Ali Amad

Resting-State Functional Connectivity of the Nucleus Accumbens in Auditory and Visual Hallucinations in Schizophrenia

Both auditory hallucinations (AH) and visual hallucinations may occur in schizophrenia. One of the main hypotheses underlying their occurrence involves the increased activity of the mesolimbic pathway, which links the ventral tegmental area (VTA) and the nucleus accumbens (NAcc). However, the precise contribution of the mesolimbic pathway in hallucinations across various sensory modalities has not yet been explored. We compared the resting-state functional connectivity (rs-FC) of the NAcc among 16 schizophrenia patients with pure AH, 15 with both visuoauditory hallucinations (VAH), and 14 without hallucinations (NoH). A between-group comparison was performed using random-effects ANCOVA (rs-FC of the bilateral NAcc as the dependent variable, groups as the between-subjects factor, age and Positive and Negative Syndrome Scale scores as covariates; q(false discovery rate [FDR]) < .05). Compared to the NoH group, the AH group exhibited significantly enhanced NAcc rs-FC with the left temporal superior gyrus, the cingulate gyri, and the VTA, whereas the VAH group, compared to the AH group, exhibited significantly enhanced NAcc rs-FC with the bilateral insula, putamen, parahippocampal gyri, and VTA. The strength in rs-FC between the NAcc and the VTA appeared to be positively associated with the presence of hallucinations, but the NAcc FC patterns changed with the complexity of these experiences (ie, 0, 1, or 2 sensory modalities), rather than with severity. This might support the aberrant salience hypothesis of schizophrenia. Moreover, these findings suggest that future clinical and neurobiological studies of hallucinations should evaluate not only the global severity of symptoms but also their sensorial features.

The arcuate fasciculus in auditory-verbal hallucinations: A meta-analysis of diffusion-tensor-imaging studies

Auditory-verbal hallucinations (AVHs) are associated with an impaired connectivity of large-scale networks. To examine the relationship between white-matter integrity and AVHs, we conducted a meta-analysis of diffusion-tensor-imaging studies that compared patients with schizophrenia and AVHs with matched healthy controls (HCs). Five studies were retained gathering 256 DTI data points, divided into AVHs (n=106) and HCs (n=150). The meta-analysis demonstrated a reduced fractional anisotropy in the left Arcuate Fasciculus (AF) of hallucinators (hg= -0.42; CI[-0.69,-0.16]; p<10(-3)). The current meta-analysis confirmed disruptions of white matter integrity in the left AF bundle of schizophrenia patients with AVHs.

Increased prevalence of psychotic disorders among third-generation migrants: Results from the French Mental Health in General Population survey

There is very strong evidence that the prevalence of psychosis is elevated in migrant populations and that this risk persists into the second generation. However, these results have not been replicated in France, and the prevalence of psychotic disorders in the third generation of migrants remains unknown. Based on the Mental Health in General Population survey (n=37063), we report for the first time the increased prevalence of psychotic disorders in migrants in France, which persists into the second generation for a single psychotic episode (SPE) (OR=1.43, 95% CI [1.02-2.03], p<0.03) and into the third generation for recurrent psychotic disorder (RPD) (OR=1.78, 95% CI [1.45-2.18], p<0.0001) after adjustment for age, sex, level of education and cannabis use. Complementary statistical analyses of our sample showed a significantly higher risk of SPE in migrants from the French West Indies and Africa (χ(2)=17.70, p<0.01). These results are consistent with the socio-developmental model and the psychosis continuum hypothesis.

Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?

Hallucinations are complex misperceptions, that principally occur in schizophrenia or after intoxication induced by three main classes of drugs: psychostimulants, psychedelics, and dissociative anesthetics. There are at least three different pharmacological ways to induce hallucinations: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics. In schizophrenia, the relative importance of NMDAR and D2R in the occurrence of hallucinations is still debated. Slight clinical differences are observed for each etiology. Thus, we investigated whether the concept of hallucination is homogenous, both clinically and neurobiologically. A narrative review of the literature is proposed to synthesize how the main contributors in the field have approached and tried to solve these outstanding questions. While some authors prefer one explanatory mechanism, others have proposed more integrated theories based on the different pharmacological psychosis models. In this review, such theories are discussed and faced with the clinical data. In addition, the nosological aspects of hallucinations and psychosis are addressed. We suggest that if there may be common neurobiological pathways between the different pharmacological systems that are responsible for the hallucinations, there may also be unique properties of each system, which explains the clinical differences observed.

Eating Disorders in Schizophrenia: Implications for Research and Management

Objective. Despite evidence from case series, the comorbidity of eating disorders (EDs) with schizophrenia is poorly understood. This review aimed to assess the epidemiological and clinical characteristics of EDs in schizophrenia patients and to examine whether the management of EDs can be improved. Methods. A qualitative review of the published literature was performed using the following terms: “schizophrenia” in association with “eating disorders,” “anorexia nervosa,” “bulimia nervosa,” “binge eating disorder,” or “night eating syndrome.” Results. According to our literature review, there is a high prevalence of comorbidity between schizophrenia and EDs. EDs may occur together with or independent of psychotic symptoms in these patients. Binge eating disorders and night eating syndromes are frequently found in patients with schizophrenia, with a prevalence of approximately 10%. Anorexia nervosa seems to affect between 1 and 4% of schizophrenia patients. Psychopathological and neurobiological mechanisms, including effects of antipsychotic drugs, should be more extensively explored. Conclusions. The comorbidity of EDs in schizophrenia remains relatively unexplored. The clearest message of this review is the importance of screening for and assessment of comorbid EDs in schizophrenia patients. The management of EDs in schizophrenia requires a multidisciplinary approach to attain maximized health outcomes. For clinical practice, we propose some recommendations regarding patient-centered care.

Advanced glycation end products and schizophrenia: A systematic review

Oxidative stress has become an exciting area of research on schizophrenia, which is a highly prevalent condition that affects approximately 1% of the worldwide population. Advanced glycation end products (AGEs), which are considered metabolic biomarkers of increased oxidative stress, have a pathogenic role in the development and progression of different oxidative stress-based diseases including atherosclerosis, diabetes, neurodegenerative disorders and schizophrenia. AGE formation and accumulation as well as the activation of its receptor (RAGE) can lead to signaling through several inflammatory signaling pathways and further damaging effects. This systematic review is based on a search conducted in July 2014 in which 6 studies were identified that met our criteria. In this work, we describe how recent methodological advances regarding the role of AGEs may contribute to a better understanding of the pathophysiology of schizophrenia and provide a different approach in the comprehension of the relationship between cardiovascular disease and schizophrenia. These latest findings may lead to new directions for future research on novel diagnostic and treatment strategies.

Prevalence and clinical severity of mood disorders among first-, second- and third-generation migrants

BACKGROUND The role of migration as a risk factor remains unknown for mood disorders because of poor data. We sought to examine the prevalence and severity of mood disorders (bipolar disorder (BD), unipolar depressive disorder (UDD) and dysthymia) in first, second, and third generation migrants in France. METHODS The Mental Health in the General Population survey interviewed 38,694 individuals. The prevalence of lifetime mood disorders, comorbidities, and clinical features was compared between migrants and non-migrants and by generation. All analyses were adjusted for age, sex and level of education. RESULTS The prevalence of any lifetime mood disorder was higher in migrants compared with non-migrants (OR = 1.36, 95% CI [1.27 - 1.45]). This increased prevalence was significant for UDD (OR = 1.44, 95% CI [1.34 - 1.54]), but not for BD (OR = 1.15, 95% CI [0.96 - 1.36]) or dysthymia (OR = 1.09, 95% CI [0.94 - 1.27]), although the prevalence of BD was increased in the third generation (OR = 1.27, 95% CI [1.01 - 1.60]). Migrants with BD or UDD were more likely to display a comorbid psychotic disorder compared to non-migrants with BD or UDD. Cannabis-use disorders were more common in migrant groups for the 3 mood disorders, whereas alcohol-use disorders were higher in migrants with UDD. Posttraumatic stress disorder was more frequent among migrants with UDD. LIMITATIONS The study used cross-sectional prevalence data and could be biased by differences in the course of disease according to migrant status. Moreover, this design does not allow causality conclusion or generalization of the main findings. CONCLUSION Mood disorders are more common among migrants, especially UDD. Moreover, migrants with mood disorders presented with a more severe profile, with increased rates of psychotic and substance-use disorders.

Keep calm: Psychiatric disorders are organic! The power of words in medicine

Australian & New Zealand Journal of Psychiatry, 50(1) smoking since last 12 years had presented with low mood, anxiety, decreased interest in interaction and work, difficulty in concentration and reduced libido for 11 months. He also had progressive loss of smell leading to anosmia within 1 month of onset of depressive symptoms along with decreased taste perception. There was no past or family history of psychiatric illness. Obvious psychosocial stressors were absent. Mental status examination had revealed depressed affect, pessimistic views about future and death wishes. He was diagnosed with major depressive disorder and was prescribed Escitalopram 10 mg/day, which was later increased to 20 mg/day along with clonazepam 0.25 mg as and when required. Opinion was taken from oto-rhinologist and neurologist for anosmia and possible organic causes were ruled out. His routine hemogram, liver and renal function tests and thyroid profile were within normal limits. As there was no improvement in depression after adequate trial of >3 months, the patient was switched to Bupropion (300 mg/day). Serum folic acid and Vitamin-B12 level was estimated due to persistent poor response. Folic acid level was found to be significantly low for which folate supplementation (7.5 mg/day, alpha-metyl-folate) had been started. Within 2 weeks, his depressive symptoms, olfaction, gestation as well as libido had improved significantly with reduction of Hamilton Depression Rating Scale (HAM-D) score from 17 to 7. There is over-lapping between the brain areas related to depression and olfactory processing which might be responsible for occurrence of olfactory dysfunction in depression and could be considered a potential early marker (Marine and Boriana, 2014). Taste perception is dependent on olfactory perception; olfactory deficits are likely to influence taste perception. As neuroplasticity (prominently seen in the olfactory bulbs) is dependent on several nutritional elements like folate, its deficiency is likely to produce impairment of synthesis of neurotransmitters responsible for depression (i.e. serotonin, norepinephrine, dopamine) (Fava and Mischoulon, 2009). Olfactory dysfunction can be a possible phenotypic marker of folate deficiency in treatment resistant depression.

Transcranial direct-current stimulation (tDCS) for bipolar depression: A systematic review and meta-analysis

Objective: Bipolar disorder (BD) is a severe and recurrent brain disorder that can manifest in manic or depressive episodes. Transcranial Direct Current Stimulation (tDCS) has been proposed as a novel therapeutic modality for patients experiencing bipolar depression, for which standard treatments are often inefficient. While several studies have been conducted in this patient group, there has been no systematic review or meta‐analysis that specifically examines bipolar depression. We aimed to address this gap in the literature and evaluated the efficacy and tolerability of tDCS in patients fulfilling DSM‐IV‐TR criteria for BD I, II, or BD not otherwise specified (NOS). Methods: We systematically searched the literature from April 2002 to November 2016 to identify relevant publications for inclusion in our systematic review and meta‐analysis. Effect sizes for depression rating‐scale scores were expressed as the standardized mean difference (SMD) before and after tDCS. Results: Thirteen of 382 identified studies met eligibility criteria for our systematic review. The meta‐analysis included 46 patients from 7 studies with depression rating‐scale scores pre‐ and post‐tDCS. Parameters of tDCS procedures were heterogeneous. Depression scores decreased significantly with a medium effect size after acute‐phase of treatment (SMD 0.71 [0.25–1.18], z = 3.00, p = 0.003) and at the furthest endpoint (SMD 1.27 [0.57–1.97], z = 3.57, p = 0.0004). Six cases of affective switching under tDCS treatment protocols were observed. Conclusions: Depressive symptoms respond to tDCS in patients with BD. Additional studies, and particularly randomized controlled trials, are needed to clarify the effectiveness of tDCS in bipolar depression, the frequency of tDCS‐emergent hypomania/mania, and which tDCS modalities are most efficient. HIGHLIGHTStDCS significantly improves symptoms of bipolar depression.tDCS can potentially cause a manic switch in patients with bipolar depression.RCT comparing tDCS antidepressant effect vs placebo are required to explore the effectiveness of tDCS in bipolar depression.

fmri capture of auditory hallucinations: Validation of the two‐steps method

Our purpose was to validate a reliable method to capture brain activity concomitant with hallucinatory events, which constitute frequent and disabling experiences in schizophrenia. Capturing hallucinations using functional magnetic resonance imaging (fMRI) remains very challenging. We previously developed a method based on a two‐steps strategy including (1) multivariate data‐driven analysis of per‐hallucinatory fMRI recording and (2) selection of the components of interest based on a post‐fMRI interview. However, two tests still need to be conducted to rule out critical pitfalls of conventional fMRI capture methods before this two‐steps strategy can be adopted in hallucination research: replication of these findings on an independent sample and assessment of the reliability of the hallucination‐related patterns at the subject level. To do so, we recruited a sample of 45 schizophrenia patients suffering from frequent hallucinations, 20 schizophrenia patients without hallucinations and 20 matched healthy volunteers; all participants underwent four different experiments. The main findings are (1) high accuracy in reporting unexpected sensory stimuli in an MRI setting; (2) good detection concordance between hypothesis‐driven and data‐driven analysis methods (as used in the two‐steps strategy) when controlled unexpected sensory stimuli are presented; (3) good agreement of the two‐steps method with the online button‐press approach to capture hallucinatory events; (4) high spatial consistency of hallucinatory‐related networks detected using the two‐steps method on two independent samples. By validating the two‐steps method, we advance toward the possible transfer of such technology to new image‐based therapies for hallucinations. Hum Brain Mapp 38:4966–4979, 2017.