اثر رفتار درمانی بر کودات اسپارتیک اسید N-استراز-L در بزرگسالان مبتلا به اختلال وسواس

Previous studies suggest that baseline differences in neuronal markers between patients with obsessive–compulsive disorder (OCD) and healthy controls no longer exist following successful pharmacotherapy. The current study used proton magnetic resonance spectroscopy (MRS) to investigate differences in absolute concentrations of neurochemicals (i.e., N-acetyl-l-aspartic; NAA) in the head of the caudate nucleus (HOC) and orbital frontal white matter (OFWM) between 15 adults with OCD and a sex- and age-matched control group, as well as the effects of behavior therapy on these chemicals. Behavior therapy was associated with a significant increase in left HOC NAA. When the analyses were restricted to only pairings with complete data (OCD patient, control, post-treatment), the levels of left HOC NAA were significantly lower in patients compared to controls, and increased significantly with treatment. Exploratory analyses suggested that levels of NAA and Cr (creatine) in the right OFWM may be significantly lower in the OCD group than the control group. The results raise the possibility that successful behavioral treatment may be associated with increases in markers of neuronal viability, although other associations found in the literature were not replicated.

Neuroimaging studies in obsessive-compulsive disorder (OCD) have the potential to increase our understanding of how observable symptoms (i.e., obsessions and compulsions) are implemented in neurobiological processes, which could lead to improvements in treatment and matching treatment to patient needs (Rauch, 2000). With respect to neurobiology, brain regions involved in processing threat cues and routine complex motor programming have been implicated in OCD. For instance, the orbitofrontal cortex (OFC) and the caudate nucleus are thought to be involved in the mediation of emotional responses to stimuli associated with biologically based threats, a process that appears to be disrupted in OCD (Saxena et al., 2001). The most consistent differences between patients with OCD and healthy controls identified with functional neuroimaging have been in the more focal orbital gyrus and head of the caudate (HOC) nucleus (Saxena et al., 2001 and Whiteside et al., 2004). In addition, some studies have found that medication and behavioral therapy affect activity in these same areas (Benkelfat et al., 1990, Baxter et al., 1992, Swedo et al., 1992, Schwartz et al., 1996, Nakatani et al., 2003, Nakao et al., 2005 and Nabeyama et al., 2008). Compared with other imaging techniques, magnetic resonance spectroscopy (MRS) is a less invasive methodology for measuring neuronal processes associated with OCD and may be a more sensitive measure of subtle treatment effects on these processes (Cendes et al., 1994). MRS has been used primarily to measure brain tissue concentrations of metabolites such as N-acetyl-l-aspartic (NAA; a marker of neuronal viability), combined glutamate and glutamine (Glx; glutamate is the most abundant excitatory neurotransmitter, with synaptic glutamate rapidly converted into glutamine as part of neuron-astrocyte glutamate–glutamine cycling), choline (cho; a marker of cell membrane turnover), myo-inositol (mI; involved in phospholipid metabolism), and creatine (Cr; a marker of cellular energetics, commonly used as a reference level). Investigations with MRS have yielded promising, but inconsistent results. The involvement of the caudate is supported by research suggesting that compared to healthy controls, adults with OCD have unilaterally decreased NAA [relative to creatine + phosphocreatine in the right ( Ebert et al., 1997) and to water volume in the left ( Bartha et al., 1998)] striatum and bilaterally decreased mI/Cr in the HOC ( Whiteside et al., 2006). Moreover, elevated Glx in the left caudate in pediatric OCD patients has been found to decrease with paroxetine treatment ( Rosenberg et al., 2000). However, baseline differences in these neurochemicals have not been replicated as individual studies have only found differences in NAA, mI/Cr or Glx. In addition, absolute concentrations of Glx in the caudate have not changed with successful behavior therapy (BT; Benazon et al., 2003). To date, no studies have used MRS to examine the orbitofrontal cortex (OFC) or the effect of treatment (medication or BT) on any brain regions in adult patients with OCD. To further complicate the situation, the manner in which neurochemical levels are quantified can affect the results of a study. For instance, differences in thalamic NAA/(creatine/phosphocreatine + choline) and NAA/cho levels, which were originally ascribed to NAA (Fitzgerald et al., 2000), were subsequently attributed to choline after the absolute concentrations were assessed (Rosenberg et al., 2001). Thus, the results of our previous study (Whiteside et al., 2006) that found increased levels of Glx/Cr and NAA/Cr in the right orbital frontal white matter OFWM, and decreased levels of mI/Cr in the HOC bilaterally in patients with OCD compared to controls may reflect differences in Cr rather than the hypothesized Glx, NAA, and mI. More broadly, differences in quantification make it difficult to evaluate the consistency of findings across the literature. As such, the present study had two objectives. First, to address confounds associated with measuring relative neurochemical values, differences in neuronal functioning as measured by MRS in the orbital frontal white matter (OFWM) and HOC between adults with and without OCD (Whiteside et al., 2006), results were reanalyzed using tissue-volume corrected absolute concentrations. Second, for the first time MRS was used to explore the effects of BT for OCD on neurochemical levels in adult patients. Based on the previous literature we predicted that compared to healthy controls, OCD patients would evidence higher Glx and lower NAA in the left HOC (Bartha et al., 1998 and Rosenberg et al., 2000). In addition, we hypothesized that left HOC Glx would decrease and NAA would increase with BT. Secondary analyses examined baseline differences and treatment effects in the remaining neurochemicals in the HOC and OFWM, as well as correlations between neurochemical values and measures of OCD, anxiety, and depressive symptom severity.

Preliminary analyses using t-tests and chi-square tests were conducted to determine if the OCD and control participants differed on the demographic and clinical variables presented in Table 1. Given our matching procedure, the groups did not differ on age, sex or years of education. As expected, the OCD group scored higher than the control group on the OCI, STAI-T, BDI, and in their SUDS in the scanner. Inspection of the YBOCS total scores indicated that pre-test OCD symptoms were in the severe range ( Goodman et al., 1989a). No differences were found on any demographic variables at baseline between the 11 patients who completed BT and provided post-test data and the four patients who did not. However, the treatment drop-outs evidenced significantly less anxiety in the scanner (19.69 vs. 35.61; t (13) = 3.42, p < 0.05, equal variances not assumed) compared to completers, and tended to report more severe depressive symptoms on the BDI (19.25 vs. 10.82; t (13) = 2.08, p = 0.058) relative to the treatment completers. A chi-square test indicated no differences in gender make-up. Among OCD patients, the level of mI in the left OFWM was lower in patients taking medication (M = 14.67, S.D. = 4.0) than that in those not taking medication (M = 23.48, S.D. = 5.5), t (7) = 3.10, p < 0.05. There were no significant differences in the fraction of CSF in each voxel location between the groups.