Telemedicine for outpatient treatment of depressive disorders.

BACKGROUND: The newly developed app TellUs is a digital offering for psychiatric outpatient treatment that includes diagnostic and therapeutic tools. The aim of this study was to test the clinical efficiency and patient satisfaction of TellUs. METHODS: Sixty-four patients with depressive disorder took part in the study for 3 months. The intervention group was treated digitally with TellUs and the control group received visiting treatment (treatment as usual) during that time. RESULTS: In both groups, a significant decrease of depressive symptoms and general strain through psychological symptoms, along with an increase of quality of life in the psychological domain, was shown. Furthermore, both groups were highly satisfied with the treatment. CONCLUSIONS: TellUs was shown to be equivalent to treatment as usual in terms of clinical efficiency and patient satisfaction.

Psychosocial functioning as a personal resource promoting a milder course of schizophrenia.

Schizophrenia has been shown repeatedly to be associated with a low level of psychosocial functioning. It is assumable that psychosocial functioning is related not only to current, but also to future symptom severity. To test this assumption, a follow-up study with two measurement time points with an interval of 18 months was conducted. In total, 154 inpatients from five psychiatric hospitals with a diagnosis of a schizophrenic disorder took part at both visits. Psychosocial functioning was measured with the Personal and Social Performance Scale (PSP scale) at baseline, and schizophrenic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS) at baseline and at follow-up. Two PSP subscales, i.e. socially useful activities and control over disturbing and aggressive behavior, turned out to be significant predictors of symptom severity 18 months later. The findings reveal that personal resources in the occupational domain and in adequate interpersonal behavior can have a positive impact on the long-term course of schizophrenia.

Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Quality of Parental Care and Traumatic Experiences in Childhood Related to Schizophrenic Disorders.

In recent times, an increasing interest in the role of childhood adversities in schizophrenia can be seen. In this study, 37 schizophrenic patients were compared with 25 individuals from the general population with regard to the quality of parental care and traumatic experiences in childhood. Two self-report scales for retrospective measurement of these variables were used that differentiate between maternal and paternal rejection, emotional warmth and control on the one hand, and trauma subtypes on the other. The schizophrenic patients scored lower regarding both parents' emotional warmth and higher regarding emotional and physical abuse and neglect. Group membership was correctly predicted with these childhood variables in 83% of cases, with the mother's emotional warmth being the best predictor. The findings underline the relevance of childhood adversities in schizophrenic diseases in adulthood, with special emphasis on the role of emotional acceptance from the primary caregiver.

Adjuvant Guided Exercise Therapy Versus Self-Organized Activity in Patients With Major Depression.

Exercise seems to be effective in reducing depression itself, as well as the risk of relapse. This study evaluated whether standardized guided exercise therapy (GET) in comparison with self-organized activity (SOA) is an effective augmentation therapy in depressive adults. A total of 111 inpatients (66.7% women; mean age, 45.05 ± 12.19 years) with major depression were randomly assigned to either GET or SOA. Interventions were performed three times a week, with each session lasting 50 minutes. Both GET and SOA exerted effects even after a short-term application of 6 weeks. GET was superior to SOA in reducing depression symptom severity, as measured by the Hamilton Depression Scale (p = 0.017), specifically improving suicidality (p = 0.028) as well as time (p = 0.003) and severity of diurnal variation (p = 0.027). The findings support the beneficial role of adjuvant GET in patients with major depression as a feasible treatment in a psychiatric short-term inpatient setting.

Role of child maltreatment and gender for bipolar symptoms in young adults.

BACKGROUND: Child maltreatment has been shown to be associated with a wide range of mental disorders, including bipolar disorders. In this 2-year follow-up study, recollections of emotional, physical and sexual abuse were related to bipolar symptoms, namely depressive, hypomanic and manic symptoms. METHODS: The sample consists of 134 students who took part at five measurement times within the 2-year period. Data were collected with self-report scales. RESULTS: The results show that recollections of abuse, particularly emotional abuse, were associated with more severe depressive symptoms; this finding, however, only applied to women. Hypomanic and manic symptoms were not associated with recollections of abuse. For hypomanic symptoms, however, a significant decrease over the 2 years was observed. CONCLUSIONS: The findings of this study suggest that recollections of abusive experiences in childhood combined with female gender increase the risk for depression, whereas hypomanic and manic states are probably better predicted by other factors, such as current life circumstances.

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study.

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

At-risk symptoms of bipolar disorder in a university student cohort.

To assess the occurrence and frequency of bipolar at-risk symptoms in a large sample of previously undiagnosed students using the new screening tool Bochumer Screeningbogen Bipolar (BSB). 2329 students of the Ruhr-University Bochum, Germany completed online demographic data as well as various self-rating questionnaires (BSB; Hypomania Checklist 32; Altman Self-Rating Mania Scale; Beck Depression Inventory). Within the student cohort (64.4% female, mean age 24.3 years) every fifth student currently suffered from moderate to severe depressive symptoms; every sixth student had already thought about suicide and every other student reported a history of mood swings. The most frequently reported depressive symptoms included physical exhaustion, depressed mood, and tiredness. The most frequently reported (hypo)manic symptoms included physical agitation, feeling extremely energetic, and lack of concentration. The BSB showed good convergent validity with other established questionnaires capturing depressive or (hypo)manic symptoms, as well as a stable administration of underlying constructs. The BSB correlated significantly with the already established applied questionnaires. The predictive power of the BSB regarding the development of bipolar disorder cannot be correctly quantified at present. The further purpose of this exploratory web-based study should be to examine the validity of the presented measures in a longitudinal design.

A case of GABAR antibodies in schizophrenia.

BACKGROUND: In the last couple of years, schizophrenia was often discussed as autoimmune disease. Several antibodies were suspected, but so far there has been no proof of Gamma-aminobutyric acid (GABA) receptor antibodies in patients with schizophrenia. CASE PRESENTATION: In this case report we present a 21-year old woman with schizophrenic symptoms, who showed anti-GABAB1 antibodies when screened by a vast recombinant neurology mosaic on Human Embryonic Kidney Cells 293 (HEK293) cells. The young woman presented with various psychotic symptoms as well as speech and motor ataxia, with the neurological signs starting in childhood. CONCLUSION: A hypofunction of the GABAergic system is a possible cause of severe schizophrenic symptoms. Postmortem studies proved this hypothesis by showing dysfunctional GABAergic interneurons in various brain areas. Therefore one should always think of an immune-mediated pathogenesis as well memory impairment and behavioral changes co-occur with frequent seizures.

Digital comparison of healthy young adults and borderline patients engaged in non-suicidal self-injury.

BACKGROUND: It still remains unclear whether non-suicidal self-injury (NSSI) in young adult populations represents an actual symptom leading to psychiatric illness, constitutes a disorder itself or is rather a cultural peer influence. The purpose of this web-based qualitative cross-sectional study was to characterize NSSI (type of injury, frequency, tools, body parts, circumstances) in 50 patients with borderline personality disorder (NSSI + BPD) in direct comparison with 50 age and gender matched non-clinical young adults (NSSI - BPD), all of them currently or previously engaged in NSSI. METHODS: Self-harming participants completed an open-access, anonymous 75-items questionnaire including the temperament questionnaire briefTEMPS-M. RESULTS: The mean age of NSSI onset was 20.56 ± 6.36 (NSSI + BPD) and 17.5 ± 9.28 years (NSSI - BPD), respectively (p = 0.261). NSSI - BPD participants (1) rarely sought out medical treatment (p < 0.001) and differed significantly from BPD patients; They (2) reported more often fear and disappointment as feelings preceding their self-harm (p < 0.001 each); (3) cut themselves in more locations (p = 0.005) and (4) in rather hidden areas (lower limb, proximal) (p = 0.002); (5) had lower depressive temperament scores (p = 0.007); and (6) scored generally fewer character traits "at risk" (p = 0.043) with a lower total score (p = 0.018). NSSI tended to onset slightly earlier in life and in different shape when BPD was absent. CONCLUSIONS: Our findings support current approaches of early NSSI recognition and identification of risk profiles. Further prospective studies, which have to be sufficiently large and longitudinal, are needed and of great importance.

The bipolar disorder prodrome revisited: Is there a symptomatic pattern?

OBJECTIVES: To assess the phenomenology and course of pre-(hypo)manic and pre-depressed prodromal symptoms, including mood swings, as precursors of bipolar disorder (BD) in a German multi-center study. METHODS: Semi-structured interviews [Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R); Semi-structured Interview for Mood Swings] were administered to patients within 8 years of BD (BD I, BD II) onset. RESULTS: Forty two outpatients were included (40.5% male, mean age 35.1±10.0 years, illness onset at 30.5±9.5 years). Feeling extremely energetic (85.7%), racing thoughts (78.6%), physical agitation (76.2%), overtalkativeness (71.4%), and low sleep requirement (71.4%) occurred most frequently prior to the first (hypo)manic episode, whereas depressed mood (83.0%), reduced vitality (81.0%), physical exhaustion (78.6%), tiredness (76.2%), and insomnia (66.7%) preceded pre-depressively. Mood lability (p=.006), odd ideas (p=.003) and the psychosis index score (p=.003) differed significantly in prevalence depending on the episodes' mood. Extremely energetic (p=.046), overtalkativeness (p<.001), and racing thoughts (p=.013) lasted significantly longer prior to depression. Neither severity nor frequency of prodromal symptoms differed significantly. Most of the symptoms emerged during the proximal prodromal phase. Links between mood swings and subsequent BD were found. LIMITATIONS: Symptoms were evaluated retrospectively with self-reporting tools in bipolar patients from academic treatment settings without comparison to clinical controls. CONCLUSIONS: Not only specific depressive or manic but also general symptoms occurred prior to both affective episodes. The pre-depressive prodrome lasted longer than the pre-manic one, but severity and frequency did not differ significantly. Mood swings and disturbed diurnal rhythm occurred prior to both episodes as early signs of BD.

[Negative emotions and understanding - patients' perspective on coercion]. / Negative Emotionen und Verständnis - Zwangsmaßnahmen aus Patientensicht.

OBJECTIVE: This study evaluated involuntarily admitted psychiatric patients' and their perception of coercive measures (i. e. involuntary admission and physical or pharmacological restraint) by asking retrospectively which emotions were induced during the process of coercion. METHOD: Interviews were carried out around 3 weeks after coercion. The interview consisted of 31 items categorized into demographic, nosological and coercion-related themes. Patients were also asked about their subjective experiences of the coercion. 40 patients were recruited, with 72 % suffering from psychosis-related and 21 % with affective disorders. For 22.5 % of the patients, this was their first psychiatric hospitalization. The most frequently reported emotions were rage, anger and despair. Patients who were more stable, according to the Clinical Global Impressions scale (CGI), generally evaluated the coercion as being worse. CONCLUSION: More than half of the patients were satisfied with the treatment received during hospitalization. The potential suffering caused as a result of patients' perceptions of the coercion, and the impact of this on the course of the disease should be taken into account when developing new treatment strategies.

Influence of (S)-ketamine on human motor cortex excitability.

Previous studies demonstrated a reduction of motor cortical excitability through pharmacological NMDA receptor blockage. Interestingly, subanesthetic doses of racemic ketamine, a non-competitive NMDA receptor antagonist, had no effects on intracortical excitability evoked by transcranial magnetic stimulation. In this study, we aimed to substantiate these findings by using the more active enantiomer (S)-ketamine. (S)-ketamine has a threefold higher affinity for the NMDA receptor, but relatively little is known about its specific effects on human motor cortex excitability. Eleven healthy subjects (two female) participated in a randomized, double-blind, placebo-controlled cross-over study with four treatment conditions: either placebo or one of three subanesthetic doses of intravenous (S)-ketamine (serum target 10, 30 and 50 ng/ml, respectively). We assessed intracortical inhibition and facilitation using a paired-pulse TMS-paradigm. Resting motor threshold and cortical silent period were assessed as additional parameters. Solely at highest (S)-ketamine concentrations, intracortical inhibition was significantly reduced and intracortical facilitation strongly tended to be enhanced. In addition, we found a tendency to a prolonged silent period, while resting motor threshold was unaffected. We conclude that subanesthetic doses of (S)-ketamine show an enhancement on excitability in human motor cortex. Similar to findings using the racemic mixture of ketamine, the effect may be due to an increase in non-NMDA glutamatergic transmission which outweighs the NMDA receptor blockade.

Antipsychotic-like effects of cannabidiol and rimonabant: systematic review of animal and human studies.

Several lines of experimental and clinical evidence point to a close relationship between cannabis, the endogenous cannabinoid system, and schizophrenia. A variety of animal and human studies found a dysregulation of endocannabinoid signalling in psychosis. Elevated anandamide levels in schizophrenia patients that are negatively correlated with psychotic symptomatology indicate a protective role, whereas 2-arachidonoylglycerol appears to counteract psychosis-related cognitive impairments. Thus, pharmacological manipulation of the endogenous cannabinoid system might be associated with potential antipsychotic properties. In the present systematic review, both preclinical studies using different animal models of psychosis as well as clinical trials investigating the antipsychotic effects of both cannabidiol and rimonabant are presented together with the possible underlying mechanisms of action. The results predominantly confirm the hypothesis of an antipsychotic activity of both cannabinoids. In comparison, cannabidiol appears to be superior to rimonabant with a pharmacological profile similar to atypical antipsychotic drugs.

Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia.

RATIONALE: Preclinical and clinical research suggests that the endogenous cannabinoid system is involved in cognitive impairments related to schizophrenia. In particular, the deficient generation of mismatch negativity (MMN) indicating auditory sensory memory is a characteristic finding in schizophrenic patients. Experimental studies implicate deficient N-methyl-D: -aspartate (NMDA) receptor functioning in such abnormalities. OBJECTIVES: The primary aim of this study was to investigate the effects of the cannabinoid CB(1) receptor antagonist rimonabant on MMN deficits in the NMDA receptor antagonist model of schizophrenia by using ketamine. METHODS: Twenty-four healthy male subjects participated in a randomized, double-blind, placebo-controlled cross-over study with subanesthetic doses of intravenous ketamine. The MMNs to frequency and duration deviants were elicited within an auditory oddball paradigm and recorded by a 32-channel EEG. Psychopathology was assessed using the Psychotomimetic States Inventory. RESULTS: Twenty subjects completed both experimental sessions. Ketamine infusion had no significant effect on MMN amplitudes in both deviance conditions. In contrast to placebo, co-administration of rimonabant produced significant deficits in MMN amplitudes to duration deviants at electrode position Fz. CONCLUSIONS: The results point to the involvement of the endogenous cannabinoid system in auditory sensory memory as a cognitive key feature in schizophrenia. They particularly suggest that CB(1) receptor antagonism may impair cognitive performance by a disturbed interaction between endocannabinergic activity and glutamatergic neurotransmission implied in schizophrenia.

Sensory changes and loss of intraepidermal nerve fibers in painful unilateral nerve injury.

OBJECTIVES: Dysaesthesias is a common symptom in patients with neuropathic pain after peripheral nerve injury (PNI). In contrast to neuropathies with comparable symptoms there is little knowledge of the underlying mechanisms in PNI patients. METHODS: Quantitative sensory testing according to the German Research Network on Neuropathic Pain protocol, and changes in intraepidermal nerve fiber density were assessed in 15 patients with dysaesthesias after PNI of the lower limb. According to their small-fiber function patients were assigned into 2 subgroups. RESULTS: The sensory profiles of PNI patients were characterized predominantly by minus symptoms (significantly increased thresholds for perception of cold, warm, touch and vibration, and significantly increased thresholds for heat and mechanical pain) on the affected compared with the unaffected side. The only plus symptom reported was a significantly reduced pressure pain threshold. The sensory profile of patients with a severe loss of small-fiber function (n=7) showed a thermal and tactile hypoaesthesia and hypoalgesia; this was in contrast to patients with a moderate loss of small-fiber function, who showed a mild thermal and tactile hypoaesthesia associated with an increased mechanical pain sensitivity. Mean intraepidermal nerve fiber density was significantly decreased in the affected compared with unaffected skin [3.50 (4.00) vs. 11.10 (7.60) fibers/mm] and correlated with warm and mechanical detection thresholds (both r=-0.60). DISCUSSION: In conclusion, even though patients presented with comparable clinical symptoms, their sensory profiles differed, supporting the concept of different underlying mechanisms leading to chronic pain in PNI patients. Skin biopsies support the validity of quantitative sensory testing.

Significant difference between three observers in the assessment of intraepidermal nerve fiber density in skin biopsy.

BACKGROUND: The determination of Intraepidermal Nerve Fiber Density (IENFD) in skin biopsy is a useful method for the evaluation of different types of peripheral neuropathies. To allow a reliable use of the method it is necessary to determine interobserver reliability. Previous studies dealing with this topic used limited suitable statistical methods. METHODS: In the present study three observers determined the IENFD and estimated the staining quality of the basement membrane for an adequate quantity of 120 skin biopsies (stained with indirect immunofluorescence technique) from 68 patients. More adequate statistical methods like intraclass correlation coefficient and Bland Altman Plot were chosen to estimate interobserver reliability. RESULTS: We found an unexpected significant difference in IENFD between the observers (p < 0.05) and so the results of this study are not in line with the high interobserver reliability reported before (intraclass correlation coefficient: 0.73). The Bland Altmann Plot showed a variance growing with rising mean. The difference in IENFD between the observers and the resulting low interobserver reliability is likely caused by different interpretations of the standard counting rules. There was no significant difference in IENFD between observers for biopsies with a well-defined basement membrane. Thus skin biopsies with an inexactly defined basement membrane should not be used diagnostically for the determination of IENFD. CONCLUSION: These results emphasise that standardisation of the method is extremely important and at least two observers should analyse skin biopsies with critical IENFD near the cut-off values.

Psychopathology in multiple sclerosis: diagnosis, prevalence and treatment.

Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system. Demyelinization of nerve fibres not only affects the motor and sensory systems functionally, but may also cause psychopathological signs and symptoms. In addition to the psychiatric manifestations of MS, many patients have reactive psychological problems that are often hard to distinguish from the 'organic' causation of psychopathology. In any event, psychiatric comorbidity in MS deserves greater clinical attention than has been previously paid, because the presence of psychopathology may have deleterious effects on the disease process and impair coping with disability.