Memory performance predicts recurrence of mania in bipolar disorder following psychotherapy: A preliminary study
Introduction
The integration of non-pharmacological and pharmacological interventions has been shown to be beneficial and improves the long-term therapeutic outcomes of mood disorder patients (Lobban et al., 2007, Miklowitz et al., 2007, Oestergaard and Møldrup, 2011, Pfennig et al., 2013). The majority of studies in this field had ‘prevention of relapse’ as the primary outcome measure (Castle et al., 2010, Colom et al., 2003, Oestergaard and Møldrup, 2011), but improvements in medication adherence (Colom and Lam, 2005, Pampallona et al., 2004), mood symptoms (Colom et al., 2009), quality of life, and well-being have also been reported (Zilcha-Mano et al., 2014).
While some studies concluded that interventions such as cognitive behavioral therapy (CBT) are highly effective in bipolar disorder (BD), other trials including heterogeneous populations during both acute and euthymic phases of BD did not show significant changes in mood or relapse (Driessen and Hollon, 2010, Parikh, 2008). However, Colom et al.’s study showed that combining medication and psychosocial intervention in a stabilized population led to a reduced number of relapses and improved medication adherence, as well as improved psychosocial functioning. Notably these effects lasted up to 5 years post-intervention (Colom et al., 2009).
The number of studies investigating the factors predicting the efficacy of psychological treatments is limited and usually focused on predictors such as age of onset or number of prior mood episodes (Lam et al., 2009, Reinares et al., 2014). One potential predictor or moderator of outcome could be cognitive abilities. However, only few studies have investigated this area in psychiatry and, to date, no published study has examined cognitive functioning as part of psychological treatments for bipolar disorder (BD). In a study of older adults with anxiety disorders, there was a positive association between general intelligence and improvement in anxiety symptoms in the supportive counseling condition but not CBT (Doubleday et al., 2002). Similar findings by D'Alcante et al. revealed that higher verbal intelligence scores and immediate verbal recall predicted a better treatment response to both CBT and fluoxetine in adults with OCD (D'Alcante et al., 2012). Furthermore, lower intelligence scores appeared to be predictors of poor treatment response in adults with depression (Fournier et al., 2009) and Post-traumatic Stress Disorder (Rizvi et al., 2009). Looking at psychosis, only a very small number of studies have investigated this issue with one study reporting that treatment response to CBT in patients with psychosis was not related to cognitive performance (Granholm et al., 2008).
This kind of research is relevant because memory, executive functions and pre-morbid intelligence are essential for completing daily activities involving goal setting and planning (Lezak, 2004). Thus, it is possible that pre-existing interindividual differences in cognitive abilities affect the extent to which people benefit from different psychological interventions (Doubleday et al., 2002). However, the literature in this field is a) very heterogeneous and b) also still controversial as a number of studies have not found a consistent link between cognitive performance and response to therapy across mood disorders (Knekt et al., 2014, Voderholzer et al., 2013). Thus, further research is needed to test this link.
Results about a potential link between cognitive functioning and outcome of talking therapies are highly relevant to BD as impairment in cognitive functions have been observed across all phases of BD (Bora et al., 2009, Glahn et al., 2007, Quraishi and Frangou, 2002), and cognitive impairment is especially pronounced during the manic and depressive phases of the disorder (Robinson et al., 2006). Additionally, all of the studies we identified and that looked at whether cognitive performance is related to outcome of talking therapies have focused on acute patient populations. However, most studies evaluating psychological interventions for BD, so far, have focused on relapse prevention and recruited patients in remission or immediately after an acute episode. Therefore, it is not known whether neuropsychological functioning in remitted patients will predict or moderate the outcome of talking therapies.
In sum, studies focusing on the impact of neuropsychological performance on treatment response to talking therapies in general and to CBT specifically are lacking. Furthermore, it is unclear whether differences in cognitive performance in patients with BD are prospectively associated with the risk of relapse. The current paper focuses on unpublished neuropsychological data collected as part of a randomized controlled trial (RCT) (Meyer and Hautzinger, 2012) comparing CBT and Supportive Therapy (ST) for remitted patients with BD. In this RCT, CBT and ST were matched with regards to number and duration of sessions, and both conditions included psychoeducation and a mood diary. While CBT additionally included typical cognitive and behavioral strategies and techniques to prevent relapse or how to cope with symptoms (e.g Basco and Rush, 1996). ST had a client-centered focus and was less structured and less directive. While this RCT found no overall difference in relapse rates between CBT and ST over almost 3 years, a higher number of prior mood episodes and a lower number of attended therapy sessions were associated with a shorter time before relapse. These findings suggest that characteristics shared by both treatments may contribute to the outcome. However, this prompted us to explore post hoc other potential moderators, and in this case whether indicators of general intelligence, verbal learning and memory predict recurrence of mood episodes during follow-up and whether there is an indication that cognitive performance and treatment interact. Verbal learning and memory were originally chosen because prior research showed that patients with BD demonstrated deficits in this area (Deckersbach et al., 2004, van Gorp et al., 1998).
Section snippets
Participants
One-hundred-forty adults with BD were either referred by local hospitals, psychiatrists, or self-referred in response to advertisements. Nine of 107 participants who completed the baseline assessment voluntarily withdrew from the study (n = 9) and 22 were excluded because they did not have bipolar disorder (n = 20) and had current opiate or alcohol dependency (n = 2). The analyses for the current paper include the clinical and cognitive data from all 76 participants which were randomized into
Demographics
As reported in Meyer and Hautzinger's study (Meyer and Hautzinger, 2012), participants allocated to the CBT and ST therapy were comparable in terms of age, gender, and clinical status as measured by the lifetime number of mood episodes, age of onset of the disease, and severity of the depressive and manic symptoms (e.g. HAMD, SRMI). In terms of cognitive measures participants displayed a comparable performance on LPS, Trials 1–5, Free Recall and Recognition scores (p > 0.05) (Table 1). As
Discussion
To the authors’ knowledge this is the first study exploring whether indicators of general intelligence, verbal learning and memory predict recurrence of mood episodes in euthymic adults with BD who received either 9 months of CBT or ST. The most important finding of the post-hoc analyses of this RCT is that although there was no overall significant difference in the risk of recurrence between CBT and ST (Meyer and Hautzinger, 2012) and general intelligence did not predict outcome of
Conflicts of interest
Dr Bauer has no conflicts of interest.
Professor Martin Hautzinger has received honorarium from Lundbeck, Sevier, and Merk.
Professor Thomas D. Meyer has been a speaker for Pfizer and Lundbeck.
Contribution
IB analyzed the data and wrote the first draft of the manuscript. MH and TDM designed the study, wrote the protocol and collected the data. All authors contributed to the interpretation of the data, and have approved the final manuscript.
Role of funding source
This research was supported by a grant provided from the Deutsche Forschungsgemeinschaft (DFG ME 1681/6-1 to 6.3) and, in part, by NIMH grant R01 085667 and the Pat Rutherford, Jr. Endowed Chair in Psychiatry (UTHealth).
Acknowledgement
We are indebted to all the therapists and independent raters, especially Dr. Peter Peukert and Dr. Katja Salkow as well as research assistants for their enormous work, support and help.
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