Roselinde H. Kaiser

Large-Scale Network Dysfunction in Major Depressive Disorder: A Meta-analysis of Resting-State Functional Connectivity

IMPORTANCE Major depressive disorder (MDD) has been linked to imbalanced communication among large-scale brain networks, as reflected by abnormal resting-state functional connectivity (rsFC). However, given variable methods and results across studies, identifying consistent patterns of network dysfunction in MDD has been elusive. OBJECTIVE To investigate network dysfunction in MDD through a meta-analysis of rsFC studies. DATA SOURCES Seed-based voxelwise rsFC studies comparing individuals with MDD with healthy controls (published before June 30, 2014) were retrieved from electronic databases (PubMed, Web of Science, and EMBASE) and authors contacted for additional data. STUDY SELECTION Twenty-seven seed-based voxel-wise rsFC data sets from 25 publications (556 individuals with MDD and 518 healthy controls) were included in the meta-analysis. DATA EXTRACTION AND SYNTHESIS Coordinates of seed regions of interest and between-group effects were extracted. Seeds were categorized into seed-networks by their location within a priori functional networks. Multilevel kernel density analysis of between-group effects identified brain systems in which MDD was associated with hyperconnectivity (increased positive or reduced negative connectivity) or hypoconnectivity (increased negative or reduced positive connectivity) with each seed-network. RESULTS Major depressive disorder was characterized by hypoconnectivity within the frontoparietal network, a set of regions involved in cognitive control of attention and emotion regulation, and hypoconnectivity between frontoparietal systems and parietal regions of the dorsal attention network involved in attending to the external environment. Major depressive disorder was also associated with hyperconnectivity within the default network, a network believed to support internally oriented and self-referential thought, and hyperconnectivity between frontoparietal control systems and regions of the default network. Finally, the MDD groups exhibited hypoconnectivity between neural systems involved in processing emotion or salience and midline cortical regions that may mediate top-down regulation of such functions. CONCLUSIONS AND RELEVANCE Reduced connectivity within frontoparietal control systems and imbalanced connectivity between control systems and networks involved in internal or external attention may reflect depressive biases toward internal thoughts at the cost of engaging with the external world. Meanwhile, altered connectivity between neural systems involved in cognitive control and those that support salience or emotion processing may relate to deficits regulating mood. These findings provide an empirical foundation for a neurocognitive model in which network dysfunction underlies core cognitive and affective abnormalities in depression.

Obsessive-compulsive disorder is associated with broad impairments in executive function: A meta-analysis

Obsessive-compulsive disorder (OCD) is a serious and often chronically disabling condition. The current dominant model of OCD focuses on abnormalities in prefrontal-striatal circuits that support executive function (EF). Although there is growing evidence for EF impairments associated with OCD, results have been inconsistent, which makes the nature and magnitude of these impairments controversial. The current meta-analysis uses random-effects models to synthesize 110 studies in which participants with OCD were compared with healthy control participants on at least one neuropsychological measure of EF. The results indicate that individuals with OCD are impaired on tasks measuring most aspects of EF, consistent with broad impairment in EF. EF deficits were not explained by general motor slowness or depression. Effect sizes were largely stable across variation in demographic and clinical characteristics of samples, although medication use, age, and gender moderated some effects.

Dynamic Resting-State Functional Connectivity in Major Depression

Major depressive disorder (MDD) is characterized by abnormal resting-state functional connectivity (RSFC), especially in medial prefrontal cortical (MPFC) regions of the default network. However, prior research in MDD has not examined dynamic changes in functional connectivity as networks form, interact, and dissolve over time. We compared unmedicated individuals with MDD (n=100) to control participants (n=109) on dynamic RSFC (operationalized as SD in RSFC over a series of sliding windows) of an MPFC seed region during a resting-state functional magnetic resonance imaging scan. Among participants with MDD, we also investigated the relationship between symptom severity and RSFC. Secondary analyses probed the association between dynamic RSFC and rumination. Results showed that individuals with MDD were characterized by decreased dynamic (less variable) RSFC between MPFC and regions of parahippocampal gyrus within the default network, a pattern related to sustained positive connectivity between these regions across sliding windows. In contrast, the MDD group exhibited increased dynamic (more variable) RSFC between MPFC and regions of insula, and higher severity of depression was related to increased dynamic RSFC between MPFC and dorsolateral prefrontal cortex. These patterns of highly variable RSFC were related to greater frequency of strong positive and negative correlations in activity across sliding windows. Secondary analyses indicated that increased dynamic RSFC between MPFC and insula was related to higher levels of recent rumination. These findings provide initial evidence that depression, and ruminative thinking in depression, are related to abnormal patterns of fluctuating communication among brain systems involved in regulating attention and self-referential thinking.

A penny for your thoughts: dimensions of self-generated thought content and relationships with individual differences in emotional wellbeing

A core aspect of human cognition involves overcoming the constraints of the present environment by mentally simulating another time, place, or perspective. Although these self-generated processes confer many benefits, they can come at an important cost, and this cost is greater for some individuals than for others. Here we explore the possibility that the costs and benefits of self-generated thought depend, in part, upon its phenomenological content. To test these hypotheses, we first developed a novel thought sampling paradigm in which a large sample of young adults recalled several recurring thoughts and rated each thought on multiple content variables (i.e., valence, specificity, self-relevance, etc.). Next, we examined multi-level relationships among these content variables and used a hierarchical clustering approach to partition self-generated thought into distinct dimensions. Finally, we investigated whether these content dimensions predicted individual differences in the costs and benefits of the experience, assessed with questionnaires measuring emotional health and wellbeing. Individuals who characterized their thoughts as more negative and more personally significant scored higher on constructs associated with Depression and Trait Negative Affect, whereas those who characterized their thoughts as less specific scored higher on constructs linked to Rumination. In contrast, individuals who characterized their thoughts as more positive, less personally significant, and more specific scored higher on constructs linked to improved wellbeing (Mindfulness). Collectively, these findings suggest that the content of people’s inner thoughts can (1) be productively examined, (2) be distilled into several major dimensions, and (3) account for a large portion of variability in their functional outcomes.

CBCL Clinical Scales Discriminate ADHD Youth With Structured-Interview Derived Diagnosis of Oppositional Defiant Disorder (ODD)

Objective: To evaluate the association between the clinical scales of the child behavior checklist (CBCL) and the comorbid diagnosis of oppositional defiant disorder (ODD) in a large sample of youth with attention deficit hyperactivity disorder (ADHD). Method: The sample consisted of 101 girls and 106 boys ages 6 to17 with ADHD. Conditional probability analysis was used to examine the correspondence between CBCL Clinical Scales with the structured-interview derived diagnosis of ODD. Results: Conditional probability analysis showed that the CBCL Aggression Scale best predicted a structured-interview derived diagnosis of ODD in boys and girls with ADHD. Conclusion: These findings suggest that the CBCL Aggression Scale could serve as a rapid and cost-effective screening instrument to help identify cases likely to meet clinical criteria for ODD in the context of ADHD (J. of Att. Dis. 2008; 12(1) 76-82)

Distracted and down: neural mechanisms of affective interference in subclinical depression

Previous studies have shown that depressed individuals have difficulty directing attention away from negative distractors, a phenomenon known as affective interference. However, findings are mixed regarding the neural mechanisms and network dynamics of affective interference. The present study addressed these issues by comparing neural activation during emotion-word and color-word Stroop tasks in participants with varying levels of (primarily subclinical) depression. Depressive symptoms predicted increased activation to negative distractors in areas of dorsal anterior cingulate cortex (dACC) and posterior cingulate cortex (PCC), regions implicated in cognitive control and internally directed attention, respectively. Increased dACC activity was also observed in the group-average response to incongruent distractors, suggesting that dACC activity during affective interference is related to overtaxed cognitive control. In contrast, regions of PCC were deactivated across the group in response to incongruent distractors, suggesting that PCC activity during affective interference represents task-independent processing. A psychophysiological interaction emerged in which higher depression predicted more positively correlated activity between dACC and PCC during affective interference, i.e. greater connectivity between cognitive control and internal-attention systems. These findings suggest that, when individuals high in depression are confronted by negative material, increased attention to internal thoughts and difficulty shifting resources to the external world interfere with goal-directed behavior.

Dopaminergic Enhancement of Striatal Response to Reward in Major Depression

OBJECTIVE Major depressive disorder is characterized by reduced reward-related striatal activation and dysfunctional reward learning, putatively reflecting decreased dopaminergic signaling. The goal of this study was to test whether a pharmacological challenge designed to facilitate dopaminergic transmission can enhance striatal responses to reward and improve reward learning in depressed individuals. METHOD In a double-blind placebo-controlled design, 46 unmedicated depressed participants and 43 healthy control participants were randomly assigned to receive either placebo or a single low dose (50 mg) of the D2/D3 receptor antagonist amisulpride, which is believed to increase dopamine signaling through presynaptic autoreceptor blockade. To investigate the effects of increased dopaminergic transmission on reward-related striatal function and behavior, a monetary incentive delay task (in conjunction with functional MRI) and a probabilistic reward learning task were administered at absorption peaks of amisulpride. RESULTS Depressed participants selected previously rewarded stimuli less frequently than did control participants, indicating reduced reward learning, but this effect was not modulated by amisulpride. Relative to depressed participants receiving placebo (and control participants receiving amisulpride), depressed participants receiving amisulpride exhibited increased striatal activation and potentiated corticostriatal functional connectivity between the nucleus accumbens and the midcingulate cortex in response to monetary rewards. Stronger corticostriatal connectivity in response to rewards predicted better reward learning among depressed individuals receiving amisulpride as well as among control participants receiving placebo. CONCLUSIONS Acute enhancement of dopaminergic transmission potentiated reward-related striatal activation and corticostriatal functional connectivity in depressed individuals but had no behavioral effects. Taken together, the results suggest that targeted pharmacological treatments may normalize neural correlates of reward processing in depression; despite such acute effects on neural function, behavioral modification may require more chronic exposure. This is consistent with previous reports that antidepressant effects of amisulpride in depression emerged after sustained administration.

Informativeness of maternal reports on the diagnosis of ADHD: an analysis of mother and youth reports.

Objective: We evaluated correlates of the diagnosis of ADHD in youth by informant source. Method: Ninety-four pairs of mother reports and youth self-reports on ADHD were independently assessed, using diagnostic interviews from a large study of youth of both genders with and without ADHD. Comparisons were made on measures of interpersonal, school, and family functioning; treatment history; and parental psychopathology by informant source. Results: With the exception of higher rates of ADHD-associated impairment and higher frequency of treatment for ADHD in the combined youth-mother group. There were no other differences in any other clinical or familial correlates by informant source; both informant groups had higher levels of impairment in multiple nonoverlapping measures of dysfunction than controls. Males were overrepresented among the mother-only group. Conclusion: Maternal reports of ADHD result in a meaningful diagnosis of ADHD with high levels of impairment, regardless of endorsement by the affected youth. (J. of Att. Dis. 2007; 10(4) 410-417)

Opposite effects of anxiety and depressive symptoms on executive function: The case of selecting among competing options

People constantly face the need to choose one option from among many, such as when selecting words to express a thought. Selecting between many options can be difficult for anyone, and can feel overwhelming for individuals with elevated anxiety. The current study demonstrates that anxiety is associated with impaired selection across three different verbal tasks, and tests the specificity of this finding to anxiety. Anxiety and depression frequently co-occur; thus, it might be assumed that they would demonstrate similar associations with selection, although they also have distinct profiles of symptoms, neuroanatomy and neurochemistry. Here, we report for the first time that anxiety and depressive symptoms counter-intuitively have opposite effects on selection among competing options. Specifically, whereas anxiety symptoms are associated with impairments in verbal selection, depressive symptoms are associated with better selection performance. Implications for understanding the mechanisms of anxiety, depression and selection are discussed.

Self-directedness and the susceptibility to distraction by saliency

ABSTRACT People with low Self-directedness (SD) tend to explain their behaviour as being significantly influenced by events in the external environment. One important dimension of external cues is their level of salience: highly salient external stimuli are more likely to capture attention, even when such stimuli are not relevant to goals. We examined whether adults reporting low SD would exhibit greater susceptibility to distraction by highly salient external stimuli. Fifty-four (42 males) subjects completed the Attention Modulation by Salience Task (AMST) measuring reaction times to early- or late-onset auditory stimuli in the presence of high- or low-salience visual distractors. SD was assessed via self-report, and analyses tested the relationship between SD and performance on the AMST. Results showed a slowed early response to auditory cues during high salience compared to low salience. Indeed, individuals reporting low SD showed stronger salience interference, suggesting that external causality attribution is accompanied by a subconscious perceptual deficit.