The purpose was to systematically investigate which pharmacological strategies are effective to reduce the risk of violence among patients with Schizophrenia Spectrum Disorders (SSD) in forensic settings.

For this systematic review six electronic data bases were searched. Two researchers independently screened the 6,003 abstracts resulting in 143 potential papers. These were then analyzed in detail by two independent researchers. Of these, 133 were excluded for various reasons leaving 10 articles in the present review.

Of the 10 articles included, five were merely observational, and three were pre-post studies without controls. One study applied a matched case-control design and one was a non-randomized controlled trial. Clozapine was investigated most frequently, followed by olanzapine and risperidone. Often, outcome measures were specific to the study and sample sizes were small. Frequently, relevant methodological information was missing. Due to heterogeneous study designs and outcomes meta-analytic methods could not be applied.

Due to substantial methodological limitations it is difficult to draw any firm conclusions about the most effective pharmacological strategies to reduce the risk of violence in patents with SSD in forensic psychiatry settings. Studies applying more rigorous methods regarding case-definition, outcome measures, sample sizes, and study designs are urgently needed.

Major depressive disorder (MDD) is a heterogeneous condition characterized by depressed mood and/or loss of interest/pleasure in activities, among other symptoms. Most currently available treatments for depression were developed on the hypothesis that depressive symptoms arise from a depletion of monoamines within the central nervous system (CNS). However, clinical understanding has advanced to identify brain network dysregulation as the primary driver of depression, with monoamines playing a lesser role. Prolonged inability to regulate brain networks may lead to the core symptoms and clinical presentation of MDD. Depression has been linked to impaired neuronal activity in brain networks (e.g., central executive network [CEN], default mode network [DMN], and salience network [SN]). It is hypothesized that improvement in depressive symptoms may result from restoring balance in brain networks governing mood.

γ-aminobutyric acid (GABA) is critical for maintaining and restoring excitatory-inhibitory balance in the brain and regulating brain networks. Approximately one-third of neurons in the CNS are GABAergic, regulating network activity throughout the brain, including regions involved in mood, sleep, and cognition. GABA activates GABAA receptors (GABAAR), inhibiting neuronal activity through phasic (via synaptic GABAAR) and tonic (via extrasynaptic GABAAR) currents. Tonic GABA currents may play a particularly important role in regulating network activity, since they produce a large net inhibitory effect and are also involved in controlling the excitability of inhibitory interneurons, the key regulators of rhythmic brain network activity.

Zuranolone is an investigational oral GABAAR positive allosteric modulator and neuroactive steroid. In clinical trials, treatment with zuranolone has shown significant improvement over placebo in depressive symptoms in adults with MDD or postpartum depression, with a generally well-tolerated and consistent safety profile.

The hypothesized mechanism of zuranolone differs from monoamine-based antidepressants and from benzodiazepines. Unlike benzodiazepines, which bind to the α/γ subunit interface in synaptic GABAAR and enhance phasic inhibitory currents, zuranolone binds to the α/β subunit interface present in nearly all GABAAR, leading to enhanced phasic (synaptic) and tonic (extrasynaptic) inhibitory currents. Furthermore, in vitro evidence suggests that whereas benzodiazepines are associated with GABAAR downregulation, zuranolone upregulates the surface expression of GABAAR.

In conclusion, by upregulating GABAAR expression and increasing phasic and tonic inhibitory GABAergic signaling, zuranolone may rapidly restore and maintain excitatory-inhibitory balance in brain networks, thus allowing the brain to potentially respond appropriately to internal and external stimuli.

Sage Therapeutics, Inc., and Biogen Inc.

Mental pain has been proposed as a global person-centered outcome measure. The aim of this cross-sectional study was to test an essential requisite of such a measure, namely that mental pain incorporates independent contributions from a range of discrete but disparate outcome measures.

Two hundred migraine patients were assessed concerning migraine disability, psychosomatic syndromes, mental pain, depression, anxiety, and psychosocial dimensions. General linear models were tested to verify which measures would individually make unique contributions to overall mental pain.

The final model, accounting for 44% of variance, identified that higher mental pain was associated with more severe depressive symptoms, higher migraine disability, lower well-being, and poorer quality of life.

In this sample, mental pain was shown to behave as expected of a global outcome measure, since multiple measures of symptomatology and quality of life showed modest but significant bivariate correlations with mental pain and some of these measures individually made unique contributions to overall mental pain.

To evaluate the effects of tetrahydrobiopterin (BH4) on maladaptive behavior in patients with phenylketonuria (PKU).

In an effort to determine if BH4 has any effects on the central nervous system, we studied 10 individuals with PKU and measurable maladaptive behaviors for 1 year. Behavioral assessments using the Vineland Adaptive Behavior Scales–Second Edition and a PKU Behavior Checklist were obtained at baseline, 6 months, and at the end of the study. Biochemical measures including plasma amino acids were obtained quarterly, and phenylalanine (Phe) and tyrosine (Tyr) were obtained monthly.

Out of the 10 subjects, 2 were responders to BH4, as determined by a blood Phe reduction >30%. While blood Phe in the 8 nonresponders did not change significantly throughout the study, their Tyr levels were significantly higher at 6 months (p=0.012), but not at 12 months (p=0.23). By the end of the study, 8 subjects exhibited fewer maladaptive behaviors on the components of the Vineland Maladaptive Behavior Index, and all 10 had lower total scores on the PKU Behavior Checklist.

These findings suggest that there may be direct effects of BH4 on the central nervous system, independent of lowering blood Phe.

Literature shows that migrants—a generic definition for persons who leave their own country of origin—have increased psychopathological vulnerability. Between 2014 and 2017, 976 963 non-European Union (non-EU) people arrived in Italy, of which 30% for humanitarian reasons. This study is aimed at a better understanding of the experience of asylum seekers who transferred to Italy were subjected to the EU Dublin Regulation and most of them suspended in their asylum application.

We elaborate a descriptive study based on a population of refugees and asylum seekers who have suffered from social and personal migratory stressful factors. Clinical data was collected between 2011 and 2013 at the “A. Gemelli” General Hospital IRCCS, Rome, Italy. Minors, elderly people, and patients who are unable to declare a voluntary consensus and economic migrants were excluded from the study. Candidates for the status of refugee or asylum seekers were included.

The sample consisted of 180 asylum seekers aged 25.52 ± 5.6 years. Most frequently diagnosis was post-traumatic stress disorder (PTSD) (53%), subthreshold PTSD was reported in 22% of subjects. We found phenomenological patterns highly representative of PTSD of the dissociative subtype. Around 20% of the sample suffered from psychotic symptomatology.

Loss of the migratory project and the alienation mediated by chronic social defeat paradigm may trigger a psychopathological condition described by the failure to cope with the negative emotional context of social exclusion and solitude. A common and integrated treatment project is needed, with the scope of reintegrating the migrant’s personal and narrative identity.

To characterize the premorbid cognitive and behavioral abilities in apparently healthy adolescents who at a later time will be diagnosed with schizophreniform disorder or schizophrenia.

Clarifying the pathological relationship between subtle intellectual and behavioral abnormalities and disease could provide markers for the early prediction of future psychosis.

Premorbid data on young male patients admitted to the Department of Psychiatry of the Central Military Hospital in Bucharest, Romania, between 1996 and 2002 and diagnosed with a first episode of psychosis or schizophreniform disorder were collected. The premorbid data consisted in the test scores of intellectual functioning and personality traits were collected by the Romanian Draft Board in order to assesses their aptitude to serve in the military. Premorbid cognitive and behavioral scores of male patients (cases=157) were compared with the scores of healthy male individuals (non-cases=169) matched for age, education, and geographic area of residence. The tests were administered when subjects were 18 years of age (initial screening) and the entire assessment was completed and concluded when subjects reached 20 years of age (actual conscription).

As a group, apparently healthy males later admitted for a first episode of psychosis or schizophreniform disorder, obtained lower (worse) scores on the Raven Progressive Matrices test and on relevant personality traits in comparison to controls.

The results add to the accumulating body of evidence suggesting that aspects of schizophrenia manifest years before the illness is formally diagnosed. Despite these results, more studies are needed to improve the diagnosing specificity and predictive value of the premorbid cognitive and behavioral manifestations, before they can be used as markers in models of primary or secondary prevention.

For some time now, there has been a strong consensus that the migration process can influence the onset, course, development, outcome, and clinical aspects of psychiatric pathologies.

In this study, we have analyzed the influence of the migration process on the clinical expression of heroin use disorder (HUD). In a naturalistic case–control study, we compared, both at univariate and multivariate level, 30 migrant HUD (M-HUD) patients with 30 age/gender-matched Italian HUD (IT-HUD) patients. We also analyzed demographic data, drug addiction history, psychopathological symptoms, addictive behavior, and emotional reactivity to life events.

Compared with IT-HUD pairs, at HUD Agonist Opioid Treatment, M-HUD patients were characterized by inadequate income and the presence of legal problems. They were more frequently at stage 3 of heroin addiction, with a concomitantly less frequent use of stimulants. Their age at the onset of heroin use was greater than that of subjects in the IT-HUD group. HUD post-traumatic stress disorder spectrum was present and was more severe in all M-HUD patients, but grief reactions and maladaptive behavior were the most discriminant traits. No differences were found in terms of addictive behaviors related to heroin craving or with respect to the severity/typology of psychopathology specific to HUD.

The migratory process does not seem to be correlated with addictive behaviors or with psychopathology specific to HUD. It partly affects HUD history, and specifically correlates with emotional reactivity to loss and traumatic life events, so suggesting that in M-HUD individuals, the link between the migratory syndrome and HUD is very close.