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Objective Catatonia is a disorder characterized by psychomotor symptoms. The etiology, symptomatology, response and outcome of catatonia in the medically ill has not been vigorously studied. Those who have catatonia associated with another mental disorder versus. catatonic disorder due to another medical condition may differ. The aim of this study is to study the causes, phenomenology and outcomes of medically ill patients with catatonia and explore differences among those who have catatonia associated with psychiatric illness vs. systemic medical illness. Method We studied the incidence of catatonic symptoms in medically hospitalized patients to identify any apparent differences in clinical manifestations due to distinctive etiologies. Specifically, we assessed if there are differences between those who had catatonia associated with another mental disorder versus those with catatonic disorder due to another medical condition in their phenomenology, management and likelihood of response to treatment. Results Of our 40 patients, 18 patients (45%) had catatonia associated with another mental disorder, 17 (42.5%) had catatonic disorder due to another medical condition, and in 5 patients (12.5%) the cause of catatonia was not identified. The most common catatonic symptoms regardless of etiology in our medically ill were mutism, followed by rigidity, and immobility. Bipolar disorder, schizophrenia, major depressive disorder, metabolic abnormalities, anti NMDAR encephalitis were the most frequent causes of catatonia in our medically ill patients. Compared to subjects with catatonic disorder due to another medical condition, those with catatonia associated with another mental disorder had more frequent mannerisms (Chi-square = 4.27; p = 0.039), waxy flexibility (Chi-square = 11.0; p Discussion Our data supports phenomenological differences between medical and psychiatric causes of catatonia in the medically ill.

Background Late Life Bipolar Disorder (LLBD) is associated with a high prevalence of cognitive impairments, but few studies have examined their risk factors and clinical correlates Methods Participants with bipolar disorder older than 60 ( n = 86) were recruited from psychiatric outpatient and inpatients units. Patients were assessed with various instruments, including the Clinical Dementia Rating scale, the Montreal Cognitive Assessment and the Cumulative Illness Rating Scale. The distribution of disorder-specific and general risk factors was compared between patients with LLBD plus cognitive impairments (mild cognitive impairment or dementia) and those with LLBD but no cognitive impairment. Analyses were first conducted at the bivariate level, then using multiple regression. The association with disability, aggressive behavior and suicidal ideation was also explored. Results Cognitive impairments in LLBD were associated with a diagnosis of type 1 bipolar disorder (OR = 6.40, 95%CI: 1.84 – 22.31, p = 0.004), fewer years of education (OR = 0.79, 95%CI: 0.69 – 0.91, p = 0.001) and higher severity of physical diseases (OR 26.54, 95%CI: 2.07 – 340.37, p = 0.01). Moreover, cognitive impairments were associated with an increased likelihood of disability and recent aggressive behavior, but not suicidal ideation. Limitations retrospective design, conflation of MCI and dementia, not all subjects were in euthymia Conclusions In LLBD, the presence of cognitive impairments was associated with a diagnosis of type I bipolar disorder, lower education and more severe physical comorbidities. In turn, MCI or dementia were associated with increased disability and aggressive behavior. These findings may aid the identification of patients at risk for cognitive deterioration in everyday clinical practice.

Objective White matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural, and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults. Design Cross-sectional study. Setting Community. Participants Fifty-eight cognitively-healthy older adults. Measurements Tasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject's WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks. We evaluated the interaction of regional WMH burden and RSFC in predicting cognitive control and memory. Results The interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with delayed recall. Models predicting working memory, cognitive inhibition, and set-shifting were not significant. Conclusion Findings highlight the role of network-level structural and functional alterations in resting state networks that are related to WMH and impact memory in older adults.

Background Negative self-referential thinking is a common symptom of depression associated with poor treatment response. In late-life depression, white matter abnormalities may contribute to negative self-referential thoughts following antidepressant treatment. We investigated the association of fractional anisotropy (FA) in select regions of the negative valence system (NVS) with residual negative self-referential thoughts following treatment with escitalopram for late-life depression. Methods The participants were older adults with major depression and psychiatrically normal controls. Depressed participants received 12 weeks of treatment with escitalopram. To assess self-referential thinking, participants completed a Trait Adjective Task at baseline and at week 12. Baseline MRI scans included a diffusion imaging sequence for FA analyses. Results Participants with late-life depression differed from controls on all performance measures of the Trait Adjective Task at baseline and at 12 weeks. Depressed participants endorsed fewer negative personality traits and more positive personality traits at week 12 compared to baseline. Lower FA in the dorsal anterior cingulate and in the uncinate fasciculus in depressed participants was correlated with residual negative self-referential thinking (e.g., more endorsed negative adjectives, fewer rejected negative adjectives) at treatment end. Limitations The sample size is modest so the findings are preliminary. FA analyses were restricted to predetermined regions. Conclusions Negative self-referential thinking improved in depressed older adults following 12 weeks of treatment with escitalopram. Baseline FA in select white matter regions of the NVS was associated with residual negative self-referential thinking. These findings may help identify treatment targets for residual negative self-referential thoughts.

ObjectiveWhite matter hyperintensities (WMH) are linked to deficits in cognitive functioning, including cognitive control and memory; however, the structural and functional mechanisms are largely unknown. We investigated the relationship between estimated regional disruptions to white matter fiber tracts from WMH, resting state functional connectivity (RSFC), and cognitive functions in older adults.DesignCross-sectional study.SettingCommunity.ParticipantsFifty-eight cognitively-healthy older adults.MeasurementsTasks of cognitive control and memory, structural MRI, and resting state fMRI. We estimated the disruption to white matter fiber tracts from WMH and its impact on gray matter regions in the cortical and subcortical frontoparietal network, default mode network, and ventral attention network by overlaying each subject’s WMH mask on a normative tractogram dataset. We calculated RSFC between nodes in those same networks.ResultsThe interaction of estimated regional WMH burden and RSFC in cortico-striatal regions of the default mode network and frontoparietal network was associated with memory retrieval. Models predicting working memory, cognitive inhibition, and set-shifting were not significant.ConclusionsFindings highlight the role of circuit-level alterations at the structural and functional levels in resting state networks that are related to WMH and impact memory retrieval in older adults.

Background Problem solving therapy (PST) and “Engage,” a reward-exposure” based therapy, are important treatment options for late-life depression, given modest efficacy of antidepressants in this disorder. Abnormal function of the reward and default mode networks has been observed during depressive episodes. This study examined whether resting state functional connectivity (rsFC) of reward and DMN circuitries is associated with treatment outcomes. Methods Thirty-two older adults with major depression (mean age = 72.7) were randomized to 9-weeks of either PST or “Engage.” We assessed rsFC at baseline and week 6. We placed seeds in three a priori regions of interest: subgenual anterior cingulate cortex (sgACC), dorsal anterior cingulate cortex (dACC), and nucleus accumbens (NAcc). Outcome measures included the Hamilton Depression Rating Scale (HAMD) and the Behavioral Activation for Depression Scale (BADS). Results In both PST and “Engage,” higher rsFC between the sgACC and middle temporal gyrus at baseline was associated with greater improvement in depression severity (HAMD). Preliminary findings suggested that in “Engage” treated participants, lower rsFC between the dACC and dorsomedial prefrontal cortex at baseline was associated with HAMD improvement. Finally, in Engage only, increased rsFC from baseline to week 6 between NAcc and Superior Parietal Cortex was associated with increased BADS scores. Conclusion The results suggest that patients who present with higher rsFC between the sgACC and a structure within the DMN may benefit from behavioral psychotherapies for late life depression. “Engage” may lead to increased rsFC within the reward system reflecting a reconditioning of the reward systems by reward exposure

Background Late-life depression is characterized by network abnormalities, especially within the cognitive control network. We used alternative functional connectivity approaches, regional homogeneity (ReHo) and network homogeneity, to investigate late-life depression functional homogeneity. We examined the association between cognitive control network homogeneity and executive functions. Methods Resting-state functional magnetic resonance imaging data were analyzed for 33 older adults with depression and 43 healthy control subjects. ReHo was performed as the correlation between each voxel and the 27 neighbor voxels. Network homogeneity was calculated as global brain connectivity restricted to 7 networks. T-maps were generated for group comparisons. We measured cognitive performance and executive functions with the Dementia Rating Scale, Trail-Making Test (A and B), Stroop Color Word Test, and Digit Span Test. Results Older adults with depression showed increased ReHo in the bilateral dorsal anterior cingulate cortex (dACC) and the right middle temporal gyrus, with no significant findings for network homogeneity. Hierarchical linear regression models showed that higher ReHo in the dACC predicted better performance on Trail-Making Test B (p Conclusions Higher ReHo within the dACC and right middle temporal gyrus distinguish older adults with depression from control subjects. The correlations with executive function performance support increased ReHo in the dACC as a meaningful measure of the organization of the cognitive control network and a potential compensatory mechanism. Lower functional connectivity between the dACC and the precuneus in late-life depression suggests that clusters of increased ReHo may be functionally segregated.

The duration of untreated depression (DUD) might have a substantial impact on the clinical outcomes; however, there are important knowledge gaps including the effects on disability and potential differences between first-episode and recurrent episodes of depression.We recruited 121 outpatients with first episode and recurrent major depression, and conducted prospective clinical assessments over six months. Clinical outcomes included response to antidepressant therapy, remission and changes in disability.Patients with a DUD of six months or shorter were more frequently young, unemployed and had higher levels of physical illnesses than those with a longer DUD (all p0.05). A shorter DUD was associated with significantly higher odds of response at 12 weeks (adjusted odds ratio 2.8; 95% CI: 1.2-6.8) and remission at 24 weeks (4.1; 95% CI: 1.6-10.5) after adjusting for relevant confounders. Changes in disability ratings were analyzed with growth curve analysis and showed steeper declines among those with a shorter DUD. The associations of DUD on clinical outcomes were evident both in patients with first-episode and recurrent depression.Naturalistic design. Self-rated assessment of disability. Findings from subgroup analyses should be replicated in larger sample size.A shorter duration of untreated depression is associated with more favorable outcomes for major depression, including depression-related disability. This association seems to work both at the first and recurrent episodes, which might have direct implications for both primary and secondary prevention.

Background Neuroleptic malignant syndrome (NMS) is a rare, severe, idiosyncratic adverse reaction to antipsychotics. Second-generation antipsychotics (SGAs) were originally assumed to be free from the risk of causing NMS, however several cases of NMS induced by SGAs (SGA-NMS) have been reported. Objectives The aim of this study was to systematically review available studies and case reports on SGA-NMS and compare the presentation of NMS induced by different SGAs. Data Sources Citations were retrieved from PubMed up to November 2013, and from reference lists of relevant citations. Study Eligibility Criteria Eligibility criteria included (a) primary studies reporting data on NMS, with at least 50 % of the sample receiving SGAs; or (b) case reports and case reviews reporting on NMS induced by SGA monotherapy, excluding those due to antipsychotic withdrawal. Study Appraisal and Synthesis Methods A standardized method for data extraction and coding was developed for the analysis of eligible case reports. Results Six primary studies and 186 individual cases of NMS induced by SGAs were included. Primary studies suggest that SGA-NMS is characterized by lower incidence, lower clinical severity, and less frequent lethal outcome than NMS induced by first-generation antipsychotics. Systematic analysis of case reports suggests that even the most recently marketed antipsychotics are not free from the risk of inducing NMS. Furthermore, clozapine-, aripiprazole- and amisulpride-induced NMS can present with atypical features more frequently than other SGA-NMS, i.e. displaying less intense extrapyramidal symptoms or high fever. Limitations Case reports report non-systematic data, therefore analyses may be subject to bias. Conclusions and Implications of Key Findings Clinicians should be aware that NMS is virtually associated with all antipsychotics, including those most recently marketed. Although apparently less severe than NMS induced by older antipsychotics, SGA-NMS still represent a relevant clinical issue. Electronic supplementary material The online version of this article (doi:10.1007/s40268-014-0078-0) contains supplementary material, which is available to authorized users.

Background: Repetitive transcranial magnetic stimulation (TMS) is a non-invasive, safe, and efficacious treatment for depression. TMS has been shown to normalize abnormal functional connectivity of cortico-cortical circuits in depression and baseline functional connectivity of these circuits predicts treatment response. Less is known about the relationship between functional connectivity of frontostriatal circuits and treatment response. Objective/Hypothesis: We investigated whether baseline functional connectivity of distinct frontostriatal circuits predicted response to TMS. Methods: Resting-state fMRI (rsfMRI) was acquired in 27 currently depressed subjects with treatment resistant depression and 27 healthy controls. Depressed subjects were treated with 5 weeks of daily TMS over the left dorsolateral prefrontal cortex (DLPFC). The functional connectivity between limbic, executive, rostral motor, and caudal motor regions of frontal cortex and their corresponding striatal targets were determined at baseline using an existing atlas based on diffusion tensor imaging. TMS treatment response was measured by percent reduction in the 24-item Hamilton Depression Rating Scale (HAMD24). In an exploratory analysis, correlations were determined between baseline functional connectivity and TMS treatment response. Results: Seven cortical clusters belonging to the executive and rostral motor frontostriatal projections had reduced functional connectivity in depression compared to healthy controls. No frontostriatal projections showed increased functional connectivity in depression (voxel-wise p

Riassunto Introduzione Nel 1999 alcuni psichiatri genovesi iniziarono a operare come consulenti psichiatri per conto del Dipartimento di Salute Mentale (DSM) nel carcere di Marassi, il maggiore istituto penitenziario della Liguria. Negli anni successivi l’interesse dei DSM della regione e della Sezione ligure della Societa Italiana di Psichiatria nei confronti dell’assistenza psichiatrica negli istituti di pena e andato crescendo e, contemporaneamente, si e cominciato a ragionare sulla chiusura degli Ospedali Psichiatrici Giudiziari (OPG). Discussione L’intreccio tra mondo della psichiatria e mondo della giustizia e diventato sempre piu stretto e oggi emergono questioni prioritarie: l’organizzazione dell’assistenza psichiatrica in ambiente carcerario; la presa in carico presso il Centro di Salute Mentale e i Centri Diurni di soggetti con problemi di salute mentale che scontano la pena o la misura di sicurezza al domicilio; il trattamento in struttura residenziale psichiatrica come misura alternativa all’OPG o al carcere; la progettazione di una struttura regionale in grado di accogliere i soggetti prosciolti per infermita di mente con pericolosita sociale elevata nel momento in cui sara chiuso l’OPG.

Background: White matter hyperintensities (WMH) represent ischemic white matter damage in late-life depression (LLD) and are associated with cognitive control dysfunction. Understanding the impact of WMH on the structural connectivity of gray matter and the cognitive control correlates of WMH-related structural dysconnectivity can provide insight into the pathophysiology of LLD. Methods: We compared WMH burden and performance on clinical measures of cognitive control in patients with LLD (N = 44) and a control group of non-depressed older adults (N = 59). We used the Network Modification (NeMo) Tool to investigate the impact of WMH on structural dysconnectivity in specific gray matter regions, and how such connectivity was related to cognitive control functions. Results: Compared to the control group, LLD participants had greater WMH burden, poorer performance on Trail Making Test (TMT) A & B, and greater self-reported dysexecutive behavior on the Frosntal Systems Behavior Scale-Executive Function subscale (FrSBe-EF). Within the LLD group, disrupted connectivity in the left supramarginal gyrus, paracentral lobule, thalamus, and pallidum was associated with psychomotor slowing (TMT-A). Altered connectivity in the left supramarginal gyrus, paracentral lobule, precentral gyrus, postcentral gyrus, thalamus, and pallidum was associated with poor attentional set-shifting (TMT-B). A follow-up analysis that isolated set-shifting ability (TMT-B/A ratio) confirmed the association with dysconnectivity in the bilateral paracentral lobule, right thalamus, left precentral gyrus, postcentral gyrus, and pallidum; additionally, it revealed associations with dysconnectivity in the right posterior cingulate, and left anterior cingulate, middle frontal cortex, and putamen. Conclusions: In LLD, WMH are associated with region-specific disruptions in cortical and subcortical gray matter areas involved in attentional aspects of cognitive control systems and sensorimotor processing, which in turn are associated with slower processing speed, and reduced attentional set-shifting. Clinical trials registration: https://clinicaltrials.gov/ct2/show/NCT01728194 Keywords: Late life depression, cognitive control, executive functions, White matter hyperintensities, Structural connectivity, MRI

Introduction The insight paradox posits that among patients with schizophrenia, better insight is associated with depressive symptoms. However, available studies are characterized by conflicting results. Methods First, we conducted a systematic review, a meta-analysis and a meta-regression based on 59 available correlational studies. Second, we examined a cross-sectional examination on 80 patients diagnosed with schizophrenia in stable phase of the illness. Measures of depressive dimension were based on the Calgary Depression Scale for Schizophrenia (CDSS) and Beck Depression Inventory (BDI), for insight the Scale to assess Unawareness of Mental Disorder (SUMD). Furthermore, we assessed self-stigma, self-esteem and psychotic symptoms to test mediating and moderating models (Preacher and Hayes models). Results In the meta-analysis, global insight was associated weakly, but significantly with depression (effect size r=0.14), as were the insight into the mental disorder (r=0.14), insight into symptoms (r=0.14) and symptoms’ attributions (r=0.17). Whereas, insight into the social consequences of the disorder or into the need for treatment were not associated with symptoms of depression. Better cognitive insight was associated with higher levels of depression. Methodological and clinical factors moderated the magnitude of the association between insight and depression. Similar results were observed in the clinical sample, where self-stigma significantly mediated the association between insight and depression. Conclusions In conclusion, both literature and clinical findings indicate that better insight is associated with higher levels of depressive symptoms among patients with schizophrenia: interventions that are aimed at improving insight need to take into account the implications of these findings