Hypothalamic-pituitary axis response to a 0.25-MG dexamethasone test in women with fibromyalgia.

Fibromyalgia has been reported as having some clinical overlap with both depression and emotionally-unstable disorders, although both types of disorders present different cortisol suppression response to dexamethasone. In this study we investigated the hypothalamic-pituitary-adrenal system (HPA) in the fibromyalgic syndrome (FMS) using a dexamethasone suppression test (DST) of 0.25 mg designed to specifically detect cortisol hypersuppression. We studied 59 women (20 patients and 39 healthy controls) to whom the DST was administered together with a battery of psychometric tests. In our results, patients with FMS had significant lower levels of basal cortisol pre- and post-DST compared with control subjects. However, cortisol suppression rate in patients after DST was not significantly different than in controls. As other syndromes like post-traumatic stress disorder or emotionally unstable personality disorders, also related with high incidence of severe trauma, FMS patients presented significant low basal cortisol. However, they did not have cortisol hypersuppression as is commonly found in the mentioned disorders. The relation of FMS with lifetime traumas and with emotional instability should be further investigated in order to improve psychological treatment approaches for these patients.LAY SUMMARYPatients with fibromyalgic syndrome have basal hypocortisoism but no cortisol hypersuppression after dexamethasone infusion compared to control subjects, as other trauma-related syndromes.

Ankyrin Repeat and Kinase Domain Containing 1 Gene, and Addiction Vulnerability.

The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.

The relationships between sociodemographic, psychosocial and clinical variables with personal-stigma in patients diagnosed with schizophrenia.

BACKGROUND: Studies suggest that people with a diagnosis of schizophrenia are one of the most stigmatized groups in society. AIM: To comprehensively analyze personal stigma in patients diagnosed with schizophrenia. METHOD: Data were obtained from 89 patients. Patients were evaluated with the following scales: a sociodemographic and clinical questionnaire, the Discrimination and Stigma Scale, the Self-perception of Stigma Questionnaire for People with Schizophrenia, the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, the Global Assessment of Functioning Scale, and the Brief Social Functioning Scale. RESULTS: Relations between personal stigma and sociodemographic and psychosocial variables were poor. However, clinical variables correlated with different facets of personal stigma. Personal stigma subscales´ correlations were between experienced stigma, anticipated stigma, and self-stigma to each other. 29.5% of the experienced stigma subscale variance was explained by age of onset and level of depression. 20.1% of the anticipated stigma subscale variance was explained by level of depression and gender. 27.3% of the overcoming stigma subscale variance was explained by level of depression and positive and negative psychotic symptoms. 35.8% of the self-stigma scale variance was explained by the level of depression. CONCLUSIONS: Addressing stigma within treatment seems of crucial importance since all stigma facets seem to be highly related to clinical dimensions, especially depression Therefore, including strategies to reduce stigma in care programs may help patients with schizophrenia to better adjust in life and improve their illness process.

The Addiction-Related Protein ANKK1 is Differentially Expressed During the Cell Cycle in Neural Precursors.

TaqIA is a polymorphism associated with addictions and dopamine-related traits. It is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) nearby the gene for the dopamine D2 receptor (D2R). Since ANKK1 function is unknown, TaqIA-associated traits have been explained only by differences in D2R. Here we report ANKK1 studies in mouse and human brain using quantitative real-time PCR, Western blot, immunohistochemistry, and flow cytometry. ANKK1 mRNA and protein isoforms vary along neurodevelopment in the human and mouse brain. In mouse adult brain ANKK1 is located in astrocytes, nuclei of postmitotic neurons and neural precursors from neurogenic niches. In both embryos and adults, nuclei of neural precursors show significant variation of ANKK1 intensity. We demonstrate a correlation between ANKK1 and the cell cycle. Cell synchronization experiments showed a significant increment of ANKK1-kinase in mitotic cells while ANKK1-kinase overexpression affects G1 and M phase that were found to be modulated by ANKK1 alleles and apomorphine treatment. Furthermore, during embryonic neurogenesis ANKK1 was expressed in slow-dividing neuroblasts and rapidly dividing precursors which are mitotic cells. These results suggest a role of ANKK1 during the cell cycle in neural precursors thus providing biological support to brain structure involvement in the TaqIA-associated phenotypes.

Elevated midline-parietal gamma band noise power in schizophrenia but not in bipolar patients.

Gamma oscillations are key in coordinating brain activity and seem to be altered in schizophrenia. In previous work, we studied the spatial distribution of a noise power measure (scalp-recorded electroencephalographic activity unlocked to stimuli) and found higher magnitudes in the gamma band related to symptoms and cognition in schizophrenia. In the current study, we sought to replicate those findings and to study its specificity for schizophrenia in a completely independent sample. A principal component analysis (PCA) was used to determine the factorial structure of gamma noise power acquired with an electroencephalographic recording during an odd-ball P300 paradigm in the 250- to 550-ms window in 70 patients with schizophrenia (16 patients with first episode), 45 bipolar patients and 65 healthy controls. Clinical and cognitive correlates of the resulting factors were also assessed. Three factors arose from the PCA. The first displayed a midline-parietal distribution (roughly corresponding to the default mode network), the second was centro-temporal and the third anterior-frontal. Schizophrenia but not bipolar patients showed higher gamma noise power loadings in the first factor in comparison with controls. Scores for this factor were significantly and directly associated with positive and total symptoms in patients and inversely associated with global cognition in all participants. The results of this study replicate those of our previous publication and suggest an elevated midline-parietal gamma noise power specific to schizophrenia. The gamma noise power measure seems to be a useful tool for studying background oscillatory activity during performance of cognitive tasks.

Negative symptoms and executive function in schizophrenia: does their relationship change with illness duration?

BACKGROUND: Negative symptoms and cognitive dysfunction are of crucial functional and prognostic importance in schizophrenia. However, the nature of the relationship between them and the factors that may influence it have not been well established. AIMS: To investigate whether the relationship between negative symptoms and executive function changes according to the duration of illness in schizophrenia. METHODS: The Positive and Negative Syndrome Scale was used to assess psychopathology and the Wisconsin Card Sorting Test (WCST) to evaluate executive function in a sample of 200 schizophrenic patients who were classified in 3 groups according to their duration of illness: up to 5 years (short duration group), 6-20 years (intermediate duration group) and over 20 years of illness (long duration group). RESULTS: Medium-sized correlations were found between negative symptoms and WCST performance as assessed by the number of completed categories in all 3 groups. However, differences were found according to the duration of schizophrenia. For patients in the short duration group, negative symptoms correlated with WCST nonperseverative errors, but for those in the long duration group the correlation was with perseverative errors. CONCLUSION: We found a differential relationship between negative and cognitive symptoms in different stages of schizophrenia. Illness duration should be considered when studying the relationship between negative symptoms and cognition.

The gut-microbiota-brain axis in a Spanish population in the aftermath of the COVID-19 pandemic: microbiota composition linked to anxiety, trauma, and depression profiles.

The prevalence of anxiety and depression soared following the COVID-19 pandemic. To effectively treat these conditions, a comprehensive understanding of all etiological factors is needed. This study investigated fecal microbial features associated with mental health outcomes (symptoms of anxiety, depression, or posttraumatic stress disorder (PTSD)) in a Spanish cohort in the aftermath of the COVID-19 pandemic. Microbial communities from stool samples were profiled in 198 individuals who completed validated, self-report questionnaires. 16S ribosomal RNA gene V3-4 amplicon sequencing was performed. Microbial diversity and community structure were analyzed, together with relative taxonomic abundance. In our cohort of N=198, 17.17% reported depressive symptoms, 37.37% state anxiety symptoms, 40.90% trait anxiety symptoms, and 8.08% PTSD symptoms, with high levels of comorbidity. Individuals with trait anxiety had lower Simpson's diversity. Fusicatenibacter saccharivorans was reduced in individuals with comorbid PTSD + depression + state and trait anxiety symptoms, whilst an expansion of Proteobacteria and depletion of Synergistetes phyla were noted in individuals with depressive symptoms. The relative abundance of Anaerostipes was positively correlated with childhood trauma, and higher levels of Turicibacter sanguinis and lower levels of Lentisphaerae were found in individuals who experienced life-threatening traumas. COVID-19 infection and vaccination influenced the overall microbial composition and were associated with distinct relative taxonomic abundance profiles. These findings will help lay the foundation for future studies to identify microbial role players in symptoms of anxiety, depression, and PTSD and provide future therapeutic targets to improve mental health outcomes.

Failure of deactivation in bipolar disorder during performance of an fMRI adapted version of the Stroop task.

INTRODUCTION: Few studies have examined the functional brain correlates of the performance of the Stroop task in bipolar disorder (BD). It is also not known whether it is associated with failure of de-activation in the default mode network, as has been found in studies using other tasks. METHODS: Twenty-four BD patients and 48 age, sex and educationally estimated intellectual quotient (IQ) matched healthy subjects (HS) underwent a functional MRI during performance of the counting Stroop task. Task-related activations (incongruent versus congruent condition) and de-activations (incongruent versus fixation) were examined using whole-brain, voxel-based methodology. RESULTS: Both the BD patients and the HS showed activation in a cluster encompassing the left dorsolateral and ventrolateral prefrontal cortex and the rostral anterior cingulate cortex and supplementary motor area, with no differences between them. The BD patients, however, showed significant failure of de-activation in the medial frontal cortex and the posterior cingulate cortex/precuneus. CONCLUSIONS: The failure to find activation differences between BD patients and controls suggests that the 'regulative' component of cognitive control remains intact in the disorder, at least outside episodes of illness. The failure of de-activation found adds to evidence documenting trait-like default mode network dysfunction in the disorder.

Psychopathologic differences between cannabis-induced psychoses and recent-onset primary psychoses with abuse of cannabis.

The study aims to identify psychopathologic variables in cannabis-induced psychosis and recent-onset primary psychoses using the Symptom Checklist-90-R and the Psychiatric Research Interview for Substance and Mental Disorders. A sample of 181 subjects with psychotic symptoms and cannabis use referred to the psychiatry inpatient units of 3 university general hospitals were assessed. The final sample included 50 subjects with a diagnosis of cannabis-induced psychotic disorder (CIPD) and 104 subjects with primary psychotic disorders. Using receiver operating characteristic curves, the most efficient psychopathologic variables for classifying CIPD were interpersonal sensitivity, "depression," phobic anxiety, and Scale to Assess Unawareness of Mental Disorders subscales. The area under the receiver operating characteristic curve of the model including depression and "misattribution" scores was 96.78% (95% confidence interval, 94.43-99.13). Depressive symptoms could be used to distinguish CIPD from other primary psychotic disorders. Clinical variables related to "neurotic" symptoms could be involved in the susceptibility to cannabis-induced psychosis.

Prevalence and clinical correlates of restless legs syndrome among psychogeriatric patients.

OBJECTIVE: To evaluate the prevalence, clinical features, and comorbidities of restless legs syndrome (RLS) among psychogeriatric patients in an out-patient clinical setting. METHODS: Cross-sectional study of a sample of 100 non-demented psychogeriatric outpatients that were assessed for the presence of RLS using the Revised International Restless Legs Syndrome Study Group criteria and other support criteria. Medical and psychiatric illnesses, drug treatments, and other risk factors for RLS were documented. RESULTS: Prevalence of definite RLS in our sample was 11.11% with an additional prevalence of 10.10% of possible RLS. None of these patients had received a diagnosis of RLS previously. RLS was associated with major depressive disorder and with hypertension, but not with other previously described risk factors as female gender, some medical conditions, or psychoactive drug treatments. CONCLUSIONS: RLS is a frequent condition in psychogeriatric patients, especially among those with depression, and is commonly underdiagnosed and undertreated. Clinicians should routinely ask for RLS symptoms when assessing their patients in their regular clinical practice.

Activation and deactivation patterns in schizophrenia during performance of an fMRI adapted version of the stroop task.

The Stroop task, which examines an aspect of executive function/cognitive control, the ability to inhibit prepotent responses, has been relatively little examined in schizophrenia, and the findings have been inconsistent. Whether performance of this task is associated with failure of de-activation in the disorder is also uncertain. We examined 42 schizophrenic patients and 61 healthy controls during performance of an fMRI-adapted version of the Stroop task, the counting Stroop task. Task-related activations (incongruent > congruent condition) and de-activations (baseline > incongruent) were examined using whole-brain, voxel-based methods. In the healthy controls, task performance was found to be associated with activations in the left dorsolateral prefrontal cortex and the dorsal anterior cingulate cortex, among other regions. De-activations were seen in the medial frontal cortex, the middle and posterior cingulate gyrus and cuneus, the parahippocampal gyrus and the hippocampus. The schizophrenic patients did not show reduced activation compared to the healthy controls. They did, however, show failure of de-activation in the medial frontal cortex. Our negative finding with respect to hypoactivation during performance of a task requiring inhibition of prepotent responses suggests that brain functional abnormality in schizophrenia may not affect all aspects of executive function/cognitive control. The finding of medial frontal cortex failure of de-activation adds to existing findings of default mode network dysfunction in the disorder.

Sexually dimorphic interaction between the DRD1 and COMT genes in schizophrenia.

Dopaminergic dysfunction in the prefrontal cortex (PFC) is involved in the pathophysiology of schizophrenia. In the PFC, dopamine signalling largely depends on the D1 receptors, which are coded by the DRD1 gene, and on the regulation of dopamine levels by the enzyme catechol-O-methyltransferase (COMT). Here, we investigate the role of DRD1 and its interaction with the COMT gene in schizophrenic patients. In two gender-limited independent patient and control samples, we genotype five Tag single nucleotide polymorphisms (tagSNPs) of DRD1. The DRD1 SNP and haplotype associations, as well as interaction effects with the Val158Met COMT SNP were analyzed. In the male sample, we found the rs11746641 and rs11749676 DRD1 SNPs were associated with schizophrenia. Haplotype analyses identified the T-A-T-C-T variant related to a protective effect (P = 0.008) and the G-G-T-C-C variant that showed a tendency to be a risk factor for the disorder (P = 0.012). A logistic regression analysis revealed a significant pattern of interaction between DRD1 and COMT for both the rs11746641 (P = 0.002) and rs11749676 (P = 4.5 x 10(-5)) SNPs. DRD1-associated haplotypes were exclusively related to schizophrenia in the Val homozygous subgroup of patients (T-A-T-C-T: P = 0.003; G-G-T-C-C: P = 0.006). In females, none of the DRD1 SNPs were linked to the disorder. Our genetic data suggest that DRD1 and COMT are epistatically associated with protection against and the risk of developing schizophrenia in a gender-dependent fashion, and support the role of dopamine dysfunction at the PFC in the pathophysiology of this disorder.

Gender-specific COMT Val158Met polymorphism association in Spanish schizophrenic patients.

The functional Val158Met polymorphism (rs4680) located at the gene that codes for the catechol-O-methyltransferase (COMT) has been extensively investigated in schizophrenia although current data are still controversial. Since COMT activity is sexually dimorphic, we carried out two independent studies in homogeneous samples of male and female Spanish schizophrenic patients. In males, we found an association between the homozygous Val genotype and the disorder, which resembled a recessive model (P = 0.022; odds ratio [OR] = 1.67). This Val homozygotes overrepresentation is produced at the expense of the heterozygous individuals decrease, whilst the Met homozygotes showed no differences when compared controls and patients. As a consequence, the heterozygous genotype in this sample had a protective effect (P = 0.03; OR = 0.65) and a strong deviation from Hardy-Weinberg equilibrium in male cases was observed (P = 0.006). In addition, a 2-SNP haplotype analysis (rs4818-Val158Met) confirmed there is an overrepresentation of the different homozygous Val genotypes in the male schizophrenic sample. Regarding females, we did not find any statistically significant association between COMT SNP and schizophrenia. In the light of this we suggest that the Val158Met SNP is involved in risk and protective genotypes for the vulnerability to schizophrenia in Spanish male population.

Staging of depressive disorders: Relevance of resistance to treatment and residual symptoms.

BACKGROUND: Clinical staging model for depression helps to better define the clinical situation of patients. The objectives of this study are: to correlate the Hetrick's staging model of depression with the severity of depression, associated disability, and resistance to treatment in the established disease stages and to test the modification introduced by our group consisting in the introduction of a substage for recurrence from a previous episode that was stabilized with a complete remission. METHODS: A Cross-sectional study with 133 adult subjects having a current and primary diagnosis of Depressive disorder was developed. Patients were classified according to the model and assessed with: 17-item Hamilton Depression Scale (HAM-D), Clinical Global Impression (CGI); Global Assessment of Function (GAF); Maudsley Staging Method for treatment resistance (MSM) and Sheeham Disability Schedule (SDS). RESULTS: The variable that best contributes to the differentiation between clinical stages, in established Depression, is resistance to treatment evaluated by the MSM. Correlations between MSM and the clinical stages were statistically significant between most pairs of stages. Finally, we showed preliminary data in order to prove that a differential sub-stage for recurrent depression with and without inter-episodic remission in the current heuristic models could be a possible stage for better define depression staging model. CONCLUSIONS: Resistance to treatment should be included in the definition of clinical stages in established depression. Despite the difficulty of establishing a valid model for the staging of depression, it can certainly add great value to diagnosis, therapeutic interventions and clinical research.

Association between cerebral metabolic and structural abnormalities and cognitive performance in schizophrenia.

The possible association in schizophrenia between frontal abnormalities, such as hypofrontality and frontal grey matter (GM) deficits, and neuropsychological deficits is not yet well defined. Our objective was to study such an association and to clarify the cognitive relevance of metabolic and anatomical variability across schizophrenia patients. To do so, we studied dorsolateral prefrontal (DLPF) metabolism during an attention test using fluoro-deoxy-glucose positron emission tomography and DLPF structure with magnetic resonance imaging (MRI) in 22 schizophrenia patients [9 neuroleptic-naïve (NN) first episodes]. These patients also underwent a comprehensive battery of neuropsychological tests aimed at evaluating global intelligence and the proposed domains of cognitive alteration in schizophrenia, i.e., attention, visual and verbal learning and memory, working memory, problem solving and processing speed. The metabolic activity in the right DLPF region was significantly and directly related to processing speed, and a measure of structural deficit in the same area was directly related to working memory scores. In the NN group studied alone, these associations were replicated. We may conclude that hypofrontality during cognitive activation, and the degree of DLPF structural deficit may be associated to a particular profile of cognitive deficit, including lower processing speed and working memory capacity.

The role of behavioral impulsivity in the development of alcohol dependence: a 4-year follow-up study.

BACKGROUND: Although many studies have established a close relation between impulsivity and alcohol use disorders, little is known about the role of behavioral impulsivity in the development of these disorders. OBJECTIVES: To determine the role of 2 laboratory paradigms of impulsivity in the development of alcohol use disorders. METHODS: Follow-up study carried out with 471 participants diagnosed as heavy drinkers (HD) and followed-up for 4 years. Initially, they were compared with a healthy control group. Assessment of behavioral impulsivity was carried out with the Continuous Performance Test (CPT), and the Stop-Signal Task (SST) assessed behavioral inhibitory control. Differential reinforcement for low-rate responding (DRLR) was used to evaluate the delay reward dimension. The Structured Clinical Interview (SCID-DSM-IV) was used to diagnose alcohol dependence. RESULTS: The HD performed worse than the control group in all the behavioral tests of impulsivity. Performance in DRLR was the only behavioral impulsivity test that classified the HD correctly compared to controls. Logistic regression analysis indicated that performance on SST was a significant predictor [odds = 1.52(CI = 1.08-2.31)] of developing alcohol dependence. CONCLUSIONS: Our results support the relation between behavioral impulsivity and alcohol use disorders. The paradigm related to delay of reward may be a factor associated with the use of alcohol and the incapacity to control inhibition as dependence develops.

Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS): a commentary.

BACKGROUND AND HYPOTHESIS: Based on neurochemical and genetic evidence, we suggest that both prevention and treatment of multiple addictions, such as dependence to alcohol, nicotine and glucose, should involve a biphasic approach. Thus, acute treatment should consist of preferential blocking of postsynaptic Nucleus Accumbens (NAc) dopamine receptors (D1-D5), whereas long term activation of the mesolimbic dopaminergic system should involve activation and/or release of Dopamine (DA) at the NAc site. Failure to do so will result in abnormal mood, behavior and potential suicide ideation. Individuals possessing a paucity of serotonergic and/or dopaminergic receptors, and an increased rate of synaptic DA catabolism due to high catabolic genotype of the COMT gene, are predisposed to self-medicating any substance or behavior that will activate DA release, including alcohol, opiates, psychostimulants, nicotine, gambling, sex, and even excessive internet gaming. Acute utilization of these substances and/or stimulatory behaviors induces a feeling of well being. Unfortunately, sustained and prolonged abuse leads to a toxic" pseudo feeling" of well being resulting in tolerance and disease or discomfort. Thus, a reduced number of DA receptors, due to carrying the DRD2 A1 allelic genotype, results in excessive craving behavior; whereas a normal or sufficient amount of DA receptors results in low craving behavior. In terms of preventing substance abuse, one goal would be to induce a proliferation of DA D2 receptors in genetically prone individuals. While in vivo experiments using a typical D2 receptor agonist induce down regulation, experiments in vitro have shown that constant stimulation of the DA receptor system via a known D2 agonist results in significant proliferation of D2 receptors in spite of genetic antecedents. In essence, D2 receptor stimulation signals negative feedback mechanisms in the mesolimbic system to induce mRNA expression causing proliferation of D2 receptors. PROPOSAL AND CONCLUSION: The authors propose that D2 receptor stimulation can be accomplished via the use of Synapatmine, a natural but therapeutic nutraceutical formulation that potentially induces DA release, causing the same induction of D2-directed mRNA and thus proliferation of D2 receptors in the human. This proliferation of D2 receptors in turn will induce the attenuation of craving behavior. In fact as mentioned earlier, this model has been proven in research showing DNA-directed compensatory overexpression (a form of gene therapy) of the DRD2 receptors, resulting in a significant reduction in alcohol craving behavior in alcohol preferring rodents. Utilizing natural dopaminergic repletion therapy to promote long term dopaminergic activation will ultimately lead to a common, safe and effective modality to treat Reward Deficiency Syndrome (RDS) behaviors including Substance Use Disorders (SUD), Attention Deficit Hyperactivity Disorder (ADHD), Obesity and other reward deficient aberrant behaviors. This concept is further supported by the more comprehensive understanding of the role of dopamine in the NAc as a "wanting" messenger in the meso-limbic DA system.

Schizopsychotic symptom-profiles and biomarkers: beacons in diagnostic labyrinths.

Several avenues of investigation through which the 'labyrinths' of schizopsychotic diagnosis may be examined, are offered by the consideration of the 'beacons' of symptom-profiles and biomarkers. Neurodevelopmental issues and risk assessment, neurocognitive factors of predictive necessity, supersensitivity in neurotransmitter systems, the implications of prodromal expressions of the disorder, functional dysconnectivity arising from prefrontal to diverse regional patterns and circuits with a neurodevelopmental origin, and heritable gene characteristics are viewed against the backdrop of the schizophrenia spectrum disorders. The associations between adolescent-adult use of cannabis, on the one hand, and, alternatively, the prevalence of chromosomal abnormalities, e.g., GRIK4 and NPAS3, and mental retardation, on the other hand, with the symptom-profiles of schizopsychosis provide further evidence of emerging biomarkers of biological inheritance factors. The involvement of dopamine D1 and D2 receptors, particularly in prefrontal region, with regard to functional integrity of cognitive systems is reviewed. It would appear that considerations of these disorders imply that one essential hub around which much of the neuropathology revolves may be observed in the various expressions of the cognitive and structural insufficiency.

Affective status in relation to impulsive, motor and motivational symptoms: personality, development and physical exercise.

The contributions of impulsive and risk-taking behaviour in depressive and bipolar disorders, motivational and motor behaviours in anhedonic and substance addictive states, and the factors, particularly distress and trauma, underlying the development of neuropathology in affective status are described from clinical, epidemiological and laboratory perspectives. In order to distinguish one case factor for biopsychological substrates of health, an array of self-reported characteristics, e.g., positive or negative affect, stress or energy, optimism, etc., that may be predictive or counterpredictive for the propensity for physical exercise and activity were analysed using a linear regression in twelve different studies. Several individual characteristics were found to be markedly and significantly predictive of the exercise propensity, i.e., positive affect, energy, health-seeking behaviour and character, while optimism was of lesser, though significant, importance. Several individual characteristics were found to be significantly counterpredictive: expression of BDI- and HAD-depression, major sleep problems and lack/negligence of health-seeking behaviour. The consequences of physical activity and exercise for both affective well-being, cognitive mobility and neurogenesis is noted, particularly with regard to developmental assets for younger individuals. Affective disorder states may be studied through analyses of personal characteristics that unfold predispositions for symptoms-profiles and biomarkers derived from properties of dysfunction, such as impulsiveness, temperament dimensions, anhedonia and 'over-sensitivity', whether interpersonal or to reward.

Cognitive symptoms facilitatory for diagnoses in neuropsychiatric disorders: executive functions and locus of control.

Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurodevelopmental components, demonstrate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cognitive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, 'healthy' young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed.