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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.

Neuroimaging features of small vessel disease (SVD) are highly prevalent in older adulthood and associated with significant variability in clinical symptoms, yet the factors predicting these symptom disparities are poorly understood. We employed a novel metric of SVD, peak width of skeletonized mean diffusivity (PSMD), to elucidate the relationship of late-life depression (LLD) to the cognitive presentation of vascular pathology. A total of 109 older adults without a diagnosis of a neurocognitive disorder were enrolled in the study; 44 with major depressive disorder and 65 age-matched controls. Subjects completed neuropsychological testing and magnetic resonance imaging including FLAIR and diffusion tensor imaging sequences, from which white matter hyperintensity volume and diffusion metrics (fractional anisotropy, mean diffusivity, PSMD) were quantified. In hierarchical models, the relationship between vascular burden and cognitive performance varied as a function of diagnostic status, such that the negative association between PSMD and processing speed was significantly stronger in participants with LLD compared to controls. Greater PSMD also predicted poorer performance on delayed memory and executive function tasks specifically among those with LLD, while there were no associations between PSMD and task performance among controls. PSMD outperformed conventional SVD and diffusion markers in predicting cognitive performance and dysexecutive behaviors in participants with LLD. These data suggest that LLD may confer a vulnerability to the cognitive manifestations of white matter abnormalities in older adulthood. PSMD, a novel biomarker of diffuse microstructural changes in SVD, may be a more sensitive marker of subtle cognitive deficits stemming from vascular pathology in LLD.

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

Psychomotor symptoms of depression are understudied despite having a severe impact on patient outcomes. This review aims to summarize the evidence on motor features of depression assessed with instrumental procedures, and examine age-related differences. We included studies investigating posture, balance and gait ascertained with instrumental measurements among individuals with depressive symptoms or disorders. Studies on subjects with specific physical illnesses were excluded. Methodological quality was assessed with the Newcastle - Ottawa Scale (NOS) and PRISMA guidelines were followed. 33 studies (13 case-control, five cross-sectional, nine longitudinal and six intervention) with overall low-medium quality were included. Different instruments were employed to assess posture (e.g. digital cameras), balance (balance, stepping platform) or gait (e.g. Six-Minute-Walking Test, instrumented walkways). Results suggest that depression in adults is associated with significant impairments of posture, balance and gait. Motor abnormalities among depressed older adults may depend on the interplay of physical diseases, cognitive impairment and mood. Very few intervention studies measured motor symptoms as outcome. Available evidence suggests, however, that antidepressant drugs and physical exercise may be beneficial for motor abnormalities. Despite the lack of high-quality studies, instrumental assessments confirm the presence and importance of motor abnormalities in depression, with potential age-related differences in their pathophysiology.

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

Objectives To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic–Pituitary–Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Methods Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Results Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p = 0.005) and participants’ age (p = 0.08), and negatively with antipsychotics use (p = 0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. Conclusions BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunction s might be a novel strategy to improve the outcomes of BD.

The so-called "insight paradox" posits that among patients with schizophrenia higher levels of insight are associated with increased levels of depression. Although different studies examined this issue, only few took in account potential confounders or factors that could influence this association. In a sample of clinically stable patients with schizophrenia, insight and depression were evaluated using the Scale to assess Unawareness of Mental Disorder and the Calgary Depression Scale for Schizophrenia. Other rating scales were used to assess the severity of psychotic symptoms, extrapyramidal symptoms, hopelessness, internalized stigma, self-esteem, and service engagement. Regression models were used to estimate the magnitude of the association between insight and depression while accounting for the role of confounders. Putative psychological and sociodemographic factors that could act as mediators and moderators were examined using the PROCESS macro. By accounting for the role of confounding factors, the strength of the association between insight into symptoms and depression increased from 13% to 25% explained covariance. Patients with lower socioeconomic status (F = 8.5, P = .04), more severe illness (F = 4.8, P = .03) and lower levels of service engagement (F = 4.7, P = .03) displayed the strongest association between insight and depression. Lastly, hopelessness, internalized stigma and perceived discrimination acted as significant mediators. The relationship between insight and depression should be considered a well established phenomenon among patients with schizophrenia: it seems stronger than previously reported especially among patients with lower socioeconomic status, severe illness and poor engagement with services. These findings may have relevant implications for the promotion of insight among patients with schizophrenia.

Background: Major depressive disorder (MDD) is a disabling illness associated with significant functional and psychosocial impairment. Although many psychopharmacological agents are currently available for its treatment, many MDD patients suffer from treatment-resistant depression (TRD). Methods: A systematic review of the current literature (Pubmed/Medline, Scopus and ScienceDirect search) has been conducted with the primary aim to investigate the role of repetitive transcranial magnetic stimulation (rTMS) in improving neurocognition in patients with TRD. Studies were included according to the following criteria: (a) being an original paper in a peer-reviewed journal and (b) having analyzed the effect of rTMS on neurocognitive functioning in TRD. Results: The combined search strategy yielded a total of 91 articles, of which, after a complete analysis, 22 fulfilled our inclusion criteria. Based on the main findings, most of the selected studies suggested the existence of a trend towards improvements in the neurocognitive profile using rTMS. Negative findings have also been reported. However, most studies were limited by their small sample size or included mixed samples, or the adopted single-blind designs potentially biased the blinding of the study design. Conclusion: rTMS is a noninvasive brain stimulation that may be considered a valuable and promising technique for cognitive enhancement in TRD.

Among patients with schizophrenia, better insight may be associated with depression, but the findings on this issue are mixed. We examined the association between insight and depression in schizophrenia by conducting a systematic review and meta-analysis. The meta-analysis was based on 59 correlational studies and showed that global clinical 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). Conversely, neither insight into the social consequences of the disorder nor into the need for treatment was associated with symptoms of depression. Better cognitive insight was significantly associated with higher levels of depression. The exploratory meta-regression showed that methodological factors (e.g. the instrument used to assess depression and the phase of the illness) can significantly influence the magnitude of the association between insight and depression. Moreover, results from longitudinal studies suggest that the relation between insight and depression might be stronger than what is observed at the cross-sectional level. Finally, internalized stigma, illness perception, recovery attitudes, ruminative style, and premorbid adjustment seem to be relevant moderators and/or mediators of the association between insight and depression. In conclusion, literature indicates that among patients with schizophrenia, better insight is associated with higher levels of depressive symptoms. Thus, interventions aimed at promoting patients' insight should take into account the clinical implications of these findings.

Gamma butyrolactone (GBL) is an increasingly popular drug of abuse that is readily available in most countries, and it is often purchased over the Internet. In addition to the acute hazards of intoxication and overdose, users who are dependent on GBL can also experience severe withdrawal reactions, including hallucinations, agitation, confusion, delusions, delirium, rhabdomyolysis, and seizures. Most of the existing literature suggests the use of a high-dose benzodiazepine as a first-line treatment for GBL withdrawal. However, several cases of resistance to benzodiazepines have been observed, which likely reflect some pharmacological differences between benzodiazepines and GBL. Specifically, the effects of benzodiazepines are primarily mediated by gamma-aminobutyric acid (GABA)-A receptors, while GBL and its analogues act mainly at GABA-B receptors, with possible additional effects via the ionotropic GABA-A receptors. In this regard, recent studies have found that GBL and its analogues possess a high affinity for a specific form of extrasynaptic GABA-A receptors that are strongly activated by barbiturates, such as phenobarbital, but that are insensitive to benzodiazepines. Taken together, these findings suggest that barbiturates could be evaluated as first-choice agents for the treatment of GBL/gamma hydroxybutyrate (GHB) withdrawal instead of benzodiazepines. In support of this view, we describe a clinical case of difficult to manage GBL withdrawal symptoms in a 42-year-old male. We also review the literature on treatment options for GBL/GHB withdrawal, including benzodiazepine-resistant withdrawal.

Individuals with psychotic disorders are more likely to have vitamin D (VD) deficiency, while evidence suggests VD could have pathophysiological roles. We summarized meta-analytically the available evidence on VD levels in psychotic disorders in comparison with healthy controls and other psychiatric illnesses. We found seven studies, all reporting insufficient VD levels in patients with psychosis. Schizophrenia had a medium effect size for lower VD than healthy controls, and a trend for lower levels than other psychoses. There were non-significant differences between schizophrenia and major depression. No study has investigated the potential psychotropic effects of VD supplementation in patients with psychosis.

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