Elsevier

Journal of Affective Disorders

Volume 206, December 2016, Pages 115-124
Journal of Affective Disorders

Research paper
Corpus callosum integrity is affected by mood disorders and also by the suicide attempt history: A diffusion tensor imaging study

https://doi.org/10.1016/j.jad.2016.07.026Get rights and content

Highlights

  • Corpus callosum (CC) is altered in bipolar disorders (BD).

  • Genu and body CC areas are altered in BD without suicide Attempt (SA).

  • History of SA exerts also a specific effect on CC integrity.

  • Splenium is specifically altered in SA independently from psychiatric status.

  • Screening for history of SA is crucial in future analyses of CC in affective disorders.

Abstract

Background

Some MRI studies have noted alterations in the corpus callosum (CC) white matter integrity of individuals with mood disorders and also in patients with suicidal behavior. We investigated the specific impact of suicidal behavior on CC integrity in mood disorders.

Methods

CC structural changes were assessed by diffusion tensor imaging (DTI) in 121 women 18-50-year-old): 41 with bipolar disorder (BD), 50 with major depressive disorder (MDD) and 30 healthy controls (HC). Fractional anisotropy (FA) and DTI metrics were calculated for the genu, body and splenium of CC and compared in the three groups by MANCOVA. Then, they were re-analyzed relative to the suicide attempt history within the MDD and BD groups and to the suicide number/severity.

Results

FA values for the CC genu and body were lower in non-suicide attempters with BD than with MDD and in HC. Conversely, FA values for all CC regions were significantly lower in suicide attempters with BD than in HC. Finally, higher number of suicide attempts (>2) and elevated Suicidal Intent Scale score were associated with significant splenium alterations.

Limitations

Limitations include the cross-sectional design (non-causal study), the potential influence of medications and concerns about the generalizability to men.

Conclusion

Genu and body are altered in non-suicide attempters with BD, while splenium is specifically altered in suicide attempters, independently from their psychiatric status. History of suicide attempts may be a source of heterogeneity in the association between CC alterations and BD and may partially explain the variable results of previous studies.

Introduction

Mood disorders are chronic mental diseases associated with significant functional impairment. Major depressive episodes are a common feature of Bipolar Disorder (BD), a serious mental illness that affects approximately 1–4% of the adult population, and of Major Depressive Disorder (MDD), which shows a lifetime prevalence up to 20% (Kessler et al., 2005). The presence/absence of manic or hypomanic episodes, the median age at onset (Kessler et al., 2005), the number of depressive episodes (Perlis et al., 2006) and the prevalence of suicide attempts distinguish these two disorders. Indeed, the lifetime rate of attempted suicide is between 9% and 30% in MDD and up to 61% in BD, compared with 3–5% in the general population (Rihmer, 2005). In recent years, studies using neuroimaging methods have tried to clarify the neurobiology of mood disorders. Earlier studies focused mainly on gray matter alterations. More recently, deep white matter (WM) abnormalities, including anterior cingulum, anterior corona radiata, internal capsule, fronto-occipital lobes and corpus callosum (CC) changes, have been consistently reported in neuroimaging and neuropathological studies of mood disorders (Kemp et al., 2013, Marlinge et al., 2014, Toteja et al., 2014).

CC is the main commissure between the two cerebral hemispheres, traversing the subcortical WM. It contains between 200 and 800 million axon fibers and is of crucial importance for interconnecting associative brain areas that play a pivotal role in the integration of inter-hemispheric information and higher cognitive functions. CC alterations have been increasingly reported in mood disorders (Arnone et al., 2012, Lavagnino et al., 2015, Phillips and Swartz, 2014) and it has been suggested that reduced myelination could underlie these findings (Brambilla et al., 2004). The development of Diffusion Tensor Imaging (DTI) has allowed exploring CC changes in greater detail (Marlinge et al., 2014). For instance, a review of DTI studies on CC integrity in BD (Bellani et al., 2009) found evidence for decreased fractional anisotropy (FA) values, a metric influenced by various mechanisms, including fiber organization and myelination, in the genu, body and splenium of CC of adult and juvenile patients with BD. Moreover, a recent meta-analysis of DTI studies in patients with MDD emphasized the consistent finding of reduced FA values, particularly for the inter-hemispheric fibers running through the CC genu and body (Liao et al., 2013). However, studies comparing DTI data in CC of patients with BD and MDD are lacking. To our knowledge, only one DTI study reported lower FA values in the CC of patients with late-life BD than in patients with unipolar disorder and healthy controls (Sexton et al., 2012).

Classical MRI studies have described CC abnormalities also in other psychiatric disorders. Particularly, the size of the posterior third of CC is smaller in elderly patients with suicidal behavior compared with healthy controls or with patients with history of depression but without suicidal behavior. This finding, based on structural data, suggests the presence of a specific abnormal inter-hemispheric connectivity in subjects with suicidal behavior, independently from any history of mood disorder (Cyprien et al., 2011). Moreover, it further supports previous reports suggesting that suicidal behavior has a specific underlying biological basis and therefore might constitute a separate nosological entity, now included in the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5).

However, to our knowledge, none of the published DTI studies on CC integrated in their analyses the potential confounding effect of suicidal behavior on CC alterations. This omission could partially explain the reported variability in CC regional abnormalities. We hypothesized that CC integrity is affected in BP and in people with suicidal behavior and that different CC areas are altered in these two conditions. This could represent a possible source of heterogeneity in DTI results in patients with BP with or without suicidal behavior. To test this hypothesis, First CC integrity was assessed using DTI and results were compared in euthymic women with BD or MDD and in healthy control women. Then, the groups of this first analysis were stratified relative to the presence or absence of suicide attempt in the BD and MDD groups to detect a potential specific effect of suicidal behavior on CC integrity in mood disorders. This approach should allow identifying CC areas specifically involved in BP and in suicidal behavior in the same dataset.

Section snippets

Participants / clinical assessment

One hundred and twenty-four non-menopausal right-handed women (age: 18-50-year-old) were included in this study. Only women were selected to take into account the current controversy concerning the effects of sex on CC morphology (Prendergast et al., 2015). Patients were euthymic on the day of the magnetic resonance examination, as indicated by the scores lower than 7 at the 17-item Hamilton Depression Rating Scale (HDRS) (Hamilton, 1960) and Young Mania Rating Scale (YMRS) (Young et al., 1978

Characteristics of the HC, MDD and BD groups

The demographic and clinical data are summarized in Table 1. Mean age (p=.778), educational level (p=.291) and NART score (p=.823) were comparable in the three groups (HC, MDD and BD). Patients with BD reported more depressive episodes (p<.001), more mood episodes with psychotic symptoms (p=0.003), a higher number of hospitalizations in psychiatric wards (p<.001), more use of lithium (p<.001), anticonvulsants (p<.001) and antipsychotics (p<.001) than women with MDD. Conversely, patients with

Discussion

The present study suggests a specific alteration of CC integrity in female SA, particularly a significant lower FA value of the splenium. As in previous studies, anomalies of all CC regions were observed among patients with BD compared with the MDD and HC groups, but not between patients with MDD and HC. CC anomalies, including with DTI techniques, have been consistently reported in patients with BD (Arnone et al., 2008, Bellani et al., 2009, Walterfang et al., 2009), but the affected CC

Limitations

This study has should however be considered with the following limitations. First, we could not examine the correlations between CC alterations and key features of suicidal behavior, such as attempt method or seriousness of the medical consequences, due to lack of statistical power. Indeed, violent and serious SA seem to present a profile close to that of suicide completers, compared to other SA. Common features between SA and suicide completers might include family history of suicidal

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