Reduced frontopolar activation during verbal fluency task associated with poor social functioning in late‐onset major depression: Multi‐channel near‐infrared spectroscopy study

Aim: Functional neuroimaging studies to date have indicated prefrontal dysfunction in late‐onset major depression (LOD). The relationships between prefrontal dysfunction and clinical characteristics including social functioning, however, have been unclear. The objective of the present study was to evaluate prefrontal hemodynamic response related to an executive task in LOD and to assess the relationship between activation in the prefrontal regions and clinical characteristics including social functioning. Methods: Twenty‐four subjects with LOD and 30 age‐ and gender‐matched healthy subjects were recruited for the present study. Hemoglobin concentration changes in the prefrontal and superior temporal cortical surface area were measured during verbal fluency task (VFT) using 52‐channel near‐infrared spectroscopy (NIRS), which enables real‐time monitoring of cerebral blood volume (CBV) in the cortical surface area. Results: The two groups had a distinct spatiotemporal pattern of oxy‐hemoglobin concentration change; LOD patients had less activation in a broad area covering both prefrontal and superior temporal cortices than healthy controls. In addition, reduced activation of the frontopolar region had a significant positive correlation with lower self‐assessment of social functioning scores in the patient group. Conclusion: Reduced frontopolar cortical activation was associated with social functioning impairment in patients with LOD, and NIRS may be an efficient clinical tool for monitoring these characteristics.     

SSRIs对首发抑郁症患者社会功能的改善作用

目的 评价同一临床治疗模式下,SSRIs对首发抑郁症患者社会功能的改善作用.方法 对符合要求的124例首发抑郁症患者,接受患者教育课程后随机给予4种SSRIs抗抑郁药物,分别在治疗前及治疗后第6、12周末采用汉密尔顿抑郁量表(HAMD)进行症状评估、WSAS和SF-12量表进行社会功能评估.结果 共有81例患者完成整个随访研究,其中79例达到有效标准,76例达到临床治愈标准,无效2例.SF-12评分较治疗前PF、RP、SF、RE维度得分显著升高,BP、GH、VT维度得分显著下降,总分、PCS和MCS显著升高,其差异均具有统计学意义(P均＜0.05).WSAS各条目分和总分评分治疗前后差异均有统计学意义(P均＜0.05).结论 在同一临床治疗模式下,临床一线SSRIs治疗首发抑郁症,临床疗效显著,社会功能方面,除SF-12评分中BP、GH、VT三个维度外,总的来说随着治疗时间的延长逐渐改善,有利于患者适应社会.     

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

ObjectiveStudies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. MethodsWe included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. ResultsThe high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. ConclusionOur findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.     

Prefrontal and striatal activation during sequence learning in geriatric depression.

BACKGROUND: Frontostriatal dysfunction is a primary hypothesis for the neurocognitive changes of depression in late life. The aim of the present study was to test this hypothesis with the use of functional magnetic resonance imaging (fMRI) tasks that are known to engage the prefrontal and neostriatal cognitive circuits. METHODS: Twenty-three elderly subjects (mean age, 69.9 years) participated: 11 subjects with a current major depressive episode and 12 nondepressed elderly control subjects. Subjects underwent fMRI while performing a concurrent implicit and explicit sequence learning task. Region of interest (ROI)-based analyses were conducted, focusing on the dorsal anterior cingulate cortex, the dorsolateral prefrontal cortex, and the neostriatum. RESULTS: As expected, both the control and depressed subjects learned the sequence during both implicit and explicit conditions. During explicit learning, decreased prefrontal activation was found in the depressed subjects, along with increased striatal activation. The increased striatal activity in the depressed subjects was due to increased activity on the trials that violated the sequence. During implicit learning, no significant differences were found between the groups in the identified ROIs. CONCLUSIONS: The increased striatal activation on trials that violated the sequence demonstrates a greater response to negative feedback for depressed compared with control subjects. Our observations of significant differences in both prefrontal and striatal regions in the depressed elderly subjects relative to elderly control subjects supports the frontostriatal dysfunction hypothesis of late-life depression.     

Hemodynamic differences in the activation of the prefrontal cortex: attention vs. higher cognitive processing

Both simple attention tasks (e.g. letter cancellation) and most tasks of higher cognitive processing (e.g. word generation) are known to activate the dorsolateral prefrontal cortex (PFC). While attention and higher cognitive processing differ phenomenologically, with attention tasks requiring great subjective effort despite their simplicity, possible physiological differences in the activation of the PFC between the two types of cognitive processing have remained uninvestigated. Hemodynamic changes in the PFC during activation due to tasks of attention and those of higher cognitive processing were examined using near-infrared spectroscopy in 10 Japanese and 10 American healthy adults. In tasks of higher cognitive processing, which included both verbal and non-verbal tasks, the concentration of oxygenated hemoglobin ([HbO2]) increased, and that of deoxygenated hemoglobin ([HbR]) decreased, with an increase in the tissue hemoglobin saturation (THS). In tasks of attention, which consisted of the letter cancellation and continuous performance test, both [HbO2] and [HbR] increased, with no significant changes in the THS observed. The distinctive patterns of hemodynamic changes were not affected by the factors of task difficulty or language. The change in [HbR] may be a physiological marker of the prefrontal lobe activation that discriminates between attention and higher cognitive processing. The increase in [HbR] suggests increased oxygen consumption of the PFC during tasks of attention, which might be related to the disproportionately great subjective effort associated with sustained attention. The physiological alteration in hemodynamic patterns according to changes in cognition needs to be examined in subjects with prefrontal lobe dysfunction, such as schizophrenia and mood disorder.     

Abnormal Prefrontal Brain Activation During a Verbal Fluency Task in Treatment-Resistant Depression Using Near-Infrared Spectroscopy

ObjectiveThe study investigated cognitive performance and brain function between treatment-resistant depression (TRD) and non-TRD patients to find potential neurobiological markers associated with refractoriness in depression patients. MethodsFourteen TRD patients, 26 non-TRD patients and 23 healthy controls (HC) were included in the present study. The neural function of prefrontal cortex (PFC) and cognitive performance among the three group were examined using near-infrared spectroscopy (NIRS) during verbal fluency task (VFT). ResultsBoth TRD and non-TRD groups exhibited significantly worse VFT performance and lower activation of oxygenated hemoglobin (oxy-Hb) changes in the bilateral dorsolateral PFC (DLPFC) compared to the HC group. Within the TRD and non-TRD groups, VFT performance was no significant difference, but activation of oxy-Hb changes in dorsomedial PFC (DMPFC) in TRD patients was significantly lower than non-TRD patients. In addition, activation of oxy-Hb changes in right DLPFC were negatively correlated with the severity of depressive symptoms in depression patients. ConclusionBoth TRD patients and non-TRD patients exhibited lower oxy-Hb activation in DLPFC. TRD patients exhibit lower oxy-Hb activation in DMPFC than non-TRD patients. fNIRS maybe a useful tool for predict depressive patients with or without treatment resistant.     

Long-term social functioning after depression treated by psychiatrists: a review

OBJECTIVES: Numerous long-term studies of depression in psychiatric settings have shown a poor clinical outcome but little emphasis has been placed on psychosocial or functional outcome in studies to date. This article reviews published data on long-term social functioning after depression and considers why psychosocial recovery appears delayed compared with clinical recovery. METHODS: Searches were carried out of the databases MEDLINE, PSYCHLIT and EMBASE for articles published from 1980 using keywords relating to social and functional outcomes of unipolar and bipolar depression. Review articles and relevant textbooks were also searched. RESULTS: The few outcome studies published have described long-term functional impairment in the majority of patients but have been limited by methodological shortcomings. Psychosocial impairment tends to persist even after clinical remission from depression. Residual symptomatology after remission from depression may lead to enduring psychosocial impairment, as may subtle neurocognitive deficits. Axis I and II comorbidities predict a poor psychosocial outcome, but episodes of depression do not appear to lead to personality 'scarring'. CONCLUSIONS: Future outcome studies need to focus on longitudinal social functioning. Full functional recovery after an episode of depression should be the goal of treatment as enduring residual symptoms lead to long-term psychosocial impairment.     

Multichannel near-infrared spectroscopy in depression and schizophrenia: cognitive brain activation study.

BACKGROUND: Recent developments in near-infrared spectroscopy (NIRS) have enabled the noninvasive clarification of brain functions in psychiatric disorders with measurement of hemoglobin concentrations as cerebral blood volume. METHODS: Ten patients with depression, 13 patients with schizophrenia, and 16 age- and gender-matched healthy control subjects participated in the study after giving consent. The relative concentrations of oxyhemoglobin [oxyHb] were measured with frontal and temporal probes every.1 sec during word fluency and unilateral finger tapping tasks, with two 24-channel NIRS machines. RESULTS: The [oxyHb] increase patterns during the word fluency task varied among the three groups, although their task performances were similar: the depression group was characterized by a smaller [oxyHb] increase during the first half of the task period and the schizophrenic group by a small trough of [oxyHb] at the start of the task period and [oxyHb] re-increase in the posttask period. [OxyHb] increases during the finger-tapping task were rather larger in the patient groups than in the control group. CONCLUSIONS: The characteristic time courses of [oxyHb] changes in the frontal lobe were elucidated for depression and schizophrenia. Near-infrared spectroscopy, with its noninvasiveness and high time resolution, can be a useful tool for research and clinical purposes in psychiatry.     

Brain activation predicts treatment improvement in patients with major depressive disorder

Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.     

Functional near-infrared spectroscopy reveals altered hemispheric laterality in relation to schizotypy during verbal fluency task

Previous functional neuroimaging studies have demonstrated that patients with schizophrenia and those with schizotypal personality disorder (SPD) show reduced laterality, or relative right hemispheric dominance, during the performance of cognitive activation tasks; however, neuroimaging studies looking at non-clinical schizotypy have been few. We have recently reported that schizotypal traits at a non-clinical level are associated with right prefrontal dominance during a letter version of the verbal fluency task (VFT), but it is unknown whether such relationship between schizotypy and functional laterality would be observed across various cognitive tasks. Here we examined the relationships of schizotypal traits as measured by the Schizotypal Personality Questionnaire (SPQ) in healthy adults with hemispheric lateralization of prefrontal activation during letter and category VFTs, using near-infrared spectroscopy. Thirty-two participants were divided into high- (n = 16) and low- (n = 16) SPQ groups by the median split of the total SPQ score. The high-SPQ group, but not low-SPQ group, showed significantly right-greater-than-left asymmetry of prefrontal activation during letter VFT, whereas such pronounced hemispheric asymmetry in relation to schizotypy was not found during category VFT. These results indicate that non-clinical schizotypy is related to right prefrontal preference during the letter version of VFT in particular, suggesting that the association between schizotypal traits and functional laterality may vary depending on cognitive activation tasks.     

影响抑郁性神经症患者社会功能的相关因素分析

目的：探讨影响抑郁性神经症社会功能的相关因素。方法：采用精神症状自评量表（ＳＣＬ－９０）、社会功能缺陷筛选量表（ＳＤＳＳ）、社会支持量表（ＳＳＲＳ）对来我院门诊就诊的抑郁性神经症病人３０例逐一测评。结果：多元回归分析显示,焦虑、客观支持与社会功能障碍呈正相关,主观支持与社会功能障碍呈负相关,结论：影响抑郁性神经症社会功能障碍的主要因素为焦虑、客观支持及主观支持。     

Social Adaptation Self-evaluation Scale (SASS): Psychometric analysis as outcome measure in the treatment of patients with major depression in the remission phase

INTRODUCTION: To carry out a psychometric analysis of the Social Adaptation Self-evaluation Scale (SASS), which has been found very promising during first experiences with it in the treatment of depression. METHOD: Patients in the remission phase during treatment for a major depressive episode completed the SASS over a period of 12 weeks, with monthly assessments. For comparison, the Hamilton Depression Scale with the Melancholia Scale (HAM-D/MES) was used as well as a self-reporting questionnaire, the Major Depression Inventory (MDI). In the psychometric analysis both classical tests (e.g. principal component analysis) and modern tests (Mokken analysis with the Loevinger coefficient of homogeneity) were applied. RESULTS: The SASS scale with its 21 items was found to contain at least three factors, of which the first was a general factor; this however explained less than 50% of the variance. A subscale containing the six items with the highest factor loadings was found to be a unidimensional scale. This subscale showed a much higher responsiveness than the total SASS. However, both SASS scales were found to have a lower responsiveness than the Major Depression Inventory (MDI) during the first weeks of treatment. CONCLUSION: The SASS was found to be a multidimensional scale. However, a six-items subscale (covering items with the highest loadings on the first use) was shown to be a unidimensional scale and to have a greater responsiveness than the total SASS, but still lower than the MDI. (Int J Psych Clin Pract 2002; 6: 141-146)     

The Multifaceted Role of the Ventromedial Prefrontal Cortex in Emotion,Decision Making,Social Cognition,and Psychopathology

The ventromedial prefrontal cortex (vmPFC) has been implicated in a variety of social, cognitive, and affective functions that are commonly disrupted in mental illness. In this review, we summarize data from a diverse array of human and animal studies demonstrating that the vmPFC is a key node of cortical and subcortical networks that subserve at least three broad domains of psychological function linked to psychopathology. One track of research indicates that the vmPFC is critical for the representation of reward- and value-based decision making, through interactions with the ventral striatum and amygdala. A second track of research demonstrates that the vmPFC is critical for the generation and regulation of negative emotion, through its interactions with the amygdala, bed nucleus of the stria terminalis, periaqueductal gray, hippocampus, and dorsal anterior cingulate cortex. A third track of research shows the importance of the vmPFC in multiple aspects of social cognition, such as facial emotion recognition, theory-of-mind ability, and processing self-relevant information, through its interactions with the posterior cingulate cortex, precuneus, dorsomedial PFC, and amygdala. We then present meta-analytic data revealing distinct subregions within the vmPFC that correspond to each of these three functions, as well as the associations between these subregions and specific psychiatric disorders (depression, posttraumatic stress disorder, addiction, social anxiety disorder, bipolar disorder, schizophrenia, and attention-deficit/hyperactivity disorder). We conclude by describing several translational possibilities for clinical studies of vmPFC-based circuits, including neuropsychological assessment of transdiagnostic functions, anatomical targets for intervention, predictors of treatment response, markers of treatment efficacy, and subtyping within disorders.     

抑郁症患者前额叶、海马磁共振质子波谱成像的研究

目的探讨抑郁症患者前额叶、海马的磁共振质子波谱(1H-MRS)变化特点。方法应用1H-MRS成像技术检测26例抑郁症患者(抑郁症组)和20名健康对照者(对照组)的前额叶、海马N-乙酰天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)3种代谢物,计算NAA/Cr和Cho/Cr比值。以抑郁症组年龄的中位数(38.5岁)为界将抑郁症组和对照组分为低年龄组[(28±7)岁,14例;(22±6)岁,9名]与高年龄组[(54±9)岁,12例;(53±7)岁,11名]。按病程分为首次发病组(19例,以下简称首发组)和复发组(7例)。采用方差分析进行统计比较。结果高年龄组患者左侧前额叶Cho/Cr(1.60±0.45)×10-6高于对照组(1.28±0.20)×10-6,差异有统计学意义(P<0.05);低年龄组患者右侧前额叶Cho/Cr(1.74±0.51)×10-6高于对照组(1.22±0.40)×10-6,差异有统计学意义(P<0.01)。高年龄组患者左侧海马NAA/Cr(1.16±0.31)×10-6低于对照组(2.21±0.83)×10-6,差异有统计学意义(P<0.01);低年龄组患者左侧海马Cho/Cr(1.54±0.44)×10-6高于对照组(1.08±0.35)×10-6,差异有统计学意义(P<0.05)。首发组患者左侧前额叶Cho/Cr(1.57±0.42)×10-6高于对照组(1.26±0.21)×10-6,复发组患者右侧前额叶Cho/Cr(1.77±0.50)×10-6高于对照组(1.29±0.32)×10-6,差异均有统计学意义(P均<0.01)。首发组患者左侧海马NAA/Cr(1.19±0.26)×10-6及复发组患者左侧海马NAA/Cr(1.10±0.29)×10-6均低于对照组(1.87±0.81)×10-6,复发组患者右侧海马Cho/Cr(2.13±0.51)×10-6高于对照组(1.51±0.52)×10-6,差异均有统计学意义(P均<0.01)。结论抑郁症患者可能存在前额叶、左侧海马细胞膜代谢异常,高年龄抑郁症患者的左侧海马神经元活力下降。     

Using social epidemiology and neuroscience to explore the relationship between job stress and frontotemporal cortex activity among workers

Mental health problems, such as depression, are increasingly common among workers. Job-related stresses, including psychological demands and a lack of discretion in controlling one’s own work environment, are important causal factors. However, the mechanisms through which job-related stress may affect brain function remain unknown. We sought to identify the relationship between job-related stress and frontotemporal cortex activation using near-infrared spectroscopy. Seventy-nine (45 females, 34 males) Japanese employees, aged 26–51 years, were recruited from respondents to the Japanese Study of Stratification, Health, Income, and Neighborhood survey. Job-related stress was measured using the Japanese version of Job Content Questionnaire, which can index “job demand” and “job control”. We found a significant correlation between higher “job demand” and smaller oxygenated hemoglobin [oxy-Hb] changes in the left dorsolateral prefrontal cortex in female (r = ?.54 to ?.44). Significant correlations between higher “job control” and greater [oxy-Hb] changes in the right temporal cortex were observed among male, and in the combined sample (r = .46–.64). This initial cross-sectional observation suggests that elevated job-related stress is related to decrease frontotemporal cortex activation among workers. Integrating social epidemiology and neuroscience may be a powerful strategy for understanding how individuals’ brain functions may mediate between the job-related stress or psychosocial work characteristics and public mental health.     

Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression

Early emotional stress is associated with a life-long burden of risk for later depression and stressful life events contribute to the development of depressive episodes. In this study we investigated whether childhood stress is associated with structural brain alterations in patients with major depression (MD). Forty-three patients with MD and 44 age as well as gender matched healthy control subjects were investigated using high-resolution magnetic resonance imaging (MRI). Region of interest analysis of the hippocampus, whole brain voxel-based morphometry (VBM) and assessment of childhood stress was carried out. Significantly smaller hippocampal white matter and prefrontal gray matter volume was observed in patients with MD compared to healthy controls. In particular left hippocampal white matter was smaller in patients, who had emotional childhood neglect, compared to those without neglect. For male patients this effect was seen in the left and right hippocampus. Moreover, physical neglect during childhood affected prefrontal gray matter volume in healthy subjects. Both emotional neglect and brain structural abnormalities predicted cumulative illness duration and there was a significant interaction between emotional neglect and prefrontal volumes as well as hippocampal white matter on the illness course. Childhood neglect resulted in hippocampal white matter changes in patients with major depression, pronounced at the left side and in males. Most interestingly, childhood stress and brain structure volumes independently predicted cumulative illness course. Subjects with both, structural brain changes and childhood emotional neglect seem to be at a very high risk to develop a more severe illness course.     

Anomalous functional brain activation following negative mood induction in children with pre-school onset major depression

While major depressive disorder has been shown to be a significant mental health issue for school-age children, recent research indicates that depression can be observed in children as early as the preschool period. Yet, little work has been done to explore the neurobiological factors associated with this early form of depression. Given research suggesting a relation between adult depression and anomalies in emotion-related neural circuitry, the goal of the current study was to elucidate changes in functional activation during negative mood induction and emotion regulation in school-age children with a history of preschool-onset depression. The results suggest that a history of depression during the preschool period is associated with decreased activity in prefrontal cortex during mood induction and regulation. Moreover, the severity of current depressed mood was associated with increased activity in limbic regions, such as the amygdala, particularly in children with a history of depression. Similar to results observed in adult depression, the current findings indicate disruptions in emotion-related neural circuitry associated with preschool-onset depression.     

Altered prefrontal cortical function during processing of fear-relevant stimuli in pregnancy

In non-pregnant individuals, the prefrontal cortex (PFC) is involved in the regulation of emotion, and appears to play a role in anxiety. Near-infrared spectroscopy (NIRS) detects cortical neural activation without harmful radiation making it safe for use in pregnancy. The aims of this study were to assess neural circuitry involved in processing fear-relevant stimuli during pregnancy using NIRS, and to determine associations between activation of this circuitry, distress and anxiety symptoms, attention to threat, cortisol, estrogen, progesterone and testosterone levels. There was significant activation of the PFC in response to fearful faces compared to rest in both pregnant and control groups. Within pregnancy, the activation was most pronounced at trimester 2, compared to the other trimesters. In pregnant women only (all trimesters), PFC activation was significantly associated with increased distress and anxiety, but with decreased selective attention to masked fear. PFC activation was also significantly associated with increased levels of cortisol and testosterone in pregnancy. PFC function appears to be altered during processing of fear-relevant stimuli in pregnancy. Changes in hormone levels may lead to changes in PFC function, and in turn to changes in cognitive-affective processing and anxiety. Further work is needed, however, to explore precisely how PFC function is altered in pregnancy; it is possible that certain changes reflect altered processing of threat stimuli, while others reflect attempts to compensate for distressing and anxious symptoms that emerge during pregnancy.     

Attenuated prefrontal activation during a verbal fluency task in remitted major depression

The aim of the present study was to investigate whether a functional abnormality in the left prefrontal cortex observed in patients with major depression performing a verbal fluency task is present after remission of depression. Functional magnetic resonance imaging was used to study changes in cerebral blood oxygenation in eight remitted patients with major depression and 10 healthy control subjects during a verbal fluency task. Compared to the control subjects, the patients had a reduced response in the left prefrontal cortex (middle frontal gyrus, Brodmann area 10). These findings suggest the presence of dysfunction in the left prefrontal cortex during remission in major depression.