Health-related quality of life among adolescents and young adults with mood and anxiety concerns.

OBJECTIVES: To characterize health related quality of life (HRQOL) for Canadians aged 16 to 25 (adolescents and young adults, AYAs) seeking care for mood and anxiety concerns at the First Episode Mood and Anxiety Program, in London, Ontario and to identify factors associated with HRQOL in this population. METHODS: AYAs completed demographic, psychometric, and HRQOL questionnaires. We calculated 36-Item Short-Form Health Survey (SF-36) scores standardized to Canadian and US population norms. We computed Short Form 6 Dimension (SF-6D) utilities conducting multivariable linear regression analysis, adjusting for age, sex, ethnoracial minority status, parental marital/cohabitation status, parental education, the Anxiety Sensitivity Index (ASI-R), Montgomery-Åsberg Depression Rating Scale Self-Report (MADRS-S), Sheehan Disability Scale (SDS), and a modified Inventory of College Students' Recent Life Experiences (ICSRLE-M). RESULTS: Amongst 182 AYAs who completed questionnaires, mean physical component summary (PCS), mental component summary (MCS) and SF-6D utility scores were low, 43.8 (SD = 16.6), 19.0 (SD = 11.9) and .576 (SD = .074), respectively. Maternal post-secondary education, depression (MADRS-S) and functional impairment (SDS) were significantly associated with SF-6D utility. CONCLUSION: This cohort of mental healthcare-seeking AYAs had significantly impaired psychometric and utility-based measures of quality of life, underscoring the importance of timely access to healthcare services for this population.

Drugs, Guts, Brains, but Not Rock and Roll: The Need to Consider the Role of Gut Microbiota in Contemporary Mental Health and Wellness of Emerging Adults.

Emerging adulthood (ages 18-25) is a critical period for neurobiological development and the maturation of the hypothalamic-pituitary-adrenal axis. Recent findings also suggest that a natural perturbation of the gut microbiota (GM), combined with other factors, may create a unique vulnerability during this period of life. The GM of emerging adults is thought to be simpler, less diverse, and more unstable than either younger or older people. We postulate that this plasticity in the GM suggests a role in the rising mental health issues seen in westernized societies today via the gut-brain-microbiota axis. Studies have paid particular attention to the diversity of the microbiota, the specific function and abundance of bacteria, and the production of metabolites. In this narrative review, we focus specifically on diet, physical activity/exercise, substance use, and sleep in the context of the emerging adult. We propose that this is a crucial period for establishing a stable and more resilient microbiome for optimal health into adulthood. Recommendations will be made about future research into possible behavioral adjustments that may be beneficial to endorse during this critical period to reduce the probability of a "dysbiotic" GM and the emergence and severity of mental health concerns.

Emotion regulation in emerging adults with major depressive disorder and frequent cannabis use.

In people with mental health issues, approximately 20% have co-occurring substance use, often involving cannabis. Although emotion regulation can be affected both by major depressive disorder (MDD) and by cannabis use, the relationship among all three factors is unknown. In this study, we used fMRI to evaluate the effect that cannabis use and MDD have on brain activation during an emotion regulation task. Differences were assessed in 74 emerging adults aged 16-23 with and without MDD who either used or did not use cannabis. Severity of depressive symptoms, emotion regulation style, and age of cannabis use onset were also measured. Both MDD and cannabis use interacted with the emotion regulation task in the left temporal lobe, however the location of the interaction differed for each factor. Specifically, MDD showed an interaction with emotion regulation in the middle temporal gyrus, whereas cannabis use showed an interaction in the superior temporal gyrus. Emotion regulation style predicted activity in the right superior frontal gyrus, however, this did not interact with MDD or cannabis use. Severity of depressive symptoms interacted with the emotion regulation task in the left middle temporal gyrus. The results highlight the influence of cannabis use and MDD on emotion regulation processing, suggesting that both may have a broader impact on the brain than previously thought.

NeuroMark: An automated and adaptive ICA based pipeline to identify reproducible fMRI markers of brain disorders.

Many mental illnesses share overlapping or similar clinical symptoms, confounding the diagnosis. It is important to systematically characterize the degree to which unique and similar changing patterns are reflective of brain disorders. Increasing sharing initiatives on neuroimaging data have provided unprecedented opportunities to study brain disorders. However, it is still an open question on replicating and translating findings across studies. Standardized approaches for capturing reproducible and comparable imaging markers are greatly needed. Here, we propose a pipeline based on the priori-driven independent component analysis, NeuroMark, which is capable of estimating brain functional network measures from functional magnetic resonance imaging (fMRI) data that can be used to link brain network abnormalities among different datasets, studies, and disorders. NeuroMark automatically estimates features adaptable to each individual subject and comparable across datasets/studies/disorders by taking advantage of the reliable brain network templates extracted from 1828 healthy controls as guidance. Four studies including 2442 subjects were conducted spanning six brain disorders (schizophrenia, autism spectrum disorder, mild cognitive impairment, Alzheimer's disease, bipolar disorder, and major depressive disorder) to evaluate validity of the proposed pipeline from different perspectives (replication of brain abnormalities, cross-study comparison, identification of subtle brain changes, and multi-disorder classification using identified biomarkers). Our results highlight that NeuroMark effectively identified replicated brain network abnormalities of schizophrenia across different datasets; revealed interesting neural clues on the overlap and specificity between autism and schizophrenia; demonstrated brain functional impairments present to varying degrees in mild cognitive impairments and Alzheimer's disease; and captured biomarkers that achieved good performance in classifying bipolar disorder and major depressive disorder.

Access and Health System Impact of an Early Intervention Treatment Program for Emerging Adults with Mood and Anxiety Disorders.

OBJECTIVES: Early intervention programs are effective for improving outcomes in first-episode psychosis; however, less is known about their effectiveness for mood and anxiety disorders. We sought to evaluate the impact of an early intervention program for emerging adults with mood and anxiety disorders in the larger health system context, relative to standard care. METHODS: Using health administrative data, we constructed a retrospective cohort of cases of mood and anxiety disorders among emerging adults aged 16 to 25 years in the catchment of the First Episode Mood and Anxiety Program (FEMAP) in London, Ontario, between 2009 and 2014. This cohort was linked to primary data from FEMAP to identify service users. We used proportional hazards models to compare indicators of service use between FEMAP users and a propensity score-matched group of nonusers receiving care elsewhere in the health system. RESULTS: FEMAP users (n = 490) had more rapid access to a psychiatrist relative to nonusers (hazard ratio [HR], 2.82; 95% confidence interval, 2.45 to 3.26; median time, 16 vs. 71 days). In the year following admission, FEMAP users also had lower rates of emergency department use for mental health reasons (HR, 0.73; 95% CI, 0.53 to 0.99). We did not observe differences in psychiatric hospitalization rates. CONCLUSIONS: An early intervention model of care for mood and anxiety disorders is associated with better access to psychiatric care and lower use of the emergency department. Our findings suggest that early intervention services for mood and anxiety disorders may be beneficial from a health systems perspective, and further research on the effectiveness of this model of care is warranted.

Temporoparietal Junction Functional Connectivity in Early Schizophrenia and Major Depressive Disorder.

BACKGROUND: The temporoparietal junction (TPJ) has been linked to lower-level attentional and higher-level social processing, both of which are affected in schizophrenia (SZ) and major depressive disorder (MDD). We examined resting functional connectivity of bilateral anterior and posterior TPJ in SZ and MDD to evaluate potential anomalies in each disorder and differences between disorders. METHODS: Resting-state functional magnetic resonance imaging data were acquired from 24 patients with SZ, 24 patients with MDD, and 24 age-matched healthy controls. We performed seed-based functional connectivity analyses with seed regions in bilateral anterior and posterior TPJ, covarying for gender and smoking. RESULTS: SZ had reduced connectivity versus controls between left anterior TPJ and dorsolateral prefrontal cortex (dlPFC) and posterior cingulate cortex (PCC); between left posterior TPJ and middle cingulate cortex, left dorsal PFC, and right lateral PFC; between right anterior TPJ and bilateral PCC; and between right posterior TPJ and middle cingulate cortex, left posterior insula, and right insula. MDD had reduced connectivity versus controls between left posterior TPJ and right dlPFC and between right posterior TPJ and PCC and dlPFC. SZ had reduced connectivity versus MDD between right posterior TPJ and left fusiform gyrus and right superior-posterior temporal cortex. CONCLUSION: Functional connectivity to the TPJ was demonstrated to be disrupted in both SZ and MDD. However, TPJ connectivity may differ in these disorders with reduced connectivity in SZ versus MDD between TPJ and posterior brain regions.

Higher order thalamic nuclei resting network connectivity in early schizophrenia and major depressive disorder.

The pulvinar and the mediodorsal (MDN) nuclei of the thalamus are higher order nuclei which have been implicated in directed effort and corollary discharge systems. We used seed-based resting fMRI to examine functional connectivity to bilateral pulvinar and MDN in 24 schizophrenic patients (SZ), 24 major depressive disorder patients (MDD), and 24 age-matched healthy controls. SZ had less connectivity than controls between the left pulvinar and precuneus, left ventral-lateral prefrontal cortex (vlPFC), and superior and medial-frontal regions, between the right pulvinar and right frontal pole, and greater connectivity between the right MDN and left dorsolateral prefrontal cortex (dlPFC). SZ had less connectivity than MDD between the left pulvinar and ventral anterior cingulate (vACC), left vlPFC, anterior insula, posterior cingulate cortex (PCC), and right hippocampus, between the right pulvinar and right PCC, and between the right MDN and right dorsal anterior cingulate (dACC). This is the first study to measure the functional connectivity to the higher order nuclei of the thalamus in both SZ and MDD. We observed less connectivity in SZ than MDD between pulvinar and emotional encoding regions, a directed effort region, and a region involved in representation and salience, and between MDN and a directed effort region.

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T.

BACKGROUND: Examining neurometabolic abnormalities in critical brain areas in schizophrenia and major depressive disorder (MDD) may help guide future pharmacological interventions including glutamate-modulating treatments. AIMS: To measure metabolite concentrations within the anterior cingulate cortex (ACC) and thalamus of people with schizophrenia and people with MDD. METHODS: Spectra were acquired from 16 volunteers with schizophrenia, 17 with MDD and 18 healthy controls using magnetic resonance spectroscopy on a 7 Tesla scanner. RESULTS: In the thalamus, there were lower glycine concentrations in the schizophrenia group relative to control (P=0.017) and MDD groups (P=0.012), and higher glutamine concentrations relative to healthy controls (P=0.009). In the thalamus and the ACC, the MDD group had lower myo-inositol concentrations than the control (P=0.014, P=0.009, respectively) and schizophrenia (P=0.004, P=0.002, respectively) groups. CONCLUSION: These results support the glutamatergic theory of schizophrenia and indicate a potential glycine deficiency in the thalamus. In addition, reduced myo-inositol concentrations in MDD suggest its involvement in the disorder. DECLARATION OF INTEREST: None. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Medial Prefrontal and Anterior Insular Connectivity in Early Schizophrenia and Major Depressive Disorder: A Resting Functional MRI Evaluation of Large-Scale Brain Network Models.

Anomalies in the medial prefrontal cortex, anterior insulae, and large-scale brain networks associated with them have been proposed to underlie the pathophysiology of schizophrenia and major depressive disorder (MDD). In this study, we examined the connectivity of the medial prefrontal cortices and anterior insulae in 24 healthy controls, 24 patients with schizophrenia, and 24 patients with MDD early in illness with seed-based resting state functional magnetic resonance imaging analysis using Statistical Probability Mapping. As hypothesized, reduced connectivity was found between the medial prefrontal cortex and the dorsal anterior cingulate cortex and other nodes associated with directed effort in patients with schizophrenia compared to controls while patients with MDD had reduced connectivity between the medial prefrontal cortex and ventral prefrontal emotional encoding regions compared to controls. Reduced connectivity was found between the anterior insulae and the medial prefrontal cortex in schizophrenia compared to controls, but contrary to some models emotion processing regions failed to demonstrate increased connectivity with the medial prefrontal cortex in MDD compared to controls. Although, not statistically significant after correction for multiple comparisons, patients with schizophrenia tended to demonstrate decreased connectivity between basal ganglia-thalamocortical regions and the medial prefrontal cortex compared to patients with MDD, which might be expected as these regions effect action. Results were interpreted to support anomalies in nodes associated with directed effort in schizophrenia and nodes associated with emotional encoding network in MDD compared to healthy controls.

Early Intervention in Mood and Anxiety Disorders: The First Episode Mood and Anxiety Program (FEMAP).

The First Episode Mood and Anxiety Program (FEMAP) was developed for youth with mood and/or anxiety concerns in London, Ontario, to provide early intervention for these disorders, similar to the first-episode psychosis programs across Ontario and Canada. The logic and causal models of the pathway to and through FEMAP are described and inclusion/exclusion criteria are delineated. Results of the process evaluation of the model and preliminary data from a treatment-effectiveness evaluation and ongoing cost-comparison evaluation are provided. Several characteristic quotes from youth utilizing the service are included, as is an overview of utilization statistics. Challenges and lessons learned are conveyed.

Process Evaluation of an Early-Intervention Program for Mood and Anxiety Disorders Among Older Adolescents and Young Adults.

OBJECTIVE: Research to determine the best approach for providing early intervention for mood and anxiety disorders is imperative. The authors describe a process evaluation of an early-intervention program for transition-age youths with mood or anxiety disorders. METHODS: Causal and logic models for pathways to care for the program, as well as descriptive data from 548 participating youths, are presented. Follow-up measures of functional improvement are reported. RESULTS: Diagnostic characterization, symptom severity, and functional impairment of participants indicated that the model selected an appropriate catchment population without creating excessive overinclusion. Self-referred youths reported greater anxiety and substance use. Acceptance by the program was predictive of greater follow-through with treatment. Several variables, including frequent lifetime marijuana use, predicted loss to follow-up. At follow-up, youths were significantly functionally improved. CONCLUSIONS: This process evaluation indicated that the model provided appropriate early intervention for youths with mood or anxiety disorders without causing excessive overinclusion.

Discriminating Bipolar Disorder From Major Depression Based on SVM-FoBa: Efficient Feature Selection With Multimodal Brain Imaging Data.

Discriminating between bipolar disorder (BD) and major depressive disorder (MDD) is a major clinical challenge due to the absence of known biomarkers; hence a better understanding of their pathophysiology and brain alterations is urgently needed. Given the complexity, feature selection is especially important in neuroimaging applications, however, feature dimension and model understanding present serious challenges. In this study, a novel feature selection approach based on linear support vector machine with a forward-backward search strategy (SVM-FoBa) was developed and applied to structural and resting-state functional magnetic resonance imaging data collected from 21 BD, 25 MDD and 23 healthy controls. Discriminative features were drawn from both data modalities, with which the classification of BD and MDD achieved an accuracy of 92.1% (1,000 bootstrap resamples). Weight analysis of the selected features further revealed that the inferior frontal gyrus may characterize a central role in BD-MDD differentiation, in addition to the default mode network and the cerebellum. A modality-wise comparison also suggested that functional information outweighs anatomical by a large margin when classifying the two clinical disorders. This work validated the advantages of multimodal joint analysis and the effectiveness of SVM-FoBa, which has potential for use in identifying possible biomarkers for several mental disorders.

Functional magnetic resonance spectroscopy of glutamate in schizophrenia and major depressive disorder: anterior cingulate activity during a color-word Stroop task.

BACKGROUND: Glutamate abnormalities have been suggested to be associated with symptoms of schizophrenia. Using functional magnetic resonance spectroscopy ((1)H-fMRS), it is possible to monitor glutamate dynamically in the activated brain areas, which has yet to be reported in schizophrenia. It was hypothesized that subjects with schizophrenia would have weaker glutamatergic responses in the anterior cingulate to a color-word Stroop Task. AIMS: The aim of this study was to gain insight into the health of GLU neurotransmission and the GLU-GLN cycle in SZ using a (1)H-fMRS protocol. METHODS: Spectra were acquired from the anterior cingulate of 16 participants with schizophrenia, 16 healthy controls and 16 participants with major depressive disorder (MDD) while performing the Stroop task in a 7T magnetic resonance imaging scanner. (1)H-fMRS spectra were acquired for 20 min in which there were three 4-min blocks of cross fixation interleaved with two 4-min blocks of the Stroop paradigm. RESULTS: A repeated-measures analysis of variance revealed a main effect of time for glutamate concentrations of all groups (P<0.001). The healthy control group increased glutamate concentrations in the first run of the Stroop task (P=0.006) followed by a decrease in the recovery period (P=0.007). Neither the schizophrenia (P=0.107) nor MDD (P=0.081) groups had significant glutamate changes in the first run of the task, while the schizophrenia group had a significant increase in glutamine (P=0.005). The MDD group decreased glutamate concentrations in the second run of the task (P=0.003), as did all the groups combined (P=0.003). CONCLUSIONS: (1)H-fMRS data were successfully acquired from psychiatric subjects with schizophrenia and mood disorder using a cognitive paradigm for the first time. Future study designs should further elucidate the glutamatergic response to functional activation in schizophrenia.

Unique functional abnormalities in youth with combined marijuana use and depression: an FMRI study.

Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD + MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants were carried forward for analysis (17 HC, 15 MDD, 15 MJ, 14 MDD + MJ). Two statistical analyses were performed using SPM8, an analysis of covariance with two factors (group × music type) and a whole brain, multiple regression analysis incorporating two predictors of interest [MJ use in past 28 days; and Beck Depression Inventory (BDI) score]. We identified a significant group × music type interaction. Post hoc comparisons showed that the preferred music had significantly greater activation in the MDD + MJ group in areas including the right middle and inferior frontal gyri extending into the claustrum and putamen and the anterior cingulate. No significant differences were identified in MDD, MJ, or HC groups. Multiple regression analysis showed that activation in medial frontal cortex was positively correlated with amount of MJ use, and activation in areas including the insula was negatively correlated with BDI score. Results showed modulation in brain activation during passive music listening specific to MDD, frequent MJ users. This supports the suggestion that frequent MJ use, when combined with MDD, is associated with changes in neurocircuitry involved in reward processing in ways that are absent with either frequent MJ use or MDD alone. This could help inform clinical recommendations for youth with MDD.

"I just have to stick with it and it'll work": experiences of adolescents and young adults with mental health concerns.

Mental health issues are common among adolescents and young adults but service utilization in this group is low. This study aimed to better understand the experiences of older adolescents and young adults who were experiencing symptoms of depression or anxiety, including the factors that affected their decision to seek treatment and their feelings about their experience of mental health issues. We conducted semi-structured interviews with 37 older adolescents and young adults. Participants tended to have a sophisticated understanding of the causes of mental disorders, but to have been unsure about whether their own experiences of depression or anxiety were the result of a mental disorder, or just "normal" experiences. They reported concerns about taking medication and about keeping information about their condition private. They also felt that it was important to them to be active participants in their own care.

The neural correlates of regulating positive and negative emotions in medication-free major depression.

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect.

Correlation of brain default mode network activation with bipolarity index in youth with mood disorders.

BACKGROUND: Major Depressive Disorder (MDD) and Bipolar Disorder (BD) can be difficult to differentiate, as both feature depressive episodes. Here we have utilized fMRI and a measure of trait bipolarity to examine resting-state functional connectivity of brain activation in the default mode network in youth with MDD and BD to isolate trait-specific patterns. METHODS: We collected resting-state fMRI scans from thirty youth (15 MDD; 15 BD, Type 1). The Bipolarity Index (BI) was completed by each patient's treating psychiatrist. Independent components analysis was used to extract a default mode network component from each participant, and then multiple regression was used to identify correlations between bipolarity and network activation. RESULTS: Activation in putamen/claustrum/insula correlated positively with BI; activation in the postcentral gyrus/posterior cingulate gyrus correlated negatively with BI. These correlations did not appear to be driven by movement in the scanner, state depression, gender or lithium use. LIMITATIONS: There were group differences in state depression and sex that needed to be statistically covaried; differences in medication use existed between the groups; sample size was not large. CONCLUSIONS: The identification of the putamen/claustrum in our positive correlation may indicate a potential trait marker for the psychomotor activation unique to bipolar mania. The negative correlation in the postcentral gyrus/posterior cingulate suggests that this functional inactivation is more specific to MDD and is consistent with previous research. Ultimately, this approach may help to develop techniques to minimize the current clinical dilemma by facilitating the classification between BD and MDD.

Emotion-related brain activity to conflicting socio-emotional cues in unmedicated depression.

BACKGROUND: Abnormalities in amygdala function have been implicated in major depression. However, results are inconsistent, and little is known about how the depressed brain encodes conflicting social signals. We sought to determine how the task relevance of socio-emotional cues impacts neural encoding of emotion in depression. METHODS: Eighteen medication-free depressed patients and 18 matched controls participated in an FMRI experiment. Whole-brain analyses and a region-of-interest approach was used to measure amygdala activity during the presentation of fearful, happy, or neutral target faces with congruent, incongruent, or neutral distracters. RESULTS: Greater amygdala activity to target fearful faces was associated with depression, as was attenuated amygdala activity to target and peripheral happy faces. Although no group differences emerged in the amygdala to unattended fearful faces, we observed reduced ventrolateral and dorsomedial prefrontal activity in depressed individuals during this condition. LIMITATIONS: Nine patients had a history of anti-depressant use, though they were unmedicated for at least three months at testing. CONCLUSIONS: Depression was associated with reduced amygdala reactivity to positive social stimuli. However, enhanced amygdala responsiveness to negative emotional cues was only observed to target (attended) expressions. The results highlight the need to further determine factors that affect emotional reactivity in depression.

Retrosplenial cortex connectivity in schizophrenia.

In this paper, we build on our previous analysis [Bluhm, R.L., Miller, J., Lanius, R.A., Osuch, E.A., Boksman, K., Neufeld, R.W.J., et al., 2007 Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophrenia Bulletin 33, 1004-1012] of resting state connectivity in schizophrenia by examining alterations in connectivity of the retrosplenial cortex. We have previously demonstrated altered connectivity of the posterior cingulate/precuneus, particularly with other regions of the "default network" (which includes the medial prefrontal cortex and bilateral lateral parietal cortex). It was hypothesized that the retrosplenial cortex would show aberrant patterns of connectivity with regions of the default network and regions associated with memory. Patients with schizophrenia (N=17) and healthy controls (N=17) underwent a 5.5-min resting functional magnetic resonance imaging scan. Lower correlations were observed in patients with schizophrenia than in healthy controls between the retrosplenial cortex and both the temporal lobe and regions of the default network. In patients with schizophrenia, activity in the retrosplenial cortex correlated negatively with activity in bilateral anterior cingulate gyrus/medial prefrontal cortex (BA 32/10), despite the fact that these regions, as part of the default network, were expected to show positive correlations in activity. Connectivity of the retrosplenial cortex was greater in patients with more positive symptoms with areas previously associated with hallucinations, particularly the left superior temporal gyrus. These results suggest that spontaneous activity in the retrosplenial cortex during rest is altered in patients with schizophrenia. These alterations may help to explain alterations in self-oriented processing in this patient population.

Brain activation to favorite music in healthy controls and depressed patients.

Reward-processing neurocircuitry has been delineated using verbal or visual processing and/or decision-making tasks. We examined more basic processes of listening to enjoyable music in healthy and depressed patients. The paradigm was passive, individualized, and brief. Sixteen depressed and 15 control individuals provided favorite music and identified neutral music from selections provided. In the fMRI scanner, individuals heard their neutral and their favorite music for 3 min each. Favorite versus neutral music-listening contrasts showed greater activation in controls than depressed patients in medial orbital frontal cortex and nucleus accumbens/ventral striatum. Left medial prefrontal cortex activity was positively correlated with pleasure scores, whereas middle temporal cortex and globus pallidus were negatively correlated with pleasure. This paradigm activated neurocircuitry of reward processing and showed clinically meaningful alterations in depression.