Linking connectivity of deep brain stimulation of nucleus accumbens area with clinical depression improvements: a retrospective longitudinal case series.

Treatment-resistant depression is a severe form of major depressive disorder and deep brain stimulation is currently an investigational treatment. The stimulation's therapeutic effect may be explained through the functional and structural connectivities between the stimulated area and other brain regions, or to depression-associated networks. In this longitudinal, retrospective study, four female patients with treatment-resistant depression were implanted for stimulation in the nucleus accumbens area at our center. We analyzed the structural and functional connectivity of the stimulation area: the structural connectivity was investigated with probabilistic tractography; the functional connectivity was estimated by combining patient-specific stimulation volumes and a normative functional connectome. These structural and functional connectivity profiles were then related to four clinical outcome scores. At 1-year follow-up, the remission rate was 66%. We observed a consistent structural connectivity to Brodmann area 25 in the patient with the longest remission phase. The functional connectivity analysis resulted in patient-specific R-maps describing brain areas significantly correlated with symptom improvement in this patient, notably the prefrontal cortex. But the connectivity analysis was mixed across patients, calling for confirmation in a larger cohort and over longer time periods.

Low physical activity is associated with two hypokinetic motor abnormalities in psychosis.

Individuals with schizophrenia engage in more sedentary behavior than healthy controls, which is thought to contribute to multiple health adversities. Age, medication side effects and environment are critical determinants of physical activity in psychosis. While motor abnormalities are frequently observed in psychosis, their association with low physical activity has received little interest. Here, we aimed to explore the association of actigraphy as an objective measure of physical activity with clinician assessed hypokinetic movement disorders such as parkinsonism and catatonia. Furthermore, we studied whether patients with current catatonia would differ on motor rating scales and actigraphy from patients without catatonia. In 52 patients with schizophrenia spectrum disorders, we cross-sectionally assessed physical activity using wrist actigraphy and ratings of catatonia, parkinsonism, and negative syndrome. The sample was enriched with subjects with severe psychomotor slowing. Lower activity levels correlated with increased age and severity of catatonia and parkinsonism. The 22 patients with catatonia had lower activity as well as higher scores on parkinsonism, involuntary movements, and negative symptoms compared to the 30 patients without catatonia. Collectively, these results suggest that various hypokinetic motor abnormalities are linked to lower physical activity. Therefore, future research should determine the direction of the associations between hypokinetic motor abnormalities and physical activity using longitudinal assessments and interventional trials.

Nonverbal communication remains untouched: No beneficial effect of symptomatic improvement on poor gesture performance in schizophrenia.

BACKGROUND: Gestures are an important part of communication. Patients with schizophrenia present gesture deficits that tend to deteriorate in the course of the disease and hamper functional outcome. This gesture deficit has been associated with motor abnormalities, cognitive impairment, and psychotic symptoms. Unaffected, first-degree relatives of schizophrenia patients share some subclinical motor and cognitive abnormalities. We aimed to investigate, whether gesture performance changes with symptomatic improvement in patients, and to test the longitudinal performance in unaffected, first-degree relatives. METHODS: In this study, we measured gesture performance using a validated test in 33 patients, 29 first-degree relatives and 38 healthy controls. Measurements were completed shortly after admission and before discharge in patients. Performance was rated blindly by experts using video recordings of the gesture task. Additionally, we evaluated cognitive function and psychotic symptoms at both visits. RESULTS: Gesture performance was poorer in relatives compared to controls and poorer in patients compared to both relatives and controls. Patients showed an improvement in psychopathology but a significant decrease in gesture performance at follow-up, while performance in the other groups remained stable. Proportional change of gesture performance correlated with change of cognitive function in patients, whereas there were no correlations with change of cognitive function in the other groups. CONCLUSION: While symptom severity was reduced, the gesture deficit further deteriorated in schizophrenia. The finding argues for distinct processes contributing to poor nonverbal communication skills in patients, requiring novel alternative treatment efforts.

Distinct Associations of Motor Domains in Relatives of Schizophrenia Patients-Different Pathways to Motor Abnormalities in Schizophrenia?

INTRODUCTION: Aberrant motor function is an integral part of schizophrenia. In fact, abnormalities are frequently found in patients, in populations at risk, and in unaffected relatives. Motor abnormalities are suspected to be relevant for the clinical outcome and could probably predict the conversion from at-risk individuals to schizophrenia. Furthermore, motor function has been argued as endophenotype of the disorder. Yet, which particular motor domain may classify as a potential endophenotype is unknown. We aimed to compare schizophrenia patients, unaffected first-degree relatives and healthy controls for different motor domains. We expected impairments in all domains in patients and in some domains in relatives. METHOD: We included 43 schizophrenia patients, 34 unaffected first-degree relatives of schizophrenia patients, and 29 healthy control subjects, matched for age, gender, and education level. We compared motor function of four motor domains between the groups. The domains comprise neurological soft signs (NSS), abnormal involuntary movements (dyskinesia), Parkinsonism, and fine motor function including simple [finger tapping (FT)] and complex fine motor function, (i.e., dexterity as measured with the coin rotation test). Furthermore, we tested the association of motor function of the four domains with working memory, frontal lobe function, and nonverbal intelligence for each group separately using within-group bivariate correlations. RESULTS: Schizophrenia patients showed poorer motor function in all tested domains compared to healthy controls. First-degree relatives had intermediate ratings with aberrant function in two motor domains. In detail, relatives had significantly more NSS and performed poorer in the FT task than controls. In contrast, complex fine motor function was intact in relatives. Relatives did not differ from controls in dyskinesia or Parkinsonism severity. DISCUSSION: Taken together, schizophrenia patients have motor abnormalities in all tested domains. Thus, motor abnormalities are a key element of the disorder. Likewise, first-degree relatives presented motor deficits in two domains. A clear difference between relatives and healthy controls was found for NSS and FT. Thus, NSS and FT may be potential markers of vulnerability for schizophrenia. The lack of association between genetic risk and dyskinesia or Parkinsonism suggests distinct pathobiological mechanisms in the various motor abnormalities in schizophrenia.

Resting-State Hyperperfusion of the Supplementary Motor Area in Catatonia.

Catatonia is a psychomotor syndrome that not only frequently occurs in the context of schizophrenia but also in other conditions. The neural correlates of catatonia remain unclear due to small-sized studies. We therefore compared resting-state cerebral blood flow (rCBF) and gray matter (GM) density between schizophrenia patients with current catatonia and without catatonia and healthy controls. We included 42 schizophrenia patients and 41 controls. Catatonia was currently present in 15 patients (scoring >2 items on the Bush Francis Catatonia Rating Scale screening). Patients did not differ in antipsychotic medication or positive symptoms. We acquired whole-brain rCBF using arterial spin labeling and GM density. We compared whole-brain perfusion and GM density over all and between the groups using 1-way ANCOVAs (F and T tests). We found a group effect (F test) of rCBF within bilateral supplementary motor area (SMA), anterior cingulate cortex, dorsolateral prefrontal cortex, left interior parietal lobe, and cerebellum. T tests indicated 1 cluster (SMA) to be specific to catatonia. Moreover, catatonia of excited and retarded types differed in SMA perfusion. Furthermore, increased catatonia severity was associated with higher perfusion in SMA. Finally, catatonia patients had a distinct pattern of GM density reduction compared to controls with prominent GM loss in frontal and insular cortices. SMA resting-state hyperperfusion is a marker of current catatonia in schizophrenia. This is highly compatible with a dysregulated motor system in catatonia, particularly affecting premotor areas. Moreover, SMA perfusion was differentially altered in retarded and excited catatonia subtypes, arguing for distinct pathobiology.