Psychiatry and Clinical Neurosciences

Abstract  The Mini‐International Neuropsychiatric Interview (MINI) is a short, structured diagnostic interview used as a tool to diagnose 16 axis I (Diagnostic and Statistical Manual) DSM‐IV disorders and one personality disorder. Its original version was developed by Sheehan and Lecrubier. We translated the MINI into Japanese, and investigated the reliability and validity of the Japanese version of MINI. Eighty‐two subjects participated in the validation of the MINI versus the Structured Clinical Interview for DSM‐III‐R (SCID‐P). One hundred and sixty‐nine subjects participated in the validation of the MINI versus an expert's professional opinion. Seventy‐seven subjects were interviewed by two investigators and subsequently readministered by a third interviewer blind to the results of initial evaluation 1–2 days later. In general, kappa values indicated good or excellent agreement between MINI and SCID‐P diagnoses. Kappa values indicated poor agreement between MINI and expert's diagnoses for most diagnoses. Interrater and test–retest reliabilities were good or excellent. The mean durations of the interview were 18.8 min for MINI and 45.4 min for corresponding sections of SCID‐P. Overall, the results suggest that the MINI Japanese version succeeds in reliably and validly eliciting symptom criteria used in making DSM‐III‐R diagnoses, and can be performed in less than half the time required for the SCID‐P.

Psychotropic dose equivalence is an important concept when estimating the approximate psychotropic doses patients receive, and deciding on the approximate titration dose when switching from one psychotropic agent to another. It is also useful from a research viewpoint when defining and extracting specific subgroups of subjects. Unification of various agents into a single standard agent facilitates easier analytical comparisons. On the basis of differences in psychopharmacological prescription features, those of available psychotropic agents and their approved doses, and racial differences between Japan and other countries, psychotropic dose equivalency tables designed specifically for Japanese patients have been widely used in Japan since 1998. Here we introduce dose equivalency tables for: (i) antipsychotics; (ii) antiparkinsonian agents; (iii) antidepressants; and (iv) anxiolytics, sedatives and hypnotics available in Japan. Equivalent doses for the therapeutic effects of individual psychotropic compounds were determined principally on the basis of randomized controlled trials conducted in Japan and consensus among dose equivalency tables reported previously by psychopharmacological experts. As these tables are intended to merely suggest approximate standard values, physicians should use them with discretion. Updated information of psychotropic dose equivalence in Japan is available at http://www.jsprs.org/en/equivalence.tables/. [Correction added on 8 July 2015, after first online publication: A link to the updated information has been added.]

Mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BPD), are the most prevalent psychiatric conditions, and are also among the most severe and debilitating. However, the precise neurobiology underlying these disorders is currently unknown. One way to combat these disorders is to discover novel biomarkers for them. The development of such biomarkers will aid both in the diagnosis of mood disorders and in the development of effective psychiatric medications to treat them. A number of preclinical studies have suggested that the brain‐derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of MDD. In 2003, we reported that serum levels of BDNF in antidepressant‐naive patients with MDD were significantly lower than those of patients medicated with antidepressants and normal controls, and that serum BDNF levels were negatively correlated with the severity of depression. Additionally, we found that decreased serum levels of BDNF in antidepressant‐naive patients recovered to normal levels associated with the recovery of depression after treatment with antidepressant medication. This review article will provide an historical overview of the role played by BDNF in the pathophysiology of mood disorders and in the mechanism of action of therapeutic agents. Particular focus will be given to the potential use of BDNF as a biomarker for mood disorders. BDNF is initially synthesized as a precursor protein proBDNF, and then proBDNF is proteolytically cleaved to the mature BDNF. Finally, future perspectives on the use of proBDNF as a novel biomarker for mood disorders will be discussed.

Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

Aim:  Reports on resting brain activity in healthy controls have described a default‐mode network (DMN) and important differences in DMN connectivity have emerged for several psychiatric conditions. No study to date, however, has investigated resting‐state DMN in relatively early depression before years of medication treatment. The objective of the present study was, therefore, to investigate the DMN in patients seeking help from specialized mental health services for the first time for symptoms of depression.

Methods:  Fourteen depressed subjects and 15 matched controls were scanned using 4‐T functional magnetic resonance imaging while resting with eyes closed. All but one subject was medication free. A precuneus/posterior cingulate cortex (P/PCC) seed‐region connectivity analysis was used to identify the DMN and compare study groups in regions of relevance to depression.

Results:  The P/PCC analysis identified the DMN well in both study groups, consistent with prior literature. Direct comparison showed significantly reduced correlation between the P/PCC and the bilateral caudate in depression compared with controls and no areas of increased connectivity in the depressed group.

Conclusions:  The present study is the first to investigate resting‐state DMN in the early stages of treatment‐seeking for depression. Depressed subjects had decreased connectivity between the P/PCC and the bilateral caudate, regions known to be involved in motivation and reward processing. Deficits in DMN connectivity with the caudate may be an early manifestation of major depressive disorder.

Aim:  Violence risk prediction is a priority issue for clinicians working with mentally disordered offenders. The aim of the present study was to determine violence risk factors in acute psychiatric inpatients.

Methods:  The study was conducted in a locked, short‐term psychiatric inpatient unit and involved 374 patients consecutively admitted in a 1‐year period. Sociodemographic and clinical data were obtained through a review of the medical records and patient interviews. Psychiatric symptoms at admission were assessed using the Brief Psychiatric Rating Scale (BPRS). Psychiatric diagnosis was formulated using the Structured Clinical Interview for DSM‐IV. Past aggressive behavior was evaluated by interviewing patients, caregivers or other collateral informants. Aggressive behaviors in the ward were assessed using the Overt Aggression Scale. Patients who perpetrated verbal and against‐object aggression or physical aggression in the month before admission were compared to non‐aggressive patients, moreover, aggressive behavior during hospitalization and persistence of physical violence after admission were evaluated.

Results:  Violent behavior in the month before admission was associated with male sex, substance abuse and positive symptoms. The most significant risk factor for physical violence was a past history of physically aggressive behavior. The persistent physical assaultiveness before and during hospitalization was related to higher BPRS total scores and to more severe thought disturbances. Higher levels of hostility–suspiciousness BPRS scores predicted a change for the worse in violent behavior, from verbal to physical.

Conclusion:  A comprehensive evaluation of the history of past aggressive behavior and psychopathological variables has important implications for the prediction of violence in psychiatric settings.

Aims:  Anxiety a core feature of panic disorder, is linked to function of the amygdala. Volume alterations in the brain of patients with panic disorder have previously been reported, but there has been no report of amygdala volume association with anxiety.

Methods:  Volumes of hippocampus and amygdala were manually measured using magnetic resonance imaging obtained from 27 patients with panic disorder and 30 healthy comparison subjects. In addition the amygdala was focused on, applying small volume correction to optimized voxel‐based morphometry (VBM). State–Trait Anxiety Inventory and the NEO Personality Inventory Revised were also used to evaluate anxiety.

Results:  Amygdala volumes in both hemispheres were significantly smaller in patients with panic disorder compared with control subjects (left: t = −2.248, d.f. = 55, P = 0.029; right: t = −2.892, d.f. = 55, P = 0.005). VBM showed that structural alteration in the panic disorder group occurred on the corticomedial nuclear group within the right amygdala (coordinates [x,y,z (mm)]: [26,−6,−16], Z score = 3.92, family‐wise error‐corrected P = 0.002). The state anxiety was negatively correlated with the left amygdala volume in patients with panic disorder (r = −0.545, P = 0.016).

Conclusions:  These findings suggested that the smaller volume of the amygdala may be associated with anxiety in panic disorder. Of note, the smaller subregion in the amygdala estimated on VBM could correspond to the corticomedial nuclear group including the central nucleus, which may play a crucial role in panic attack.

Abstract  Several studies have discussed the relationships between T‐helper 1 (Th1) or Th2 cytokines and major depression. The aim of the present study was to investigate the relationships between Th1/Th2 cytokine balance and clinical phenotypes of acute‐phase major depression. A total of 82 subjects including 42 patients with major depressive disorder and 40 healthy controls were recruited. Serum cytokine levels of interleukin‐1β (IL‐1β), tumor necrosis factor‐α (TNF‐α) and IL‐10 were examined. Using ancova with age and body mass index (BMI) adjustments, there were no significant differences in serum IL‐1β, TNF‐α, and IL‐10 levels between patients with major depressive disorder and healthy controls. However, using ancova with BMI adjustment only, the results showed that patients with major depressive disorder had significantly higher TNF‐α levels than control subjects. In addition, using ancova with age and BMI adjustments, significantly higher serum IL‐1β level and IL‐1β/IL‐10 ratio were noted in patients with melancholic features than patients with non‐melancholic features. However, there were no significant differences in serum IL‐1β, TNF‐α and IL‐10 levels between patients with and without suicide attempt. In conclusion, serum TNF‐α, IL‐1β level and IL‐1β/IL‐10 ratio might play an important role in the psychopathology of acute‐phase major depressive disorder.