely, which, in turn, should positively impact on depression symptoms.”

May combine two claims.

In traditional group CBT for social phobia, IU decreased and these decreases were linked to symptom improvement even though the protocol did not mention IU.

“Another study by Mahoney and McEvoy (2012b) also found that IU reduced during traditional group cognitive behaviour therapy (CBT) for social phobia, and these reductions were associated with symptom improvement, despite the fact that IU was not explicitly mentioned in the protocol.”

• cites Mahoney and McEvoy (2012b)Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

These findings are broadly consistent with IU being a universal process of change, defined as both a transdiagnostic and trans-therapy construct.

“These findings are broadly consistent with IU being a universal process of change, defined here as both a transdiagnostic and trans-therapy construct.”

May combine two claims.

The three group protocols used in this study had previously been evaluated, found highly effective, and met international benchmarks.

“protocols used in this study have previously been evaluated and found to be highly effective and to meet international benchmarks (i.e.efficacy and effectiveness trials).”

• cites McEvoy et al., 2015Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites McEvoy & Saulsman, 2014 sourceNot checked — no full text of the source
• cites McEvoy & Nathan, 2007 sourceNot checked — no full text of the source

May combine two claims.

While IU may increase vulnerability to anxiety and depression via RNT, additional intermediate processes may be particularly important for understanding the relationship between IU and depression symptoms.

“Therefore, while IU may increase vulnerability to anxiety and depression via RNT, additional intermediate processes may be particularly important for more fully understanding the relationship between IU and depression symptoms.”

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

In the current study, the PANAS negative affect subscale had high internal consistency.

“Internal consistency in the current study was high (α = .84).”

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

In the current study, the SIAS and SPS had high internal consistency.

“Internal consistencies in the current study were high for the SIAS (α = .85)and the SPS (α = .90).”

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

Talkovsky and Norton's (2014) transdiagnostic intervention may operate more broadly on NA compared to treatments in the current study.

“Second, although there are commonalities in the techniques used across the treatments (e.g., forms of exposure and cognitive restructuring), Talkovsky and Norton's (2014) transdiagnostic intervention may operate more broadly on NA compared to the treatments in the current study.”

May combine two claims.

The treatment protocols did not explicitly discuss intolerance of uncertainty, which allowed the study to assess whether IU changes through standard procedures while reducing social desirability bias.

“Importantly, the concept of IU is not explicitly discussed in any of the protocols, thereby allowing an assessment of whether IU changes as a consequence of implementing the standard procedures within each treatment whilst minimizing social desirability biases.”

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

In the current study, the PSWQ had high internal consistency.

“Internal consistency in the current study was high (α=.92).”

May combine two claims.

Overall, patients in all three programs were less fearful of (Prospective IU) and paralyzed by (Inhibitory IU) the unknown following treatment, and these changes were associated with reductions in RNT and anxiety symptoms.

“Overall, our findings suggest that patients in all three programs were less fearful of (Prospective IU) and paralyzed by (Inhibitory IU) the unknown following treatment, and these changes were associated with reductions in RNT and anxiety symptoms.”

May combine two claims.

The STAI shared 74% of variance with the PANAS negative affect subscale in Talkovsky and Norton's (2014) study, leaving little variance to be explained by IU.

“Moreover, the STAI shared a substantial proportion of variance (74%) with the PANAS negative affect subscale in Talkovsky and Norton's (2014) study, leaving little variance to be explained by IU.”

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

Patients in the social anxiety program regularly engage in inherently uncertain social situations, and patients in the worry and rumination group are required to disengage from habitual RNT, which may result in a larger dose of uncertainty than CBT for depression.

“In contrast, patients in the social anxiety program regularly engage in inherently uncertain social situations with unfamiliar conversational partners and where the outcomes of the interactions are largely unknown.Likewise, patients in the worry and rumination group are required to disengage from habitual RNT and overcontrol strategies, which may result in a larger dose of uncertainty than CBT for”

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

In the current study, the RTQ had high internal consistency.

“Internal consistency in the current study was high (α = .88).”

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

In the current study, the IUS-12 subscales and total score had high internal consistency.

“Internal consistencies in the current study were high for the subscales (Prospective IU α = .88,Inhibitory IU α = .87),and for the total score (α = .92).”

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

One potential explanation for the lack of association between IU changes and depression symptoms is that the impact of IU on depression symptoms is indirect, perhaps via other constructs such as negative thoughts about the certainty of negative outcomes and absence of positive outcomes.

“One potential explanation for the lack of an association in this study is therefore that the impact of IU on depression symptoms is indirect, perhaps via other constructs such as negative thoughts about the certainty of negative outcomes and absence of positive outcomes (Miranda, Rontes, & Marroquín, 2008).”

• cites Miranda, Rontes, & Marroquín, 2008Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Behavioral activation within traditional CBT for depression involves a lower dose of exposure to uncertainty than the other treatments.

“It is plausible that behavioral activation within traditional CBT for depression involves a lower dose of exposure to uncertainty that the other treatments, as patients are encouraged to engage with activities known to be previously associated with pleasure and achievement.”

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

Talkovsky and Norton (2014) used the state anxiety scale of the STAI as outcome variable, which may have been differentially sensitive to disorder-specific symptom changes than measures used in this study.

“First, Talkovsky and Norton (2014) used the state anxiety scale of the State Trait Anxiety Inventory (STAI, Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 2003) as the outcome variable, which may have been differentially sensitive to disorder-specific symptom changes than the measures used in this study.”

• cites Spielberger, Gorsuch, Lushene, Vagg, & Jacobs, 2003Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

These forms of depressive certainty may be acquired with increasing fluency via RNT and lead to hopelessness and worsening symptoms.

“These forms of depressive certainty may be acquired with increasing fluency via RNT and, in turn, lead to hopelessness and worsening symptoms.”

May combine two claims.

Changes in Inhibitory IU across therapy probably are associated with changes in RNT and worry after controlling for negative affect, but the sample size in the current study was too small to demonstrate a statistically significant relationship.

“This suggest that changes in Inhibitory IU across therapy probably are associated with changes in RNT and worry after controlling for negative affect, but that the sample size in the current study was too small to demonstrate a statistically significant relationship.”

May combine two claims.

Miranda and colleagues (2008) found evidence that while both anxiety and depression are characterized by pessimistic certainty about negative events, pessimistic certainty about the absence of positive events is unique to depression, and these beliefs may be more proximal than IU to depression symptoms.

“Miranda and colleagues (2008) found evidence that while both anxiety and depression are characterized by pessimistic certainty about negative events, pessimistic certainty about the absence of positive events is unique to depression, and that these beliefs may be more proximal than IU to depression symptoms.”

• cites Miranda et al., 2008 sourceNot checked — no full text of the source

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

All analyses used an intent-to-treat approach with all available data.

“All analyses were intent-to-treat, with all available data used in each analysis.”

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

In the current sample, the BDI-II had high internal consistency.

“Internal consistency in the current sample was high (α = .88).”

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

The use of self-reported outcomes, which are vulnerable to social desirability biases, is a limitation.

“The use of self-reported outcomes, which are vulnerable to social desirability biases, is another limitation.”

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

Rescaling the symptom measures for plotting only changes the y-axis labels, not the shape of the change trajectories.

“The rescaling only affects the numbers printed on the y-axis for these measures, not the shape of the trajectories.”

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

Patients who were more likely to report lower symptoms at post-treatment to please clinicians may have been more likely to also report lower IU, even though IU was not explicitly mentioned as a treatment target.

“Patients who were more likely to report lower symptoms at post-treatment to please the clinicians may have been more likely to also report lower IU, even though IU was not explicitly mentioned as a treatment target.”

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

The inclusion of anxiety sensitivity within Talkovsky and Norton's (2014) model may have usurped variance that would have been captured by IU.

“Third, the inclusion of anxiety sensitivity within Talkovsky and Norton's (2014) model may have usurped variance that would have been captured by IU.”

Probably not a substantial claim: may not pass S2 (checkable). May combine two claims.

The déjà-variable phenomenon is alive and well in the clinical psychology literature, which can result in inefficiencies and obfuscations that retard the accumulation and synthesis of knowledge.

“We argue that the déjà-variable phenomenon is alive and well in the clinical psychology literature, which can result in considerable inefficiencies and obfuscations that retard the accumulation and synthesis of knowledge.”

Classified as probably not a substantial claim.

The absence of a control group is a limitation of this study.

“The absence of a control group is another limitation of this study.”

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

IU, RNT, and NA are only a subset of potential universal change processes, which precluded evaluation of the relative contribution of these factors to other potentially important change processes.

“Another limitation was that IU, RNT, and NA are only a subset of potential universal change processes, which precluded an evaluation of the relative contribution of these factors to other potentially important change processes.”

Probably not a substantial claim: may not pass S2 (checkable).

IU may provide a useful framework within which to target these common processes in therapy.

“IU may therefore provide a useful framework within which to target these common processes in therapy.”

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

The correlational nature of this study is an important limitation, so we are unable to draw any causal conclusions about the relationship between changes in IU and outcomes.

“The correlational nature of this study is an important limitation, so we are unable to draw any causal conclusions about the relationship between changes in IU and outcomes.”

May combine two claims.

The treatment protocols in the current study were limited to forms of cognitive behavior therapy and to a restricted range of emotional disorders, so the findings may not generalize to other treatment approaches or disorders.

“The treatment protocols in the current study were also limited to forms of cognitive behavior therapy and to a restricted range of emotional disorders, so the findings may not generalize to other treatment approaches or disorders.”

May combine two claims.

The associations found in our study are necessary for a universal process and provide some empirical justification for further research in this area.

“Although insufficient, the associations found in our study are necessary for a universal process and provide some empirical justification for further research in this area.”

Probably not a substantial claim: may not pass S2 (checkable).

The findings from our study suggest that applying techniques to contexts, attentional biases, and cognitive content associated with IU may be important for promoting behavioral adaptation for individuals high on this dimension.

“The findings from our study suggest that applying techniques to contexts, attentional biases, and cognitive content associated with IU may be important for promoting behavioral adaption for individuals high on this dimension.”

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

Exposure to uncertainty may be important for reducing relapse in emotional disorders.

“Exposure to uncertainty may also be important for reducing relapse in emotional disorders (Arch & Abramowitz, 2015), so assessing the relationship between reductions in IU and longer-term outcomes is another important future research direction.”

• cites Arch & Abramowitz, 2015 sourceNot checked — no full text of the source

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

Changes in IU may be a cause, consequence, or epiphenomenon of RNT and symptom change.

“Changes in IU may be a cause, consequence, or epiphenomenon of RNT and symptom change.”