Avinash Hosanagar

Meta-Analysis of Functional Neuroimaging Studies of Emotion Perception and Experience in Schizophrenia

BACKGROUND Neuroimaging studies of emotion in schizophrenia have reported abnormalities in amygdala and other regions, although divergent results and heterogeneous paradigms complicate conclusions from single experiments. To identify more consistent patterns of dysfunction, a meta-analysis of functional imaging studies of emotion was undertaken. METHODS Searching Medline and PsycINFO databases through January 2011, 88 potential articles were identified, of which 26 met inclusion criteria, comprising 450 patients with schizophrenia and 422 healthy comparison subjects. Contrasts were selected to include emotion perception and emotion experience. Foci from individual studies were subjected to a voxelwise meta-analysis using multilevel kernel density analysis. RESULTS For emotional experience, comparison subjects showed greater activation in the left occipital pole. For emotional perception, schizophrenia subjects showed reduced activation in bilateral amygdala, visual processing areas, anterior cingulate cortex, dorsolateral frontal cortex, medial frontal cortex, and subcortical structures. Schizophrenia subjects showed greater activation in the cuneus, parietal lobule, precentral gyrus, and superior temporal gyrus. Combining across studies and eliminating studies that did not balance on effort and stimulus complexity eliminated most differences in visual processing regions as well as most areas where schizophrenia subjects showed a greater signal. Reduced reactivity of the amygdala appeared primarily in implicit studies of emotion, whereas deficits in anterior cingulate cortex activity appeared throughout all contrasts. CONCLUSIONS Processing emotional stimuli, schizophrenia patients show reduced activation in areas engaged by emotional stimuli, although in some conditions, schizophrenia patients exhibit increased activation in areas outside those traditionally associated with emotion, possibly representing compensatory processing.

Modulation of resting-state amygdala-frontal functional connectivity by oxytocin in generalized social anxiety disorder.

Generalized social anxiety disorder (GSAD) is characterized by aberrant patterns of amygdala-frontal connectivity to social signals of threat and at rest. The neuropeptide oxytocin (OXT) modulates anxiety, stress, and social behaviors. Recent functional neuroimaging studies suggest that these effects are mediated through OXT’s effects on amygdala reactivity and/or amygdala-frontal connectivity. The aim of the current study was to examine OXT’s effects on amygdala-frontal resting-state functional connectivity (rsFC) in GSAD patients and healthy controls (HCs). In a randomized, double-blind, cross-over design, 18 GSAD and 18 HC participants received intranasal OXT (24 IU or 40.32 μg) or placebo (PBO) before resting-state functional magnetic resonance imaging. In individuals with GSAD, OXT enhanced rsFC of the left and right amygdala with rostral anterior cingulate cortex (ACC)/medial prefrontal cortex (mPFC), and in doing so, reversed (ie, ‘normalized’) the reduced amygdala-frontal connectivity observed relative to HCs evident on PBO. Higher social anxiety severity in GSAD subjects correlated with lower amygdala-ACC/mPFC connectivity on PBO and higher social anxiety also correlated with greater enhancement in amygdala-frontal connectivity induced by OXT. These findings show that OXT modulates a neural circuit known for social threat processing and emotion regulation, suggesting a neural mechanism by which OXT may have a role in the pathophysiology and treatment of social anxiety disorder.

Oxytocin Modulation of Amygdala Functional Connectivity to Fearful Faces in Generalized Social Anxiety Disorder

The neuropeptide oxytocin (OXT) is thought to attenuate anxiety by dampening amygdala reactivity to threat in individuals with generalized social anxiety disorder (GSAD). Because the brain is organized into networks of interconnected areas, it is likely that OXT impacts functional coupling between the amygdala and other socio-emotional areas of the brain. Therefore, the aim of the current study was to examine the effects of OXT on amygdala functional connectivity during the processing of fearful faces in GSAD subjects and healthy controls (HCs). In a randomized, double-blind, placebo (PBO)-controlled, within-subjects design, 18 HCs and 17 GSAD subjects performed a functional magnetic resonance imaging task designed to probe amygdala response to fearful faces following acute intranasal administration of PBO or OXT. Functional connectivity between the amygdala and the rest of the brain was compared between OXT and PBO sessions using generalized psychophysiological interaction analyses. Results indicated that within individuals with GSAD, but not HCs, OXT enhanced functional connectivity between the amygdala and the bilateral insula and middle cingulate/dorsal anterior cingulate gyrus during the processing of fearful faces. These findings suggest that OXT may have broad pro-social implications such as enhancing the integration and modulation of social responses.

Working memory and attention deficits in adolescent offspring of schizophrenia or bipolar patients: Comparing vulnerability markers

BACKGROUND Working memory deficits abound in schizophrenia and attention deficits have been documented in schizophrenia and bipolar disorder. Adolescent offspring of patients may inherit vulnerabilities in brain circuits that subserve these cognitive domains. Here we assess impairments in offspring of schizophrenia (SCZ-Offspring) or bipolar (BP-Offspring) patients compared to controls (HC) with no family history of mood or psychotic disorders to the second degree. METHODS Three groups (n=100 subjects; range: 10-20 yrs) of HC, SCZ-Offspring and BP-Offspring gave informed consent. Working memory was assessed using a delayed spatial memory paradigm with two levels of delay (2s & 12s); sustained attention processing was assessed using the Continuous Performance Task-Identical Pairs version. RESULTS SCZ-Offspring (but not BP-Offspring) showed impairments in working memory (relative to HC) at the longer memory delay indicating a unique deficit. Both groups showed reduced sensitivity during attention but only BP-Offspring significantly differed from controls. CONCLUSIONS These results suggest unique (working memory/dorsal frontal cortex) and potentially overlapping (attention/fronto-striatal cortex) vulnerability pathways in adolescent offspring of patients with schizophrenia and bipolar disorder. Working memory and attention assessments in these offspring may assist in the clinical characterization of the adolescents vulnerable to SCZ or BP.

Hippocampal volume development in healthy siblings of childhood-onset schizophrenia patients

OBJECTIVE Previous anatomic studies have established a reduction in hippocampal volume in schizophrenia, but few have investigated the progressive course of these changes and whether they are trait markers. In the present study, the authors examined hippocampal volumes in relation to age for patients with childhood-onset schizophrenia, their nonpsychotic healthy siblings, and healthy comparison subjects. METHOD Anatomic brain magnetic resonance scans were obtained in childhood-onset schizophrenia probands (N=89, 198 scans), their nonpsychotic full siblings (N=78, 172 scans), and matched healthy comparison subjects (N=79, 198 scans) between the ages of 10 and 29 years. Total, left, and right hippocampal volumes were measured using FreeSurfer software and analyzed using a linear mixed-model regression covarying for sex and intracranial volume. RESULTS Childhood-onset schizophrenia probands had a fixed reduction in hippocampal volumes (total, left, and right) relative to both nonpsychotic siblings and healthy comparison subjects, whereas there were no significant volumetric or trajectory differences between nonpsychotic siblings and healthy comparison subjects. CONCLUSIONS Fixed hippocampal volume loss seen in childhood-onset schizophrenia, which is not shared by healthy siblings, appears to be related to the illness. Decreased hippocampal volume is not strongly genetically related but represents an important intermediate disease phenotype.

A systematic review of psychological interventions for adult and pediatric patients with vocal cord dysfunction

Background: Vocal cord dysfunction (VCD) or paradoxical vocal-fold motion (PVFM) is a functional disorder of the vocal cords that requires multidisciplinary treatment. Besides relaxation techniques, the use of psychological interventions can help treat the underlying psychological co-morbidities. There is currently no literature that examines the effectiveness of psychological interventions for VCD/PVFM. Objectives: To review the evidence for psychological interventions used for the treatment of patients with VCD/PVFM. Data sources: We searched electronic databases for English medical literature using Pubmed (Medline), PsycInfo, Cochrane Database of Systematic Reviews, Cochrane Central Registry of Controlled Trials, and Clinicaltrials.gov. The date range for our search is from June 1964 to June 2014. Study eligibility criteria, participants, and interventions: We included studies that reported the use of psychological interventions in both adults and children diagnosed with VCD/PVFM. We included randomized controlled trials, case-control studies, retrospective chart reviews, prospective case series, and individual case reports. Results: Most reported studies are small case series or individual case reports that have described the use of interventions such as psychotherapy, behavioral therapy, use of anti-anxiety and anti-depressant medications, and hypnotherapy in conjunction with breathing exercises taught by speech therapists for symptomatic relief. Among the various psychological interventions that have been reported, there is no data regarding effectiveness and/or superiority of one approach over another in either adult or pediatric patients. Conclusions: Psychological interventions have a role to play in the management of adult and pediatric patients with VCD/PVFM. Future prospective studies using uniform approaches for treatment of associated psychopathology may help address this question.

Acute urinary retention secondary to buprenorphine administration

Urinary retention is associated with buprenorphine, particularly with epidural/intrathecal delivery. However, it is rare with oral administration. This case report illustrates an occurrence of acute urinary retention after initiation of oral buprenorphine/naloxone.

Pain moderates changes in psychological flexibility but not substance use symptoms during substance use disorder treatment

Pain-related problems frequently complicate substance use disorder (SUD) course and prognosis. However, it is unclear if the negative outcomes associated with co-occurring pain are due to its link with greater SUD severity, disruption of SUD treatment processes, or connection to a third psychological process. The current study modeled the longitudinal effects of pain during a 4-week intensive outpatient treatment (IOP) on SUD symptoms and limited psychological flexibility (PF), a common feature of psychological well being that is commonly restricted in both SUD and pain patients. After controlling for initial severity of SUD symptoms, current pain level at treatment intake moderated change in a sub-component of PF, values commitment, but not SUD symptoms during the IOP. During the treatment, pain level also limited improvement in PF but not self-reported SUD symptoms. Targeting additional increases in psychological flexibility surrounding commitment to values during SUD treatment may help improve outcomes among patients who began treatment with significant pain symptoms.