فعال سازی هایپو فرونتال لوب در آزاد داروی بزرگسالان با افسردگی دوم دو قطبی در دوران بازدارندگی واکنش
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|29752||2015||8 صفحه PDF||سفارش دهید||محاسبه نشده|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Psychiatry Research: Neuroimaging, Volume 231, Issue 3, 30 March 2015, Pages 202–209
In executive function, specifically in response inhibition, numerous studies support the essential role for the inferior frontal cortex (IFC). Hypoactivation of the IFC during response-inhibition tasks has been found consistently in subjects with bipolar disorder during manic and euthymic states. The aim of this study was to examine whether reduced IFC activation also exists in unmedicated subjects with bipolar disorder during the depressed phase of the disorder. Participants comprised 19 medication-free bipolar II (BP II) depressed patients and 20 healthy control subjects who underwent functional magnetic resonance imaging (fMRI) while performing a Go/NoGo response-inhibition task. Whole-brain analyses were conducted to assess activation differences within and between groups. The BP II depressed group, compared with the control group, showed significantly reduced activation in right frontal regions, including the IFC (Brodmann’s area (BA) 47), middle frontal gyrus (BA 10), as well as other frontal and temporal regions. IFC hypoactivation may be a persistent deficit in subjects with bipolar disorder in both acute mood states as well as euthymia, thus representing a trait feature of bipolar disorder.
Executive function refers to the complex series of actions required to plan and execute behaviors in a dynamic environment. Essential to this lies both the capacity to choose actions that are appropriate and advantageous to a given situation, while at the same time being able to suppress inappropriate or undesirable behaviors that interfere with one’s goals. The neuropsychological literature in patients with bipolar I disorder (BP I) demonstrates impairment during the performance of executive control tasks that is pervasive across all mood states (Malhi et al., 2004, Malhi et al., 2007, Martinez-Aran et al., 2004 and Henry et al., 2013). Within the domain of executive function, there is evidence of cognitive dysfunction in subjects with bipolar disorder (BP) specifically during the performance of tasks requiring response inhibition (Martinez-Aran et al., 2004, Swann et al., 2009a, Sole et al., 2011, Xu et al., 2012 and Henry et al., 2013). Impairment in inhibitory control performance has been observed in subjects with bipolar disorder during mania and euthymia, and it has been shown to be a significant predictor of functional outcomes, including disability severity, quality of life and occupational functioning (Swann et al., 2009b and Reinares et al., 2013). In healthy control subjects, functional magnetic resonance imaging (fMRI) studies of response inhibition consistently demonstrate the underlying neurobiology to involve activation of the frontal–striatal circuit (Rubia et al., 2001, Aron et al., 2004 and Simmonds et al., 2008). The prefrontal cortex (PFC), which includes the dorsolateral prefrontal cortex (DLPFC), orbital frontal cortex (OFC) and the inferior frontal cortex (IFC), plays a central role in executive functioning through its influence on subcortical and posterior cortical regions via extensive anatomical connections to these areas (Croxson et al., 2005 and Leh et al., 2007). Recent evidence suggests that successful response inhibition is mediated through striatal dopamine receptors in this frontal–striatal circuit (Ghahremani et al., 2012), and that increased activation of this network is associated with improvement in response-inhibition performance (Congdon et al., 2010). Earlier fMRI studies of bipolar disorder involving response-inhibition tasks have demonstrated frontal lobe hypoactivation during both the manic and euthymic states (Townsend et al., 2012 and Hajek et al., 2013). This suggests that IFC hypoactivation may represent a trait marker of bipolar illness, independent of mood state. However, there are very few imaging studies in depressed subjects with BP and those studies that exist are problematic, as three studies failed to separate BP type I and type II subjects into distinct diagnostic groups (Caligiuri et al., 2003, Caligiuri et al., 2006 and Hummer et al., 2013), and a fourth study included only male subjects (Marchand et al., 2007). The current study sought to explore the neurobiological abnormalities that may exist in participants with bipolar type II (BP II) depression while performing a response-inhibition task. To our knowledge, there are no response-inhibition studies to date that investigate unmedicated adult subjects with bipolar II (BP II) depression. We therefore focused exclusively on a mixed gender adult sample of BP II depressed subjects where results would be unconfounded by medication or heterogeneity of different bipolar subtypes. Based on findings in the literature (Hajek et al., 2013) and earlier research from our group pointing to reduced activation in the Brodmann area (BA) 47 region of the IFC during mania and euthymia (Altshuler et al., 2005 and Townsend et al., 2012), we hypothesized that unmedicated depressed adults with BP II disorder would exhibit the same pattern of frontal lobe hypoactivation as seen in other mood states relative to control subjects.
نتیجه گیری انگلیسی
3.1. Subject characteristics The final analysis included 19 BP II subjects (10 females [52.6%], mean age±SD=36.3±12.2 years) and 20 HC subjects (10 females (50%), mean age±SD=35.6±11.6 years). There were no significant group differences with respect to age (t(37)=0.15, p=0.88) or gender (χ2(2, n=39)=0.27, p=0.87). See Table 1 for complete clinical demographics in the bipolar group. Table 1. Clinical characteristics for the BP II depressed subjects (n=19) a. Mean SD Inventory of Depressive Symptomatology-Clinician rated score 35.9 8.9 Hamilton Depression Rating Scale 21-item score 18.5 3.4 28-item score 25.2 4.8 Young Mania Rating Scale score 2.6 1.9 Age at illness onset (years) 16.7 7.9 Duration of bipolar illness (years) 18.9 10.9 Duration of current depressive episode (weeks) 16.5 23.1 Lifetime number of major depressive episodes 7.3b 5.1 Lifetime number of hypomanic episodes 6.0c 6.2 Number of depressive episodes in past 12 months 2.7 1.5 Number of hypomanic episodes in past 12 months 3.0 3.4 Lifetime number of hospitalizations for depression 0.4 0.8 N % Current comorbidity Posttraumatic stress disorder 2 10.5 Anorexia nervosa 1 5.3 Panic disorder with agoraphobia 1 5.3 Social phobia 1 5.3 Past comorbidity Social phobia 1 5.3 Substance use disorders 4 21.1 a Inventory of Depressive Symptomatology, Hamilton Depression Rating Scale, Young Mania Rating Scale, Number of depressive episodes in past 12 months, and Number of hypomanic episodes in past 12 months were not available for one bipolar II depressed subject. b Lifetime number of major depressive episodes ranged from 2 to 15; an additional 12 subjects had a number of lifetime episodes scored as “too many to count.” c Lifetime number of hypomanic episodes ranged from 1 to 20; an additional 9 subjects had a number of lifetime episodes scored as “too many to count.” Table options 3.2. Task performance Mean accuracy for the Go condition was 97.7±6.2% for the BP II depressed group and 98.4±4.4% for the HC group (p=0.74). For the NoGo condition, mean accuracy was 95.2±4.4% for the BP II depressed group and 96.4±2.8% for the HC group (p=0.75). Go condition reaction times for the BP II depressed subjects were 0.36±0.05 s and 0.40±0.09 s for the HC subjects (U=142, p=0.18). Reaction times for the NoGo condition were 0.44±0.06 s for the BP II depressed group and 0.48±0.06 s for the HC group (U=122, p=0.06). Thus, there were no significant between-group differences in response times or accuracy for either the Go or the NoGo condition. 3.3. Blood-oxygen-level dependent (BOLD) fMRI results 3.3.1. Motion artifacts analyses Analysis of the relative motion (U=161, p=0.43) and absolute motion values (U=136, p=0.13) yielded no significant differences in motion correction between groups. Additionally, the three rotational (roll, pitch, yaw) and three translational (anterior to posterior, superior to inferior, left to right) parameters for each participant were examined to confirm that BP II depressed and HC groups did not differ significantly, which they did not. 3.3.2. Within-group results: Whole-brain analyses Within-group activation maps for BP II depressed and HC subjects during the NoGo minus Go contrast are displayed in Fig. 1. Full-size image (55 K) Fig. 1. Within-group results for healthy comparison subjects (A) and medication-free BP II depressed subjects (B) in the NoGo minus Go contrast. Maps are thresholded at Z>2.3, p<0.05 with correction for multiple comparisons. R=right, L=left. Figure options HC subjects (Fig. 1A) showed substantial bilateral IFG (BA 47), middle frontal gyrus (BA 9/46 and 10), superior frontal gyrus (BA10) and insula activation Z>2.3, p<0.05, corrected. Control subjects also activated other frontal regions including the left middle frontal gyrus (BA 46 and 6), right middle frontal gyrus (BA 9), left precentral gyrus (BA 6), right cingulate gyrus (BA 32) and right claustrum. For a complete list of regions with significant activation in HC, see Table 2. Table 2. Within-group activation results during the NoGo>Go contrast in healthy control (n=20) and bipolar II depressed (n=19) groups. BA Healthy controls Bipolar II depressed x y z Z-statistic x y z Z-statistic Frontal lobe L inferior frontal gyrus 47 −38 22 −8 5.70a −36 26 −6 3.19a R inferior frontal gyrus 47 48 18 −10 7.16 44 28 −2 5.12 L middle frontal gyrus 9/46 −38 46 26 6.06a 46 −32 38 16 3.43 10 −36 56 14 4.19 6 −32 −6 46 4.53a R middle frontal gyrus 9/46 42 46 24 6.87 36 32 30 4.00 10 40 46 20 7.26 30 52 20 3.34a 9 50 6 36 6.80 38 34 36 3.83 L superior frontal gyrus 10 −32 56 24 4.43 R superior frontal gyrus 10 28 60 24 4.73a 26 52 26 4.19a R medial frontal gyrus 8 2 32 42 4.18 L precentral gyrus 6 −52 −2 50 3.83 R cingulate 32 10 20 32 4.65a 4 22 32 4.34b L insula −32 26 −2 6.56 −30 22 4 4.74b R insula 44 18 −4 7.61b 34 18 2 4.96b R claustrum 32 16 2 5.19 28 22 2 5.03 Temporal lobe R middle temporal gyrus 22 56 −32 −2 5.27 21 64 −28 −8 5.05 R superior temporal gyrus 22 54 −46 10 5.22 62 −44 12 2.69a Parietal lobe R supramarginal gyrus 40 62 −46 36 5.26 66 −48 34 3.91 R inferior parietal lobule 40 52 −42 54 6.17b 50 −44 26 4.21b Occipital lobe L middle occipital gyrus 18 −30 −94 8 5.85 R inferior occipital gyrus 37 44 −58 −14 5.44 L fusiform gyrus 19 −32 −56 −14 4.78a R precuneus 19 24 −64 44 3.24a 26 −62 44 3.98 Subcortical regions L putamen −22 4 8 3.36a −24 8 8 3.71 R putamen 24 8 0 3.70a 26 10 8 2.69a R caudate 10 8 4 4.27a 12 8 8 3.04a L thalamus −14 −16 8 4.29 R thalamus 10 −8 8 4.43a 10 −12 4 3.21a (x, y, z) are Montreal Neurological Institute (MNI) coordinates of local maxima significant at Z>2.3 and p<0.05, corrected for multiple comparisons across whole-brain using Gaussian random field theory. BA=Brodmann area; L=left; R=right. a More than one local maxima within 10 mm corresponds to this anatomical label and BA region. b More than one local maxima cluster outside 10 mm corresponds to this anatomical label and BA region. Table options The HC group showed temporal lobe activation that occurred exclusively in the right hemisphere involving regions such as the middle temporal gyrus (BA 22 and 21) and superior temporal gyrus (BA 22). Similarly, parietal lobe activation in the HC group occurred only in the right hemisphere, particularly in BA 40 involving both the supramarginal gyrus and the inferior parietal lobule. Occipital lobe activation involved primary and associative visual regions (BA18 and 19) and the inferior temporal gyrus (BA 37). Control subjects exhibited significant subcortical activation, with bilateral activation in the putamen, the thalamus and the right caudate. Similar to the HC group, there was bilateral inferior frontal gyrus (BA 47) activation during response inhibition in the BP II depressed group. (Fig. 1B displays the within-group activation for the BP II depressed subjects.) Similar to HC subjects, BP II depressed subjects activated right middle frontal gyrus (BA 9/46, 10 and 9), right superior frontal gyrus (BA 10), right cingulate gyrus, right claustrum and bilateral insula. In the temporal and parietal lobes, bipolar II depressed subjects had right hemisphere activity in the superior temporal gyrus (BA 22), supramarginal gyrus and inferior parietal lobule (BA 40). Concerning visual regions, the BP II depressed group activated the right precuneus (BA 19). In subcortical regions, there was activation in the bilateral putamen, right caudate and right thalamus. (See Table 2 for a complete list of coordinates.)