Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation.

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.

The new profile of psychiatric disorders in patients with HIV infection.

Nowadays, HIV infection is largely considered as a chronic condition rather than a deadly disease, given that effective antiretroviral treatment allows almost complete and persistent suppression of viral replication and restoration of nearly normal CD4+ T-cell counts. Being HIV a "condition", we imply that other illnesses are more frequently seen in persons living with HIV (PLHIV), among which mental health disorders are particularly common. Despite very successful antiretroviral therapy, HIV infection may still cause a wide range of neurocognitive dysfunctions and accelerated brain ageing. Beyond direct viral effects, at least another five causes of neurological damage are more frequent among PLHIV. First, the use of neurochemical substances as sexual boosters (chemsex) has become popular in this population. Second, the rate of sexually transmitted infections as syphilis, which may affect the central nervous system, is more prevalent among PLHIV. Third, the use of certain antiretroviral drugs, such as efavirenz, has been associated with changes in mood and/or psychotic symptoms. Fourth, an increased rate of mental disorders has been reported in PLHIV, either as predisposing conditions or following the recognition of HIV diagnosis (i.e., major depression). Finally, psychosocial factors such as loneliness, isolation and stigmatization are more frequent in PLHIV and worsen their mental health. Given that the life expectancy of PLHIV has increased significantly, a new and much broader spectrum of psychiatric disorders has emerged in PLHIV. Early diagnosis and adequate management, including education and preventative interventions are warranted.

Measuring discrimination experienced by people with a mental illness: replication of the short-form DISCUS in six world regions.

BACKGROUND: The Discrimination and Stigma Scale (DISC) is a patient-reported outcome measure which assesses experiences of discrimination among persons with a mental illness globally. METHODS: This study evaluated whether the psychometric properties of a short-form version, DISC-Ultra Short (DISCUS) (11-item), could be replicated in a sample of people with a wide range of mental disorders from 21 sites in 15 countries/territories, across six global regions. The frequency of experienced discrimination was reported. Scaling assumptions (confirmatory factor analysis, inter-item and item-total correlations), reliability (internal consistency) and validity (convergent validity, known groups method) were investigated in each region, and by diagnosis group. RESULTS: 1195 people participated. The most frequently reported experiences of discrimination were being shunned or avoided at work (48.7%) and discrimination in making or keeping friends (47.2%). Confirmatory factor analysis supported a unidimensional model across all six regions and five diagnosis groups. Convergent validity was confirmed in the total sample and within all regions [ Internalised Stigma of Mental Illness (ISMI-10): 0.28-0.67, stopping self: 0.54-0.72, stigma consciousness: -0.32-0.57], as was internal consistency reliability (α = 0.74-0.84). Known groups validity was established in the global sample with levels of experienced discrimination significantly higher for those experiencing higher depression [Patient Health Questionnaire (PHQ)-2: p < 0.001], lower mental wellbeing [Warwick-Edinburgh Well-being Scale (WEMWBS): p < 0.001], higher suicidal ideation [Beck Hopelessness Scale (BHS)-4: p < 0.001] and higher risk of suicidal behaviour [Suicidal Ideation Attributes Scale (SIDAS): p < 0.001]. CONCLUSIONS: The DISCUS is a reliable and valid unidimensional measure of experienced discrimination for use in global settings with similar properties to the longer DISC. It offers a brief assessment of experienced discrimination for use in clinical and research settings.

The black hole of the transition process: dropout of care before transition age in adolescents.

Recent evidence confirms the risks of discontinuity of care when young people make a transition from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS), although robust data are still sparse. We aimed to identify when and how patients get lost to care during transition by tracking care pathways and identifying factors which influence dropping out of care during transition. This is a retrospective observational study of 760 patients who reached the transition age boundary within 12 months before transition time and being treated at CAMHS for at least during preceding 18 months. Data were collected at two time points: last visit to CAHMS and first visit to AHMS. Socio-demographic, clinical and service utilization variables on CAMHS treatment were collected. In the 12 months leading up to the transition boundary, 46.8% of subjects (n = 356) withdrew from CAHMS without further contact with AHMS, 9.3% withdrew from CAHMS but were referred to AHMS by other services, 29% were transferred from CAHMS to AHMS, 10% remained at CAHMS and 5% patients were transferred to alternative services. Fifty-six percent of subjects experience cessation of care before the transition age. The risk of dropout increases with shorter contact time in CAMHS, is greater in subjects without pharmacological treatment, and decreases in subjects with psychosis, bipolar disorder, eating disorders, mental retardation, and neurodevelopmental disorders. This study confirms that a large number of people drop out of care as they approach the CAMHS transition and experience discontinuity of care during this critical period.

Nucleus Accumbens Stimulation Modulates Inhibitory Control by Right Prefrontal Cortex Activation in Obsessive-Compulsive Disorder.

Inhibitory control is considered a compromised cognitive function in obsessive-compulsive (OCD) patients and likely linked to corticostriatal circuitry disturbances. Here, 9 refractory OCD patients treated with deep brain stimulation (DBS) were evaluated to address the dynamic modulations of large-scale cortical network activity involved in inhibitory control after nucleus accumbens (NAc) stimulation and their relationship with cortical thickness. A comparison of DBS "On/Off" states showed that patients committed fewer errors and exhibited increased intraindividual reaction time variability, resulting in improved goal maintenance abilities and proactive inhibitory control. Visual P3 event-related potentials showed increased amplitudes during Go/NoGo performance. Go and NoGo responses increased cortical activation mainly over the right inferior frontal gyrus and medial frontal gyrus, respectively. Moreover, increased cortical activation in these areas was equally associated with a higher cortical thickness within the prefrontal cortex. These results highlight the critical role of NAc DBS for preferentially modulating the neuronal activity underlying sustained speed responses and inhibitory control in OCD patients and show that it is triggered by reorganizing brain functions to the right prefrontal regions, which may depend on the underlying cortical thinning. Our findings provide updated structural and functional evidence that supports critical dopaminergic-mediated frontal-striatal network interactions in OCD.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

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.

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.

Validation of the spanish version of the discrimination and stigma scale (DISC 12).

AIMS: The "Discrimination and Stigma Scale" (DISC) was the first instrument specifically designed to evaluate reported experiences of discrimination by people with mental disorders. This study aims to validate DISC-12 version in Spanish population with Schizophrenia and, as specific objectives, to do the external validation with the Self-Stigma Questionnaire (SSQ) scale and Link PDD scale and to validate their internal consistency, temporal and inter-rater reliability. METHODS: 86 individuals with schizophrenia were interviewed at two time points (between one to two weeks) by two raters. Additionally to assess their sociodemographic and clinical characteristics, following scales were administered: DISC 12, SSQ, PDD, Social Functioning Scale (SFS) and Global Assessment of Function (GAF). RESULTS: Internal consistency as a whole results a Cronbach a between 0.741 and 0.850. Subscales "Unfair treatmen" and "Positive treatment" have a Cronbach a higher than 0.79, but the both subscales "Stopping Self" and "Overcoming stigma" do not have in themselves an adequate consistency. Test-retest reliability shows that four subscales have values higher than 0.67. Inter-rater reliability assessment result that 21 items score values above 0.8, 10 between 0.6-0.8 and one lower than 0.6. DISC-12 was significantly related with the second factor of the PDD (self-stigma) and SSQ. CONCLUSIONS: The Spanish version of the DISC 12 scale is valid, has good internal consistency, is reliable both in terms of test-retest and inter-rater reliability and has good convergent validity with the SSQ and PDD, and the "Unfair treatment" and "Positive Treatment" subscales were the most robust of the four subscales.

Personalized striatal targets for deep brain stimulation in obsessive-compulsive disorder.

BACKGROUND: Psychiatric conditions currently treated with deep brain stimulation (DBS), such as obsessive-compulsive disorder (OCD), are heterogeneous diseases with different symptomatic dimensions, indicating that fixed neuroanatomical DBS targets for all OCD cases may not be efficacious. OBJECTIVE/HYPOTHESIS: We tested whether the optimal DBS target for OCD is fixed for all patients or whether it is individualized and related to each patient's symptomatic content. Further, we explored if the optimal target can be predicted by combining functional neuroimaging and structural connectivity. METHODS: In a prospective, randomized, double-blinded study in 7 OCD patients, symptomatic content was characterized pre-operatively by clinical interview and OCD symptom-provocation during functional MRI. DBS electrode implantation followed a trajectory placing 4 contacts along a striatal axis (nucleus accumbens to caudate). Patients underwent three-month stimulation periods for each contact (and sham), followed by clinical evaluation. Probabilistic tractography, applied to diffusion-weighted images acquired pre-operatively, was used to study the overlap between projections from the prefrontal areas activated during symptom provocation and the volume of activated tissue of each electrode contact. RESULTS: Six patients were classified responders, with median symptomatic reduction of 50% achieved from each patient's best contact. This was located at the caudate in 4 cases and at the accumbens in 2. Critically, the anatomical locus of the best contact (accumbens or caudate) was related to an index derived by combining functional MRI responses to prevailing symptom provocation and prefronto-cortico-striatal projections defined by probabilistic tractography. CONCLUSION: Our results therefore represent a step towards personalized, content-specific DBS targets for OCD.

[Ability to detect psychiatric disorders by the family physician]. / Capacidad de detección de patología psiquiátrica por el médico de familia.

OBJECTIVE: To determine the ability of family physicians to detect psychiatric disorders, comparing the presence of psychiatric disorders detected using validated tests and referrals by family physicians. DESIGN: Cross-sectional, two-phase study. LOCATION: Primary healthcare centres in an urban area of Madrid. PARTICIPANTS: Patients between 18 and 65years attending primary healthcare centres for non-administrative purposes. MAIN MEASUREMENTS: To detect psychiatric disorders in the waiting room, an interview was performed using GHQ-28 and MULTICAGE CAD-4 in the screening phase (considered positive: score of 6 or higher on the GHQ-28 or a score 2 or higher on MULTICAGE CAD-4). Patients with a positive score and 20% with negative were recruited for the second phase (case identification) using MINI interview. During family physician consultation, the patient gave his doctor a card with an identification number to record the presence of psychiatric illness in his/her opinion and whether there was treatment with psychotropic drugs. RESULTS: A total of 628 subjects participated. The prevalence of psychiatric disorders corrected by two phase methodology was 31.7% (95%CI: 27.9 to 35.5). Of the 185 patients with a psychiatric disorder detected, 44.2% (95%CI: 36.7 to 51.7) were identified as patients with psychiatric disorders by their family physician. Disorders best detected were: hypomania, dysthymic disorder, depressive episode with melancholic symptoms, and panic disorder. CONCLUSIONS: A significant percentage of patients with possible psychiatric disorders detected with validated test have not been identified by their family physician.

Dynamic risk control by human nucleus accumbens.

Real-world decisions about reward often involve a complex counterbalance of risk and value. Although the nucleus accumbens has been implicated in the underlying neural substrate, its criticality to human behaviour remains an open question, best addressed with interventional methodology that probes the behavioural consequences of focal neural modulation. Combining a psychometric index of risky decision-making with transient electrical modulation of the nucleus accumbens, here we reveal profound, highly dynamic alteration of the relation between probability of reward and choice during therapeutic deep brain stimulation in four patients with treatment-resistant psychiatric disease. Short-lived phasic electrical stimulation of the region of the nucleus accumbens dynamically altered risk behaviour, transiently shifting the psychometric function towards more risky decisions only for the duration of stimulation. A critical, on-line role of human nucleus accumbens in dynamic risk control is thereby established.

A new time limited psychotherapy for BPD: preliminary results of a randomized and controlled trial.

INTRODUCTION: Psychic Representation focused Psychotherapy (PRFP) is a new time limited dynamic psychotherapy for the treatment of Borderline Personality Disorder. It is a psychodynamic technique based on brief psychoanalytic psychotherapy principles. It is manualized and designed to be applied in the framework of public health care services. A randomized and controlled study with a sample of 53 patients was conducted to assess PRFP efficacy. This work presents the results for the first 44 trial completers at termination of treatment. METHODS: Both groups, the experimental (n= 18) and control group (n= 26), received treatment as usual. The experimental group received an additional 20 (PRFP) sessions, conducted by four therapists with homogenous characteristics specifically trained in this technique. The main outcome variables measures were: Severity global index of SCL-90-R, Barrat Impulsivity Scale scores and Social Adaptation (SASS score). Baseline and final condition at termination was compared. CONCLUSIONS: Preliminary results showed significantly better outcomes for the experimental group in all the main variables measured and in most of the secondary ones. PRFP may represent an important contribution for the treatment of BPD patients. Follow-up assessment at 6 and 12 months is planned.

Global pattern of experienced and anticipated discrimination reported by people with major depressive disorder: a cross-sectional survey.

BACKGROUND: Depression is the third leading contributor to the worldwide burden of disease. We assessed the nature and severity of experienced and anticipated discrimination reported by adults with major depressive disorder worldwide. Moreover, we investigated whether experienced discrimination is related to clinical history, provision of health care, and disclosure of diagnosis and whether anticipated discrimination is associated with disclosure and previous experiences of discrimination. METHODS: In a cross-sectional survey, people with a diagnosis of major depressive disorder were interviewed in 39 sites (35 countries) worldwide with the discrimination and stigma scale (version 12; DISC-12). Other inclusion criteria were ability to understand and speak the main local language and age 18 years or older. The DISC-12 subscores assessed were reported discrimination and anticipated discrimination. Multivariable regression was used to analyse the data. FINDINGS: 1082 people with depression completed the DISC-12. Of these, 855 (79%) reported experiencing discrimination in at least one life domain. 405 (37%) participants had stopped themselves from initiating a close personal relationship, 271 (25%) from applying for work, and 218 (20%) from applying for education or training. We noted that higher levels of experienced discrimination were associated with several lifetime depressive episodes (negative binomial regression coefficient 0·20 [95% CI 0·09-0·32], p=0·001); at least one lifetime psychiatric hospital admission (0·29 [0·15-0·42], p=0·001); poorer levels of social functioning (widowed, separated, or divorced 0·10 [0·01-0·19], p=0·032; unpaid employed 0·34 [0·09-0·60], p=0·007; looking for a job 0·26 [0·09-0·43], p=0·002; and unemployed 0·22 [0·03-0·41], p=0·022). Experienced discrimination was also associated with lower willingness to disclose a diagnosis of depression (mean discrimination score 4·18 [SD 3·68] for concealing depression vs 2·25 [2·65] for disclosing depression; p<0·0001). Anticipated discrimination is not necessarily associated with experienced discrimination because 147 (47%) of 316 participants who anticipated discrimination in finding or keeping a job and 160 (45%) of 353 in their intimate relationships had not experienced discrimination. INTERPRETATION: Discrimination related to depression acts as a barrier to social participation and successful vocational integration. Non-disclosure of depression is itself a further barrier to seeking help and to receiving effective treatment. This finding suggests that new and sustained approaches are needed to prevent stigmatisation of people with depression and reduce the effects of stigma when it is already established. FUNDING: European Commission, Directorate General for Health and Consumers, Public Health Executive Agency.

The role of suicide risk in the decision for psychiatric hospitalization after a suicide attempt.

BACKGROUND: Suicide prevention can be improved by knowing which variables physicians take into account when considering hospitalization or discharge of patients who have attempted suicide. AIMS: To test whether suicide risk is an adequate explanatory variable for predicting admission to a psychiatric unit after a suicide attempt. METHODS: Analyses of 840 clinical records of patients who had attempted suicide (66.3% women) at four public general hospitals in Madrid (Spain). RESULTS: 180 (21.4%) patients were admitted to psychiatric units. Logistic regression analyses showed that explanatory variables predicting admission were: male gender; previous psychiatric hospitalization; psychiatric disorder; not having a substance-related disorder; use of a lethal method; delay until discovery of more than one hour; previous attempts; suicidal ideation; high suicidal planning; and lack of verbalization of adequate criticism of the attempt. CONCLUSIONS: Suicide risk appears to be an adequate explanatory variable for predicting the decision to admit a patient to a psychiatric ward after a suicide attempt, although the introduction of other variables improves the model. These results provide additional information regarding factors involved in everyday medical practice in emergency settings.

Differences between younger and older adults in the structure of suicidal intent and its correlates.

OBJECTIVE: To analyze differences in the variables associated with severity of suicidal intent and in the main factors associated with intent when comparing younger and older adults. DESIGN: Observational, descriptive cross-sectional study. SETTING: Four general hospitals in Madrid, Spain. PARTICIPANTS: Eight hundred seventy suicide attempts by 793 subjects split into two groups: 18-54 year olds and subjects older than 55 years. MEASUREMENTS: The authors tested the factorial latent structure of suicidal intent through multigroup confirmatory factor analysis for categorical outcomes and performed statistical tests of invariance across age groups using the DIFFTEST procedure. Then, they tested a multiple indicators-multiple causes (MIMIC) model including different covariates regressed on the latent factor "intent" and performed two separate MIMIC models for younger and older adults to test for differential patterns. RESULTS: Older adults had higher suicidal intent than younger adults (z = 2.63, p = 0.009). The final model for the whole sample showed a relationship of intent with previous attempts, support, mood disorder, personality disorder, substance-related disorder, and schizophrenia and other psychotic disorders. The model showed an adequate fit (chi²[12] = 22.23, p = 0.035; comparative fit index = 0.986; Tucker-Lewis index = 0.980; root mean square error of approximation = 0.031; weighted root mean square residual = 0.727). All covariates had significant weights in the younger group, but in the older group, only previous attempts and mood disorders were significantly related to intent severity. CONCLUSIONS: The pattern of variables associated with suicidal intent varies with age. Recognition, and treatment of geriatric depression may be the most effective measure to prevent suicidal behavior in older adults.

Quality of the written information about suicide attempters.

INTRODUCTION: The aim of the study was to assess the quality of the clinical records of the patients who are seen in public hospitals in Madrid after a suicide attempt in a blind observation. METHODS: Observational, descriptive cross-sectional study conducted at four general public hospitals in Madrid (Spain). Analyses of the presence of seven indicators of information quality (previous psychiatric treatment, recent suicidal ideation, recent suicide planning behaviour, medical lethality of suicide attempt, previous suicide attempts, attitude towards the attempt, and social or family support) in 993 clinical records of 907 patients (64.5% women), ages ranging from 6 to 92 years (mean 37.1±15), admitted to hospital after a suicide attempt or who committed an attempt whilst in hospital. RESULTS: Of patients who attempted suicide, 94.9% received a psychosocial assessment. All seven indicators were documented in 22.5% of the records, whilst 23.6% recorded four or less than four indicators. Previous suicide attempts and medical lethality of current attempt were the indicators most often missed in the records. The study found no difference between the records of men and women (z=0.296; p=0.767, two tailed Mann-Whitney U test), although clinical records of patients discharged after an emergency unit intervention were more incomplete than the ones from hospitalised patients (z=2.731; p=0.006), and clinical records of repeaters were also more incomplete than the ones from non-repeaters (z=3.511; p<0.001). CONCLUSIONS: Clinical records of patients who have attempted suicide are not complete. The use of semi-structured screening instruments may improve the evaluation of patients who have self- harmed.