Neuroimaging studies have documented brain structural changes in schizophrenia at different stages of the illness, including clinical high-risk (cHR), genetic high-risk (gHR), first-episode schizophrenia (FES), and chronic schizophrenia (ChS). There is growing awareness that neuropathological processes associated with a disease fail to map to a specific brain region but do map to a specific brain network. We sought to investigate brain structural damage networks across different stages of schizophrenia.

We initially identified gray matter alterations in 523 cHR, 855 gHR, 2162 FES, and 2640 ChS individuals relative to 6963 healthy controls. By applying novel functional connectivity network mapping to large-scale discovery and validation resting-state functional magnetic resonance imaging datasets, we mapped these affected brain locations to four specific networks.

Brain structural damage networks of cHR and gHR had limited and non-overlapping spatial distributions, with the former mainly involving the frontoparietal network and the latter principally implicating the subcortical network, indicative of distinct neuropathological mechanisms underlying cHR and gHR. By contrast, brain structural damage networks of FES and ChS manifested as similar patterns of widespread brain areas predominantly involving the somatomotor, ventral attention, and subcortical networks, suggesting an emergence of more prominent brain structural abnormalities with illness onset that have trait-like stability over time.

Our findings may not only provide a refined picture of schizophrenia neuropathology from a network perspective, but also potentially contribute to more targeted and effective intervention strategies for individuals at different schizophrenia stages.

Evidence has suggested that emotional dysregulation is a transdiagnostic feature in schizophrenia and major affective disorders. However, the relationship between emotional dysregulation and appetite hormone disturbance remains unknown in nonobese adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder.

In total, 22 adolescents with schizophrenia; 31 with bipolar disorder; 33 with major depressive disorder; and 41 healthy age-, sex-, and body mass index (BMI)/BMI percentile-matched controls were enrolled for assessing levels of appetite hormones, namely leptin, ghrelin, insulin, and adiponectin. Emotional regulation symptoms were measured using the parent-reported Child Behavior Checklist―Dysregulation Profile.

Adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder exhibited greater emotional dysregulation symptoms than the control group (P = .037). Adolescents with bipolar disorder demonstrated higher log-transformed levels of insulin (P = .029) and lower log-transformed levels of leptin (P = .018) compared with the control group. BMI (P < .05) and log-transformed ghrelin levels (P = .028) were positively correlated with emotional dysregulation symptoms.

Emotional dysregulation and appetite hormone disturbance may occur in the early stage of severe mental disorders. Further studies are required to clarify the unidirectional or bidirectional association of emotional dysregulation with BMI/BMI percentile and appetite hormones among patients with severe mental disorder.

Disengagement from care in early psychosis is frequent. In outpatient general psychiatric services rates range from 17 % to 60 %. In early intervention programs, rates range from 14 % to 33 % at two years. In Europe, a study reported an initial drop out rate at 48 %.

Measure intensity of care during two years after first hospitalization in a schizophrenia spectrum disorder population. Search for a difference between lost and maintained follow-up patients.

A monocentric retrospective study was conducted. All patients aged 16 to 30 with at least one hospitalization for schizophrenia spectrum disorder from January 2013 to December 2018 in CHAC were included. First hospitalization medical charts and all (social, nurse, psychologist, psychiatrist) outpatient appointments were assessed. A monthly mean of all appointments (MMA) was calculated for each patient. Lost or maintained groups at two years were compared with a Mann-Whitney test.

Among 48 patients, 52,1 % (N=25) disengaged from initial follow up within 2 years. The MMA for (N=46) patients was 1,45 (SD 1,35), 0,5 (SD 0,33) for psychiatrists. For lost patients, the MMA was 1,35 (SD 1,40) compared to 1,55 (SD 1,32) for maintained. No significant difference was found : U=229,50 p=0,45.

At two years, care appears more intensive for maintained patients than for lost ones, but no significant difference was found.

No significant relationships.

Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.

We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week.

The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement.

Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.

The mechanisms underlying the antipsychotic potential of cannabidiol (CBD) remain unclear but growing evidence indicates that dysfunction in the insula, a key brain region involved in the processing of motivationally salient stimuli, may have a role in the pathophysiology of psychosis. Here, we investigate whether the antipsychotic mechanisms of CBD are underpinned by their effects on insular activation, known to be involved in salience processing.

A within-subject, crossover, double-blind, placebo-controlled investigation of 19 healthy controls and 15 participants with early psychosis was conducted. Administration of a single dose of CBD was compared with placebo in psychosis participants while performing the monetary incentive delay task, an fMRI paradigm. Anticipation of reward and loss were used to contrast motivationally salient stimuli against a neutral control condition.

No group differences in brain activation between psychosis patients compared with healthy controls were observed. Attenuation of insula activation was observed following CBD, compared to placebo. Sensitivity analyses controlling for current cannabis use history did not affect the main results.

Our findings are in accordance with existing evidence suggesting that CBD modulates brain regions involved in salience processing. Whether such effects underlie the putative antipsychotic effects of CBD remains to be investigated.

Few studies have explored the complex relationship of pro- and anti-inflammatory cytokines with cognitive function in adolescents with first-episode schizophrenia, bipolar disorder, or major depressive disorder.

In total, 26, 35, and 29 adolescents with first-episode schizophrenia, bipolar disorder, and major depressive disorder, respectively, and 22 age- and sex-matched controls were included in the current study. Cytokines, namely interleukin (IL)-2, IL-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP), were assessed. The Wisconsin Card Sorting Test (WCST) and the working memory task were administered to assess cognitive function.

Using generalized linear models with adjustment for demographic data and clinical symptoms, patients with bipolar disorder were found to exhibit the highest levels of CRP (P = .023), IL-6 (P = .022), and TNF-α (P = .011), and had the lowest IL-2 levels (P = .034) among the four groups. According to the results of the WCST and working memory task, adolescents with schizophrenia exhibited the lowest performance in cognitive function. In addition, among the assessed cytokines, only CRP levels (P = .027) were negatively associated with WCST scores.

Dysregulated pro- and anti-inflammatory cytokines and impaired cognitive functioning were observed in first-episode adolescent-onset schizophrenia, bipolar disorder, and major depressive disorder. The altered cytokine profiles may play important roles in the pathophysiology of schizophrenia, bipolar disorder, and major depressive disorder.

A psychotic episode may be sufficiently traumatic to induce symptoms of post-traumatic stress disorder (PTSD), which could impact outcomes in first-episode psychosis (FEP). Yet, post-traumatic stress disorder is often left untreated and undiagnosed in the presence of psychosis.

To conduct a short review of literature on the prevalence and impact of PTSD after FEP.

We performed a literature search on PUBMED, using the query: “Stress Disorders, Post-Traumatic” [Mesh] AND “first episode” AND “psychosis”. We focused on data from systematic reviews, clinical trials and meta-analysis published on last 10 years, either in English or Portuguese.

Approximately one in two people experience PTSD symptoms and one in three experience full PTSD, following a FEP. Prevalence may be higher in affective psychosis, inpatient samples and patients previously suffering from depression and anxiety. PTSD Symptom Scale – Self-Report (PSS-SR) can be a useful screening instrument, but there is no established evidence-based intervention for PTSD in people with FEP. Coercive intervention such as involuntary hospitalization, seclusion, restraint or being forced to take medication, as well as being around sick or anxious patients, can be upsetting and traumatizing.

Our data showed high rates of psychosis-related PTSD. To prevent PTSD, conditions of hospitalization should be optimized and the use of coercive treatments should be limited. Subjects with recent-onset psychosis should be screened for PTSD symptoms. Evidence-based interventions to treat PTSD symptoms in the context of FEP are needed to address this burden and improve outcomes.

The bipolar disorder is characterized by instability mood. It normally happens in the middle-aged. In elderly patients with a first manic episode, you have to dismiss organic pathology.

To present an elderly patient with a first manic episode

A descriptive study of a clinical case and literature review

A 67-year-old man, married. Consulted Mental Health 5 years ago, about low mood after his early retirement. With no psychiatric treatment. Somatic antecedents: Acute myocardial infarction, hypertension and dyslipidemia. Came to the hospital accompanied by his son-in-law presenting rapid speech and thinking, bright clothing, risky behaviour, irritability, grandiosity deliration ideas and less sleep; being necessary a hospital admission. Blood and urine analysis: with no abnormalities. No toxics in the urine. Asenapine 20mg and Lorazepam 3mg were prescribed with clinical improvement. Brain CT: with no abnormalities. After that, Lithium 400mg per day was prescribed to avoid the induction of depression. Clinical judgement: manic episode. Bipolar disorder Type I

After dismissing somatic causes, the symptomatic treatment of a manic episode in older patients is on the same lines as the treatment for mania in young adults. 8-10% of psychiatric inpatients over age 55-60 years are diagnosed with bipolar disorder. Since there is an increase in the number of individuals living longer, an expected increase in the number of older adults who will be diagnosed with bipolar disorder. Older adults with bipolar disorder will increase in absolute numbers as well as the proportion of the general populations.

No significant relationships.

Observational studies have reported earlier onset of psychosis in schizophrenic patients with a history of cannabis use. Earlier age of onset of schizophrenia has been associated with a poorer outcome. We aimed to examine whether cannabis use determined an earlier onset of schizophrenia in a sample of first episode patients, in an area with one of Europe's highest rates of cannabis use.

116 subjects with first episode psychosis and subsequent diagnosis of schizophrenia (after a 12-month follow-up) were included Age at first antipsychotic treatment (A1T) was used as proxy for age of psychosis onset, and acted as dependent variable for the statistical analysis. Cannabis use was evaluated retrospectively, and divided into three groups according to peak frequency (never, sporadic/frequent, daily).

46 (39.7%) subjects had never used cannabis, 23 (19.9%) had done so sporadically/frequently, and 47 (40.5%) daily. A1T differed between the three groups (mean, in years and [SD]: 27.0 [4.94]; 25.7 [4.44] and 24.5 [4.36]; p = 0.033) and diminished as cannabis use increased (linear tendency; p = 0.009). Post-hoc analysis showed that cannabis use (irrespective of frequency) was significantly associated with decrease in A1T (p = 0.033), as shown by the first contrast [1 −1/2 −1/2]. Post-hoc contrast showed that cannabis users had a significantly lower age of onset of psychosis (mean decrease, in years: 1.93; CI (confidence interval) 95%: 0.17–3.70; p = 0.033).

Cannabis use was significantly associated with a decrease in age of onset of schizophrenia. Age of onset of the disease correlated with frequency of cannabis use.

To examine the relationship between the severity of neurological soft signs at onset and at the 1-year follow-up of patients with schizophrenia, and to investigate temporal stability of neurological soft signs within 1 year from the onset of the first episode schizophrenia.

The study included 92 first-episode male schizophrenic patients. Neurological soft signs were assessed on the Neurological Evaluation Scale (NES) during index hospitalization and at a 1-year follow-up. The patients were divided into remitters and non-remitters according to their psychiatric status assessed at the 1-year follow-up, using the Positive and Negative Syndrome Scale (PANSS).

A trend for a lower score for the NES item “others” in late remitters versus non-remitters at baseline was found during index hospitalization. At the 1-year follow-up, the overall severity of the neurological soft signs was statistically significantly higher in non-remitters than in remitters. Within 1 year after index hospitalization, a significant reduction of neurological soft signs, with the exception of sensory integration, occurred in remitters. Within 1 year after index hospitalization, the non-remitters reported a significant reduction of the overall NES score.

These findings in a population of patients with first episode schizophrenia are in accord with the findings of previous studies which found an association between neurological soft signs, treatment response and outcome. This association may characterize a subgroup of patients with a poor course of illness and outcome. Neurological soft signs might be regarded as one of the indicators of treatment outcome in patients suffering from their first episode of schizophrenia.

To examine the impact of alcohol and substance use on the early course of psychosis.

Methods: First-admitted subjects with psychosis (n = 58) were assessed at 6-month intervals over a 2-year follow-up. Information on substance and alcohol misuse and clinical and social outcome was collected using multiple sources of information.

After adjustment for potential confounding factors, subjects with persistent substance misuse over the follow-up were at increased risk of readmission (OR = 3.1; 95%CI = 1.0-9.4; P = 0.05), of presenting with psychotic symptoms (OR = 4.3; 95%CI = 1.0-18.1; P = 0.04), and with a non-continuous course of illness (OR = 11; 95%CI = 1-122; P = 0.05). No significant association was found between substance misuse and social outcome, or between alcohol misuse and clinical and social outcome.

Persistent substance misuse after a first admission for psychosis has a deleterious impact on clinical outcome. Early identification and treatment of substance use is essential in the care of subjects with incipient psychosis.

To compare the treatment of patients with early psychosis, 2 years after the introduction of an integrated model of enhanced management within a public adult mental health service, with an historic cohort from the same service.

Variables examined in the 2001 cohort were compared with 2008 patients. Computer database review and a file audit were conducted for all patients with early psychosis across the first 2 years of the program.

Compared to the historic cohort, patients in the current cohort were 24% less likely to have been admitted (P = 0.004). There were statistically significant reductions in involuntary status and use of a locked unit. Rates of police involvement in admission and use of seclusion were also reduced, though this trend was not significant. Average length of stay was reduced. Median duration of untreated psychosis was 3 months in both 2001 and 2008 cohorts.

The introduction of an integrated model of management within an area mental health service for patients with early psychosis contributed to significant reductions in admissions, involuntary status and use of a locked ward. The data suggests that enhanced treatment of early psychosis patients can be offered within generic services.

Several factors may contribute to duration of untreated psychosis (DUP): patient-delay, referral-delay and treatment-delay caused by mental health care services (MHS-delay). In order to find the most effective interventions to reduce DUP, it is important to know what factors in these pathways to care contribute to DUP.

To examine the relationship of the constituents of treatment delay, migration status and urbanicity.

In first episode psychotic patients (n = 182) from rural, urban and highly urbanized areas, DUP, migration status and pathways to care were determined.

Mean DUP was 53.6 weeks (median 8.9, SD=116.8). Patient-delay was significantly longer for patients from highly urbanized areas and for first generation immigrants. MHS-delay was longer for patients who were treated already by MHS for other diagnoses.

Specific interventions are needed focusing on patients living in highly urbanized areas and first generation immigrants in order to shorten patient delay. MHS should improve early detection of psychosis in patients already in treatment for other diagnosis.

The implications of cannabis use in the onset of early psychosis and the severity of psychotic symptoms have resulted in a proliferation of studies on this issue. However, few have examined the effects of cannabis use on the cognitive symptoms of psychosis (i.e., neurocognitive functioning) in patients with first-episode psychosis (FEP). This systematic review and meta-analysis aim to assess the neurocognitive functioning of cannabis users (CU) and nonusers (NU) with FEP.

Of the 110 studies identified through the systematic review of 6 databases, 7 met the inclusion criteria, resulting in 14 independent samples and 78 effect sizes. The total sample included 304 CU with FEP and 369 NU with FEP. The moderator variables were age at first use, duration of use, percentage of males, and age.

Effect sizes were not significantly different from zero in any neurocognitive domain when users and NU were compared. Part of the variability in effect sizes was explained by the inclusion of the following moderator variables: (1) frequency of cannabis use (β = 0.013, F = 7.56, p = 0.017); (2) first-generation antipsychotics (β = 0.019, F = 34.46, p ≤ 0.001); and (3) country where the study was carried out (β = 0.266, t = 2.06, p = 0.043).

This meta-analysis indicates that cannabis use is not generally associated with neurocognitive functioning in patients with FEP. However, it highlights the deleterious effect of low doses of cannabis in some patients. It also stresses the importance of the type of antipsychotic prescription and cannabis dose as moderator variables in the neurocognitive functioning of CU with FEP.