Pathways to professional mental care in the Swiss young adult community: a case-control study.

Treatment success for mental health (MH) problems depends, among others, on the timeliness of help-seeking. Therefore, we studied the effect of symptoms and reasons for help-seeking on the point-of-contact and the most intensive professional treatment in a community sample. Participants were recruited as part of the 'Bern Epidemiological At-Risk' (BEAR) study on 16-40-year-old community persons of the Swiss canton Bern. Of the 2,683 participants, 615 (22.9%) reported at least one instance of help-seeking for MH problems and were selected for the presented analyses. Help-seeking behavior was assessed by a modified version of the 'WHO pathway-to-care questionnaire', from which the outcome 'most intensive MH professional contact' was generated. The effect of symptoms and reasons for help-seeking were analyzed in separate models using path analyses. Most help-seeking persons sought MH professional help (n = 405; 65.9%) with a high number of medical pre-contacts (n = 233; 37.9%). The 'most intensive MH professional contact' was provided after an average of 1.47 contacts. Both models showed negative associations between non-MH professional pre-contacts and the most intensive, likely most adequate MH treatment. In the symptom model, 'substance misuse' and 'central-vegetative problems' increased the general likelihood of MH professional contact. Our findings highlight the importance of the first point-of-contact in pathways to adequate MH care and, when seeking help from non-MH professional, of quick referrals to MH professionals. Awareness campaigns or training of health professionals, such as general practitioners, may support timely contact with MH professionals to improve diagnosis, prognosis, and outcome.

Influence of mental health literacy on help-seeking behaviour for mental health problems in the Swiss young adult community: a cohort and longitudinal case-control study.

Poor knowledge about mental health disorders and their treatment likely contributes to the large treatment gap reported for mental health problems. Therefore, we studied the association between mental health literacy (MHL) and active help-seeking in a community sample. Participants were recruited from an add-on questionnaire study to the 'Bern Epidemiological At-Risk' (BEAR) study on 16-40-year-old community subjects of the Swiss canton Bern. At baseline, data of N = 1504, and at 3-year follow-up, data of N = 535 were available. Based on an unlabelled case vignette (on depression or schizophrenia), MHL was assessed by the questionnaire of Angermeyer and colleagues. Cross-sectional and longitudinal baseline predictors of help-seeking were analysed using path analyses. Additionally, sensitivity analyses of the prospective model were computed for sex, vignette, and baseline mental health problems/disorders. Cross-sectionally, help-seeking was associated with non-endorsement of biogenetic causal explanations, presence of mental health problems/disorders, help-seeking before baseline, poorer functioning, and lower health satisfaction. The prospective model was similar; yet, help-seeking at follow-up was associated with endorsements of the causal explanation 'biogenetics' and, additionally, 'childhood trauma' but not the presence of baseline mental health problems/disorders. Sensitivity analyses revealed a significant impact on sex, vignette, and mental health problems/disorders. For example, actual functional problems were predictive in males, while health satisfaction was predictive in females. Our findings indicate that future studies on drivers of help-seeking should assess very large community samples with case vignettes on different mental disorders to examine appropriate subgroups and their likely interaction to address group-specific factors in awareness campaigns.

Identification of voxel-based texture abnormalities as new biomarkers for schizophrenia and major depressive patients using layer-wise relevance propagation on deep learning decisions.

Non-segmented MRI brain images are used for the identification of new Magnetic Resonance Imaging (MRI) biomarkers able to differentiate between schizophrenic patients (SCZ), major depressive patients (MD) and healthy controls (HC). Brain texture measures such as entropy and contrast, capturing the neighboring variation of MRI voxel intensities, were computed and fed into deep learning technique for group classification. Layer-wise relevance was applied for the localization of the classification results. Texture feature map of non-segmented brain MRI scans were extracted from 141 SCZ, 103 MD and 238 HC. The gray level co-occurrence matrix (GLCM) was calculated on a voxel-by-voxel basis in a cube of voxels. Deep learning tested if texture feature map could predict diagnostic group membership of three classes under a binary classification (SCZ vs. HC, MD vs. HC, SCZ vs. MD). The method was applied in a repeated nested cross-validation scheme and cross-validated feature selection. The regions with the highest relevance (positive/negative) are presented. The method was applied on non-segmented images reducing the computation complexity and the error associated with segmentation process.

Effect of childhood physical abuse on social anxiety is mediated via reduced frontal lobe and amygdala-hippocampus complex volume in adult clinical high-risk subjects.

BACKGROUND: Childhood adverse experiences (CAE) are associated with clinical psychiatric disorders and symptoms, and with volumetric abnormalities in the amygdala-hippocampus complex (AmHiC) and frontal lobe (FroL) in adulthood. AIM: To study whether CAE are associated with reduced AmHiC and FroL and whether these structures mediate the effect of CAE on social anxiety and depression. METHOD: In seven European centres, 374 patients with recent onset of psychosis (n = 127), clinical high-risk to psychosis (n = 119) or recent onset of depression (n = 128) were scanned with MRI and their FroL and AmHiC volumes were measured. They all completed self-report scales for assessment of CAE, social anxiety and depression. RESULTS: Of the CAE domains, physical abuse was associated specifically with reduced grey and white matter volumes of FroL and AmHiC in psychotic and high-risk patients. After controlling intracranial volume, PhyAb associated significantly with FroL and its grey matter volume in high-risk patients only. In mediation analyses, the effect of physical abuse on social anxiety was mediated via reduced FroL grey mater volume in high-risk patients. In them, when the effects of AmHiC and depression were controlled, the effect of physical abuse on social anxiety was mediated via FroL grey matter volume reduction. CONCLUSIONS: Childhood physical abuse is associated with reduced frontal lobe and amygdala-hippocampus complex volume in adult subjects with psychotic symptoms. Reduced frontal lobe and amygdala-hippocampus complex volume mediate the effect of physical abuse on social anxiety in high-risk patients. The effect of physical abuse on depression-independent social anxiety is mediated via reduced frontal lobe.

[Early recognition and prevention of schizophrenia and other psychoses]. / Früherkennung und Prävention von Schizophrenie und anderen Psychosen.

The last two decades of clinical research have clearly demonstrated the comprehensive benefits of the early recognition and treatment of psychotic disorders. The attenuated and transient positive symptoms according to the ultrahigh risk criteria and the basic symptom criterion "Cognitive disturbances" are the main approaches for an indicated prevention. They have recently been recommended as criteria for a clinical high-risk (CHR) state of psychosis by the European Psychiatric Association (EPA) and, following these, in the German S3 guidelines for the treatment of schizophrenia by the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN); however, the efficacy of early treatment of patients with a CHR for psychoses critically depends on the development of prognostic instruments, which enable healthcare professionals to reliably identify these patients based on the individual objective risk profiles. An important goal is the treatment of functional deficits, which can be identified by an individual risk profile. The treatment of existing comorbid mental disorders, psychosocial problems and the prevention of potential future disorders also characterizes the recommendations of the EPA and DGPPN for early treatment, which favor psychotherapeutic, especially cognitive behavioral interventions over pharmacological treatment. The close interdisciplinary cross-sectoral cooperation between the disciplines of child and adolescent psychiatry, and adult psychiatry is of outstanding importance in this context.

[Internet-based interventions in the treatment of mental disorders : Overview, quality criteria, perspectives]. / Internetbasierte Interventionen in der Behandlung psychischer Störungen : Überblick, Qualitätskriterien, Perspektiven.

BACKGROUND: Mental disorders are frequently not or only insufficiently treated. Internet-based interventions offer the potential of closing the existing gaps in the treatment of mental disorders; however, it is very difficult for patients and providers to choose from the numerous interventions available. OBJECTIVE: The aim of this study was to develop a set of quality criteria that can help patients and care providers to identify recommendable internet-based interventions. METHODS: A selective literature search was carried out and the existing evidence on internet-based interventions in the treatment of mental disorders was collated. A panel of experts then developed quality criteria based on existing models for the systematic assessment of telemedicine applications. RESULTS: Internet-based interventions are effective in the treatment of a broad range of mental disorders. The best evidence is available for depression and anxiety disorders. A set of criteria is proposed for the evaluation of available internet-based interventions using a checklist. These criteria have to be developed further with input from other stakeholders. DISCUSSION: When taking these quality criteria into account, evidence-based interventions available on the internet can make an important contribution to improvement of the care of patients with mental disorders.

Reduced parahippocampal cortical thickness in subjects at ultra-high risk for psychosis.

BACKGROUND: Grey matter volume and cortical thickness represent two complementary aspects of brain structure. Several studies have described reductions in grey matter volume in people at ultra-high risk (UHR) of psychosis; however, little is known about cortical thickness in this group. The aim of the present study was to investigate cortical thickness alterations in UHR subjects and compare individuals who subsequently did and did not develop psychosis. METHOD: We examined magnetic resonance imaging data collected at four different scanning sites. The UHR subjects were followed up for at least 2 years. Subsequent to scanning, 50 UHR subjects developed psychosis and 117 did not. Cortical thickness was examined in regions previously identified as sites of neuroanatomical alterations in UHR subjects, using voxel-based cortical thickness. RESULTS: At baseline UHR subjects, compared with controls, showed reduced cortical thickness in the right parahippocampal gyrus (p < 0.05, familywise error corrected). There were no significant differences in cortical thickness between the UHR subjects who later developed psychosis and those who did not. CONCLUSIONS: These data suggest that UHR symptomatology is characterized by alterations in the thickness of the medial temporal cortex. We did not find evidence that the later progression to psychosis was linked to additional alterations in cortical thickness, although we cannot exclude the possibility that the study lacked sufficient power to detect such differences.

[Neuroimaging of bipolar disorders]. / Bildgebende Verfahren bei bipolaren Erkrankungen.

During recent years, marked progress has been made both in structural and functional neuroimaging of affective disorders. Structural changes in the limbic system, prefrontal cortex and subcortical regions including their fascicular connections appear to correlate with affective disorders in most, but not all studies. Especially for bipolar disorder, there still is a considerable heterogeneity among the results. Functional neuroimaging (fMRI, SPECT, PET) underlines the importance of paralimbic, cortical and subcortical structures in mood regulation; however, the methodology of these studies is still in its infancy meaning that the results of these studies are not always reproducible. However, in summary it can be expected that with improving methodology functional neuroimaging will play an increasing role in affective, including bipolar, disorders in the near future.

Dual-isotope SPECT imaging of striatal dopamine: a comparative study between never-treated and haloperidol-treated first-episode schizophrenic patients.

The aim of this dual-isotope SPECT imaging study was to evaluate striatal dopamine transporter (DAT) and D2 receptor availability in first-episode never-treated and haloperidol-treated schizophrenic patients and whether the availability is associated with psychopathology. Twenty-four inpatients with a first acute schizophrenic episode were enrolled in the study; 12 of these patients were treated with haloperidol for 2 weeks before dual-isotope SPECT was performed, whereas the other 12 patients underwent the SPECT evaluation directly after enrollment. Twelve healthy control persons were also recruited and evaluated with the dual-isotope SPECT protocol. Psychopathology was assessed by the Positive and Negative Syndrome Scale and other scales. D2-radioligand binding did not differ between drug-naïve patients and the control group but was significantly lower in the haloperidol-treated group. DAT availability was also significantly lower in the haloperidol patients than in the other two groups and differed significantly between drug-naïve, positive-syndrome-type patients and healthy controls. The data obtained with the new dual-isotope SPECT technique reveal a direct effect of haloperidol at the D2 and DAT receptor level.

Amygdala reduction in patients with ADHD compared with major depression and healthy volunteers.

OBJECTIVE: Results in adult attention deficit hyperactivity disorder (ADHD) on structural brain changes and the clinical relevance are contradictory. The aim of this study was to investigate whether in adult patients with ADHD hippocampal or amygdala volumes differs from that in healthy controls and patients with major depression (MD). METHOD: Twenty patients with ADHD, 20 matched patients with MD and 20 healthy controls were studied with high resolution magnetic resonance imaging. RESULTS: Amygdala volumes in patients with ADHD were bilaterally smaller than in patients with MD and healthy controls. In ADHD, more hyperactivity and less inattention were associated with smaller right amygdala volumes, and more symptoms of depression with larger amygdala volumes. CONCLUSION: This study supports findings that the amygdala plays an important role in the systemic brain pathophysiology of ADHD. Whether patients with ADHD and larger amygdala volumes are more vulnerable to affective disorders needs further investigation.

Cerebral network deficits in post-acute catatonic schizophrenic patients measured by fMRI.

Twelve patients with catatonic schizophrenia and 12 matched healthy controls were examined with functional MRI while performing a motor task. The aim of our study was to identify the intracerebral pathophysiological correlates of motor symptoms in catatonic patients. The motor task included three conditions: a self-initiated (SI), an externally triggered (ET) and a rest condition. Statistical analysis was performed with SPM5. During the self-initiated movements patients showed significantly less activation than healthy controls in the supplementary motor area (SMA), the prefrontal and parietal cortex. Our results suggest a dysfunction of the "medial motor system" in catatonic patients. Self-initiated and externally triggered movements are mediated by different motor loops. The "medial loop" includes the SMA, thalamus and basal ganglia, and is necessary for self-initiated movements. The "lateral loop" includes parts of the cerebellum, lateral premotor cortex, thalamus and parietal association areas. It is involved in the execution of externally triggered movements. Our findings are in agreement with earlier behavioral data, which show deficits in self-initiated movements in catatonic patients but no impairment of externally triggered movements.

Reduced gray matter brain volumes are associated with variants of the serotonin transporter gene in major depression.

The serotonergic system is involved in the pathophysiology of major depression as well as in the early central nervous system development and adult neuroplasticity. The aim of the study was to examine in 77 patients with major depression and 77 healthy controls the association between the triallelic polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and gray matter (GM) brain volumes measured with 1.5 T magnetic resonance imaging. Voxel-based morphometry were estimated on magnetic resonance images and genotyping was performed. We found that healthy controls have a strong association between the 5-HTTLPR and GM volumes of the dorsolateral prefrontal cortex, left anterior gyrus cinguli, left amygdala as well as right hippocampus, whereas there is no such association in patients with major depression. Healthy subjects carrying the S- or L(G)-allele have smaller GM volumes than those with the L(A)-allele, indicating that 5-HTTLPR contributes to the development of brain structures. Patients with depression show reduced GM volumes, particularly when they are homozygous for the L(A)-allele, suggesting that these patients are more vulnerable for morphological changes during depressive episodes.

Striatal D2/D3 receptor occupancy, clinical response and side effects with amisulpride: an iodine-123-iodobenzamide SPET study.

INTRODUCTION: Amisulpride appears to be an effective atypical agent for treating schizophrenia in a dose-dependent manner. METHODS: 29 patients suffering from schizophrenia or schizoaffective disorder were treated with a broad dose range of amisulpride (50-1 200 mg/day, mean: 455.2+/-278.8 mg/day). After 2 weeks, brain single photon emission tomography (SPET) scans were performed two hours after intravenous injection of 185 MBq [123I]IBZM. Clinical evaluations and ratings of extrapyramidal symptoms were performed at baseline and after steady state treatment of two weeks with amisulpride. RESULTS: In patients treated with amisulpride, specific binding of [123I]IBZM to D2 receptors was significantly decreased (p<0.001) compared to healthy controls. D2 receptor blockade correlated well with administered doses and plasma concentrations of amisulpride. Extrapyramidal side effects, which had to be treated with biperiden, were observed in 31% of the patients. Clinical response was very good, without correlation between the response and striatal D2 occupancy. DISCUSSION: Within the first two weeks of treatment with the atypical antipsychotic amisulpride a significant occupancy of striatal postsynaptic dopamine D2 receptors was achieved. At the same time amisulpride shows an excellent tolerability with good efficacy.

Structural brain alterations at different stages of schizophrenia: a voxel-based morphometric study.

Structural alterations in schizophrenia have mainly been regarded as the result of neurodevelopmental processes. However, it remains unresolved whether the pattern of morphological brain changes differs between different stages of disease. We examined structural brain changes in 93 first-episode (FES) and 72 recurrently ill (REZ) patients with schizophrenia (SZ) and 175 matched healthy control subjects (HC) using cross-sectional and conjunctional voxel-based morphometry (VBM) of whole-brain MRI data in a three-step approach. We found significant grey matter density (GMD) reductions in FES compared to HC bilaterally in the temporal and prefrontal areas, including the anterior cingulate gyrus, as well as in both thalami. Hippocampus and amygdala were affected on the left side (P<0.05, corrected). In REZ patients this pattern was spatially extended. The basal ganglia were exclusively reduced in the recurrently ill group compared to controls. Common to both disease groups were reductions in the bilateral perisylvian regions, the opercular region, the insula, prefrontal cortex, left inferior temporal gyrus, limbic system including hippocampus and amygdala, and the thalami. In FES patients there were no regions affected that were not also affected in REZ patients. In contrast, REZ patients showed extended alterations within the frontal and temporal regions, the hippocampus, amygdala and exclusively in the basal ganglia relative to the FES patients. Our findings suggest a system-specific involvement of neuronal networks in schizophrenia. Furthermore, our data suggest that in the advanced stages of schizophrenia additional cortical and subcortical brain areas become involved in the disease process. Longitudinal data will be required to further test this hypothesis.

Neuroimaging genetics: new perspectives in research on major depression?

OBJECTIVE: Stress-related changes in the hippocampus are influenced by genetic factors. To enhance our understanding of both the interaction between the brain, behaviour and genetics and of biological mechanisms in mood disorders neuroimaging genetics provide a good opportunity. METHOD: A MEDLINE search was conducted to identify articles on neuroimaging genetics in major depression (MD). RESULTS: Hippocampal volumes were found to be associated with polymorphisms in the promotor region of the serotonin transporter (5-HTTLPR) in patients with MD. Met-allele carriers of the BDNF (val66met) polymorphism had smaller hippocampal volumes in both patients and healthy controls when compared with homozygous val-allele carriers. Polymorphisms of the serotonin transporter (5-HTTLPR) and 5-HT1a receptor are associated with increased amygdala activation investigated with functional MRI in patients with MD. CONCLUSION: Genetic variants seem to modulate the effects of stress on hippocampal volumes as well as amygdala activity as well as the development of the brain.

5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder.

Alterations of amygdala structure and function have been repeatedly described in patients with borderline personality disorder (BPD). The aim of our study was to determine whether a functional polymorphism of the 5-hydroxytryptamine(1A) receptor (5-HTR(1A)) gene C -1019 G (identity number: rs6295 G/C) is associated with structural changes of the amygdala in patients with BPD. Twenty-five right-handed female inpatients with BPD according to DSM IV and 25 healthy controls matched for age, sex, handedness and educational status were enrolled. Brain volumetry of the amygdala was performed with a 1.5-T Magnetom Vision apparatus (Siemens, Erlangen, Germany) and analyzed by the software program 'BRAINS'. Patients who have the 5-HTR(1A) gene G allele had significantly smaller amygdala volumes than C/C genotype carriers (P = 0.02). While no difference of allelic distribution between patients and controls was detected, the described effect of 5-HTR(1A) genotype on amygdala volume was found for the whole group of patients, as well as in the subgroup of patients with comorbid major depression (P = 0.004) but not in controls. In contrast to these subgroups of BPD patients who had significant amygdala volume differences, the mean amygdala volume of the whole group of BPD patients was not significantly different from that of controls. In summary, our study provides first evidence that 5-HTR(1A) gene C -1019 G polymorphism is associated with structural changes in the limbic system of BPD patients, a finding that might be disease related and might contribute to explanation of previous discrepant results regarding amygdala volume changes in BPD. Future research is recommended to clarify possible interactions between this functional polymorphism and symptoms, course and treatment responses in this disorder.

Structural brain alterations in subjects at high-risk of psychosis: a voxel-based morphometric study.

Forty Untreated high-risk (HR) individuals for psychosis and 75 healthy control subjects (HC) matched for age, gender, handedness and educational level were investigated by structural MRI. HR subjects were recruited at the Early Detection and Intervention Centre for Mental Crises (FETZ) of the Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Germany. Measurements of gray matter volumes were performed by voxel-based morphometry using SPM5. The sample of HR subjects showed GM volume reductions in frontal, lateral temporal and medial temporal regions compared to the healthy control group. These regions are compatible with structural findings in the clinically apparent disease of schizophrenia.