Anhedonia Predicts Poorer Recovery Among Youth With Selective Serotonin Reuptake Inhibitor Treatment–Resistant Depression

McMakin, Dana L.; Olino, Thomas M.; Porta, Giovanna; Dietz, Laura J.; Emslie, Graham J.; Clarke, Gregory; Wagner, Karen Dineen; Asarnow, Joan Rosenbaum; Ryan, Neal D.; Birmaher, Boris; Shamseddeen, Wael; Mayes, Taryn L.; Kennard, Betsy D.; Spirito, Anthony; Keller, Martin B.; Lynch, Frances L.; Dickerson, John F.; Brent, David A.

doi:10.1016/j.jaac.2012.01.011

Cited by 355 publications

(257 citation statements)

References 36 publications

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“…However, depression severity was somewhat lower in this sample (baseline CDRS-R mean = 53.2, SD 9.3) than in other trials such as TADS (mean = 60.0, SD 10.4) 54 or TORDIA (mean = 59.0, SD 10.0). 55 That our sample was slightly less depressed is not surprising, given that these youth were initially identified as depressed in primary care. The enduring CBT benefits observed in this study for major depression recovery may have been partially due to this lower baseline depression level.…”

Section: Discussionmentioning

confidence: 70%

Cognitive Behavioral Therapy in Primary Care for Youth Declining Antidepressants: A Randomized Trial

et al. 2016

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Section: Discussionmentioning

confidence: 70%

Cognitive Behavioral Therapy in Primary Care for Youth Declining Antidepressants: A Randomized Trial

et al. 2016

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“…Given anhedonia was previously reported as a valid predictor of poor response to antidepressant treatment (McMakin et al.,2012) and adversity during childhood was more frequently observed in patients with treatment‐resistant depression than patients with treatment‐sensitive depression (Tunnard et al., 2014). It could be naturally speculated that the depression induced by early life stress tends to exhibit treatment resistance, and this needs to be assessed in further studies.…”

Section: Discussionmentioning

confidence: 99%

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

et al. 2017

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BackgroundThe mesocorticolimbic dopamine system, which originates from the ventral tegmental area (VTA) and projects primarily to the prefrontal cortex (PFC), olfactory tubercle (OT), nucleus accumbens (NAc), dorsal striatum (ST), and the amygdala (AMy), plays a pivotal role in determining individual motivation and sensitivity to rewards, namely, anhedonia. Not all depressive individuals exhibited anhedonia, thus, it is natural to speculate that the heterogenous manifestations of depression might be related to the mesocorticolimbic dopamine system. Maternal deprivation (MD) and chronic unpredictable stress (CUPS) are two well‐established depressogenic stressors, and they were proven to induce different depressive phenotypes.MethodsThe depressive and anxiety‐like behaviors of MD and CUPS‐treated rats were measured by classical behavioral tests including open field, forced swimming, and sucrose preference test. The expression of D1‐5 dopamine receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system of rats exposed to MD and CUPS were measured by real‐time PCR and Western blot, respectively.ResultsSevere anhedonia was observed in MD but not CUPS rats. Divergent expression of D1 and D2 receptors and DAT mRNA and protein in the mesocorticolimbic dopamine system were found between MD and CUPS rats. Significant correlations between different depressive behaviors and D1‐/D2‐like receptors and DAT protein levels in the mesocorticolimbic dopamine system were observed.ConclusionDifferent depressive behaviors of rats such as anhedonia, passive coping behavior, and declined exploratory interest might be related to divergent dopaminergic pathways. Anhedonia is associated with the dysfunction of VTA‐NAc and VTA‐OT dopaminergic pathways, the passive coping behavior is related to the dysregulation of VTA‐PFC and VTA‐AMy pathways, and individual exploratory interest is associated with abnormal activity of VTA‐PFC and VTA‐ST pathways.

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“…Parent-child conflict has a bidirectional relationship with treatment outcome in adolescent treatment resistant depression [17]. Anhedonia in depressed adolescent's refractory to medication treatment predicted longer time to remission and fewer depression-free days [18]. Depression severity and subsyndromal manic symptoms predicted poor treatment response in this sample [19].…”

Section: Other Factors Associated With Poor Treatment Responsementioning

confidence: 84%

Treatment-Resistant Depression in Adolescents: A Comprehensive Review

Carandang¹

2013

J Depress Anxiety

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disorder due to a general medical condition (including substanceinduced depression). Detailed information on the clinical assessment of children and adolescents with depression can be found elsewhere [13]. Other Factors Associated with Poor Treatment ResponseOther than the correct diagnosis of depression, clinicians should explore other factors which contribute to poor treatment response. Exploring other factors leading to treatment-resistant depression will also guide why a patient is not responding. Depressed adolescent patients with a history of abuse, especially physical abuse, had a poorer response to combination treatment with medication and psychotherapy [14]. These patients with a history of abuse may require specialized treatment. Adolescents with treatment-resistant depression had better treatment response if substance abuse-related impairment was low at baseline or reduced during treatment [15]. Suicidal adverse events during treatment of adolescent refractory depression were predicted by high suicidal ideations, family conflict and drug abuse at baseline. These predictors of suicidal adverse events also predict poor treatment response, and hence targeting suicidal ideations, family conflict and drug abuse can improve treatment outcomes [16]. Parent-child conflict has a bidirectional relationship with treatment outcome in adolescent treatment resistant depression [17]. Anhedonia in depressed adolescent's refractory to medication treatment predicted longer time to remission and fewer depression-free days [18]. Depression severity and subsyndromal manic symptoms predicted poor treatment response in this sample [19]. There is also suggestion that adjunctive sleep medication to SSRI treatment in this sample may be associated with poor response [20]. Interestingly, if treatment ends during school summer break, AbstractTreatment nonresponse in adolescent depression is a major public health problem, as untreated depression is associated with significant mortality by suicide, protracted course of illness, and recurrence into adulthood. Even with the gold-standard treatment with a Selective Serotonin Reuptake Inhibitor (SSRI) and concurrent Cognitive Behavioral Therapy (CBT), 30% to 40% will not respond to treatment, thus classified as "treatment-resistant". These depressed adolescent patients who are refractory to first-line treatments are often in such mental anguish that they are not functioning, and some have considered their only option left to end the misery is to suicide. These are the patients who are often referred to psychiatry, but the treatment options for adolescents with treatment-resistant depression are limited due to lack of research in this area. This review will consider the various treatment options that may help to alleviate the suffering of adolescents afflicted with this devastating illness, with the caveat that there are few controlled studies focused on refractory depression in adolescents.

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Anhedonia Predicts Poorer Recovery Among Youth With Selective Serotonin Reuptake Inhibitor Treatment–Resistant Depression

Cited by 355 publications

References 36 publications

Cognitive Behavioral Therapy in Primary Care for Youth Declining Antidepressants: A Randomized Trial

Cognitive Behavioral Therapy in Primary Care for Youth Declining Antidepressants: A Randomized Trial

Divergent anomaly in mesocorticolimbic dopaminergic circuits might be associated with different depressive behaviors, an animal study

Treatment-Resistant Depression in Adolescents: A Comprehensive Review

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