Artuner Deveci, MD, Celal Bayar University School of Medicine, Department of Psychiatry, 45030 Manisa, Turkey. Email: email@example.com
Abstract The aim of the present study was to compare serum brain-derived neurotrophic factor (BDNF) levels of patients with major depressive disorder (MDD) and conversion disorder (CD). Serum BDNF levels were measured in the following three groups: 15 CD patients without any comorbid diagnosis of psychiatric disorder, 24 patients with MDD, and 26 healthy subjects without any psychiatric diagnosis or psychiatric treatment. The serum BDNF level of the healthy control group (31.4 ± 8.8 ng/mL) was statistically higher than the level of the MDD group (21.2 ± 11.3 ng/mL) and the CD group (24.3 ± 9.0 ng/mL; P = 0.008). This suggests that BDNF level may play a similar role in the pathophysiology of MDD and CD.
Conversion disorder (CD) is a psychiatric disorder that is related to either psychic conflict or stressful life events and is characterized by symptoms or deficits affecting voluntary motor or sensory function that suggest the presence of a neurological condition.1 In Western countries this rate is between 1% and 3% of psychiatric outpatient, while in developing countries this rate is approximately 10%.2
The psychosocial component becomes more important in the etiology of CD, but studies concerning the biological component in the etiology of CD are also carried out. The studies on the neurobiological basis of CD are based on regional blood flow changes and somatosensory evoked potentials, indicating lateralized hemispheric dysfunction or neuroendocrine impairment.3,4
Because CD occurs in response to psychosocial stress, neural plasticity promises hope in explaining the effect of stress on brain. One candidate mechanism that has been proposed as the site of a possible flaw in signal transduction from monoamine receptors is the target gene for brain-derived neurotrophic factor (BDNF). Normally, BDNF sustains the viability of brain neurons, but under stress the gene for BDNF is repressed.5 These are studies determining structural changes in response to stress, especially in patients with affective disorders. Antidepressants increase BDNF mRNA in the brain, via serotonin (5-HT2A) receptor and β-adrenoceptor subtypes and prevent the stress-induced decreases in BDNF mRNA.6,7
It has been considered that in the neurobiology of CD and depression common points exist. It is suggested that serum BDNF levels can be considered as a biological marker for stress-related psychiatric disorders. The aim of the present study was to investigate serum BDNF levels in CD compared to depression, to determine whether stress-related CD has decreased BDNF serum concentrations, similar to other stress-related disorders.
This study was carried out at Celal Bayar University Hospital, Manisa, Turkey.
Fifteen CD patients diagnosed according to Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I) Clinical Version admitted to the outpatient clinics at the Department of Psychiatry, Celal Bayar University Hospital, were recruited. Exclusion criteria were comorbid psychiatric disorder, current or lifetime neurologic diseases, current medical problems, or alcohol/substance abuse within the 6 months preceding the study. Two control groups were established. The first group consisted of patients with major depressive disorder (n = 24). SCID-I was performed to rule out other axis I disorders. The inclusion criterion for the major depressive disorder (MDD) group was lack of psychopharmacological treatment for at least 1 year. The healthy control group (n = 26) consisted of randomly selected healthy individuals working at Celal Bayar University Hospital with regular health screenings. Inclusion criteria were age between 18 and 65 years, no history of other psychiatric disorder or physical/neurological disease, and no lifetime psychopharmacological treatment.
The mean age of the MDD group was 33.9 ±15.7 years; the mean age of the CD group was 30.4 ±11.9 years; the mean age of the control group was 32.6 ± 5.4 years (P = 0.291). Sixteen of all subjects were male (MDD group, n = 7, 29.2%; CD group, n = 2, 13.3%; control group, n = 7, 26.9%; P = 0.873; Table 1).
Serum BDNF levels were measured using solid-phase sandwich, two-site, enzyme-linked immunoassay (ELISA), using the BDNF Emax Immunassay System reagents (Promega, Madison, WI, USA) according to the manufacturer's instructions. Collection of blood samples was done for CD or MDD patients who were symptomatic.
The severity of depression was evaluated by 17-item Hamilton Depression Rating Scale (HAM-D). It was adapted into Turkish by the authors and was shown to be reliable and valid in Turkish.8 HAM-D was used in the CD group in order to determine absence of depression.
Statistical analysis was done using SPSS 10.0 for Windows (SPSS, Chicago, IL, USA). Kruskal–Wallis test was used for non-parametric analysis of variance.
Mean HAM-D score was 21.0 ± 3.66 in the MDD group and 7.9 ± 2.0 in the CD group. Mean serum BDNF level was 21.2 ± 11.3 ng/mL in the MDD group, 24.3 ± 9.0 ng/mL in the CD group and 31.4 ±8.8 ng/mL in the control group (F = 9.702, d.f. = 2, P = 0.008; Table 1; Fig. 1).
These results suggest that serum BDNF levels were not significantly different in patients with CD and MDD. To our knowledge, this is the first study on serum BDNF levels in CD. Several studies suggest that neurotrophins are regulated in response to stress.5,6 BDNF, one of the most important neurotrophins in the brain, has a known association with the pathophysiology of stress-related psychiatric disorders.
Further studies have shown that BDNF expression is also downregulated by other types of stress.6 However, there is one study that did not find an effect of chronic (21 days) restraint stress on BDNF.9 The reason for this discrepancy is unclear but could be related to the period of time (21 h) after stress at which BDNF was assessed. Alternatively, there could be desensitization to the effects of repeated stress for 21 days and 6 h/day.5
In the neurobiology of CD, stress-related parameters gain importance; thus, studies on BDNF may be one of the biological parameters that can demonstrate stress-related occurrence of CD. The present study demonstrates the importance of BDNF in the pathogenesis of CD, and suggests a new aspect for research.
There were two limitations in the present study. First, the number of patients in the study groups, especially in the CD group, was too small to generalize the results. The second limitation was measuring BDNF in serum because it is an indirect way to demonstrate the gene expression of BDNF. However, because Pan et al. demonstrated the ability of BDNF to cross the blood–brain barrier, BDNF serum concentrations may reflect BDNF brain concentrations.10 Further studies with wider patient groups addressing all variables such as stress, other neurotrophic factors or stress-related psychiatric disorders at the same time should be conducted. The strength of the study is that the CD group without comorbidity of depression was confirmed by significantly lower score with HAM-D.
Serum BDNF levels can not only be used as a biological marker in MDD, but may also be used in other stress-related psychiatric disorders such as CD.
The authors wish to thank Wyeth Turkey for partially supporting this study by financing the laboratory kits.