Cognitive behavioural therapy leaflet.

This leaflet is for anyone who wants to know more about Cognitive Behavioural Therapy (CBT).It discusses how it works, why it is used, its effects, its side-effects, and alternative treatments. If you can't find what you want here, there are sources of further information at the end of this leaflet. What is CBT? It is a way of talking about: ï,§ how you think about yourself, the world and other people ï,§ how what you do affects your thoughts and feelings. CBT can help you to change how you think ('Cognitive') and what you do ('Behaviour'). These changes can help you to feel better. Unlike some of the other talking treatments, it focuses on the 'here and now' problems and difficulties. Instead of focusing on the causes of your distress or symptoms in the past, it looks for ways to improve your state of mind now. When does CBT help? CBT has been shown to help with many different types of problems. These include: anxiety, depression, panic, phobias (including agoraphobia and social phobia), stress, bulimia, obsessive compulsive disorder, post-traumatic stress disorder, bipolar disorder and psychosis. CBT may also help if you have difficulties with anger, a low opinion of yourself or physical health problems, like pain or fatigue. How does it work? CBT can help you to make sense of overwhelming problems by breaking them down into smaller parts. This makes it easier to see how they are connected and how they affect you. These parts are: ï,§ A Situation - a problem, event or difficult situation. From this can follow: ï,§ Thoughts ï,§ Emotions ï,§ Physical feelings ï,§ Actions Each of these areas can affect the others. How you think about a problem can affect how you feel physically and emotionally. All these areas of life can connect like this: {5 Areas - click related link below} What happens in one of these areas can affect all the others. There are helpful and unhelpful ways of reacting to most situations, depending on how you think about it. The way you think can be helpful - or unhelpful. An example: If you go home feeling depressed, you'll probably brood on what has happened and feel worse. If you get in touch with the other person, there's a good chance you'll feel better about yourself. If you avoid the other person, you won't be able to correct any misunderstandings about what they think of you - and you will probably feel worse. This 'vicious circle' can make you feel worse. It can even create new situations that make you feel worse. You can start to believe quite unrealistic (and unpleasant) things about yourself. This happens because, when we are distressed, we are more likely to jump to conclusions and to interpret things in extreme and unhelpful ways. CBT can help you to break this vicious circle of altered thinking, feelings and behaviour. When you see the parts of the sequence clearly, you can change them - and so change the way you feel. CBT aims to get you to a point where you can 'do it yourself', and work out your own ways of tackling these problems. [For full factsheet â?" click on link above]This resource was contributed by the National Documentation Centre on Drug Use.

Mental illness, offending and substance misuse.

This leaflet is for members of the public who want to know more about mental illness, offending and substance misuse. We describe what is meant by mental disorder, offending and substance misuse and how often they are seen together. Also we will talk about treatments and other sources of help. We examine whether people with mental illness are more likely to commit violent crimes. Offending and mental health: Mental illness is sometimes called a â?~mental disorderâ?T. This includes schizophrenia, bipolar disorder, drug-induced psychosis, personality disorder, depression, anxiety and post-traumatic stress disorder. These are just some examples of mental disorders. The branch of psychiatry dealing with the assessment and treatment of offenders with mental health problems is called â?~forensic psychiatryâ?T.This resource was contributed by The National Documentation Centre on Drug Use.

Mental health and growing up factsheet. Drugs and alcohol - what parents need to know.

Information about drugs and alcohol - what parents need to know: information for parents, carers and anyone who works with young people. About this leaflet This is one in a series of leaflets for parents, teachers and young people entitled Mental Health and Growing Up. These leaflets aim to provide practical, up-to-date information about mental health problems (emotional, behavioural and psychiatric disorders) that can affect children and young people. This leaflet offers practical advice for parents, teachers and carers who are worried that a young person is misusing drugs or alcohol. Why do I need to know about a young person using drugs or alcohol? Many young people smoke, drink alcohol and may try drugs. It is important you are aware of this and do not ignore it as a time when they are just having fun or experimenting. It doesnââ,‰"¢t take much for the young people to soon lose control and to need help to recover from this problem. How common is it? By the age of 16, up to half of young people have tried an illegal drug. Young people are trying drugs earlier and more are drinking alcohol. What are the different types of drugs which cause problems? The most commonly used, readily available and strongly addictive drugs are tobacco and alcohol. There are numerous others that can be addictive. Alcohol and cannabis are sometimes seen as ââ,¬Ëogatewayââ,‰"¢ drugs that lead to the world of other drugs like cocaine and heroin. Drugs are also classed as ââ,¬Ëolegalââ,‰"¢ andââ,¬Ëoillegalââ,‰"¢. The obviously illegal drugs include cannabis (hash), speed (amphetamines), ecstasy (E), cocaine and heroin. Using ââ,¬Ëolegalââ,‰"¢ drugs (like cigarettes, alcohol, petrol, glue) does not mean they are safe or allowed to be misused. It just means they may be bought or sold for specific purposes and are limited to use by specific age groups. There are clear laws regarding alcohol and young people. For more detailed information on various drugs, their side-effects and the law, see ââ,¬ËoFurther Informationââ,‰"¢ at the end of the factsheet. Why do young people use drugs or alcohol? Young people may try or use drugs or alcohol for various reasons. They may do it for fun, because they are curious, or to be like their friends. Some are experimenting with the feeling of intoxication. Sometimes they use it to cope with difficult situations or feelings of worry and low mood. A young person is more likely to try or use drugs or alcohol if they hang out or stay with friends or family who use them. What can be the problems related to using drugs or alcohol? Drugs and alcohol can have different effects on different people. In young people especially the effects can be unpredictable and potentially dangerous. Even medications for sleep or painkillers can be addictive and harmful if not used the way they are prescribed by a doctor. Drugs and alcohol can damage health. Sharing needles or equipment can cause serious infections, such as HIV and hepatitis. Accidents, arguments and fights are more likely after drinking and drug use. Young people are more likely to engage in unprotected sex when using drugs. Using drugs can lead to serious mental illnesses, such as psychosis and depression. When does it become addiction or problem? It is very difficult to know when exactly using drugs or alcohol is more than just ââ,¬Ëocasualââ,‰"¢. Addiction becomes more obvious when the young person spends most of their time thinking about, looking for or using drugs. Drugs or alcohol then become the focus of the young personââ,‰"¢s life. They ignore their usual work, such as not doing their schoolwork, or stop doing their usual hobbies/sports such as dancing or football. How do I know if there is a problem or addiction? Occasional use can be very difficult to detect. If the young person is using on a regular basis, their behaviour often changes. Look for signs such as: ïâ?s§ unexplained moodiness ïâ?s§ behaviour that is ââ,¬Ëoout of character' ïâ?s§ loss of interest in school or friends ïâ?s§ unexplained loss of clothes or money ïâ?s§ unusual smells and items like silver foil, needle covers. Remember, the above changes can also mean other problems, such as depression, rather than using drugs. What do I do if I am worried? If you suspect young person is using drugs, remember some general rules. ïâ?s§ Pay attention to what the child is doing, including schoolwork, friends and leisure time. ïâ?s§ Learn about the effects of alcohol and drugs (see websites listed below). ïâ?s§ Listen to what the child says about alcohol and drugs, and talk about it with them. ïâ?s§ Encourage the young person to be informed and responsible about drugs and alcohol. ïâ?s§ Talk to other parents, friends or teachers about drugs - the facts and your fears and seek help. If someone in the family or close friend is using drugs or alcohol, it is important that they seek help too. It may be hard to expect the young person to give up, especially if a parent or carer is using it too. My child is abusing drugs. What do I do? ïâ?s§ If your child is using drugs or alcohol, seek help. ïâ?s§ Do stay calm and make sure of facts. ïâ?s§ Don't give up on them, get into long debates or arguments when they are drunk, stoned or high. ïâ?s§ Donââ,‰"¢t be angry or blame themââ,‰?othey need your help and trust to make journey of recovery. Where can I get help? You can talk in confidence to a professional like your GP or practice nurse, a local drug project or your local child and adolescent mental health. They can refer your child to relevant services and they will be able to offer you advice and support. You may also be able to seek help through a school nurse, teacher or social worker. You can find this information from your local area telephone book or council website, or ask for the address from your health centre. [For the full factsheet, click on the link above]This resource was contributed by The National Documentation Centre on Drug Use.

Mental Health First Aid Training Programme

The Mental Health First Aid (MHFA) Training Programme for Northern Ireland has been adapted from the original MHFA programme established in Australia by Betty Kitchener and Anthony Jorm. MHFA is the help provided to a person who is developing a mental health problem or who is currently in a mental health crisis. The first aid is given until professional help is available or until the crisis resolves. More than 4,500 people have attended MHFA training in Northern Ireland since it began in 2009 following a successful pilot in 2005. The aims of MHFA are to: preserve life where a person may be a danger to themselves or others; provide help to prevent the mental health problem becoming more serious; promote the recovery of good mental health; provide comfort to a person experiencing a mental health problem. MHFA teaches participants: how to recognise the symptoms of mental health problems; how to provide initial help; how to go about guiding a person towards appropriate professional help. The training programme is available to people from all backgrounds and has proved successful with different professional groups. MHFA training involves teaching participants how to recognise the symptoms of mental health problems such as depression, anxiety and psychosis. Each course is delivered by two MHFA instructors, usually over two consecutive days and four sessions to a maximum of 20 delegates. The course can also be delivered one day a week for two weeks or in four three-hour sessions. To apply for the training programme, people should contact their local Health and Social care Trust. Each Trust runs MHFA training several times a year. Topics covered include: What is meant by mental health/mental ill health? Dealing with crisis situations such as suicidal behaviour, self-harm, panic attacks and acute psychotic behaviour. Recognising the signs and symptoms of common mental health problems including depression, anxiety disorders, psychosis and substance use disorders. Where and how to get help. Self help strategies.

Redox dysregulation in schizophrenia : implication for oligodendrocyte maturation and structural connectivity

Schizophrenia, which results from an interaction between gene and environmental factors, is a psychiatric disorder characterized by reality distortion. The clinical symptoms, which are generally diagnosed in late adolescence or early adulthood, partly derive from altered brain connectivity especially in prefrontal cortex. Disruption of neuronal networks implies oligodendrocyte and myelin abnormalities in schizophrenia pathophysiology. The mechanisms of these impairments are still unclear. Converging evidences indicate a role of redox dysregulation, generated by an imbalance between pro-oxidants and antioxidant defense mechanisms, in the development of schizophrenia pathophysiology. In particular, genetic and biochemical data indicate impaired synthesis of glutathione, the main cellular antioxidant and redox regulator. As oligodendrocyte maturation is dependent on redox state, we evaluated whether abnormal redox control could contribute to oligodendrocyte and myelin impairments in schizophrenia. We found that glutathione in prefrontal cortex of early psychosis patients and control subjects positively correlated with white matter integrity. We then further explored the interplay between glutathione and myelin using a translational approach. Our data showed that in mice with genetically impaired glutathione synthesis, oligodendrocyte late maturation as well as myelination was delayed in the anterior cingulate cortex. Specifically, oligodendrocyte number and myelin levels were lowered at peripubertal age, coincident in time with the peak of myelin- related gene expression during normal brain development. These data suggest that early adolescence is a vulnerable developmental period during which an adequate redox control is required for oligodendrocyte maturation and active myelination process. Consistently, oxidative stress mediated by psychosocial stress also delayed myelination in peripubertal mice. At cellular levels, impaired glutathione synthesis altered oligodendrocyte development at several levels. Using oligodendrocyte progenitor cells cultures, our data showed that glutathione deficiency was associated with (i) cell cycle arrest and a reduction in oligodendrocyte proliferation, and (ii) an impairment in oligodendrocyte maturation. Abnormal oligodendrocyte proliferation was mediated by upregulation of Fyn kinase activity. Consistently, under oxidative stress conditions, we observed abnormal regulation of Fyn kinase in fibroblasts of patients deficient in glutathione synthesis. Together, our data support that a redox dysregulation due to glutathione deficit could underlie myelination impairment in schizophrenia, possibly mediated by dysregulated Fyn pathway. Better characterization of Fyn mechanisms would pave the way towards new drug targets. -- La schizophrénie est une maladie psychiatrique qui se définit par une distorsion de la perception de la réalité. Les symptômes cliniques sont généralement diagnostiqués durant l'adolescence ou au début de l'âge adulte et proviennent de troubles de la connectivité, principalement au niveau du cortex préfrontal. Les dysfonctionnements des réseaux neuronaux impliquent des anomalies au niveau des oligodendrocytes et de la myéline dans la pathophysiologie de la schizophrénie. Les mécanismes responsables des ces altérations restent encore mal compris. Dans le développement de la schizophrénie, des évidences mettent en avant un rôle de la dérégulation rédox, traduit par un déséquilibre entre facteurs pro-oxydants et défenses antioxydantes. Des données génétiques et biochimiques indiquent notamment un défaut de la synthèse du glutathion, le principal antioxydant et rédox régulateur des cellules. Etant donné que la maturation des oligodendrocytes est dépendante de l'état rédox, nous avons regardé si une dérégulation rédox contribue aux anomalies de la myéline dans le cadre de la schizophrénie. Dans le cortex préfrontal des sujets contrôles et des patients en phase précoce de psychose, nous avons montré que le glutathion était positivement associé à l'intégrité de matière blanche. Afin d'explorer plus en détail la relation entre le glutathion et la myéline, nous avons mené une étude translationnelle. Nos résultats ont montré que des souris ayant un déficit de la synthèse du glutathion présentaient un retard dans les processus de maturation des oligodendrocytes et de la myélinisation dans le cortex cingulaire antérieure. Plus précisément, le nombre d'oligodendrocytes et le taux de myéline étaient uniquement diminués durant la période péripubertaire. Cette même période correspond au pic de l'expression des gènes en lien avec la myéline. Ces données soulignent le fait que l'adolescence est une période du développement particulièrement sensible durant laquelle un contrôle adéquat de l'état rédox est nécessaire aux processus de maturation des oligodendrocytes et de myélinisation. Ceci est en accord avec la diminution de myéline observée suite à un stress oxydatif généré par un stress psychosocial. Au niveau cellulaire, un déficit du glutathion affecte le développement des oligodendrocytes à différents stades. En effet, dans des cultures de progéniteurs d'oligodendrocytes, nos résultats montrent qu'une réduction du taux de glutathion était associée à (i) un arrêt du cycle cellulaire ainsi qu'une diminution de la prolifération des oligodendrocytes, et à (ii) des dysfonctionnements de la maturation des oligodendrocytes. Par ailleurs, au niveau moléculaire, les perturbations de la prolifération étaient générées par une augmentation de l'activité de la kinase Fyn. Ceci est en accord avec la dérégulation de Fyn observée dans les fibroblastes de patients ayant une déficience en synthèse du glutathion en condition de stress oxydatif. Les résultats de cette thèse soulignent qu'une dérégulation rédox induite par un déficit en glutathion peut contribuer aux anomalies des oligodendrocytes et de la myéline via le dysfonctionnement des voies de signalisation Fyn. Une recherche plus avancée de l'implication de Fyn dans la maladie pourrait ouvrir la voie à de nouvelles cibles thérapeutiques.

Drogues et psychose: que faire [Drugs and psychoses: what to do?]

Substance abuse co morbidity is frequent in psychotic disorders. General practitioners are frequently involved in such treatments. In order to be able to face this complex task, it is important to be able to identify early symptoms of psychosis in a patient abusing substances, to make the difference between psychotic symptoms and intoxication or withdrawal symptoms, to know basic principles of treatment and the type of medication used in such interventions, and finally to know when specialised treatment or hospital admission are required. This paper reviews epidemiological and diagnostic elements, outlines the various treatment stages, the type of medication currently used in such situations and provides a brief description of motivational interview techniques.

Inventory and perspectives of chronic disease management programs in Switzerland: an exploratory survey.

OBJECTIVE: To describe chronic disease management programs active in Switzerland in 2007, using an exploratory survey. METHODS: We searched the internet (Swiss official websites and Swiss web-pages, using Google), a medical electronic database (Medline), reference lists of pertinent articles, and contacted key informants. Programs met our operational definition of chronic disease management if their interventions targeted a chronic disease, included a multidisciplinary team (>/=2 healthcare professionals), lasted at least six months, and had already been implemented and were active in December 2007. We developed an extraction grid and collected data pertaining to eight domains (patient population, intervention recipient, intervention content, delivery personnel, method of communication, intensity and complexity, environment, clinical outcomes). RESULTS: We identified seven programs fulfilling our operational definition of chronic disease management. Programs targeted patients with diabetes, hypertension, heart failure, obesity, psychosis and breast cancer. Interventions were multifaceted; all included education and half considered planned follow-ups. The recipients of the interventions were patients, and healthcare professionals involved were physicians, nurses, social workers, psychologists and case managers of various backgrounds. CONCLUSIONS: In Switzerland, a country with universal healthcare insurance coverage and little incentive to develop new healthcare strategies, chronic disease management programs are scarce. For future developments, appropriate evaluations of existing programs, involvement of all healthcare stakeholders, strong leadership and political will are, at least, desirable.

First episode schizophrenia and schizoaffective disorder: A psychiatric nosology

A nosological issue that has yet to be resolved relates to the diagnostic and clinical overlap of schizophrenia and schizoaffective disorder. Thus, the aim of this study was to compare, within a treated epidemiological cohort of first episode patients, the clinical characteristics of patients with schizophrenia (FES) or schizoaffective disorder (FESA). Medical fi le audit methodology was employed to collect information on 704 first episode psychosis patients (FEP), among which 283 patients had a fi nal diagnosis of FES and 64 patients with a fi nal diagnosis of FESA. These patients were treated at the Early Psychosis Prevention and Intervention Centre (EPPIC), Melbourne, Australia. Patients with FES were signifi cantly more likely to have a longer prodrome (P = .020), longer duration of untreated psychosis (P < .001), and earlier age of onset (P = .004) compared to FESA. At service entry, FESA patients had more severe levels of psychopathology (P = .020), which was due to the presence of manic symptoms (P < .001); consequently, requiring a greater number of inpatient admissions (P = .017). At discharge, depressive symptoms were more severe in those with FESA (P = .011). There are signifi cant differences in the phenomenology of schizophrenia and schizoaffective disorder during early illness course; supporting the notion that these are two discernable disorders.

TBC1D7 mutations are associated with intellectual disability, macrocrania, patellar dislocation, and celiac disease.

TBC1D7 forms a complex with TSC1 and TSC2 that inhibits mTORC1 signaling and limits cell growth. Mutations in TBC1D7 were reported in a family with intellectual disability (ID) and macrocrania. Using exome sequencing, we identified two sisters homozygote for the novel c.17_20delAGAG, p.R7TfsX21 TBC1D7 truncating mutation. In addition to the already described macrocephaly and mild ID, they share osteoarticular defects, patella dislocation, behavioral abnormalities, psychosis, learning difficulties, celiac disease, prognathism, myopia, and astigmatism. Consistent with a loss-of-function of TBC1D7, the patient's cell lines show an increase in the phosphorylation of 4EBP1, a direct downstream target of mTORC1 and a delay in the initiation of the autophagy process. This second family allows enlarging the phenotypic spectrum associated with TBC1D7 mutations and defining a TBC1D7 syndrome. Our work reinforces the involvement of TBC1D7 in the regulation of mTORC1 pathways and suggests an altered control of autophagy as possible cause of this disease.

Inferring about individual drug and schizotypy effects on cognitive functioning in polydrug using mephedrone users before and after clubbing

Objective: Mephedrone has been recently made illegal in Europe, but little empirical evidence is available on its impact on human cognitive functions. We investigated acute and chronic effects of mephedrone consumption on drug-sensitive cognitive measures, while also accounting for the influence of associated additional drug use and personality features. Method: Twenty-six volunteers from the general population performed tasks measuring verbal learning, verbal fluency and cognitive flexibility before and after a potential drug-taking situation (pre- and post-clubbing at dance clubs, respectively). Participants also provided information on chronic and recent drug use, schizotypal (O-LIFE) and depressive symptoms (Beck depression inventory), sleep pattern and premorbid IQ. Results: We found that i) mephedrone users performed worse than non-users pre-clubbing, and deteriorated from the pre-clubbing to the post-clubbing assessment, ii) pre-clubbing cannabis and amphetamine (not mephedrone) use predicted relative cognitive attenuations, iii) post-clubbing, depression scores predicted relative cognitive attenuations, and iv) schizotypy was largely unrelated to cognitive functioning, apart from a negative relationship between cognitive disorganisation and verbal fluency. Conclusion: Results suggest that polydrug use and depressive symptoms in the general population negatively affect cognition. For schizotypy, only elevated cognitive disorganisation showed potential links to a pathological cognitive profile previously reported along the psychosis dimension.

Qualité de l'attachement dans la psychose et figures spirituelles

This study had mainly two goals: First of all, adult attachement was investigated in 28 patients with chronic psychosis and 18 controls, using the"Adult Attachment Interiew". This, as no previous research had ever done so with a scientific validated instrument. Diagnostic evaluations were performed with the SCID and symptomtic evaluation with the BPRS. Results showed that patients were more likely to have experienced traumatic experiences with their primary caregivers during their childhood then have controls. We were able to identify as well a high prevalence of insecure avoidant attachement in patients, which highlights the functional dimension of psychosis in the maintenance of the relation to primary attachement figures. This study shows that insecure avoidant attachement is related to an early outset as well as to an unfavourable prognosis. Second, quite a few researches on spirituality in psychosis have shown that patients were more likely to have spiritual believes or practices then indiviuals of a nonclinical population. Coping strategies related to spirituality and religion were identified as efficient for the majority. They can help dealing with all types of difficulties, specific symptoms and may enhance life quality (Mohr et al., 2006). Therefore we have investigated some of the underlying psychological processes in this type of coping strategies, using the conceptual framework of Bowlby's attachement theory. For most participants, both patients and controls, « spiritual figures » are functionning as attachement figures. Most of them are transposing the internal working model, achieved in relation to their primary caregivers, towards their "spiritual figure" even in case of an insecure attachement. - Cette recherche poursuit essentiellement deux objectifs. Premièrement, elle examine les modèles d'attachement à l'aide du « Adult Attachment Interview » chez 28 personnes souffrant de psychose chronique et chez 18 personnes ne souffrant d'aucune affection psychiatrique. En effet, aucune étude avant celle-ci n'avait investigué l'attachement chez des patients psychotiques chroniques à l'aide d'instruments scientifiquement validés. Les évaluations diagnostiques ont été réalisées à l'aide du SCID et les évaluations symptomatologiques à l'aide du BPRS. Dans ce contexte, nous avons pu montrer qu'une majorité de patients avaient été victimes d'expériences relationnelles traumatisantes en lien avec leurs premières figures d'attachement durant l'enfance. Nos résultats indiquent également l'importante prévalence d'un attachement insécure-détaché, qui reflète la dimension fonctionnelle des symptômes psychotiques visant la préservation du lien aux principales figures d'attachement. Ceux-ci montrent encore qu'un attachement insécure-détaché est associé à un début précoce de la maladie ainsi qu'à un pronostic défavorable. Deuxièmement, de nombreuses études ont montré que les patients psychotiques avaient davantage recours à des croyances et pratiques spirituelles/religieuses pour tenter de faire face à leurs difficultés que la population générale. Ce recours s'avère être efficace pour un grand nombre d'entre eux. Il leur permet souvent une meilleure gestion des difficultés, des symptômes et globalement améliore leur qualité de vie (Mohr et al., 2006). Nous avons donc examiné certaines des dimensions psychiques sousjacentes à ce type de stratégie de coping à l'aide de l'arrière-plan conceptuel de la théorie de l'attachement de Bowlby. Nous avons effectivement constaté qu'un grand nombre de participants, patients et contrôles, investissent des figures spirituelles sur le mode de l'attachement. Même en cas d'un attachement insécure, la majorité d'entre eux transposent leurs modèles internes opérants, acquis dans leur relation aux premières figures d'attachement, sur leur croyance en des figures spirituelles.

Redox dysregulation and oxidative stress in schizophrenia: genetic and functional anomalies of glutathione synthesis in patients and experimental models involving GABA interneurons and NMDA receptors

Objective: Converging evidence speak in favor of an abnormal susceptibility to oxidative stress in schizophrenia. A decreased level of glutathione (GSH), the principal non-protein antioxidant and redox regulator, was observed both in cerebrospinal-fluid and prefrontal cortex of schizophrenia patients (Do et al., 2000). Results: Schizophrenia patients have an abnormal GSH synthesis most likely of genetic origin: Two independent case-control studies showed a significant association between schizophrenia and a GAG trinucleotide repeat (TNR) polymorphism in the GSH key synthesizing enzyme glutamate-cysteine-ligase (GCL) catalytic subunit (GCLC) gene. The most common TNR genotype 7/7 was more frequent in controls, whereas the rarest TNR genotype 8/8 was three times more frequent in patients. The disease-associated genotypes correlated with a decrease in GCLC protein expression, GCL activity and GSH content. Such a redox dysregulation during development could underlie the structural and functional anomalies in connectivity: In experimental models, GSH deficit induced anomalies similar to those observed in patients. (a) morphology: In animal models with GSH deficit during the development we observed in prefrontal cortex a decreased dendritic spines density in pyramidal cells and an abnormal development of parvalbumine (but not of calretinine) immunoreactive GABA interneurones in anterior cingulate cortex. (b) physiology: GSH depletion in hippocampal slices induces NMDA receptors hypofunction and an impairment of long term potentiation. In addition, GSH deficit affected the modulation of dopamine on NMDA-induced Ca 2+ response in cultured cortical neurons. While dopamine enhanced NMDA responses in control neurons, it depressed NMDA responses in GSH-depleted neurons. Antagonist of D2-, but not D1-receptors, prevented this depression, a mechanism contributing to the efficacy of antipsychotics. The redox sensitive ryanodine receptors and L-type calcium channels underlie these observations. (c) cognition: Developing rats with low [GSH] and high dopamine lead deficit in olfactory integration and in object recognition which appears earlier in males that females, in analogy to the delay of the psychosis onset between man and woman. Conclusion: These clinical and experimental evidence, combined with the favorable outcome of a clinical trial with N-Acetyl Cysteine, a GSH precursor, on both the negative symptoms (Berk et al., submitted) and the mismatch negativity in an auditory oddball paradigm supported the proposal that a GSH synthesis impairment of genetic origin represent, among other factors, one major risk factor in schizophrenia.

Schizotypy : do not worry, it is not all worrisome

A long-standing tradition in personality research in psychology, and nowadays increasingly in psychiatry, is that psychotic and psychotic-like thoughts are considered common experiences in the general population. Given their widespread occurrence, such experiences cannot merely reflect pathological functioning. Moreover, reflecting the multi-dimensionality of schizotypy, some dimensions might be informative for healthy functioning while others less so. Here, we explored these possibilities by reviewing research that links schizotypy to favourable functioning such as subjective wellbeing, cognitive functioning (major focus on creativity) and personality correlates. This research highlights the existence of healthy people with psychotic-like traits who mainly experience positive schizotypy (but also affective features mapping onto bipolar disorder). These individuals seem to benefit from a healthy way to organise their thoughts and experiences, i.e. they employ an adaptive cognitive framework to explain and integrate their unusual experiences. We conclude that, instead of focussing only on the pathological, future studies should explore the behavioural, genetic, imaging and psychopharmacological correlates that define the healthy expression of psychotic-like traits. Such studies would inform on protective or compensatory mechanisms of psychosis-risk and could usefully inform us on the evolutionary advantages of the psychosis dimension.

Drugs, schizotypy and cognition: Cognitive attenuations seem more consistently associated with substance use than schizotypal symptoms

Psychosis is a debilitating disease, causing harm to the individual and society. Since early detection of the disease is associated with a more benign course, factors are warranted that enable the early detection of psychosis. In the present thesis we will be focusing on two potential risk factors, namely schizotypy and drug use. The schizotypy concept, originally developed by Meehl (1962), states that schizophrenia symptoms exist on a spectrum, with symptoms ranging from the most severe in patients with schizophrenia to the least affected individual in the general population. Along the schizophrenia spectrum cognitive impairments are commonly found, for instance reduced hemispheric asymmetry or frontal lobe functions. The second risk factor (drug use), affects similar cognitive functions as those attenuated along the schizophrenia spectrum, and drug use is elevated in schizophrenia and people scoring high on schizotypy. Therefore, we set out to investigate whether cognitive attenuations formerly allocated to schizotypal symptoms could have been influenced by elevated substance use in this population. To test this idea, we assessed various drugs (nicotine, cannabis, mephedrone, general substance dependence) and schizotypy symptoms (O-LIFE), and measured either hemispheric asymmetry of function (left hemisphere dominance for language, and right hemisphere dominance for facial processing) or functions largely relying on the frontal lobes (such as cognitive flexibility, working memory, verbal short-term memory, verbal learning and verbal fluency). Results of all studies suggest that it is mostly drugs, and not schizotypy in general that predict cognitive functioning. Therefore, cognitive attenuations subscribed to schizotypy dimensions are likely to have been affected by enhanced drug use. Future studies should extend the list of potential risk factors (e.g. depression and IQ) to acquire a comprehensive overview of the most reliable predictors of disadvantageous cognitive profiles.