Resting-state connectivity predictors of response to psychotherapy in major depressive disorder.

New Study (1)Abstract
Despite the heterogeneous symptom presentation and complex etiology of major depressive disorder (MDD), functional neuroimaging studies have shown with remarkable consistency that dysfunction in mesocorticolimbic brain systems are central to the disorder. Relatively less research has focused on the identification of biological markers of response to antidepressant treatment that would serve to improve the personalized delivery of empirically supported antidepressant interventions. In the present study, we investigated whether resting-state functional brain connectivity (rs-fcMRI) predicted response to Behavioral Activation Treatment for Depression, an empirically validated psychotherapy modality designed to increase engagement with rewarding stimuli and reduce avoidance behaviors. Twenty-three unmedicated outpatients with MDD and 20 matched nondepressed controls completed rs-fcMRI scans after which the MDD group received an average of 12 sessions of psychotherapy. The mean change in Beck Depression Inventory-II scores after psychotherapy was 12.04 points, a clinically meaningful response. Resting-state neuroimaging data were analyzed with a seed-based approach to investigate functional connectivity with four canonical resting-state networks: the default mode network, the dorsal attention network, the executive control network, and the salience network. At baseline, the MDD group was characterized by relative hyperconnectivity of multiple regions with precuneus, anterior insula, dorsal anterior cingulate cortex (dACC), and left dorsolateral prefrontal cortex seeds and by relative hypoconnectivity with intraparietal sulcus, anterior insula, and dACC seeds. Additionally, connectivity of the precuneus with the left middle temporal gyrus and connectivity of the dACC with the parahippocampal gyrus predicted the magnitude of pretreatment MDD symptoms. Hierarchical linear modeling revealed that response to psychotherapy in the MDD group was predicted by pretreatment connectivity of the right insula with the right middle temporal gyrus and the left intraparietal sulcus with the orbital frontal cortex. These results add to the nascent body of literature investigating pretreatment rs-fcMRI predictors of antidepressant treatment response and is the first study to examine rs-fcMRI predictors of response to psychotherapy.


Crowther, A., Smoski, M.J., Minkel, J., Moore, T., Gibbs, D., Petty, C., Dichter, G.S. (2015). Resting-state connectivity predictors of response to psychotherapy in major depressive disorder. Neuropsychopharmacology, 40, 1659-1673. doi: 10.038/npp205.12

Cognitive Therapy plus Medication is More Effective than Medication Alone in the Treatment of Depression

OBJECTIVE: To determine the effects of combining cognitive therapy (CT) with ADM vs ADM alone on remission and recovery in major depressive disorder (MDD).

METHOD: A total of 452 adult outpatients with chronic or recurrent MDD participated in a trial conducted in research clinics at 3 university medical centers in the United States. The patients were randomly assigned to ADM treatment alone or CT combined with ADM treatment. Treatment was continued for up to 42 months until recovery was achieved.

RESULTS: Combined treatment enhanced the rate of recovery vs treatment with ADM alone (72.6% vs 62.5%; t451?=?2.45; P?=?.01; hazard ratio [HR], 1.33; 95% CI, 1.06-1.68; number needed to treat [NNT], 10; 95% CI, 5-72). This effect was conditioned on interactions with severity (t451?=?1.97; P?=?.05; NNT,?5) and chronicity (?2?=?7.46; P?=?.02; NNT,?6) such that the advantage for combined treatment was limited to patients with severe, nonchronic MDD (81.3% vs 51.7%; n?=?146; t145 = 3.96; P?=?.001; HR, 2.34; 95% CI, 1.54-3.57; NNT, 3; 95% CI, 2-5). Fewer patients dropped out of combined treatment vs ADM treatment alone (18.9% vs 26.8%; t451?=?-2.04; P?=?.04; HR, 0.66; 95% CI, 0.45-0.98). Remission rates did not differ significantly either as a main effect of treatment or as an interaction with severity or chronicity. Patients with comorbid Axis II disorders took longer to recover than did patients without comorbid Axis II disorders regardless of the condition (P?=?.01). Patients who received combined treatment reported fewer serious adverse events than did patients who received ADMs alone (49 vs 71; P?=?.02), largely because they experienced less time in an MDD episode.

CONCLUSIONS: Cognitive therapy combined with ADM treatment enhances the rates of recovery from MDD relative to ADMs alone, with the effect limited to patients with severe, nonchronic depression.

Hollon S.D., DeRubeis R.J., Fawcett J., et al. Effect of Cognitive Therapy With Antidepressant Medications vs Antidepressants Alone on the Rate of Recovery in Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. Published online August 20, 2014. doi:10.1001/jamapsychiatry.2014.1054.

CT is as Effective as Fluoxetine in Preventing Depressive Relapses

A recent study published in JAMA Psychiatry showed Cognitive Therapy (CT) to be as effective as medication (Fluoxetine) in reducing the risk of major depressive disorder (MDD) relapse. Participants in the current study included 523 adults with a diagnosis of MDD and a score of 14 or higher on the Hamilton Rating Scale for Depression. They were recruited from clinical referrals and advertisements during 2000 to 2008. Researchers employed a sequential, 3-stage design with an acute phase in which all patients received 12 weeks of CT; an 8-month experimental phase in which responders at higher risk were randomized to receive either a continuation of CT, fluoxetine, or a pill placebo; and a 24-month longitudinal, posttreatment follow up. At the end of the 8-month experimental stage, participants were assessed without treatment at 4 month intervals, continuing for 32 months. Results showed that CT and fluoxetine had almost equal relapse rates during the 8-month experimental phase, which were maintained during the assessment following termination of treatment. While further research is needed to fully understand the differences between psychopharmacological treatment and CT for depression, these finding suggest that CT is a valid alternative to drug therapies.

Jarret, R. B., Minhajuddin, A., Gershenfeld, H., Friedman, E. S., & Thase, M. E. (2013). Preventing depressive relapse and recurrence in higher-risk cognitive therapy responders: A randomized trial of continuation phase cognitive therapy, fluoxetine, or matched pill placebo. JAMA Psychiatry, 70(11), 1152-1160. doi:10.1001/jamapsychiatry.2013.1969

Long-Term Study on Family Group Cognitive-Behavioral Preventative Intervention Shows Promising Results in Children Whose Parents Have Major Depressive Disorder

A recent study published in the Journal of Consulting and Clinical Psychology found that a family group cognitive-behavioral (FGCB) preventative intervention for children (9-15 years old) whose parents have suffered from Major Depressive Disorder (MDD) significantly lowered the rates of MDD onset in children during a 2-year intervention period. The rates of MDD in children in the FGCB preventative intervention were reduced by half compared to a written information group in which families were mailed educational materials on depression. These findings suggest a need for effective preventive interventions for children of depressed parents.

Compas, B. E., Forehand, R., Thigpen, J. C., Keller, G., Hardcastle, E. J., Cole, D. A., & … Roberts, L. (2011). Family group cognitive–behavioral preventive intervention for families of depressed parents: 18- and 24-month outcomes. Journal Of Consulting And Clinical Psychology, 79(4), 488-499. doi:10.1037/a0024254