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There is no multi-country/multi-language study testing a-priori multivariable associations between non-modifiable/modifiable factors and validated wellbeing/multidimensional mental health outcomes before/during the COVID-19 pandemic. Moreover, studies during COVID-19 pandemic generally do not report on representative/weighted non-probability samples. The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is a multi-country/multi-language survey conducting multivariable/LASSO-regularized regression models and network analyses to identify modifiable/non-modifiable factors associated with wellbeing (WHO-5)/composite psychopathology (P-score) change. It enrolled general population-representative/weighted-non-probability samples (26/04/2020-19/06/2022). Participants included 121,066 adults (age=42±15.9 years, females=64 %, representative sample=29 %) WHO-5/P-score worsened (SMD=0.53/SMD=0.74), especially initially during the pandemic. We identified 15 modifiable/nine non-modifiable risk and 13 modifiable/three non-modifiable protective factors for WHO-5, 16 modifiable/11 non-modifiable risk and 10 modifiable/six non-modifiable protective factors for P-score. The 12 shared risk/protective factors with highest centrality (network-analysis) were, for non-modifiable factors, country income, ethnicity, age, gender, education, mental disorder history, COVID-19-related restrictions, urbanicity, physical disorder history, household room numbers and green space, and socioeconomic status. For modifiable factors, we identified medications, learning, internet, pet-ownership, working and religion as coping strategies, plus pre-pandemic levels of stress, fear, TV, social media or reading time, and COVID-19 information. In multivariable models, for WHO-5, additional non-modifiable factors with |B|>1 were income loss, COVID-19 deaths. For modifiable factors we identified pre-pandemic levels of social functioning, hobbies, frustration and loneliness, and social interactions as coping strategy. For P-scores, additional non-modifiable/modifiable factors were income loss, pre-pandemic infection fear, and social interactions as coping strategy. COH-FIT identified vulnerable sub-populations and actionable individual/environmental factors to protect well-being/mental health during crisis times. Results inform public health policies, and clinical practice., Competing Interests: Conflict of interest Conflict of interest statements of all authors are detailed in eTable 12., (Copyright © 2024. Published by Elsevier B.V.)

Competing Interests: Declaration of interests PDM is a founding director, patron, and former founding board member of headspace. He is the executive director of Orygen, Australia's National Centre of Excellence in Youth Mental Health and lead agency for five headspace centres across northwest Melbourne. He is a past President of the International Association for Youth Mental Health, and a past President of the IEPA; Early Intervention in Mental Health and of the Schizophrenia International Research Society. S-JB has provided paid expert witness work for UK charities and legal organisations. She is the author of two books related to the brain, education, and learning, for which she receives royalties. She gives talks in schools in the state and private sector, at education conferences, for education organisations, and for other public, private, and third sector organisations (some talks are remunerated). She is a member of the Rethinking Assessment group, the Steering Committee of the Cambridge Centre of Science Policy, the Technical Advisory Group for the UK Government Department of Education's Education and Outcomes Panel-C Study, the Singapore Government National Research Foundation Scientific Advisory Board, and the Singapore Government Human Potential Scientific Advisory Board. She was a member of the Times Education Commission (2021–22). IBH has received honoraria for consultancy and educational activities from Janssen Cilag. He was a member of the Clinical Advisory Group for the evaluation of the Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule initiative, and is a member of Mental Health Reform Advisory Committee (Department of Health). He is the Chief Scientific Advisor to and a 3·2% equity shareholder in InnoWell, which aims to transform mental health services through the use of innovative technologies. FAEA has received honoraria for consultancy from Grand Challenges Canada and is a past member of the World Economic Forum's Global Future Council on Mental Health. AMC is a director of headspace, Australia's National Youth Mental Health Foundation, and the National Education Alliance for Borderline Personality Disorder. AD is the Academic Secretary for the Royal College of Psychiatrists’ Faculty of Child and Adolescent Psychiatry, a research advisory group member of the UK National Society for the Prevention of Cruelty to Children, a member of the UK Trauma Council, and an evidence panel member of the Early Intervention Foundation. TF's research group receives funding for consultancy to Place2Be, a third sector organisation that provides mental health training, support, and interventions to schools across the UK. JH is executive director of Youth Wellness Hubs Ontario and receives funding from Graham Boeckh Foundation and other donors through the Centre for Addiction and Mental Health Foundation. AJ is a trustee of the Samaritans and MQ. She has received fees for lecturing from the Scottish Association of Mental Health. She is an advisory board member of Our Future Health, UK. FK-L's work is the subject of publishing contracts with multiple companies in the EU, Magellan, Cobalt Therapeutics in the USA, and the National Health Service in the UK. Although she has received no remuneration to date, she might receive royalties in the future. She is a non-executive director of Orygen. CK is the founder of Wida, a digital mental health platform. He has received consulting fees from the UN Children's Fund. He has received grants from MQ: Transforming Mental Health in the UK, the Royal Academy of Engineering in the UK, the National Institutes of Health in the USA, the Medical Research Council in the UK, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul in Brazil. DR is a Chief Scientific Advisor to headspace, Australia's National Youth Mental Health Foundation. JT receives book royalties from Simon and Schuster, legal consulting fees from Bergman and Little and the Attorney General's office of the State of Tennessee, and honoraria for speaking engagements. EK is the immediate past President of the IEPA: Early Intervention in Mental Health, and during the period of the Commission was the President elect and President. All other authors declare no competing interests.

The global public health crisis caused by COVID-19 has lasted longer than many of us would have hoped and expected. With its high uncertainty and limited control, the COVID-19 pandemic has undoubtedly asked a lot from all of us. One important central question is: how resilient have we proved in face of the unprecedented and prolonged coronavirus pandemic? There is a vast and rapidly growing literature that has examined the impact of the pandemic on mental health both on the shorter (2020) and longer (2021) term. This not only concerns pandemic-related effects on resilience in the general population, but also how the pandemic has challenged stress resilience and mental health outcomes across more specific vulnerable population groups: patients with a psychiatric disorder, COVID-19 diagnosed patients, health care workers, children and adolescents, pregnant women, and elderly people. It is challenging to keep up to date with, and interpret, this rapidly increasing scientific literature. In this review, we provide a critical overview on how the COVID-19 pandemic has impacted mental health and how human stress resilience has been shaped by the pandemic on the shorter and longer term. The vast literature is dominated by a wealth of data which are, however, not always of the highest quality and heavily depend on online and self-report surveys. Nevertheless, it appears that we have proven surprisingly resilient over time, with fast recovery from COVID-19 measures. Still, vulnerable groups such as adolescents and health care personnel that have been severely impacted by the COVID-19 pandemic do exist. Large interindividual differences exist, and for future pandemics there is a clear need to comprehensively and integratively assess resilience from the start to provide personalized help and interventions tailored to the specific needs for vulnerable groups., Competing Interests: Conflicts of Interest There are no conflicts of interest, (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Promotion of good mental health in young people is important. Our aim was to evaluate the consistency and magnitude of the efficacy of universal/selective interventions to promote good mental health. A systematic PRISMA/RIGHT-compliant meta-analysis (PROSPERO: CRD42018088708) search of Web of Science until 04/31/2019 identified original studies comparing the efficacy of universal/selective interventions for good mental health vs a control group, in samples with a mean age <35 years. Meta-analytical random-effects model, heterogeneity statistics, assessment of publication bias, study quality and sensitivity analyses investigated the efficacy (Hedges' g=effect size, ES) of universal/selective interventions to promote 14 good mental health outcomes defined a-priori. 276 studies were included (total participants: 159,508, 79,142 interventions and 80,366 controls), mean age=15.0 (SD=7.4); female=56.0%. There was a significant overall improvement in 10/13 good mental health outcome categories that could be meta-analysed: compared to controls, interventions significantly improved (in descending order of magnitude) mental health literacy (ES=0.685, p<0.001), emotions (ES=0.541, p<0.001), self-perceptions and values (ES=0.49, p<0.001), quality of life (ES=0.457, p=0.001), cognitive skills (ES=0.428, p<0.001), social skills (ES=0.371, p<0.001), physical health (ES=0.285, p<0.001), sexual health (ES=0.257, p=0.017), academic/occupational performance (ES=0.211, p<0.001) and attitude towards mental disorders (ES=0.177, p=0.006). Psychoeducation was the most effective intervention for promoting mental health literacy (ES=0.774, p<0.001) and cognitive skills (ES=1.153, p=0.03). Physical therapy, exercise and relaxation were more effective than psychoeducation and psychotherapy for promoting physical health (ES=0.498, p<0.001). In conclusion, several universal/selective interventions can be effective to promote good mental health in young people. Future research should consolidate and extend these findings., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

The ability of the brain to reduce the amount of trivial or redundant sensory inputs is called gating function. Dysfunction of sensory gating may lead to cognitive fragmentation and poor real-world functioning. The auditory dual-click paradigm is a pertinent neurophysiological measure of sensory gating function. This meta-analysis aimed to examine the subcomponents of abnormal P50 waveforms in bipolar disorder and schizophrenia to assess P50 sensory gating deficits and examine effects of diagnoses, illness states (first-episode psychosis vs. schizophrenia, remission vs. episodes in bipolar disorder), and treatment status (medication-free vs. medicated). Literature search of PubMed between Jan 1st 1980 and March 31st 2019 identified 2091 records for schizophrenia, 362 for bipolar disorder. 115 studies in schizophrenia (4932 patients), 16 in bipolar disorder (975 patients) and 10 in first-degree relatives (848 subjects) met the inclusion criteria. P50 sensory gating ratio (S2/S1) and S1-S2 difference were significantly altered in schizophrenia, bipolar disorder and their first-degree relatives. First-episode psychosis did not differ from schizophrenia, however episodes altered P50 sensory gating in bipolar disorder. Medications improve P50 sensory gating alterations in schizophrenia significantly and at trend level in bipolar disorder. Future studies should examine longitudinal course of P50 sensory gating in schizophrenia and bipolar disorder., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The epidemic of the 2019 novel coronavirus SARS-CoV-2, causing the coronavirus disease 2019 (COVID-19) is a global public health emergency with multifaceted severe consequences for people's lives and their mental health. In this article, as members of the European College of Neuropsychopharmacology (ECNP) Resilience, we will discuss the urgent need for a focus on resilience during the current coronavirus pandemic. Resilience is pivotal to cope with stress and vital to stay in balance. We will discuss the importance of resilience at the individual and societal level, but also the implication for patients with a psychiatric condition and health care workers. We not only advocate for an increased focus on mental health during the coronavirus pandemic but also highlight the urgent need of augmenting our focus on resilience and on strategies to enhance it., (Copyright © 2020. Published by Elsevier B.V.)

Promotion of good mental health in young people with and without mental disorders has received little empirical research attention and interventions for improving mental health in young people are not well established. This situation could be explained among other reasons due to the difficulties to define and operationalise what good mental health is. The current manuscript, produced by the European College of Neuropsychopharmacology Thematic Working Group on the Prevention of Mental Disorders and Mental Health Promotion (ECNP TWG PMD-MHP), presents a critical review of the available operationalizations for good mental health. A pragmatic conceptual operationalisation of good mental health is a much-needed step towards more standardised research in this field. Good mental health can be defined as a state of well-being that allows individuals to cope with the normal stresses of life and function productively. Universal and selective interventions are suitable to promote mental health. Core domains that define good mental health encompass: (i) mental health literacy, (ii) attitude towards mental disorders, (iii) self-perceptions and values, (iv) cognitive skills, (v) academic/ occupational performance, (vi) emotions, (vii) behaviours, (viii) self-management strategies, (ix) social skills, (x) family and significant relationships (xi) physical health, (xii) sexual health, (xiii) meaning of life, (xiv) and quality of life. These domains should be widely traceable in the literature and can be used to conduct further empirical research in the field of good mental health. Such data can lead to more robust evidence to identify and establish the pathways to follow in order to improve mental health., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Previous research in patients with psychotic disorder has shown widespread abnormalities in brain activation during reward anticipation. Research at the level of subclinical psychotic experiences in individuals unexposed to antipsychotic medication is limited with inconclusive results. Therefore, brain activation during reward anticipation was examined in a larger sample of individuals with subclinical psychotic experiences (PE). Participants in the PE-group were included based on CAPE scores. A sample of emerging adults aged 16-26 years (n = 47) with PE and healthy controls (HC) (n = 40) underwent fMRI scanning. The Monetary Incentive Delay task was conducted with cues related to win, loss or neutral conditions. fMRI nonparametric tests were used to examine the reward versus neutral cue contrast. A significant main effect of the large win (€3.00) > neutral contrast was found in both groups showing activation in many brain areas, including classic reward regions. Whole brain analysis on the group comparison regarding the large win > neutral contrast showed significantly decreased activation in the right insula, putamen and supramarginal gyrus in the PE-group compared to controls. There was no group difference in the hypothesized reward-related region. Decreased activation in the right insula, putamen and supramarginal gyrus during reward anticipation in individuals with PE may be consistent with altered processing of sensory information, related to decreased emotional valuing and motivational tendencies and/or altered motor-cognitive processes. The absence of group differences in striatal activation suggests that activation here is intact in the earliest stages of psychosis and may exhibit progressive deterioration in as the disease develops., (Copyright © 2019. Published by Elsevier B.V.)

Prevention is the most promising way to reduce the high personal, familial, societal, clinical and economic costs of mental disorders in Europe and worldwide. A complementary approach is to go beyond the prevention of mental ill health, to promote good mental health. This manuscript highlights the first European consortium fostering cutting-edge multidisciplinary research in these two areas. The ECNP-funded Network on the Prevention of Mental Disorders and Mental Health Promotion (ECNP PMD-MHP) brings together European sites of excellence with different expertise for translational research collaboration, including partnerships with the industry. The ECNP PMD-MHP Network adopts a transdiagnostic, lifespan, clinical staging model which cuts across different mental disorders and different methodologies. The main aims of the ECNP PMD-MHP Network are to facilitate multidisciplinary collaboration, enhance knowledge and data sharing, standardise core assessment and outcome measures, promote clinical research, apply for grant funding, and generate research reports. By supporting collaborative research, the ECNP PMD-MHP Network will be vital for fostering European psychiatry in the field of prevention of mental disorders and promotion of good mental health., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a hemizygous microdeletion on the long arm of chromosome 22 and is associated with a high risk for psychosis and cognitive impairment. One of the genes located in the deleted region of 22q11DS is Proline Dehydrogenase (PRODH) which is important for conversion of proline to glutamate. Glutamate is the primary excitatory neurotransmitter and is involved in the pathophysiology of psychosis as well as in cognition. Excessive concentrations are toxic. Possibly, neuroprotective drugs modulating glutamatergic neurotransmission could be effective in treating psychotic symptoms and cognitive enhancement in patients with 22q11DS. Riluzole is a potent anti-glutamatergic drug that reduces glutamatergic neurotransmission. Here we report acute (single dose) and long-term effects of riluzole on glutamate and GABA levels in the anterior cingulate cortex (ACC) and striatum (measured with magnetic resonance spectroscopy, 1H-MRS) as well as on psychotic symptoms and cognitive functioning in a medication-free 23-year old woman with 22q11DS. Patient presented with frequent auditory and visual hallucinations and mild paranoid ideas. The 1 H-MRS measurements showed that after a single dose riluzole (50 mg), glutamate in the ACC and striatum was reduced whereas striatal GABA increased compared to baseline. Strikingly, hallucinations and paranoia disappeared. Therefore, riluzole treatment was initiated and patient was followed up after 18 months of treatment. At follow-up, patient reported no hallucinations or paranoia and several cognitive functions were improved. Furthermore, glutamate concentrations in the ACC and striatum decreased whereas GABA concentrations increased in the striatum but decreased in the ACC. These results suggests that riluzole may be an effective treatment option for psychotic symptoms and cognitive enhancement in 22q11DS. Results warrant replication in a bigger sample., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Emerging evidence shows that stress can impair the ability to learn from and pursue rewards, which in turn has been linked to motivational impairments characteristic of the psychotic disorder. Ventral striatal dopaminergic neurotransmission has been found to modulate reward processing, and appears to be disrupted by exposure to stress. We investigated the hypothesis that stress experienced in the everyday life has a blunting effect on reward-induced dopamine release in the ventral striatum of 16 individuals at a familial risk for psychosis compared to 16 matched control subjects. Six days of ecological momentary assessments quantified the amount of daily-life stress prior to [ 18 F]fallypride PET imaging while performing a probabilistic reinforcement learning task. Relative to the controls, individuals at a familial risk for psychosis who encountered more daily-life stress showed significantly diminished extent of reward-induced dopamine release in the right ventral striatum, as well as poorer performance on the reward task. These findings provide the first neuromolecular evidence for stress-related deregulation of reward processing in familial predisposition to psychosis. The implication of daily-life stress in compromised modulation of reward function may facilitate the design of targeted neuropharmacological and ecological interventions., (Copyright © 2018. Published by Elsevier B.V.)

Background: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group., Methods: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide., Results: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset., Conclusions: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia., (Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

22q11.2 deletion syndrome (22q11DS) is a genetic disorder caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk for developing psychosis. The catechol-O-methyltransferase (COMT) gene is located in the deleted region and involved in dopamine (DA) breakdown. Impaired reinforcement learning (RL) is a recurrent feature in psychosis and thought to be related to abnormal striatal DA function. This study aims to examine RL and the potential association with striatal DA-ergic neuromodulation in 22q11DS. Twelve non-psychotic adults with 22q11DS and 16 healthy controls (HC) were included. A dopamine D 2/3 receptor [ 18 F]fallypride positron emission tomography (PET) scan was acquired while participants performed a modified version of the probabilistic stimulus selection task. RL-task performance was significantly worse in 22q11DS compared to HC. There were no group difference in striatal nondisplaceable binding potential (BP ND ) and task-induced DA release. In HC, striatal task-induced DA release was positively associated with task performance, but no such relation was found in 22q11DS subjects. Moreover, higher caudate nucleus task-induced DA release was found in COMT Met hemizygotes relative to Val hemizygotes. This study is the first to show impairments in RL in 22q11DS. It suggests that potentially motivational impairments are not only present in psychosis, but also in this genetic high risk group. These deficits may be underlain by abnormal striatal task-induced DA release, perhaps as a consequence of COMT haplo-insufficiency., (Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.)

Background: It is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M 1 receptor agonists suggest alterations in M 1 receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M 1 receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M 1 receptor binding in relation to cognitive impairments have been done. As cognitive deficits have similar course and prognostic relevance across psychotic disorders, the current study assessed M 1 receptor binding in the DLPFC and hippocampus in relation to cognitive functioning., Methods: Muscarinic M 1 receptor binding potential (BP ND ) was measured using 123 I-IDEX, single photon emission computed tomography (SPECT) in 30 medication-free subjects diagnosed with a psychotic disorder. A computerized neuropsychological test battery was used to assess cognition, and the positive and negative syndrome scale (PANSS) to assess severity of psychotic symptoms., Results: Assessment of cognitive domains showed that lower M 1 BP ND in the DLPFC was related to overall lower performance in verbal learning and memory. In addition, lower M 1 BP ND in the DLPFC was related to greater negative symptom severity. Lastly, lower M 1 BP ND in the hippocampus was related to worse delayed recognition of verbal memory., Conclusion: This is the first study to show that variation in M 1 receptors in the DLPFC is related to cognitive and negative symptom outcome in psychotic disorders. The M 1 receptor may be an important biomarker in biological stratification of patients with psychotic disorders.

Experimental animal work has demonstrated that dopamine and noradrenaline play an essential role in modulating prefrontal cortex-mediated networks underlying working memory performance. Studies of functional connectivity have been instrumental in extending such notions to humans but, so far, have almost exclusively focussed on pharmacological agents with a predominant dopaminergic mechanism of action. Here, we investigate the effect of a single dose of atomoxetine 60mg, a noradrenaline transporter inhibitor, on working memory performance and associated functional connectivity during an n-back task in 19 healthy male volunteers. Atomoxetine increased functional connectivity between right anterior insula and dorsolateral prefrontal cortex, precentral gyrus, posterior parietal cortex and precuneus during the high-working memory load condition of the n-back task. Increased atomoxetine-induced insula-dorsolateral prefrontal cortex functional connectivity during this condition correlated with decreased reaction time variability and was furthermore predicted by working memory capacity. These results show for the first time that noradrenaline transporter blockade-induced increases in cortical catecholamines accentuate fronto-parietal working memory-related network integrity. The observation of significant inter-subject variability in response to atomoxetine has implications for inverted-U frameworks of dopamine and noradrenaline function, which could be useful to predict drug effects in clinical disorders with variable treatment response., (Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.)

22q11.2 Deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans, estimated to affect up to 1 in 2,000 live births. Major features of this multisystem condition include congenital anomalies, developmental delay, and an array of early- and later-onset medical and psychiatric disorders. Advances in pediatric care ensure a growing population of adults with 22q11.2DS. Informed by an international panel of multidisciplinary experts and a comprehensive review of the existing literature concerning adults, we present the first set of guidelines focused on managing the neuropsychiatric, endocrine, cardiovascular, reproductive, psychosocial, genetic counseling, and other issues that are the focus of attention in adults with 22q11.2DS. We propose practical strategies for the recognition, evaluation, surveillance, and management of the associated morbidities.Genet Med 17 8, 599-609.

Background: Obsessive-compulsive disorder is a chronic psychiatric disorder related to dysfunctional dopaminergic neurotransmission. Deep brain stimulation (DBS) targeted at the nucleus accumbens (NAc) has recently become an effective treatment for therapy-refractory obsessive-compulsive disorder, but its effect on dopaminergic transmission is unknown., Methods: We measured the effects of NAc DBS in 15 patients on the dopamine D2/3 receptor availability in the striatum with [(123)I]iodobenzamide ([(123)I]IBZM) single photon emission computed tomography. We correlated changes in [(123)I]IBZM binding potential (BP) with plasma levels of homovanillic acid (HVA) and clinical symptoms., Results: Acute (1-hour) and chronic (1-year) DBS decreased striatal [(123)I]IBZM BP compared with the nonstimulated condition in the putamen. BP decreases were observed after 1 hour of stimulation, and chronic stimulation was related to concurrent HVA plasma elevations, implying DBS-induced dopamine release. BP decreases in the area directly surrounding the electrodes were significantly correlated with changes in clinical symptoms (45% symptom decrease)., Conclusions: NAc DBS induced striatal dopamine release, which was associated with increased HVA plasma levels and improved clinical symptoms, suggesting that DBS may compensate for a defective dopaminergic system., (Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: The brain reward circuitry innervated by dopamine is critically disturbed in schizophrenia. This study aims to investigate the role of dopamine-related brain activity during prediction of monetary reward and loss in first episode schizophrenia patients., Methods: We measured blood-oxygen-level dependent (BOLD) activity in 10 patients with schizophrenia (SCH) and 12 healthy controls during dopamine depletion with α-methylparatyrosine (AMPT) and during a placebo condition (PLA)., Results: AMPT reduced the activation of striatal and cortical brain regions in SCH. In SCH vs. controls reduced activation was found in the AMPT condition in several regions during anticipation of reward and loss, including areas of the striatum and frontal cortex. In SCH vs. controls reduced activation of the superior temporal gyrus and posterior cingulate was observed in PLA during anticipation of rewarding stimuli. PLA patients had reduced activation in the ventral striatum, frontal and cingulate cortex in anticipation of loss. The findings of reduced dopamine-related brain activity during AMPT were verified by reduced levels of dopamine in urine, homovanillic-acid in plasma and increased prolactin levels., Conclusions: Our results indicate that dopamine depletion affects functioning of the cortico-striatal reward circuitry in SCH. The findings also suggest that neuronal functions associated with dopamine neurotransmission and attribution of salience to reward predicting stimuli are altered in schizophrenia., (© 2013 Elsevier B.V. and ECNP. All rights reserved.)

There is good evidence for sex differences in brain disease, and that oestrogen modulates brain development and ageing. For example, females are significantly more likely to suffer from Alzheimer's disease, depression and late-onset psychosis than are men. Moreover, hormone replacement therapy may reduce the rate of cognitive decline in post-menopausal women and reduce their risk of developing Alzheimer's disease (as compared to post-menopausal women who do not take hormone replacement therapy). The neurobiological basis of these differences in brain disease and ageing was unknown until relatively recently. In this chapter we discuss results of studies demonstrating that sex steroids (i) are crucial for development and ageing of brain regions affected in Alzheimer's disease; (ii) interact with neuronal networks and chemical systems at many different levels in brain, and (iii) affect mood and cognitive function in elderly women without Alzheimer's disease. The current literature supports the hypothesis that sex steroids can modulate brain ageing and provides a number of potential neurobiological explanations for the cognitive effects of hormone replacement therapy. There is only limited evidence that hormone replacement therapy is effective in women already suffering from Alzheimer's disease. Nonetheless, recent work may lead to new prevention strategies for age-related cognitive decline and brain diseases such as Alzheimer's disease., (Copyright 2002 Elsevier Science Ltd.)

Background: The neurobiological basis for violence in humans is poorly understood, yet violent behavior (to self or others) is associated with large social and healthcare costs in some groups of patients (e.g., the mentally retarded). The prefrontal cortex and amygdalo-hippocampal complex (AHC) are implicated in the control aggression, therefore we examined the neural integrity of these regions in violent patients with mild mental retardation and nonviolent control subjects., Methods: We used (1)H-magnetic resonance spectroscopy (MRS) to measure 1) concentrations and ratios of N-acetyl aspartate (NAA), creatine phosphocreatine (Cr+PCr), and choline-related compounds (Cho) in prefrontal lobe of 10 violent inpatients and 8 control subjects; 2) ratios of NAA, Cr+PCr, and Cho in the AHC of 13 inpatients and 14 control subjects; and 3) frequency and severity of violence in patients., Results: Compared to control subjects, violent patients had significantly (p <.05, analysis of covariance-age and IQ as confounding covariates) lower prefrontal concentrations of NAA and Cr+PCr, and a lower ratio of NAA/Cr+PCr in the AHC. Within the violent patient group, frequency of observed violence to others correlated significantly with prefrontal lobe NAA concentration (r = -0.72, p <.05)., Conclusions: NAA concentration indicates neuronal density, and Cr+PCr concentration high-energy phosphate metabolism. Our findings suggest that violent patients with mild mental retardation have reduced neuronal density, and abnormal phosphate metabolism in prefrontal lobe and AHC compared to nonviolent control subjects. Further studies are needed, however, to determine if these findings are regionally specific, or generalize to other groups of violent individuals.