Oxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset.

This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC).

Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits.

After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities.

Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.

Gambling is a commonplace phenomenon, existing along a continuum from occasional gambling to functionally impairing gambling disorder. The internet may act as a conduit for some gambling behaviors. The impact of problematic internet use on clinical and cognitive features relevant to gambling has received little research attention.

A total of 206 adults aged 18–30 years who gamble at least five times per year were recruited from the general community and undertook detailed clinical and cognitive assessments. Problematic internet use was defined using a total score of 5 or more on Young’s Diagnostic Questionnaire (YDQ). Linear regression was employed to evaluate the relative contribution of addictive-related, impulsive-related, and compulsive-related measures in predicting YDQ total scores in gamblers.

Gamblers with problematic internet use (18% of the sample) reported lower quality of life, lower self-esteem, elevated rates of intermittent explosive disorder, gambling disorder symptoms, attention deficit hyperactivity disorder (ADHD) symptoms, antisocial personality disorder, and posttraumatic stress disorder (PTSD), as well as relative deficits in decision making and spatial working memory. In linear regression, the extent of problematic internet use was most significantly associated with increased gambling disorder symptoms and increased ADHD symptoms.

Problematic internet use in gamblers is associated with worse quality of life, more problem/pathological gambling symptoms, more psychiatric morbidities, and select cognitive impairment. Refinement of the definition of problematic internet use and exploration of its clinical and cognitive associations are likely to be highly relevant to the treatment of problematic gambling.

This study examined the chronic effects of aripiprazole and cariprazine on serotonin (5-HT1A and 5-HT2A) and glutamate (NMDA and AMPA) receptor subtypes. In addition, the effects of aripiprazole on D2 and D3 receptors were tested and compared with previously reported cariprazine data.

Rats received vehicle, aripiprazole (2, 5, or 15 mg/kg), or cariprazine (0.06, 0.2, or 0.6 mg/kg) for 28 days. Receptor levels were quantified using autoradiographic assays on brain sections from the medial prefrontal cortex (MPC), dorsolateral frontal cortex (DFC), nucleus accumbens (NAc), caudate-putamen medial (CPu–M), caudate-putamen lateral (CPu–L), hippocampal CA1 (HIPP–CA1) and CA3 (HIPP–CA3) regions, and the entorhinal cortex (EC).

Similar to previous findings with cariprazine, aripiprazole upregulated D2 receptor levels in various regions; D3 receptor changes were less than those reported with cariprazine. All aripiprazole doses and higher cariprazine doses increased 5-HT1A receptors in the MPC and DFC. Higher aripiprazole and all cariprazine doses increased 5-HT1A receptors in HIPP–CA1 and HIPP–CA3. Aripiprazole decreased 5-HT2A receptors in the MPC, DFC, HIPP–CA1, and HIPP–CA3 regions. Both compounds decreased NMDA receptors and increased AMPA receptors in select brain regions.

Long-term administration of aripiprazole and cariprazine had similar effects on 5-HT1A, NMDA, and AMPA receptors. However, cariprazine more profoundly increased D3 receptors while aripiprazole selectively reduced 5-HT2A receptors. These results suggest that the unique actions of cariprazine on dopamine D3 receptors, combined with its effects on serotonin and glutamate receptor subtypes, may confer the clinical benefits, safety, and tolerability of this novel compound in schizophrenia and bipolar mania.

The aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating patients with major depressive disorder (MDD) with mixed features who present with mild and moderate-to-severe levels of anxiety.

The data in this analysis were derived from a study of patients meeting the DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/day (n=109) or placebo (n=100). Anxiety severity was evaluated using the Hamilton Anxiety Rating Scale (HAM–A). To evaluate the effect of baseline anxiety on response to lurasidone, the following two anxiety groups were defined: mild anxiety (HAM–A≤14) and moderate-to-severe anxiety (HAM–A≥15). Change from baseline in MADRS total score was analyzed for each group using a mixed model for repeated measures.

Treatment with lurasidone was associated with a significant week 6 change versus placebo in MADRS total score for patients with both mild anxiety (–18.4 vs. –12.8, p<0.01, effect size [ES]=0.59) and moderate-to-severe anxiety (–22.0 vs. –13.0, p<0.001, ES=0.95). Treatment with lurasidone was associated with a significant week 6 change versus placebo in HAM–A total score for patients with both mild anxiety (–7.6 vs. –4.0, p<0.01, ES=0.62), and moderate-to-severe anxiety (–11.4 vs. –6.1, p<0.0001, ES=0.91).

In this post-hoc analysis of an MDD with mixed features and anxiety population, treatment with lurasidone was associated with significant improvement in both depressive and anxiety symptoms in subgroups with mild and moderate-to-severe levels of anxiety at baseline.

Findings suggest that obsessive-compulsive disorder (OCD) and related disorders, referred to as obsessive-compulsive spectrum disorders (OCSDs), are more common in patients with rheumatic fever (RF).

To determine whether RF or Sydenham's chorea increases the probability of anxiety disorders in the relatives of individuals with RF with and without SC.

This was a case-control family study in which 98 probands and 389 first-degree relatives (FDRs) were assessed using structured psychiatric interviews. A Poisson regression model was used to determine whether the presence of any disorder in one family member influences the rate of disorders in the remaining family members.

Generalized anxiety disorder (GAD) occurred more frequently in the FDRs of RF probands than in those of control probands (P=.018). The presence of RF, GAD, or separation anxiety disorder in one family member significantly increased the chance of OCSDs in another member of the family.

Several studies have shown cortical volume loss in frontotemporal regions in schizophrenia patients, and it is known that these reductions may be associated with disease symptoms and cognitive deficits. The aim of this study was to investigate possible cortical thickness correlations in frontotemporal regions in relation to age at onset and duration of illness.

One hundred forty-eight schizophrenia patients (97 males; age and SD 36.30 ± 10.06) and 87 (57 males; age and SD 36.48 ± 10.10) age-matched healthy subjects underwent a brain MRI scan. Cortical segmentation and surface statistical analysis were performed using the FreeSurfer software package. Results were corrected for multiple comparisons using the Monte Carlo method considering a cluster-corrected Type I Error of 5%.

Compared to controls, schizophrenia patients presented significant cortical thinning in the frontotemporal, parietal, and occipital cortices. No correlation between prefrontal cortex thickness and duration of illness in patients with schizophrenia or between frontotemporal cortical thickness and age at onset was found. However, a significant interaction between age and diagnosis was observed on frontal cortical thickness with patients presenting a thinner cortex than expected for age.

Although there was no correlation between age of onset and duration of illness with brain volume, our findings suggest that there is an accelerated cortical loss in schizophrenia, thus reinforcing the progressive processes of the disease.

Some antidepressants, such as trazodone or clomipramine, can be administered intravenously in patients with major depressive disorder (MDD), with potential benefits compared to the standard oral treatment, but available data about their efficacy are limited. The present study was aimed to compare the effectiveness of trazodone and clomipramine (intravenous [i.v.] followed by oral administration).

Some 42 patients with a diagnosis of MDD according to the DSM–5 were selected and treated with i.v. trazodone or clomipramine according to clinical judgment. The Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Montgomery-Åsberg Depression Rating Scale were administered at baseline, after 2 weeks, and after 6 weeks, as well as after 1 week of intravenous antidepressant administration. Raters were blinded to type of treatment.

No significant differences were found between treatment groups in terms of effectiveness at endpoint. Borderline statistical significance was found in terms of number of responders in favor of trazodone. In addition, patients treated with trazodone reported fewer total side effects than those treated with clomipramine.

Both i.v. trazodone and clomipramine are rapid and effective options for improving depressive symptoms, although trazodone appears to be tolerated better. Further studies with larger samples and double-blind conditions are warranted to confirm our results.

Minimal long-term benefit: Risk data are available regarding antipsychotic treatments for schizophrenia in pediatric populations. This study evaluated the long-term safety, tolerability, and effectiveness of lurasidone in adolescents with schizophrenia.

Patients aged from 13 to 17 who completed 6 weeks of double-blind (DB), placebo-controlled treatment with lurasidone were enrolled in a 2-year, open-label (OL), flexible dose (20-80 mg/day) lurasidone treatment study. Safety was assessed via spontaneous reporting, rating scales, body weight measurement, metabolic, and prolactin testing. Effectiveness measures included the Positive and Negative Syndrome Scale (PANSS) total score.

About 271 patients completed 6 weeks of DB treatment and entered the 2-year OL extension study. Altogether, 42.4% discontinued prematurely, 10.7% due to adverse events. During OL treatment, the most common adverse events were headache (24.0%); anxiety (12.9%), schizophrenia, and nausea (12.5%); sedation/somnolence (12.2%); and nasopharyngitis (8.9%). Minimal changes were observed on metabolic parameters and prolactin. Mean change from DB baseline in weight at week 52 and week 104 was +3.3 kg and + 4.9 kg, respectively, compared to an expected weight gain of +3.4 kg and + 5.7 kg, respectively, based on the sex- and age-matched US Center for Disease Control normative data. Continued improvement was observed in PANSS total score, with mean change from OL baseline of −15.6 at week 52 and −18.4 at week 104.

In adolescents with schizophrenia, long-term lurasidone treatment was associated with minimal effects on body weight, lipids, glycemic indices, and prolactin. Continued improvement in symptoms of schizophrenia was observed over 2 years of lurasidone treatment.

Central nervous system (CNS) may be infected by several agents, resulting in different presentations and outcomes. Analysis of cerebrospinal fluid (CSF) markers could be helpful to differentiate specific conditions and setting an appropriate therapy.

Patients presenting with signs and symptoms were enrolled if, before receiving a diagnostic lumbar puncture, signed a written informed consent. We analyzed CSF indexes of blood–brain barrier permeability (CSF to serum albumin ratio or CSAR), inflammation (CSF to serum IgG ratio, neopterin), amyloid deposition (1–42 β-amyloid), neuronal damage (Total tau (T-tau), Phosphorylated tau (P-tau), and 14.3.3 protein) and astrocyte damage (S-100β).

Two hundred and eighty-one patients were included: they were mainly affected by herpesvirus encephalitis, enterovirus meningoencephalitis, bacterial meningitis (Neisseria meningitidis and Streptococcus pneumoniae), and infection by other etiological agents or unknown pathogen. Their CSF features were compared with HIV-negative patients and native HIV-positive individuals without CNS involvement. 14.3.3 protein was found in bacterial and HSV infections while T-tau and neopterin were abnormally high in the herpesvirus group. P-tau, instead, was elevated in enterovirus meningitis. S-100β was found to be high in patients with HSV-1 and HSV-2 infections but not in those with Varicella Zoster Virus (VZV). Thirty-day mortality was unexpectedly low (2.7%): patients who died had higher levels of T-tau and, significantly, lower levels of Aβ1–42.

This work demonstrates that CSF biomarkers of neuronal damage or inflammation may vary during CNS infections according to different causative agents. The prognostic value of these biomarkers needs to be assessed in prospective studies.

To examine the prevalence of the C677T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene and the A2756G polymorphism of methionine synthase (MS), and their impact on antidepressant response.

We screened 224 subjects (52% female, mean age 39 ± 11 years) with SCID-diagnosed major depressive disorder (MDD), and obtained 194 genetic samples. 49 subjects (49% female, mean age 36 ± 11 years) participated in a 12-week open clinical trial of fluoxetine 20–60 mg/day. Association between clinical response and C677T and A2756G polymorphisms, folate, B12, and homocysteine was examined.

Prevalence of the C677T and A2756G polymorphisms was consistent with previous reports (C/C = 41%, C/T = 47%, T/T = 11%, A/A = 66%, A/G = 29%, G/G = 4%). In the fluoxetine-treated subsample (n = 49), intent-to-treat (ITT) response rates were 47% for C/C subjects and 46% for pooled C/T and T/T subjects (nonsignificant). ITT response rates were 38% for A/A subjects and 60% for A/G subjects (nonsignificant), with no subjects exhibiting the G/G homozygote. Mean baseline plasma B12 was significantly lower in A/G subjects compared to A/A, but folate and homocysteine levels were not affected by genetic status. Plasma folate was negatively associated with treatment response.

The C677T and A2756G polymorphisms did not significantly affect antidepressant response. These preliminary findings require replication in larger samples.