In this Issue–May 15th| Volume 71, ISSUE 10, P841, May 15, 2012

A brief summary of the articles appearing in this issue of Biological Psychiatry

        Action Sequence Task: Evaluating Dopamine Signaling

        Wassum et al. (pages 846–854) used fast-scan cyclic voltammetry to characterize the pattern of phasic mesolimbic dopamine release during the acquisition and performance of an action sequencing task in rodents. They found that dopamine release shifted from the reward to more distal elements of the sequence, a pattern detected in both trained and untrained rats. Dopamine response came to precede task initiation and the response magnitude predicted the speed of task completion, suggesting that phasic mesolimbic dopamine release may mediate the influence that rewards exert over the performance of self-paced behavior.

        Differential Medication Effects on Brain Structure

        Evidence from clinical neuroimaging studies suggests typical antipsychotics and lithium have contrasting effects on gray matter volume, but these data are confounded by illness, chronicity and other medications. To address this issue, Vernon et al. (pages 855–863) used a clinically relevant dosing regimen to carry out studies in rodents. Their magnetic resonance imaging (MRI) data with postmortem confirmation show that chronic haloperidol treatment induced decreases in cortical gray matter volume, accompanied by striatal hypertrophy, while lithium induced increases in cortical gray matter volume. These changes were reversed upon drug withdrawal.

        Altered Brain Functioning in Schizophrenia

        Schizophrenia is associated with reduced brain activity when monitoring one's own actions for errors. Evaluating patients with schizophrenia, patients with other psychotic disorders, and healthy controls, Foti et al. (pages 864–872) found that error-related negativity was blunted in both patient groups, whereas error positivity was blunted only among those with schizophrenia. Error-related negativity was also associated with symptom severity and real-world functioning. These findings suggest diagnostic specificity among correlates of impaired error processing.
        Recent studies have demonstrated that high-frequency oscillations are modulated by low-frequency oscillations. This is termed cross-frequency coupling and indicates that a complex and hierarchical organization governs neural oscillatory dynamics. Kirihara et al. (pages 873–880) examined theta and gamma oscillations and cross-frequency coupling during auditory steady-state stimulation. Compared to healthy controls, schizophrenia patients had increased theta amplitude, reduced gamma phase synchrony, and intact cross-frequency coupling. These findings suggest that abnormal theta and gamma oscillations occur in the context of intact hierarchical organization in schizophrenia.
        Meda et al. (pages 881–889) used functional MRI to measure differential connectivity among resting state networks in patients with schizophrenia or bipolar disorder, their respective unaffected relatives, and healthy controls. Three different network pairs were differentially connected in probands involving five individual resting-state networks. One abnormal pair was unique to schizophrenia (meso/paralimbic and sensory-motor), one was unique to bipolar disorder (meso/paralimbic and fronto-temporal/paralimbic), and one was shared (fronto/occipital and anterior default mode/prefrontal). Results suggest that these patient groups share several abnormal resting state network connections, but with unique neural network underpinnings between disorders.
        Dreher et al. (pages 890–897) report that poor working memory is accompanied by both common and differential neurofunctional changes in patients with schizophrenia and healthy aging participants matched for performance. While the parahippocampal region was atypically unsuppressed in both impaired groups, abnormalities in working memory-related recruitment of the dorsolateral prefrontal cortex differed in direction. It was underactivated in schizophrenia, whereas it was overactivated in aging subjects. These findings provide insights into the mechanisms by which impaired working memory performance can arise.
        Reward processing is altered in schizophrenia patients, but the influence of medication effects is unknown. Nielsen et al. (pages 898–905) used a monetary reward task with functional MRI to evaluate antipsychotic-naïve schizophrenia patients and healthy controls. Patients showed decreased activation in ventral tegmentum, ventral striatum, and anterior cingulate cortex during reward anticipation. Ventral striatum changes correlated with the degree of positive symptoms. These findings suggest that altered reward processing is present prior to initiation of antipsychotic treatment.

        Dendritic Spine Loss in Schizophrenia

        A consistent finding in schizophrenia has been the loss of dendritic spines in the cortex, but the mechanisms underlying this phenomenon remain unknown. From their analysis of postmortem brains from schizophrenia patients and a comparison group, Rubio et al. (pages 906–914) report disturbances in a critical intracellular pathway involving Duo, PAK and myosin light chain that likely underlies cytoskeletal rearrangement in schizophrenia. These data point to a potential mechanism for dendritic spine loss in schizophrenia.

        Familial Risks in Schizophrenia and Bipolar Disorder

        Structural brain abnormalities are consistently found in schizophrenia and have been associated with familial risk for the disorder. In a cohort of schizophrenia twins and relatives, van Haren et al. (pages 915–921) examined the relative contributions of genetic and environmental factors to the association between structural brain abnormalities and schizophrenia. Their results suggest that smaller total cerebral volume, particularly of white matter, and larger third ventricle volume is linked to schizophrenia, largely through genetic factors that are associated with risk of the disorder.
        Karlsson et al. (pages 922–930) aimed to identify genome-wide copy number variation with a focus on bipolar affective disorder, but also in schizophrenia and schizoaffective disorder due to their potentially overlapping genetic risk. From their multistage approach, they present evidence for rare mutations in the genes coding for MAGI proteins in bipolar affective disorder and schizophrenia. These post-synaptic scaffolding proteins play important roles in the assembly of synapses and two of these molecules, MAGI1 and MAGI2, have previously been implicated in psychiatric disease by means of association and pathway studies.