[Show abstract][Hide abstract] ABSTRACT: 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 o 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
This process evaluation indicated that the model provided appropriate early intervention for youths with mood or anxiety disorders without causing excessive overinclusion.
[Show abstract][Hide abstract] ABSTRACT: Non-suicidal self-injury (NSSI) is increasingly common in young psychiatric patients. It is unclear why pain, which should be aversive, becomes reinforcing in this context. We hypothesized that pain- and/or reward-processing neurocircuitry would be abnormal in NSSI patients compared with non-NSSI patients. Using functional magnetic resonance imaging, we administered a painfully cold and comparison cool stimulus under two conditions: self-administered and experimenter-administered (as a control). Participants comprised 13 NSSI patients and 15 non-NSSI control patients, who were matched for sex, age, medications, symptoms, and diagnoses. Whole-brain analyses of main effects, as well as correlational analyses with subjective pain and “relief” (suggesting reward), were performed. Significant main effects of group showed greater blood oxygenation level-dependent (BOLD) response for NSSI than controls in right midbrain/pons; culmen; amygdala; and parahippocampal, inferior frontal and superior temporal gyri; as well as orbital frontal cortex (OFC). The correlation between BOLD signal and “relief” was greater in NSSI patients in areas associated with reward/pain and addiction including thalamus, dorsal striatum and anterior precuneus. Post hoc analysis showed reduced functional connectivity between right OFC and anterior cingulate cortex in NSSI youth, implying possible deficits in the neuroregulation of emotional behavior. These findings show how pain is associated with reward for NSSI patients but not for non-NSSI patients.
[Show abstract][Hide abstract] ABSTRACT: 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.
Community Mental Health Journal 01/2014; 50(7). DOI:10.1007/s10597-014-9695-x · 1.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abstract Cannabis use is common in youth and there is evidence that the co-occurrence of cannabis use (and other substance use) with mental illnesses predicts poorer outcomes, including suicide. The main purposes of this study were to: (i) identify rates of cannabis use and substance use disorder risk, and (ii) predictors for cannabis use among youth seeking help for mood and/or anxiety concerns in a sample population prescreened to exclude primary substance use disorders; and (iii) to determine if there was an association between cannabis use and functional impairment in this sample. We investigated substance use risk as well as hypothesized predictors of cannabis use and functional impairment including demographic characteristics, socioeconomic status, trait coping style, age of onset of several risk behaviors, current use of common addictive substances, level of functional impairment, and current psychiatric symptom severity. Results showed that approximately half of the participants were at moderate to high risk for a substance use disorder, and just over 4% appeared to have a primary substance use disorder. They also suggested an association between cannabis use and gender (male), age of first cannabis use, recent cigarette use, and functional impairment. Independently, functional impairment was predicted by inattentive coping style, depression severity, and total cannabis use score. These results confirm a high risk for addictive disorders and an association between cannabis use and functional impairment in this sample. These results support the need for substance use treatment programs to optimize care wherever youth with primary mood and/or anxiety concerns are seen.
International journal of adolescent medicine and health 07/2013; 25(3):1-6. DOI:10.1515/ijamh-2013-0067
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
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.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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 when regulating both negative and positive emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in ventral striatum when enhancing positive affect; however, only in controls was 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.
Social Cognitive and Affective Neuroscience 03/2013; 9(5). DOI:10.1093/scan/nst027 · 7.37 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mood and anxiety disorders typically begin during adolescence or early adulthood. Yet services targeting this population are frequently lacking. This study implemented an outreach, access and assessment programme for youth with these concerns. The data reported constitute an evaluation of this mental healthcare delivery approach.
This evaluation included specification of both programme and implementation theories through causal and programme logic models and formative (process) evaluation. Outreach focused on access points for youth such as schools and family physicians' offices. Concerned youth were encouraged to self-refer. Participants completed a semi-structured clinical interview and symptom and function questionnaire package.
Engagement sessions were conducted and results involved 93 youth. The majority of youth self-referred, a process not possible in traditional physician-referral healthcare systems. Interestingly, almost half had received prior treatment and over half had tried a psychiatric medication. Yet participants had significant symptomatology: 81% reported moderate to severe depressive symptoms; 95% reported high levels of trait-anxiety. Functional impairment was substantial: on average, participants missed 2.6 days of school/work and functioned at reduced levels on 4.2 days in the week prior to assessment. Demographic details are presented.
This study evaluated a mental healthcare delivery system that identified individuals with significant distress and functional impairment from mood/anxiety concerns and previous unsuccessful treatment attempts, verifying that they were in need of mental health services. This approach provides a model for outreach and assessment in this population, where earlier intervention has the potential to prevent chronic mental illness and disability.
Early Intervention in Psychiatry 12/2011; 6(1):97-105. DOI:10.1111/j.1751-7893.2011.00312.x · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Psychiatry Research 09/2009; 174(1):17-23. DOI:10.1016/j.pscychresns.2009.03.010 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: The "default network" consists of a number of brain regions that exhibit correlated low-frequency activity at rest and that have been suggested to be involved in the processing of self-relevant stimuli. Activity in many of these areas has also been shown to be altered in individuals with posttraumatic stress disorder (PTSD). We hypothesized that the posterior cingulate cortex (PCC)/precuneus, part of the default network, would exhibit altered connectivity at rest with other areas of the default network and regions associated with PTSD.
Seventeen medicated and unmedicated female patients with chronic posttraumatic stress disorder (PTSD) related to early-life trauma and 15 healthy female controls underwent a 5.5-minute functional magnetic resonance imaging scan with their eyes closed. We assessed areas of the brain whose activity positively and negatively correlated with that of the PCC/precuneus in both groups.
At rest, spontaneous low-frequency activity in the PCC/precuneus was more strongly correlated with activity in other areas of the default network in healthy controls than in patients with PTSD. Direct comparison of the 2 groups showed that PCC/ precuneus connectivity was also greater in healthy controls than in patients with PTSD in a number of areas previously associated with PTSD, including the right amygdala and the hippocampus/parahippocampal gyrus.
Because our PTSD sample comprised only women with chronic early-life trauma exposure, our results may not be generalizeable to male patients, to a population with single trauma exposure or to those who were adults when the trauma occurred. In addition, our sample included patients taking medication and it is not yet clear how altered connectivity is affected by medication.
Spontaneous activity in the default network during rest, as measured using PCC correlations, is altered in patients with PTSD. The potential effects of psychotropic medications on default network connectivity in the present sample remain unknown. In this patient population, the observed alterations may be associated with the disturbances in self-referential processing often observed in patients with chronic PTSD related to early-life trauma.
[Show abstract][Hide abstract] ABSTRACT: The purpose of the pilot study was to explore the psychological, cognitive and physiological changes accompanying exercise-mediated amelioration of clinical depression. Depressed participants were randomly assigned to either a 12-week aerobic exercise (n=10) or stretching (n=13) program. The outcome variables were depression severity, coping efficacy, episodic memory and cortisol awakening response (CAR). Both aerobic exercise and stretching were associated with significant decreases in severity of depression, and increases in coping efficacy and episodic memory over 12 weeks. CAR decreased in the aerobic exercise group and increased in the stretching group over 12 weeks. Change in depression severity was significantly inversely associated with change in coping efficacy and change in episodic memory. No significant correlations were found between CAR and the other outcome variables. Overall, this study demonstrates that exercise and stretching are associated with positive psychological and cognitive changes in those with depression.
Mental Health and Physical Activity 12/2008; 1(2):69-73. DOI:10.1016/j.mhpa.2008.07.001
[Show abstract][Hide abstract] ABSTRACT: Objective: Previous studies show a state-dependent relationship between depression and post-dexamethasone suppression test (DST) cortisol level, as well as differences in DST response with age and gender.Method: In this study, 74 research in-patients with affective disorders were given the DST on placebo and in a subgroup following treatment with carbamazepine. Depression was evaluated twice daily with the Bunney–Hamburg (BH) rating scale. Data were examined for the total subject population, by gender and by menopausal status in women.Results: A robust positive correlation was observed between depression severity and post-DST cortisol in pre- and postmenopausal females, but not in males. This relationship persisted in women when restudied on a stable dose of carbamazepine (n=42).Conclusion: The pathophysiological implications of this selective positive relationship between severity of depression and post-DST cortisol in women, but not men, should be explored further.
[Show abstract][Hide abstract] ABSTRACT: The 'default mode network' is a set of brain regions showing correlated, low-frequency activity during rest. It includes the posterior cingulate/precuneus, medial prefrontal cortex, and bilateral inferior parietal cortex. Earlier studies have characterized this network using either region of interest-based correlation analyses or data-driven techniques; however, there is some disagreement over which method is superior. We conducted both types of analysis on a large (N=40) data set and also investigated age and sex differences in the network. Both region of interest-based analyses and independent component analysis identified the default mode network. Age and sex differences were small and there was less agreement between analytic techniques regarding age and sex effects than regarding default mode network structure.
[Show abstract][Hide abstract] ABSTRACT: Neuroimaging studies report that individuals with posttraumatic stress disorder show abnormal responses in the amygdala and medial prefrontal cortex (mPFC)/anterior cingulate cortex (ACC) during exposure to traumatic reminders. However, neural responses arising in the early aftermath of a traumatic event have not been studied.
Twenty-two motor vehicle collision survivors and 12 nontraumatized control subjects participated. Regional cerebral blood flow (rCBF) was measured using [(15)O]-H(2)O positron emission tomography (PET) at rest and as subjects listened to scripts of traumatic and neutral events. Self-report measures rated emotional responses to the scripts; standardized assessments (Impact of Events--Revised) evaluated acute stress symptoms at scanning and at 3-month follow-up. Most subjects improved symptomatically.
At rest, trauma subjects showed hyperperfusion in right mPFC/ACC and hypoperfusion in right amygdala compared with control subjects. In trauma subjects, listening to trauma scripts versus neutral scripts resulted in decreased flow in the right amygdala and left amygdala/perirhinal cortex, and symptom scores correlated negatively with right hippocampal flow changes. Symptom improvement at 3 months correlated negatively with rCBF changes in right perirhinal cortex and hippocampus during the trauma versus neutral script contrast. Subjective disturbance during the trauma versus neutral contrast correlated positively with rCBF changes in right amygdala and left mPFC. Functional connectivity analyses of rCBF changes during trauma versus neutral scripts demonstrated left amygdala coupling with right ACC and bilateral anterior insula, as well as coupling between the amygdala and contralateral hippocampus.
In recently traumatized subjects functional interactions between the amygdala, perirhinal cortex and ACC/mPFC that occur during exposure to traumatic reminders may underlie adaptive/recuperative processes.
[Show abstract][Hide abstract] ABSTRACT: Treatment for anxiety and post-traumatic stress disorder (PTSD) includes exposure therapy and medications, but some patients are refractory. Few studies of repetitive transcranial magnetic stimulation (rTMS) for anxiety or PTSD exist. In this preliminary report, rTMS was combined with exposure therapy for PTSD. Nine subjects with chronic, treatment-refractory PTSD were studied in a placebo-controlled, crossover design of imaginal exposure therapy with rTMS (1Hz) versus sham. PTSD symptoms, serum and 24h urine were obtained and analyzed. Effect sizes for PTSD symptoms were determined using Cohen's d. Active rTMS showed a larger effect size of improvement for hyperarousal symptoms compared to sham; 24-h urinary norepinephrine and serum T4 increased; serum prolactin decreased. Active rTMS with exposure may have symptomatic and physiological effects. Larger studies are needed to confirm these preliminary findings and verify whether rTMS plus exposure therapy has a role in the treatment of PTSD.
[Show abstract][Hide abstract] ABSTRACT: Spontaneous low-frequency fluctuations in the blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (MRI) signal have been shown to reflect neural synchrony between brain regions. A "default network" of spontaneous low-frequency fluctuations has been described in healthy volunteers during stimulus-independent thought. Negatively correlated with this network are regions activated during attention-demanding tasks. Both these networks involve brain regions and functions that have been linked with schizophrenia in previous research. The present study examined spontaneous slow fluctuations in the BOLD signal at rest, as measured by correlation with low-frequency oscillations in the posterior cingulate, in 17 schizophrenic patients, and 17 comparable healthy volunteers. Healthy volunteers demonstrated correlation between spontaneous low-frequency fluctuations of the BOLD signal in the posterior cingulate and fluctuations in the lateral parietal, medial prefrontal, and cerebellar regions, similar to previous reports. Schizophrenic patients had significantly less correlation between spontaneous slow activity in the posterior cingulate and that in the lateral parietal, medial prefrontal, and cerebellar regions. Connectivity of the posterior cingulate was found to vary with both positive and negative symptoms in schizophrenic patients. Because these data suggest significant abnormalities in resting-state neural networks in schizophrenia, further investigations of spontaneous slow fluctuations of the BOLD signal seem warranted in this population.
[Show abstract][Hide abstract] ABSTRACT: Cerebral metabolism (CMR for glucose or oxygen) and blood flow (CBF) have been reported to be closely correlated in healthy controls. Altered relationships between CMR and CBF have been reported in some brain disease states, but not others. This study examined relationships between global and regional CMRglu vs. CBF in controls and medication-free primary affective disorder patients. Nine bipolars, eight unipolars, and nine healthy controls had [15O]-water positron emission tomography (PET) scans at rest, and [18F]-fluorodeoxyglucose PET scans during an auditory continuous performance task. Patients had [15O]-water and FDG PET scans in tandem the same day; controls had an average of 45+/-27 days between scans. Maps of regional coupling were constructed for each subject group. In controls and bipolars, global and virtually all regional correlation coefficients for CMRglu and CBF were positive, albeit more robustly so in controls. However, correlative relationships in unipolars were qualitatively different, such that global and most regional measures of flow and metabolism were not positively related. Unipolars had significantly fewer positive regional correlation coefficients than healthy controls and bipolars. These were significantly different from controls in orbital cortex, anterior cingulate, posterior cingulate, and posterior temporal cortex, and different from bipolars in pregenual anterior cingulate. In unipolars, the degree of flow-metabolism uncoupling was inversely correlated with Hamilton depression scores, indicating the severity of uncoupling was directly related to the severity of depression. These preliminary data suggest abnormal relationships between cerebral metabolism and blood flow globally and regionally in patients with unipolar depression that warrant replication and extension to potential pathophysiological implications.
Psychiatry Research 12/2005; 140(2):181-98. DOI:10.1016/j.pscychresns.2005.07.005 · 2.47 Impact Factor