Alterations in gray matter volume (GMV) are a robust feature of schizophrenia. However, it is not clear to what extent these abnormalities are correlates of the genetic liability to the disorder, as opposed to environmental factors and the disorder itself.

We investigated the influence of genetic risk and illness on GMV in monozygotic (MZ) twin pairs concordant and discordant for schizophrenia.

Total and regional GMVs were measured from magnetic resonance images of 80 twins: 14 MZ pairs concordant for schizophrenia, 9 pairs discordant for schizophrenia, and 17 healthy MZ twin pairs. The three groups were matched for age, gender, handedness, level of education, parental socioeconomic status, and ethnicity.

Total GMV was smaller in twins with schizophrenia (t=-3.17, p= 0.003) and non-psychotic co-twins from discordant pairs (t=-2.66, p= 0.011) than in healthy control twins. Twin pairs concordant for schizophrenia displayed reduced regional GMV in the inferior frontal, medial frontal, and anterior cingulate gyri, the caudate, lingual gyrus and cerebellum relative to healthy twins (p< 0.05, corrected). Within discordant pairs, twins with schizophrenia had less GMV than their non-psychotic co-twins in the insula, superior/medial frontal, pre/postcentral, cingulate and superior temporal gyri, and the paracentral lobule. There were no significant differences in regional GMV between non-psychotic co-twins and healthy controls.

The presence of schizophrenia was specifically related to reduced GMV in frontal, insular, cingulate, medial parietal and temporal cortex, over and above effects of genetic risk for the disorder.

Structural brain abnormalities have consistently been found in schizophrenia, with increased familial risk for the disease associated with these abnormalities. Some brain volume changes are progressive over the course of the illness.

To investigate whether these progressive brain volume changes are mediated by genetic or disease-related factors.

We carried out a 5-year follow-up study in monozygotic (MZ) and dizygotic (DZ) twin pairs discordant for schizophrenia (DISC) and healthy comparison (HC) twin pairs using brain magnetic resonance imaging. A total of 92 participants completed the study (DISC: 9 MZ and 10 DZ; HC: 14 MZ and 13 DZ). Percentage volume changes of the whole brain and cerebral gray and white matter were estimated. Structural equation modeling was applied to estimate contributions of additive genetic and common and unique environmental factors.

Significant decreases over time in whole brain volume was found in patients with schizophrenia and their unaffected co-twins compared with control twins. Bivariate structural equation modeling using cross-trait/cross-twin correlations revealed significant additive genetic influences on the correlations between schizophrenia liability and progressive whole brain (66%; 95% confidence interval [CI], 51%-100%), frontal lobe (76%; 95% CI, 54%-100%), and temporal lobe (79%; CI, 56%-100%) volume change.

The progressive brain volume loss found in patients with schizophrenia and their unaffected co-twins is at least partly attributable to genetic factors related to the illness.

Altered neurocognitive function in schizophrenia could reflect both genetic and illness-specific effects.

To use functional magnetic resonance imaging to discriminate between the influences of the genetic risk for schizophrenia and environmental factors on the neural substrate of verbal fluency, a candidate schizophrenia endophenotype using a case control twin design.

We studied 23 monozygotic twin pairs: 13 pairs discordant for schizophrenia and 10 pairs of healthy volunteer twins. Groups were matched for age, gender, handedness, level of education, parental socio-economic status, and ethnicity. Behavioural performance and regional brain activation during a phonological verbal fluency task were assessed.

Relative to healthy control twins, both patients and their non-psychotic co-twins produced fewer correct responses and showed less activation in the medial temporal region and inferior frontal gyrus. Twins with schizophrenia showed greater activation than both their non-psychotic co-twins and controls in right lateral temporal cortex, reflecting reduced deactivation during word generation while their non-psychotic co-twins showed greater activation in the left temporal cortex.

Both genetic vulnerability to schizophrenia and schizophrenia were associated with impaired verbal fluency performance, reduced engagement of the medial temporal region and dorsal inferior frontal gyrus. Schizophrenia was specifically associated with an additional reduction in deactivation in the right temporal cortex.

It is unknown if the positive effects of intensive early intervention programmes are sustainable over time. Duration of untreated psychosis (DUP) is associated with outcome of schizophrenia, and it has been proved that DUP can be shortened. Randomized clinical trials have tested possibilities for interventions in high risk groups.

We conducted a single-blinded randomized controlled trial of two years of specialized assertive early intervention programme (OPUS) versus standard treatment. A total of 547 first-episode patients with first episode psychosis or schizotypal disorder were included in the trial and reinterviewed after one, two and five years. OPUS treatment consisted of ACT with family involvement and social skills training.

At five-year follow-up, the positive effect on psychotic and negative symptoms of the treatment seen after two years had disappeared. A significantly smaller percentage of patients from the experimental group were living in supported housing and were hospitalized fewer days during the five-year period. Among patients with schizotypal disorder, the proportion who had a transition to psychosis after one year was 8.1 vs. 28.0 percent for patients randomized to OPUS vs. standard treatment, respectively. At two-year follow-up the figures were 28.1 vs. 44.0. Duration of untreated psychosis (DUP) median was 48 weeks. Longer DUP was independently associated with more psychotic symptoms at entry and at one-year and two-year follow-up.

Due to previous findings, we have started a new trial in which we will randomize 400 patients to two years versus five years of specialized assertive treatment.

Despite significant advances, early detection and intervention regarding psychosis still face major obstacles. The Basel FePsy-study tries to contribute to optimising the methods for assessment of risk for psychosis, by describing individuals in an At Risk Mental State (ARMS) with and without later transition to psychosis as compared to healthy (HC) and depressive controls (DC) and by using a multidomain approach including not only psychopathology and clinical risk factors, but also neuropsychology, neurophysiology and neuroimaging.

60 ARMS subjects, 51 HC and 34 DC were investigated. 53 ARMS individuals could be followed up for up to 7 years.

21 ARMS individuals made the transition to psychosis (transition rate 34%). As compared to HC, they showed significant deficits in executive functions and working memory. Predictors of transition were certain attenuated psychotic and negative symptoms and certain cognitive deficits. In an integrated model for prediction of transition using these variables, the overall predictive accuracy was 80.9%, with a sensitivity of 83.3% and a specificity of 79.3%. Specificity of prediction could be further improved by EEG analysis. Furthermore, MRI showed specific differences between ARMS with and without later transition to psychosis.

Individuals at risk for psychosis do not only show psychopathological prodromes and social decline, but also neuropsychological impairments and EEG- as well as MRI-abnormalities. Hopefully in the near future, a clinical staging of individuals according to their risk for psychosis will be possible with corresponding stepwise early interventions.

Little is known about the early phases of bipolar disorders (BPAD) and most of current knowledge derives from putative “high-risk” studies conducted in populations of bipolar off-spring; such information may therefore be relevant only to a subgroup of at-risk subjects.

Retrospective assessment of the phase preceding the emergence of mania and of premorbid characteristics of patients treated for a first episode of psychotic mania. The collected data was used mainly to generate hypotheses.

Before onset of a first episode of psychotic mania, patients go through a phase of change from previous mental state where they present mood symptoms, sleep disruption and general functional decline. These clinical manifestations are likely to have low specificity. However, their occurrence in patients presenting certain risk factors or markers of vulnerability that were identified at a relatively high prevalence in our sample, may be an indicator of impending first episode mania.

This is a retrospective study, in a small sample of patients presenting with psychotic mania. Criteria identified need therefore to be validated in larger prospective studies.

Early identification of patients at risk to develop a first episode of psychotic mania is unlikely to be possible on the basis of symptoms alone. However, the occurrence of certain clinical characteristics in patients who have risk factors or markers of vulnerability to BPAD may be a sign of impending first episode mania.

Although Nicotine replacement therapy (NRT) is an effective treatment for smokers who want to quit, the rates of smoking cessation can be still improved. In an effort to increase these proportions, factors that may influence the occurrence of relapse have been increasingly studied (e.g. pharmacotherapy, socio-demographic characteristics) and there has been a growing interest in psychological and psychiatric clinical factors.

Nicotine dependence (assessed via the Fagerström Tolerance Questionnaire, FTQ), psychological distress (measured via the Symptom Rating Test, SRT), and personality traits (evaluated via the Adult Eysenck Personality Inventory, AEPI) were evaluated as possible predictors of smoking cessation in a sample of 297 cigarette smokers followed for one year as part of a NRT double-blind, parallel group, randomized trial.

Baseline nicotine dependence (weeks 12 and 26: p < 0.05), AEPI neuroticism (weeks 12 and 52: p < 0.05), and AEPI psychoticism (weeks 12 and 52: p < 0.05) scores significantly influenced the outcome of smoking cessation during one - year of follow-up. An increase in psychological distress during follow-up was associated with a lower probability of quitting smoking (p = 0.000).

Nicotine dependence, neuroticism, psychoticism and, over time, psychological distress were the main factors influencing the long-term outcome (i.e., up to 12 months) of smoking cessation under NRT. Thus, psychological distress and personality characteristics should be evaluated in smokers who apply for assistance in smoking cessation with the aim to have a complete assessment and propose tailor-made interventions.

One century ago, Elmer Southard investigated developmental brain lesions in schizophrenia from the analysis of cortex macroscopic anatomy. So far, a number of epidemiologic, genetic, and brain imaging studies have further supported the hypothesis that abnormal brain development could be a risk factor for schizophrenia. However, the mechanisms underlying its symptomatological expression are still debated, in particular for the auditory verbal hallucinations (AVH).

Brain imaging studies in schizophrenia patients with AVH have reported both functional and anatomical deviations in language-related cortical regions but it is still unclear whether these deviations relate to neurodevelopmental impairments. We investigated the cortex gyrification in schizophrenia patients with AVH as gyrification can be considered an indirect marker of gyration and sulcation, namely the development of gyri and sulci.

Using recent sophisticated computer-based morphometry methods, we detected abnormal gyrification in the language-related cortex in schizophrenia patients with persistent AVH. In addition, in comparison to healthy subjects, opposite displacements of the junction between the superior temporal sulcus and its anterior branch were found in patients with AVH heard inside the head in comparison to patients with AVH heard outside the head.

Such sulcal abnormalities support a neurodevelopmental component to AVH in schizophrenia. Furthermore, the “sulcal dysjunction” suggests impairments during early brain maturation, when the STS and its anterior branch appear and merge. Recent results on the genetic, neurochemical and biomechanical processes involved on the cortex gyrification will provide new insight into the pathophysiology of AVH in schizophrenia.

Cannabis is the world's most commonly used illicit substance. Whilst its effects on perception are well documented, little is known about the neural basis of these effects and how they are modulated by two of cannabis sativa's most abundant active ingredients, Delta-9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD).

We used fMRI to assess the effects of THC and CBD on brain activation during a simple visual and auditory stimulation paradigm in healthy volunteers.

Fourteen right handed male subjects were scanned on 3 occasions. Identical 10mg THC, 600mg CBD and placebo capsules were allocated in a balanced double blinded pseudorandomised crossover design.

Ingestion of THC and CBD led to reliable increases in plasma levels of each substance and for THC concomitant increases in anxiety, intoxication and positive psychotic symptoms; CBD and placebo caused no significant symptoms. Visual and auditory stimulation led to robust activations in occipital and temporal cortices respectively under placebo conditions. Administration of THC led to decreased activation in primary sensory cortices relative to placebo whilst CBD led to an increase in activation in right temporal regions during auditory stimulation and right striate cortex activation during visual stimulation. THC mediated reduction of activation in this area during auditory stimulation correlated with a concomitant rise in psychotic symptoms.

These data indicate that the different psychoactive constituents of cannabis have dissociable effects on sensory processing, often in opposite directions

Hallucinations are extremely distressing erroneous percepts accompanied by a powerful sense of reality. In schizophrenia, hallucinations were functionally explored in the verbal domain even if they may emerge outside the range of auditory. In the present study, we used advanced-Independent Component Analysis for fMRI-data-sets (ICA) to explore complex hallucinations and define potential rTMS targets beyond the conventional temporo-parietal junction.

16 adolescents with early-onset schizophrenia and suffering from refractory complex hallucinations were included. They all benefited from a 30-min. rest fMRI examination after which they were accurately interviewed about their psycho-sensory experiences during scanning. Using cortex-based ICA, BOLD signals related to the hallucinatory experience were extracted at the subject level and then submitted to a self-organizing-group ICA procedure to extract clusters at the group-level on the basis of a pure similarity matrix.

This method highlighted auditory, visual and multisensory hyper-active clusters after decomposition by random-effect sog-ICA (ǀZǀ=2.2; p< 0.01). The increased BOLD-signal measured in association sensory areas during hallucinations was concomitant of the de-engagement of the “resting-state” network in hallucinating subjects.

Data-driven analysis methods for rest-fMRI-data allowed evidencing the neural correlates of complex hallucinations in adolescents with schizophrenia. Despite inter-individual variability, sog-ICA clearly demonstrates that the hallucinatory experience emerges from increased activity within modality-dependent associative sensory cortices and can be fused in cross-modal areas. These brain regions constitute good candidates to guide dimensional treatment of hallucinations like rTMS.