Brain GABA levels across psychiatric disorders: A systematic literature review and meta-analysis of (1) H-MRS studies.

The inhibitory gamma-aminobutyric acid (GABA) system is involved in the etiology of most psychiatric disorders, including schizophrenia, autism spectrum disorder (ASD) and major depressive disorder (MDD). It is therefore not surprising that proton magnetic resonance spectroscopy ((1) H-MRS) is increasingly used to investigate in vivo brain GABA levels. However, integration of the evidence for altered in vivo GABA levels across psychiatric disorders is lacking. We therefore systematically searched the clinical (1) H-MRS literature and performed a meta-analysis. A total of 40 studies (N = 1,591) in seven different psychiatric disorders were included in the meta-analysis: MDD (N = 437), schizophrenia (N = 517), ASD (N = 150), bipolar disorder (N = 129), panic disorder (N = 81), posttraumatic stress disorder (PTSD) (N = 104), and attention deficit/hyperactivity disorder (ADHD) (N = 173). Brain GABA levels were lower in ASD (standardized mean difference [SMD] = -0.74, P = 0.001) and in depressed MDD patients (SMD = -0.52, P = 0.005), but not in remitted MDD patients (SMD = -0.24, P = 0.310) compared with controls. In schizophrenia this finding did not reach statistical significance (SMD = -0.23, P = 0.089). No significant differences in GABA levels were found in bipolar disorder, panic disorder, PTSD, and ADHD compared with controls. In conclusion, this meta-analysis provided evidence for lower brain GABA levels in ASD and in depressed (but not remitted) MDD patients compared with healthy controls. Findings in schizophrenia were more equivocal. Even though future (1) H-MRS studies could greatly benefit from a longitudinal design and consensus on the preferred analytical approach, it is apparent that (1) H-MRS studies have great potential in advancing our understanding of the role of the GABA system in the pathogenesis of psychiatric disorders. Hum Brain Mapp 37:3337-3352, 2016. © 2016 Wiley Periodicals, Inc.

The Association Between Emotion Recognition, Affective Empathy, and Structural Connectivity in Schizophrenia Patients.

Introduction: Emotion processing deficits often occur in patients with schizophrenia. We investigate whether patients and controls differ in the association between facial emotion recognition and experience of affective empathy and whether performance on these emotion processing domains differently relates to white matter connectivity. Materials and Methods: Forty-seven patients with schizophrenia and 47 controls performed an emotion recognition and affective empathy task. T1-weighted and diffusion-tensor images (DTI) of the brain were acquired. Using Tracula 5.3, ten fibers were reconstructed and fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were extracted. Groups were compared on task performance, white matter measures and their interactions using ANCOVAs. Correction for multiple comparisons was applied. Results: Patients scored lower on emotion recognition (p = 0.037) and reported higher levels of affective empathy (p < 0.001) than controls. Patients with poor emotion recognition (PT-low) experienced stronger affective empathy than patients with similar emotion recognition performance as controls (PT-normal; p = 0.011), who in turn reported stronger affective empathy than controls (p = 0.043). We found a significant interaction between emotion recognition, affective empathy and anterior thalamic radiation AD (p = 0.017, d = 0.43). Post hoc analyses revealed that the correlation between AD and empathy differed significantly between all groups (empathy/AD in PT-low < empathy/AD in PT-normal < empathy/AD in controls). Discussion: In patients with poor emotion recognition, the negative association between anterior thalamic radiation AD and affective empathy was stronger than in patients with normal emotion recognition capacity. Possibly, axonal damage in fronto-thalamic structural connections, as part of a larger frontotemporal network, underlies the association between poor emotion recognition and higher levels of affective empathy in schizophrenia patients.

Brain structure, IQ, and psychopathology in young offspring of patients with schizophrenia or bipolar disorder.

BACKGROUND: Studying offspring of schizophrenia (SZo) and bipolar disorder patients (BDo) provides important information on the putative neurodevelopmental trajectories underlying development toward severe mental illnesses. We compared intracranial volume (ICV), as a marker for neurodevelopment, and global and local brain measures between SZo or BDo and control offspring (Co) in relation to IQ and psychopathology. METHODS: T1-weighted magnetic resonance imaging (MRI) brain scans were obtained from 146 participants (8-19 years; 40 SZo, 66 BDo, 40 Co). Linear mixed models were applied to compare ICV, global, and local brain measures between groups. To investigate the effect of ICV, IQ (four subtests Wechsler Intelligence Scale for Children/Wechsler Adult Intelligence Scale-III) or presence of psychopathology these variables were each added to the model. RESULTS: SZo and BDo had significantly lower IQ and more often met criteria for a lifetime psychiatric disorder than Co. ICV was significantly smaller in SZo than in BDo (d = -0.56) and Co (d = -0.59), which was largely independent of IQ (respectively, d = -0.54 and d = -0.35). After ICV correction, the cortex was significantly thinner in SZo than in BDo (d = -0.42) and Co (d = -0.75) and lateral ventricles were larger in BDo than in Co (d = 0.55). Correction for IQ or lifetime psychiatric diagnosis did not change these findings. CONCLUSIONS: Despite sharing a lower IQ and a higher prevalence of psychiatric disorders, brain abnormalities in BDo appear less pronounced (but are not absent) than in SZo. Lower ICV in SZo implies that familial risk for schizophrenia has a stronger association with stunted early brain development than familial risk for bipolar disorder.

Visualizing mental representations in schizophrenia patients: A reverse correlation approach.

Schizophrenia patients have difficulties recognizing emotional states from faces, in particular those with negative valence, with severe consequences for daily life. What do these patients see in their minds eye, when they think of a face expressing a particular emotion or trait? The content of such mental representations can shed light into the nature of their deficits, but are usually inaccessible. For the first time, we explored the applicability of reverse correlation, which has been successfully used to visualize mental representations in healthy populations, to visualize mental representations in schizophrenia patients. We investigated mental representations of trustworthy faces, a primary dimension of social face evaluation that is highly correlated with valence. Patients (n = 23) and healthy controls (n = 34) classified images of noise-distorted faces as 'trustworthy', 'untrustworthy' or 'neutral'. We visualized their mental representations of these concepts by averaging the noise patterns based on their classifications. These visualizations were then rated on trustworthiness by an independent sample of participants. Patients were able to perform the reverse correlation task, with response times and biases similar to those of healthy controls, and the obtained images vividly reflected the respective constructs of interest. However, there were no significant differences between the ratings of the visualizations of patients and controls. Conclusion: These novel findings provide a proof of principle that the reverse correlation technique can be applied to investigate mental representations in schizophrenia patients.

10Kin1day: A Bottom-Up Neuroimaging Initiative.

We organized 10Kin1day, a pop-up scientific event with the goal to bring together neuroimaging groups from around the world to jointly analyze 10,000+ existing MRI connectivity datasets during a 3-day workshop. In this report, we describe the motivation and principles of 10Kin1day, together with a public release of 8,000+ MRI connectome maps of the human brain.

Abnormal agency experiences in schizophrenia patients: Examining the role of psychotic symptoms and familial risk.

Experiencing self-agency over one's own action outcomes is essential for social functioning. Recent research revealed that patients with schizophrenia do not use implicitly available information about their action-outcomes (i.e., prime-based agency inference) to arrive at self-agency experiences. Here, we examined whether this is related to symptoms and/or familial risk to develop the disease. Fifty-four patients, 54 controls, and 19 unaffected (and unrelated) siblings performed an agency inference task, in which experienced agency was measured over action-outcomes that matched or mismatched outcome-primes that were presented before action performance. The Positive and Negative Syndrome Scale (PANSS) and Comprehensive Assessment of Symptoms and History (CASH) were administered to assess psychopathology. Impairments in prime-based inferences did not differ between patients with symptoms of over- and underattribution. However, patients with agency underattribution symptoms reported significantly lower overall self-agency experiences. Siblings displayed stronger prime-based agency inferences than patients, but weaker prime-based inferences than healthy controls. However, these differences were not statistically significant. Findings suggest that impairments in prime-based agency inferences may be a trait characteristic of schizophrenia. Moreover, this study may stimulate further research on the familial basis and the clinical relevance of impairments in implicit agency inferences.

Impaired frontal processing during agency inferences in schizophrenia.

People generally experience themselves as the cause of outcomes following from their own actions. Such agency inferences occur fluently and are essential to social interaction. However, schizophrenia patients often experience difficulties in distinguishing their own actions from those of others. Building on recent research into the neural substrates underlying agency inferences in healthy individuals, the present study investigates how these inferences are represented on a neural level in patients with schizophrenia. Thirty-one schizophrenia patients and 31 healthy controls performed an agency inference task while functional magnetic resonance images were obtained. Participants were presented with a task wherein the relationship between their actions and the subsequent outcomes was ambiguous. They received instructions to cause specific outcomes to occur by pressing a key, but the task was designed to match or mismatch the color outcome with the participants' goal. Both groups experienced stronger agency when their goal matched (vs. mismatched) the outcome. However, region of interest analyses revealed that only controls showed the expected involvement of the medial prefrontal cortex and superior frontal gyrus, whereas in patients the agency experience was not related to brain activation. These findings are discussed in light of a hypofrontality model of schizophrenia.