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Genetic risk for depressive disorders is poorly understood despite consistent suggestions of a high heritable component. Most genetic studies have focused on risk associated with single variants, a strategy which has so far only yielded small (often non-replicable) risks for depressive disorders. In this paper we argue that more substantial risks are likely to emerge from genetic variants acting in synergy within and across larger neurobiological systems (polygenic risk factors). We show how knowledge of major integrated neurobiological systems provides a robust basis for defining and testing theoretically defensible polygenic risk factors. We do this by describing the architecture of the overall stress response. Maladaptation via impaired stress responsiveness is central to the aetiology of depression and anxiety and provides a framework for a systems biology approach to candidate gene selection. We propose principles for identifying genes and gene networks within the neurosystems involved in the stress response and for defining polygenic risk factors based on the neurobiology of stress-related behaviour. We conclude that knowledge of the neurobiology of the stress response system is likely to play a central role in future efforts to improve genetic prediction of depression and related disorders.

Repetitive transcranial magnetic stimulation (rTMS) is a neurostimulatory technique used to modulate orbital frontal corticostriatal (OFC) activity and clinical symptomatology for psychiatric disorders involving OFC dysfunction. We examined the effectiveness of rTMS in the treatment of major depressive disorder in an applied clinical setting (Awakening KC CNI) to assess efficacy and optimize rTMS parameters within clinical practice. A retrospective review of medical records was carried out on patients with major depressive disorder undergoing rTMS therapy at Awakenings KC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. A detailed de-identified data set of clinical outcomes was compiled. Patient Health Questionnaire 9 (PHQ-9) total score, clinical remission rate and week achieved were evaluated over 6 weeks of treatment to assess clinical response referencing two different rTMS instruments (MagVenture; NeuroStar). Our survey included 247 participants from males (N=98) and females (N=149) with average baseline PHQ-9 scores of 21.7±4, classified as severe depression. Clinically rated remission rates of 72% were achieved in 3.1±1.0 weeks and associated with prior history of psychiatric hospitalization, suicide attempts and substance use disorder. Average baseline PHQ-9 scores decreased significantly over time with proportionately greater remission rates achieved for patients treated using the MagVenture over NeuroStar instrument. rTMS in applied clinical practice is efficacious over a wide range of settings and patients. Clinical response was related to severity of depression symptoms (e.g., prior hospitalization; suicide attempts) validating efficacy in critically ill groups. Clinical response may be impacted by rTMS instrument, magnetic field parameters or individual factors.

This study is a follow-up of inpatients diagnosed with severe depression/melancholia between 1956 and 1969. During this period, all inpatients at the Department of Psychiatry, University Hospital, Lund, were rated on a multidimensional diagnostic schedule on discharge. There were 471 patients born from 1920 onward. In the present follow-up, 2006 to 2010, 169 survivors could be traced. They were asked to participate in the study involving a telephone interview, in which a structured life chart was used. Of the patients contacted, 16 were ill or confused and 3 did not remember ever being depressed, leaving 150 who could participate. Seventy-five of these agreed to participate in the study. Long-term course of depression was evaluated by cluster analysis and compared to background variables, such as heredity for depression, perceived parental rearing behaviour, and treatment of index depressive episode. Using a cluster analysis the patients could be separated into six clusters describing the course: i) single or few episodes followed by long-lasting remission; ii) single or few episodes followed by long-lasting remission, although shorter; iii) single or few episodes followed by late recurrence; iv) single or few episodes, but more frequently ill, followed by late recurrence; v) several episodes followed by lasting remission; vi) chronic course of episodes. Remission or recurrence could therefore occur even after more than a decade. In summary, there was a short-term course with or without recurrence or a chronic course with or without late remission. Heredity for depression was significantly related to a chronic course with or without late remission.

Anxiety, depression and impaired health-related quality of life (HRQoL) are commonly reported in patients with multiple sclerosis (MS) and are of great interest for therapeutic approaches. Based on regional differences a quantitative assessment of these factors in comparison to the general population, and the consideration of demographic cofactors, would be useful when designing specific interventions. We adopted such an approach in a German cohort of MS patients. Anxiety, depression (HADS) and HRQoL (SF-36) were measured in 49 consecutive outpatients with MS and compared to age- and gender-adjusted control groups (n=1330 for HADS; n=5087 for SF-36) extracted from German National Health Surveys. Patients with MS showed significantly increased levels of anxiety and depression as well as decreased HRQoL with the exception of mental health; the effect sizes ranged from 0.39 (depression) to 1.06 (physical functioning). As could be expected, MS patients with relapsing-remitting clinical course had better physical functioning than patients with secondary progressive MS. There were strong relations between anxiety and depression (r=0.54; P<0.01), and between neurological impairment (EDSS) and physical functioning (r=-0.80; P<0.001) as well as depression (r=0.48; P<0.05). This investigation of MS patients confirms the prevalence and impact of anxiety, depression and most of the HRQoL dimensions in MS patients and provides evidence for the usefulness of a quantitative comparison to a region-specific general population as a starting point for therapeutic approaches.

Mental disorders lead to difficulties in social, occupational and marital relations. Failure to detect mental disorder denies patients potentially effective treatment. This study aimed to assess the prevalence and nature of mental disorders at the primary care settings and the recognition of these disorders by the attending physicians. Over a period of eight weeks, consecutive and consenting patients who attended three randomly selected primary health care facilities in Sagamu Local Government Area of Ogun state were recruited and administered a questionnaire that included a socio-demographic section and Patient Health Questionnaire (PHQ). A total of 412 subjects took part in the study. Subject age ranged from 18-90 years with a mean age of 52.50±21.08 years. One hundred and seventy-six (42.7%) of the subjects were males. A total of 120 (29.1%) of the subjects had depressive disorder, 100 (24.3%) had anxiety disorder, 196 (47.6%) somatoform disorder and 104 (25.2%) met the criteria for an alcohol related problem. The PHC physicians were only able to diagnose disorders relating to mental health in 52 (12.6%) of the subjects. Health and work situations accounted for more than three-quarters of the causes of stress experienced by the subjects. We conclude that there is a high prevalence of mental disorders among patients seen in primary care settings and that a significant proportion of them are not recognized by the primary care physicians. Stress relating to health, work and financial problems is common among primary health care attendees. Physicians in primary health care should be alert to the possibility and the impact of undetected psychiatric morbidity.

We previously examined the efficacy of rTMS for major depressive disorder in an applied clinical practice. Clinical response was related to severity of depression as well as the rTMS instrument utilized suggesting a relationship to instrument or magnetic field parameters and individual factors. The effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder was further evaluated using Log-Rank statistics for time to remission outcomes. A follow-up retrospective medical records study was carried out on patients with major depressive disorder undergoing rTMS therapy at AwakeningsKC Clinical Neuroscience Institute (CNI), a suburban tertiary psychiatric clinic. Cox Proportional Hazard with Log-Rank statistics were applied and the time course to clinical remission was evaluated over a 6-week period with respect to age, gender, and depression severity. Clinical response was observed referencing two different rTMS instruments (MagVenture; NeuroStar). Time to remission studies of 247 case reports (N=98 males; N=149 females) showed consistently greater clinically defined remission rates after 6 weeks of rTMS treatment for patients using the MagVenture vs NeuroStar instrument. Patients previously admitted for inpatient psychiatric hospitalization exhibited higher response rates when treated with the MagVenture rTMS unit. Stepwise Cox Proportional Hazards Regression final model of time to remission included rTMS unit, inpatient psychiatric hospitalization and obese body habitus. Response to rTMS in applied clinical practice is related to severity of psychiatric illness and may require consideration of magnetic field parameters of the rTMS unit with respect to individual factors such as sex or body composition.

Previous research has found that individuals with social phobia differ from controls in their processing of emotional faces. For instance, people with social phobia show increased attention to briefly presented threatening faces. However, when exposure times are increased, the direction of this attentional bias is more unclear. Studies investigating eye movements have found both increased as well as decreased attention to threatening faces in socially anxious participants. The current study investigated eye movements to emotional faces in eight patients with social phobia and 34 controls. Three different tasks with different exposure durations were used, which allowed for an investigation of the time course of attention. At the early time interval, patients showed a complex pattern of both vigilance and avoidance of threatening faces. At the longest time interval, patients avoided the eyes of sad, disgust, and neutral faces more than controls, whereas there were no group differences for angry faces.

We set out to carry out a case-control evaluation of psychological distress and emotional pain among adult attendees of a Nigerian dental clinic. A total of 201 subjects, made up of 101 dental patients (test group) matched with age and sex with 100 normal subjects (controls), was recruited into the study. All participants completed a designed socio-demographic questionnaire. General Health Question naire and Psyche ache Assessment Schedule were also administered to assess psychological distress based on cut-off scores ?3 and emotional pain based on cut-off scores ?28 respectively. The mean ages of study and control group were 33 (±12) and 36 (±13) years respectively, and both study and control groups were not significantly different in all the assessed socio-demographic parameters. Overall, 21.8% (n=22) of the subjects had psychological distress, while only 7% of the control group had psychological distress. This difference was statistically significant (P=0.003). Similarly, there was significant difference in the experience of psyche ache (unbearable psychological pain) as over a third of the dental patients (37.6%, n=38) had emotional pain, while only 13% of the controls experienced psych ache (P<0.001). In this study, the burden of psychological distress and emotional pain was many-fold in dental patients when compared with the controls.

This study aims to examine the association of frontal functioning with subclinical bipolar spectrum by a newly developed convenient method. We investigated subclinical bipolar tendency and frontal lobe activation during word productions using multi-channel near infrared spectroscopy. Participants: 44 healthy university students (mean ages 20.5 years old, and 29 female) gave their written informed consent, and we strictly protected privacy and anonymity was carefully preserved. A 13-items self-report questionnaire (Mood Disorders Questionnaire; MDQ) and a 16-channel near-infrared spectroscopy were used to compare frontal activations between two samples divided by median (4 points) of the total MDQ scores and to analyze correlations between relative changes of cerebral blood volume and bipolarity levels. There was no case suspected as bipolar disorders by MDQ screening (mean 3.4, max 10). Significant differences in lower activations were noted in the right and left pre-frontal cortex (PFC) with higher bipolarity scores using the specific software to analyze the NIRS waveform (P<0.05). Total MDQ were correlated significantly with frontal activation negatively in many channels; therefore, we conducted multiple linear regression to select significant frontal activations using the MDQ as a dependent variable. Stepwise method revealed that activation in left lateral PFC was negatively associated to bipolar tendency, and this regression model was significant (R2=0.10, F=4.5, P=0.04). Differences in frontal functioning suggest that subclinical bipolar tendencies might be related to left lateral PFC activations. It should be confirmed whether the identical pattern can be identified for clinical subjects with bipolar disorders.

Stigmatising attitudes towards persons with mental illness are commonly reported among health professionals. Familiarity with mental illness has been reported to improve these attitudes. Very few studies have compared future medical doctors' attitudes toward types of mental illness, substance use disorders and physical illness. A cross-sectional survey of 5th and 6th year medical students as well as recently graduated medical doctors was conducted in April 2011. The 12-item level of contact report and the Attitude towards Mental Illness Questionnaire were administered. Partici -pants endorsed stigmatising attitudes towards mental illness; with attitudes more adverse for schizophrenia compared to depression. Stigmatising attitudes were similarly endorsed for substance use disorders. Paradoxically, attitudes towards HIV/AIDS were positive and similar to diabetes mellitus. Increasing familiarity with mental illness was weakly associated with better attitudes towards depression and schizophrenia. Stigmatising attitudes towards depression and schizophrenia are common among future doctors. Efforts to combat stigma are urgently needed and should be promoted among medical students and recent medical graduates.